NZ793839A - New anthelmintic quinoline-3-carboxamide derivatives - Google Patents
New anthelmintic quinoline-3-carboxamide derivativesInfo
- Publication number
- NZ793839A NZ793839A NZ793839A NZ79383917A NZ793839A NZ 793839 A NZ793839 A NZ 793839A NZ 793839 A NZ793839 A NZ 793839A NZ 79383917 A NZ79383917 A NZ 79383917A NZ 793839 A NZ793839 A NZ 793839A
- Authority
- NZ
- New Zealand
- Prior art keywords
- alkyl
- group
- halogen atoms
- halogenoalkyl
- alkoxy
- Prior art date
Links
- 230000000507 anthelmentic Effects 0.000 title 1
- BLTDCIWCFCUQCB-UHFFFAOYSA-N quinoline-3-carboxamide Chemical class C1=CC=CC2=CC(C(=O)N)=CN=C21 BLTDCIWCFCUQCB-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 55
- 239000000203 mixture Substances 0.000 claims abstract 11
- 201000010099 disease Diseases 0.000 claims abstract 6
- 230000002265 prevention Effects 0.000 claims abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 4
- 201000001181 parasitic helminthiasis infectious disease Diseases 0.000 claims abstract 3
- 125000005843 halogen group Chemical group 0.000 claims 296
- -1 C3-C4-alkenyl Chemical group 0.000 claims 122
- 125000004093 cyano group Chemical group *C#N 0.000 claims 108
- 229910052739 hydrogen Inorganic materials 0.000 claims 105
- 239000001257 hydrogen Substances 0.000 claims 105
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 96
- 229910052736 halogen Inorganic materials 0.000 claims 86
- 150000002367 halogens Chemical group 0.000 claims 86
- 125000001424 substituent group Chemical group 0.000 claims 80
- 150000002431 hydrogen Chemical group 0.000 claims 75
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 59
- 125000002496 methyl group Chemical compound [H]C([H])([H])* 0.000 claims 44
- 229910052731 fluorine Inorganic materials 0.000 claims 41
- 239000011737 fluorine Substances 0.000 claims 41
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 39
- 125000004043 oxo group Chemical group O=* 0.000 claims 39
- 125000001072 heteroaryl group Chemical group 0.000 claims 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 34
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 30
- 125000004429 atoms Chemical group 0.000 claims 29
- YCKRFDGAMUMZLT-UHFFFAOYSA-N fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 28
- 229910052801 chlorine Inorganic materials 0.000 claims 26
- 239000000460 chlorine Substances 0.000 claims 26
- 125000000217 alkyl group Chemical group 0.000 claims 24
- 229940035295 Ting Drugs 0.000 claims 22
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 22
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims 18
- 125000002950 monocyclic group Chemical group 0.000 claims 17
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims 14
- 125000000623 heterocyclic group Chemical group 0.000 claims 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 14
- 125000001153 fluoro group Chemical group F* 0.000 claims 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 13
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 12
- 125000001188 haloalkyl group Chemical group 0.000 claims 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 12
- 229910052717 sulfur Inorganic materials 0.000 claims 12
- 229910052760 oxygen Inorganic materials 0.000 claims 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 10
- 125000004438 haloalkoxy group Chemical group 0.000 claims 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 10
- 229910052757 nitrogen Inorganic materials 0.000 claims 9
- DHXVGJBLRPWPCS-UHFFFAOYSA-N THP Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 8
- WTKZEGDFNFYCGP-UHFFFAOYSA-N pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 8
- 150000003839 salts Chemical compound 0.000 claims 8
- 239000011780 sodium chloride Substances 0.000 claims 8
- 239000012453 solvate Substances 0.000 claims 8
- 125000003545 alkoxy group Chemical group 0.000 claims 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 7
- 125000004432 carbon atoms Chemical group C* 0.000 claims 7
- 150000001204 N-oxides Chemical class 0.000 claims 6
- AHHWIHXENZJRFG-UHFFFAOYSA-N Oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 6
- 229940113083 morpholine Drugs 0.000 claims 6
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 5
- 125000002887 hydroxy group Chemical compound [H]O* 0.000 claims 5
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 4
- 125000002853 C1-C4 hydroxyalkyl group Chemical compound 0.000 claims 4
- 229910018482 SF5 Inorganic materials 0.000 claims 4
- 125000003118 aryl group Chemical compound 0.000 claims 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 4
- 125000002757 morpholinyl group Chemical group 0.000 claims 4
- 150000003222 pyridines Chemical group 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 4
- 125000004758 (C1-C4) alkoxyimino group Chemical compound 0.000 claims 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 3
- 150000001804 chlorine Chemical compound 0.000 claims 3
- 229910052740 iodine Inorganic materials 0.000 claims 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 3
- 239000011630 iodine Substances 0.000 claims 3
- 125000004433 nitrogen atoms Chemical compound N* 0.000 claims 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- OTPDWCMLUKMQNO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrimidine Chemical compound C1NCC=CN1 OTPDWCMLUKMQNO-UHFFFAOYSA-N 0.000 claims 2
- WNBQDDAKLKODPH-UHFFFAOYSA-N 1,2,4-triazolidine Chemical compound C1NCNN1 WNBQDDAKLKODPH-UHFFFAOYSA-N 0.000 claims 2
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N 289-95-2 Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- NKSZCPBUWGZONP-UHFFFAOYSA-N 3,4-dihydroisoquinoline Chemical compound C1=CC=C2C=NCCC2=C1 NKSZCPBUWGZONP-UHFFFAOYSA-N 0.000 claims 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N Imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N Indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims 2
- 125000000815 N-oxide group Chemical compound 0.000 claims 2
- BRNULMACUQOKMR-UHFFFAOYSA-N Thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims 2
- 125000002485 formyl group Chemical compound [H]C(*)=O 0.000 claims 2
- WRYCSMQKUKOKBP-UHFFFAOYSA-N imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 2
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1,2,3-triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 1H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N 2,3-dihydro-1H-indole Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2H-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims 1
- BRHLUMXQJTXKMY-UHFFFAOYSA-N 8-oxa-1-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCN1O2 BRHLUMXQJTXKMY-UHFFFAOYSA-N 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N Azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- 125000001313 C5-C10 heteroaryl group Chemical compound 0.000 claims 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N Isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims 1
- OEWKYIRDOBSMPR-UHFFFAOYSA-N N12OCCC(CC1)C2 Chemical compound N12OCCC(CC1)C2 OEWKYIRDOBSMPR-UHFFFAOYSA-N 0.000 claims 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N Thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 claims 1
- 101710010068 YLR154C-H Proteins 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000005418 aryl aryl group Chemical compound 0.000 claims 1
- 125000002393 azetidinyl group Chemical group 0.000 claims 1
- 125000006367 bivalent amino carbonyl group Chemical compound [H]N([*:1])C([*:2])=O 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N n-heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims 1
- 150000003230 pyrimidines Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 150000003852 triazoles Chemical class 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract 2
- 238000004519 manufacturing process Methods 0.000 abstract 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 abstract 1
Abstract
The present invention covers new quinoline compounds of general formula (I) in which A, R1, R2, R3, R4, R5, R6, and Q are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients. ompounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment, control and/or prevention of diseases, in particular of helminth infections, as a sole agent or in combination with other active ingredients.
Description
The present invention covers new quinoline nds of l formula (I) in which A, R1, R2,
R3, R4, R5, R6, and Q are as defined herein, methods of preparing said compounds, intermediate
compounds useful for preparing said compounds, pharmaceutical itions and combinations
comprising said compounds and the use of said compounds for manufacturing pharmaceutical
compositions for the treatment, control and/or prevention of diseases, in particular of helminth
infections, as a sole agent or in combination with other active ingredients.
NZ 793839
NEW ANTHELMINTIC QUINOLINECARBOXAMIDE TIVES
This application is a divisional of New Zealand patent application 752550, which is the national phase
entry of , filed 6 November 2017, and published as
content of each of these applications is incorporated herein by reference.
The present invention covers new quinoline derivatives of general formula (I) as bed and
defined herein, methods of preparing said nds, intermediate compounds useful for
preparing said compounds, pharmaceutical compositions and combinations comprising said
compounds, and the use of said nds for manufacturing pharmaceutical compositions
for the control, treatment and/or prevention of diseases, in particular for the control, treatment
and/or prevention of infections with helminths, more particularly of infections with intestinal
and extra-intestinal nematodes, in animals and humans, formulations containing such
nds and methods for the control, treatment and/or prevention of infections with
helminths, more particularly of infections with gastro-intestinal and intestinal des,
in animals and humans as a sole agent or in combination with other active ingredients.
BACKGROUND
The occurrence of resistances against all commercial anthelmintics seems to be a growing
problem in the area of veterinary medicine. The extensive utilisation of anthelmintics to
manage the control of nematodes resulted in significant selection of highly resistant worm
populations. Therefore, the spread of ance against all anthelmintic drug classes ens
effective worm control in cattle, goats, sheep and horses. Furthermore, successful tion
of heartworm disease in dogs, which currently solely relies on the ation of macrocyclic
lactones, is in danger as loss of efficacy for le macrocyclic lactones has been described
for some regions of the United States of America - especially in those areas where the
orm challenge for infection is high. Finally, mental infection studies with Dirofilaria
immitis larvae from suspected field loss of efficacy cases in the Lower Mississippi Delta
provided in vivo confirmation of the existence of macrocyclic lactone resistance.
Although resistance of human helminths against anthelmintics seems currently to be rare, the
spread of anthelmintic resistance in the nary field as mentioned before needs to be
considered in the treatment of human helminthosis as well. Persistent underdosed treatments
against filariosis may lead to highly resistant genotypes and resistances have already been
described for n anthelmintics (e.g. praziquantel, benzimidazole and niclosamide).
Therefore, resistance-breaking anthelmintics with new molecular modes of action are urgently
required.
It is an object of the present invention to provide compounds which can be used as
mintics in the medical, especially veterinary, field with a satisfactory or improved
anthelmintic activity against a broad spectrum of helminths, ularly at relatively low
dosages, for the control, treatment and/or prevention of infections with helminths in animals
and humans, preferably without any adverse toxic effects to the treated organism.
Certain quinoline carboxamides are described in JP2008-214323A as agents suitable for
treatment and/or prevention of skin diseases, like acne vulgaris, dermatitis or the like.
The WO2017103851 discloses quinolinecarboxamides as H-PGDS inhibitors, useful for
treating atherosclerosis, psoriasis, sinusitis, and duchenne ar dystrophy.
However, the state of the art does not describe the new quinoline tives of general
formula (I) of the t invention as described and defined herein.
It has now been found, and this constitutes the basis of the present ion, that the
compounds of the present invention have surprising and advantageous properties.
In particular, the compounds of the present invention have surprisingly been found to
ively interact with Slo-1 calcium-gated ium channels of nematodes. This interaction
is characterized by ing paralysis/inhibition in particular of gastro-intestinal nematodes, of
free-living nematodes, and of filariae, for which data are given in the biological experimental
section. Therefore the compounds of the present invention may be used as anthelmintics for
the l, treatment and/or prevention of gastro-intestinal and extra-intestinal helminth
ions, in particular gastro-intestinal and extra-intestinal ions with nematodes,
including filariae.
DESCRIPTION of the INVENTION
In accordance with a first aspect, the present invention covers compounds of general
formula (I):
in which :
A is A1 or A2,
A1 A2
o is 0, 1, 2, 3 or 4,
R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -OH, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
noalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
noalkyl, –S(O)-C1-C4-halogenoalkyl and –SO2-C1-C4-halogenoalkyl having 1 to 5
halogen atoms,
Rp is ed from the group consisting of hydrogen, alkyl,
X, Y are ndently selected from the group consisting of CR7R8, O, S, and N-R9,
wherein at least one of X and Y is CR7R8, or
X, Y form together a ring member selected from the group consisting of -C(O)-O-, -C(O)-
NR9-, -S(O)-NR9-, -SO2-NR9- and -SO2-O-,
R1 is selected from the group consisting of hydrogen, cyano, -CHO, -OH, C1-C4-alkyl, C1-
C4-halogenoalkyl having 1 to 5 halogen atoms, alkoxy, halogenoalkoxy
having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5
halogen atoms, C3-C4-alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-
cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, -NH-C1-C4-alkyl, -N(C1-C4-alkyl)2, NH2-C1-C4-
alkyl-, C1-C4-alkyl-NH-C1-C4-alkyl-, (C1-C4-alkyl)2N-C1-C4-alkyl-, C1-C4-alkyl-C(O)-, C1-
C4-halogenoalkyl-C(O)- having 1 to 5 n atoms, C1-C4-alkoxy-C(O)-, benzyloxy-
C(O)-, C1-C4-alkoxy-C1-C4-alkyl-C(O)-, -SO2-C1-C4-alkyl, and –SO2-C1-C4-halogenoalkyl
having 1 to 5 halogen atoms;
phenyl-C1-C4-alkyl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently
selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-halogenoalkyl
having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5
halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-
alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-
C4-halogenoalkyl having 1 to 5 n atoms and –SO2-C1-C4-halogenoalkyl having 1
to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, n the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, halogenoalkoxy having
1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-
C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen
atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-
noalkyl having 1 to 5 halogen atoms,
R2 is selected from the group consisting of
hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-
alkyl), -C(O)-N(C1-C4-alkyl)2;
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C6-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents
independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-
alkyl-C(O)-, C1-C4-alkoxy-C(O)-, -C(O)-NH2, NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -
NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1-
C4-alkyl), -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, C4-halogenoalkyl
having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms
and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered cycloalkyl, 5-membered heteroaryl and 6-
ed heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-
C1-C4-alkyl, 1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –
S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl
having 1 to 5 halogen atoms;
phenyl which is optionally substituted by 1, 2 or 3 substituents independently selected
from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-
C4-alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered cycloalkyl, spirocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is ally substituted by 1, 2, 3 or 4
substituents independently selected from the group consisting of halogen, cyano,
nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl),
-C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)--, C1-C4-halogenoalkyl having 1 to
5 halogen atoms, C1-C4-alkoxy, y-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
n atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, and 4- to 10-
membered heterocycloalkyl,
R3 is en or C1-C4-alkyl,
R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
cycloalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy-C1-
C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-alkyl-
C(O)-, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-
C1-C4-alkyl,
R5 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C3-C6-cycloalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy-C1-
C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,C1-C4-alkyl-
C(O)-, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-
C1-C4-alkyl,
R6 is selected from the group ting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C3-C6-cycloalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy-C1-
C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-alkyl-
C(O)-, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-
C1-C4-alkyl,
R7 is selected from the group consisting of en, -OH, fluorine, C1-C4-alkyl and C1-C4-
alkoxy,
R8 is selected from the group consisting of hydrogen, -OH, fluorine, C1-C4-alkyl and C1-C4-
,
or R7 and R8 er form an oxo group (=O),
or R7 and R8 form, together with the carbon atom to which they are attached, a 3- to 6-
membered ring selected from the group consisting of C3-C6-cycloalkyl and 3- to 6-
membered heterocycloalkyl,
R9 is selected from the group consisting of hydrogen, alkyl, C1-C4-halogenoalkyl
having 1 to 5 halogen atoms and C1-C4-alkoxy,
R10 is selected from the group consisting of en, -OH, C1-C4-alkyl and C1-C4-alkoxy,
R11 is selected from the group consisting of hydrogen, C1-C4-alkyl and C1-C4-alkoxy,
or R10 and R11 form, together with the carbon atom to which they are attached, a 3- to 6-
membered ring ed from the group ting of C3-C6-cycloalkyl and 3- to 6-
membered heterocycloalkyl,
R12 and R13 are independently selected from the group consisting of
hydrogen, -OH, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(-C(O)-C1-C4-alkyl), -N(C1-
C4-alkyl)(-C(O)-C1-C4-alkyl), C1-C4-alkoxy, alkoxy-C(O)-;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)(-C(O)-C1-C4-alkyl), C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-
alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, ered aryl and 6-
membered heteroaryl, each of which is optionally tuted by 1, 2 or 3 substituents
independently selected from the group consisting of n, cyano, nitro, -OH, oxo,
thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-
cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -
SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 n atoms, –S(O)-C1-C4-
noalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to
halogen atoms;
phenyl, benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, cyano,
nitro, -OH, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-
alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 n atoms;
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is
optionally substituted by 1, 2 or 3 substituents independently selected from the group
consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -
C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, y-C1-C4-alkyl, C1-C4-
noalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
R14 is selected from the group ting of
-NH2, -NH(C1-C4-alkyl), C4-alkyl)2;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently ed from the group consisting of
halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
C(O)-N(C1-C4-alkyl)2, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-
C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -
NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –
S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having
1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl utent is selected from the group
ting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo,
thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-
cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -
SO2-C1-C4-alkyl, C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-
noalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to
halogen atoms;
phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected
from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-
C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle ed from the group consisting of 4- to 10-
ed heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each
of which is ally substituted by 1, 2 or 3 substituents independently selected from
the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-
C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-
noalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-
noalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
noalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, -COOH, alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms, C1-
C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -
NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –
S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having
1 to 5 n atoms and 1-C4-halogenoalkyl having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is ally substituted by 1, 2 or 3 substituents
independently ed from the group consisting of halogen, cyano, nitro, -OH, oxo,
thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-
cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -
SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to
5 halogen atoms;
phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected
from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, halogenoalkoxy having
1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-
C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a clic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each
of which is optionally substituted by 1, 2 or 3 substituents independently selected from
the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-
C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
Q is selected from the group consisting of 6- or 10-membered aryl and 5- to
-membered aryl, each of which is optionally substituted by 1, 2, 3, 4 or 5
tuents ed from the group consisting of halogen, SF5, cyano, -CHO, nitro,
oxo, C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms,
hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NHSO2-
(C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl,
4- to 6-membered heterocyclyl, which is optionally substituted with 1 or 2 substituents
selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -
CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, methyl substituted
with a 4- to ered heterocyclyl which itself is optionally substituted with 1 or 2
substituents selected from the group consisting of fluorine, chlorine, bromine, methyl
and cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S-
(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1
to 5 halogen atoms, (C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-
-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-
cycloalkyl), -NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-
halogenoalkyl) having 1 to 5 halogen atoms,
wherein when Y is O, S or N-R9, none of R7, R8, R10 and R11 is -OH, and wherein when X is O,
S or N-R9, none of R7 and R8 is -OH,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
DEFINITIONS
The term “substituted” means that one or more en atoms on the designated atom or
group are replaced with a selection from the indicated group, provided that the designated
atom's normal valency under the existing circumstances is not exceeded. Combinations of
tuents and/or variables are permissible.
The term nally substituted” means that the number of substituents can be equal to or
different from zero. Unless otherwise indicated, it is le that optionally substituted groups
are substituted with as many optional substituents as can be odated by replacing a
hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom.
Commonly, it is possible for the number of optional substituents, when present, to be 1, 2, 3, 4
or 5, in particular 1, 2 or 3.
As used herein, the term “one or more”, e.g. in the definition of the substituents of the
compounds of general formula (I) of the present invention, means “1, 2, 3, 4 or 5, ularly 1,
2, 3 or 4, more particularly 1, 2 or 3, even more particularly 1 or 2”.
As used herein, an oxo substituent represents an oxygen atom, which is bound to a carbon
atom or to a sulfur atom via a double bond.
The term “ring substituent” means a substituent attached to an aromatic or nonaromatic ring
which replaces an available hydrogen atom on the ring.
Should a composite substituent be composed of more than one parts, e.g.
(C1-C4-alkoxy)-(C1-C4-alkyl)-, it is possible for the position of a given part to be at any suitable
position of said composite substituent, i.e. the C1-C4-alkoxy part can be attached to any carbon
atom of the C1-C4-alkyl part of said (C1-C4-alkoxy)-(C1-C4-alkyl)- group. A hyphen at the
beginning or at the end of such a ite substituent indicates the point of attachment of
said composite substituent to the rest of the molecule. Should a ring, comprising carbon atoms
and optionally one or more heteroatoms, such as nitrogen, oxygen or sulfur atoms for
example, be substituted with a substituent, it is possible for said substituent to be bound at any
suitable position of said ring, be it bound to a suitable carbon atom and/or to a le
atom.
As used herein, the position via which a respective uent is connected to the rest of the
molecule may in a drawn ure be depicted by a hash sign (#) or a dashed line in said
substituent.
The term “comprising” when used in the specification es “consisting of”.
If within the present text any item is referred to as “as mentioned herein”, it means that it may
be mentioned anywhere in the present text.
The terms as mentioned in the present text have the following meanings:
The term “halogen atom” means a fluorine, chlorine, bromine or iodine atom, particularly a
fluorine, chlorine or bromine atom.
The term “C1-C6-alkyl” means a linear or branched, saturated, monovalent hydrocarbon group
having 1, 2, 3, 4, 5 or 6 carbon atoms. The term “C1-C4-alkyl” means a linear or ed,
ted, monovalent hydrocarbon group having 1, 2, 3, or 4 carbon atoms, e.g. a methyl,
ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or a tert-butyl group, or an isomer thereof.
Particularly, said group has 1, 2 or 3 carbon atoms (“C1-C3-alkyl”), e.g. a methyl, ethyl, n-propyl
or isopropyl group.
The term “C1-C4-hydroxyalkyl” means a linear or branched, saturated, monovalent hydrocarbon
group in which the term “C1-C4-alkyl” is defined supra, and in which 1 or 2 hydrogen atoms are
replaced with a hydroxy group, e.g. a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,
1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropanyl,
2-hydroxypropanyl, 2,3-dihydroxypropyl, hydroxypropanyl,
3-hydroxymethyl-propyl, 2-hydroxymethyl-propyl, 1-hydroxymethyl-propyl group.
The term “-NH(C1-C4-alkyl)” or “-N(C1-C4-alkyl)2” means a linear or branched, saturated,
monovalent group in which the term “C1-C4-alkyl” is as defined supra, e.g. a amino,
ethylamino, n-propylamino, isopropylamino, N,N-dimethylamino, N-methyl-N-ethylamino or
N,N-diethylamino group.
The term “-S-C1-C4-alkyl”, “-S(O)-C1-C4-alkyl” or “-SO2-C1-C4-alkyl” means a linear or
branched, saturated group in which the term -alkyl” is as defined supra, e.g. a
sulfanyl, ethylsulfanyl, ylsulfanyl, isopropylsulfanyl, n-butylsulfanyl, sec-
butylsulfanyl, isobutylsulfanyl or tert-butylsulfanyl group, a methylsulfinyl, ethylsulfinyl, n-
sulfinyl, pylsulfinyl, lsulfinyl, sec-butylsulfinyl, isobutylsulfinyl or tert-
butylsulfinyl group, or a methylsulfonyl, ethylsulfonyl, ylsulfonyl, isopropylsulfonyl, n-
butylsulfonyl, sec-butylsulfonyl, isobutylsulfonyl or utylsulfonyl group.
The term “C1-C4-halogenoalkyl” means a linear or branched, saturated, monovalent
hydrocarbon group in which the term “C1-C4-alkyl” is as defined supra, and in which one or
more of the hydrogen atoms are replaced, identically or differently, with a halogen atom.
ularly, said halogen atom is a fluorine atom. More particularly, all said halogen atoms are
fluorine atoms (“C1-C4-fluoroalkyl”). Said C1-C4-halogenoalkyl group is, for example,
fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl,
pentafluoroethyl, 3,3,3-trifluoropropyl or 1,3-difluoropropanyl.
The term “C1-C4-alkoxy” means a linear or branched, saturated, monovalent group of formula
(C1-C4-alkyl)-O-, in which the term “C1-C4-alkyl” is as defined supra, e.g. a methoxy, ,
n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy or tert-butoxy group, or an isomer
thereof.
The term “C1-C4-halogenoalkoxy” means a linear or ed, saturated, monovalent
C1-C4-alkoxy group, as defined supra, in which one or more of the hydrogen atoms is replaced,
identically or differently, with a halogen atom. Particularly, said halogen atom is a fluorine
atom. Said C1-C4-halogenoalkoxy group is, for example, fluoromethoxy, difluoromethoxy,
oromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy.
The term “C2-C4-alkenyl” means a linear or branched, monovalent hydrocarbon group, which
contains one double bond, and which has 2, 3 or 4 carbon atoms. Said C2-C4-alkenyl group is,
for example, an ethenyl (or “vinyl”), a propenyl (or “allyl”), propenyl, butenyl,
butenyl, butenyl, propenyl (or “isopropenyl”), 2-methylpropenyl,
1-methylpropenyl, 2-methylpropenyl or a 1-methylpropenyl, group. Particularly, said
group is allyl.
The term “C2-C4-alkynyl” means a linear monovalent hydrocarbon group which contains one
triple bond, and which contains 2, 3 or 4 carbon atoms. Said alkynyl group is, for
e, an ethynyl, a -ynyl, propynyl (or “propargyl”), butynyl, ynyl,
butynyl or 1-methylpropynyl, group. Particularly, said alkynyl group is propynyl or
-ynyl.
The term “C3-C6-cycloalkyl” means a ted, monovalent, monocyclic hydrocarbon ring
which contains 3, 4, 5 or 6 carbon atoms (“C3-C6-cycloalkyl”). Said C3-C6-cycloalkyl group is for
example, a monocyclic hydrocarbon ring, e.g. a cyclopropyl, cyclobutyl, cyclopentyl or
cyclohexyl group.
The term “C3-C6-halogenocycloalkyl” means a saturated, monovalent, monocyclic arbon
ring in which the term “C3-C6-cycloalkyl” is as defined supra, and in which one or more of the
hydrogen atoms are replaced, identically or differently, with a halogen atom. Particularly, said
halogen atom is a fluorine or chlorine atom. Said C3-C6-halogenocycloalkyl group is for
example, a clic hydrocarbon ring substituted with one or two fluorine or chlorine atoms,
e.g. a 1-fluoro-cyclopropyl, 2-fluorocyclopropyl, 2,2-difluorocyclopropyl, 2,3-difluorocyclopropyl,
rocyclopropyl, 2-chlorocyclopropyl, 2,2-dichlorocyclopropyl, 2,3-dichlorocyclopropyl, 2-
fluorochlorocyclopropyl and 2-fluorochlorocyclopropyl group.
The term “benzo-C5-C6-cycloalkyl” means a monovalent, bicyclic arbon ring wherein a
saturated, monovalent, clic hydrocarbon ring which contains 5 or 6 carbon atoms
(“C5-C6-cycloalkyl”) is annelated to a phenyl ring. Said benzo-C5-C6-cycloalkyl group is for
example, a bicyclic hydrocarbon ring, e.g. an indane (i.e. 2,3-dihydro-1H-indene) or ine
(i.e. 1,2,3,4-tetrahydronaphthalene) group.
The term "spirocycloalkyl" means a saturated, monovalent bicyclic hydrocarbon group in which
the two rings share one common ring carbon atom, and wherein said bicyclic hydrocarbon
group contains 5, 6, 7, 8, 9, 10 or 11 carbon atoms, it being possible for said spirocycloalkyl
group to be attached to the rest of the molecule via any one of the carbon atoms except the
spiro carbon atom. Said spirocycloalkyl group is, for example, spiro[2.2]pentyl, spiro[2.3]hexyl,
spiro[2.4]heptyl, spiro[2.5]octyl, spiro[2.6]nonyl, 3.3]heptyl, spiro[3.4]octyl, spiro[3.5]nonyl,
spiro[3.6]decyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.6]undecyl or spiro[5.5]undecyl.
The term “heterocycloalkyl” means a monocyclic or ic, saturated or partially saturated
heterocycle with 4, 5, 6, 7, 8, 9 or 10 ring atoms in total (a “4- to 10-membered
heterocycloalkyl” group), ularly 4, 5 or 6 ring atoms (a “4- to 6-membered
heterocycloalkyl” group), which contains one or two identical or different ring heteroatoms from
the series N, O and S, it being possible for said heterocycloalkyl group to be attached to the
rest of the le via any one of the carbon atoms or, if present, a nitrogen atom.
Said heterocycloalkyl group, without being limited thereto, can be a ered ring, such as
azetidinyl, oxetanyl or thietanyl, for example; or a 5-membered ring, such as ydrofuranyl,
oxolanyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, oxidothiolanyl,
1,2-oxazolidinyl, 1,3-oxazolidinyl, 1,3-thiazolidinyl or 1,2,4-triazolidinyl, for example; or a
6-membered ring, such as tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl,
dithianyl, thiomorpholinyl, piperazinyl, oxanyl, 1,3-dioxanyl, oxanyl or 1,2-oxazinanyl, for
example; or a 7-membered ring, such as azepanyl, 1,4-diazepanyl or 1,4-oxazepanyl, for
e; or a bicyclic 7-membered ring, such as 6-oxaazabicyclo[3.1.1]heptan, for
example; or a bicyclic 8-membered ring, such as 5,6-dihydro-4H-furo[2,3-c]pyrrole or 8-oxa
azabicyclo[3.2.1]octan, for example; or a bicyclic ered ring, such as octahydro-1H-
o[3,4-b]pyridine, 1,3-dihydro-isoindol, 2,3-dihydro-indol or 3,9-dioxa
yclo[3.3.1]nonan, for example; or a ic 10-membered ring, such as
decahydroquinoline or 3,4-dihydroisoquinolin, for example.
The term “heterospirocycloalkyl” means a bicyclic, saturated heterocycle with 6, 7, 8, 9, 10 or
11 ring atoms in total, in which the two rings share one common ring carbon atom, which
“heterospirocycloalkyl” contains one or two identical or different ring heteroatoms from the
series: N, O, S; it being possible for said heterospirocycloalkyl group to be attached to the rest
of the molecule via any one of the carbon atoms, except the spiro carbon atom, or, if present, a
nitrogen atom.
Said heterospirocycloalkyl group is, for example, azaspiro[2.3]hexyl, azaspiro[3.3]heptyl,
oxaazaspiro[3.3]heptyl, thiaazaspiro[3.3]heptyl, ro[3.3]heptyl, oxazaspiro[5.3]nonyl,
oxazaspiro[4.3]octyl, oxaazaspiro[2.5]octyl, azaspiro[4.5]decyl, oxazaspiro[5.5]undecyl,
diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one
of the further homologous scaffolds such as spiro[3.4]-, spiro[4.4]-, 2.4]-, spiro[2.5]-,
2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-.
The term “6- or 10-membered aryl” means a monovalent, monocyclic or bicyclic aromatic ring
having 6 or 10 carbon ring atoms, e.g. a phenyl or yl group.
The term “heteroaryl” means a monovalent, monocyclic, bicyclic or tricyclic aromatic ring
having 5, 6, 9 or 10 ring atoms (a “5- to 10-membered heteroaryl” group), particularly 5 or 6
ring atoms (a “5- to 6-membered heteroaryl” group), which ns at least one ring
heteroatom and optionally one, two or three further ring heteroatoms from the series: N, O
and/or S, and which is bound via a ring carbon atom or optionally via a ring nitrogen atom (if
allowed by valency).
Said heteroaryl group can be a 5-membered heteroaryl group, such as, for example, thienyl,
furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, azolyl, oxadiazolyl,
triazolyl, thiadiazolyl or tetrazolyl; or a ered heteroaryl group, such as, for example,
pyridinyl, opyridinyl, pyridazinyl, pyrimidinyl, tetrahydropyrimidinyl, pyrazinyl or triazinyl.
The term “heterocyclyl” means a heterocycle selected from the group consisting of
heterocycloalkyl and heteroaryl. Particularly, the term “4- to 6-membered heterocyclyl” means
a heterocycle ed from the group ting of 4- to 6-membered heterocycloalkyl and 5-
to 6-membered heteroaryl.
In general, and unless ise mentioned, the heteroaryl or heteroarylene groups include all
possible isomeric forms thereof, e.g.: ers and positional isomers with respect to the
point of linkage to the rest of the molecule. Thus, for some illustrative non-restricting examples,
the term pyridinyl includes pyridinyl, pyridinyl and pyridinyl; or the term thienyl includes
thienyl and 3-yl.
The term “C1-C4”, as used in the present text, e.g. in the context of the definition of
“C1-C4-alkyl”, “C1-C4-halogenoalkyl”, “C1-C4-hydroxyalkyl”, “C1-C4-alkoxy” or
“C1-C4-halogenoalkoxy” means an alkyl group having a finite number of carbon atoms of 1 to 4,
i.e. 1, 2, 3 or 4 carbon atoms.
Further, as used herein, the term “C3-C6”, as used in the present text, e.g. in the context of the
definition of “C3-C6-cycloalkyl” or C3-C6-halogenocycloalkyl, means a cycloalkyl group having a
finite number of carbon atoms of 3 to 6, i.e. 3, 4, 5 or 6 carbon atoms.
When a range of values is given, said range encompasses each value and sub-range within
said range.
For example:
"C1-C4" encompasses C1, C2, C3, C4, C1-C4, C1-C3, C1-C2, C2-C4, C2-C3, and C3-C4;
"C2-C6" encompasses C2, C3, C4, C5, C6, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5,
C3-C4, C4-C6, C4-C5, and C5-C6;
"C3-C4" encompasses C3, C4, and C3-C4;
"C3-C10" encompasses C3, C4, C5, C6, C7, C8, C9, C10, , C3-C9, C3-C8, C3-C7,
C3-C6, C3-C5, C3-C4, C4-C10, C4-C9, C4-C8, C4-C7, C4-C6, C4-C5, C5-C10, C5-C9, C5-C8,
C5-C7, C5-C6, C6-C10, C6-C9, C6-C8, C6-C7, C7-C10, C7-C9, C7-C8, C8-C10, C8-C9 and
C9-C10;
"C3-C8" encompasses C3, C4, C5, C6, C7, C8, C3-C8, C3-C7, C3-C6, C3-C5, C3-C4, C4-C8, C4-C7,
C4-C6, C4-C5, C5-C8, C5-C7, C5-C6, C6-C8, C6-C7 and C7-C8;
"C3-C6" encompasses C3, C4, C5, C6, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5, and C5-C6;
"C4-C8" asses C4, C5, C6, C7, C8, C4-C8, C4-C7, C4-C6, C4-C5, C5-C8, C5-C7,
C5-C6, C6-C8, C6-C7 and C7-C8;
"C4-C7" asses C4, C5, C6, C7, C4-C7, C4-C6, C4-C5, C5-C7, C5-C6 and C6-C7;
"C4-C6" encompasses C4, C5, C6, C4-C6, C4-C5 and C5-C6;
"C5-C10" encompasses C5, C6, C7, C8, C9, C10, C5-C10, C5-C9, C5-C8, C5-C7, C5-C6, C6-C10, C6-
C9, C6-C8, C6-C7, C7-C10, C7-C9, C7-C8, C8-C10, C8-C9 and C9-C10;
"C6-C10" encompasses C6, C7, C8, C9, C10, C6-C10, C6-C9, C6-C8, C6-C7, C7-C10, C7-C9, C7-C8,
C8-C10, C8-C9 and .
As used herein, the term “leaving group” means an atom or a group of atoms that is displaced
in a chemical reaction as stable species taking with it the bonding electrons. In particular, such
a leaving group is selected from the group sing: halide, in particular fluoride, chloride,
e or iodide, (methylsulfonyl)oxy, luoromethyl)sulfonyl]oxy, fluorobutyl)-
sulfonyl]oxy, (phenylsulfonyl)oxy, [(4-methylphenyl)sulfonyl]oxy, [(4-bromophenyl)sulfonyl]oxy,
[(4-nitrophenyl)sulfonyl]oxy, [(2-nitrophenyl)sulfonyl]oxy, [(4-isopropylphenyl)sulfonyl]oxy,
[(2,4,6-triisopropylphenyl)sulfonyl]oxy, [(2,4,6-trimethylphenyl)sulfonyl]oxy, [(4-tert-butylphenyl
)sulfonyl]oxy and [(4-methoxyphenyl)sulfonyl]oxy.
An oxo substituent in the context of the invention means an oxygen atom, which is bound to a
carbon atom via a double bond.
It is possible for the compounds of general formula (I) to exist as isotopic variants. The
invention therefore includes one or more isotopic variant(s) of the nds of general
formula (I), particularly deuterium-containing compounds of general formula (I).
The term “Isotopic variant” of a nd or a reagent is defined as a compound exhibiting an
unnatural proportion of one or more of the isotopes that constitute such a compound.
The term “Isotopic variant of the compound of l formula (I)” is defined as a compound of
general formula (I) exhibiting an ral proportion of one or more of the isotopes that
constitute such a compound.
The expression “unnatural proportion” means a proportion of such isotope which is higher than
its natural abundance. The natural abundances of isotopes to be d in this t are
described in “Isotopic Compositions of the Elements 1997”, Pure Appl. Chem., 70(1), 217-235,
1998.
Examples of such isotopes include stable and radioactive isotopes of hydrogen, carbon,
nitrogen, oxygen, phosphorus, sulfur, ne, chlorine, bromine and iodine, such as 2H
(deuterium), 3H (tritium), 11C, 13C, 14C, 15N, 17O, 18O, 32P, 33P, 33S, 34S, 35S, 36S, 18F, 36Cl, 82Br,
123I, 124I, 125I, 129I and 131I, respectively.
With respect to the treatment and/or prevention of the disorders specified herein the isotopic
t(s) of the nds of general formula (I) preferably contain deuterium (“deuteriumcontaining
compounds of general formula (I)”). Isotopic variants of the nds of general
formula (I) in which one or more radioactive isotopes, such as 3H or 14C, are incorporated are
useful e.g. in drug and/or substrate tissue distribution studies. These isotopes are particularly
preferred for the ease of their incorporation and detectability. Positron emitting isotopes such
as 18F or 11C may be incorporated into a compound of general formula (I). These isotopic
variants of the nds of general formula (I) are useful for in vivo imaging applications.
ium-containing and ntaining compounds of general formula (I) can be used in
mass spectrometry analyses in the context of preclinical or clinical studies.
ic variants of the compounds of general formula (I) can generally be prepared by
s known to a person skilled in the art, such as those described in the schemes and/or
examples , by substituting a reagent for an isotopic variant of said reagent, preferably for
a ium-containing reagent. Depending on the desired sites of deuteration, in some cases
deuterium from D2O can be incorporated either directly into the compounds or into reagents
that are useful for synthesizing such compounds. Deuterium gas is also a useful reagent for
orating deuterium into molecules. Catalytic deuteration of olefinic bonds and acetylenic
bonds is a rapid route for incorporation of deuterium. Metal catalysts (i.e. Pd, Pt, and Rh) in the
presence of deuterium gas can be used to directly exchange ium for hydrogen in
functional groups containing hydrocarbons. A variety of deuterated reagents and synthetic
building blocks are commercially available from companies such as for example C/D/N
Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, MA, USA; and
CombiPhos Catalysts, Inc., Princeton, NJ, USA.
The term “deuterium-containing compound of general formula (I)” is d as a compound of
general formula (I), in which one or more hydrogen atom(s) is/are replaced by one or more
deuterium atom(s) and in which the abundance of deuterium at each deuterated position of the
compound of l formula (I) is higher than the natural nce of deuterium, which is
about 0.015%. Particularly, in a deuterium-containing compound of general formula (I) the
abundance of ium at each deuterated position of the compound of general formula (I) is
higher than 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80%, preferably higher than 90%, 95%,
96% or 97%, even more preferably higher than 98% or 99% at said position(s). It is tood
that the abundance of deuterium at each deuterated position is independent of the abundance
of deuterium at other deuterated position(s).
The selective incorporation of one or more deuterium atom(s) into a compound of general
formula (I) may alter the physicochemical properties (such as for example acidity [C. L. Perrin,
et al., J. Am. Chem. Soc., 2007, 129, 4490], basicity [C. L. Perrin et al., J. Am. Chem. Soc.,
2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984, 19(3), 271]) and/or the
metabolic profile of the molecule and may result in changes in the ratio of parent compound to
metabolites or in the s of metabolites formed. Such changes may result in certain
therapeutic ages and hence may be preferred in some circumstances. Reduced rates of
metabolism and metabolic switching, where the ratio of metabolites is changed, have been
reported (A. E. Mutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in the
exposure to parent drug and metabolites can have important consequences with respect to the
pharmacodynamics, tolerability and cy of a deuterium-containing compound of general
formula (I). In some cases deuterium substitution reduces or eliminates the formation of an
undesired or toxic metabolite and enhances the formation of a desired metabolite (e.g.
Nevirapine: A. M. Sharma et al., Chem. Res. Toxicol., 2013, 26, 410; Efavirenz: A. E. Mutlib et
al., Toxicol. Appl. Pharmacol., 2000, 169, 102). In other cases the major effect of deuteration is
to reduce the rate of systemic clearance. As a , the biological half-life of the compound is
increased. The potential clinical benefits would include the ability to in similar systemic
exposure with decreased peak levels and increased trough levels. This could result in lower
side effects and enhanced efficacy, depending on the particular compound’s pharmacokinetic/
pharmacodynamic relationship. ML-337 (C. J. Wenthur et al., J. Med. Chem., 2013, 56, 5208)
and Odanacatib (K. Kassahun et al., WO2012/112363) are examples for this deuterium effect.
Still other cases have been reported in which d rates of metabolism result in an
increase in re of the drug without changing the rate of ic clearance (e.g.
Rofecoxib: F. Schneider et al., Arzneim. . / Drug. Res., 2006, 56, 295; evir: F.
s et al., J. Med. Chem., 2009, 52, 7993). Deuterated drugs showing this effect may have
reduced dosing requirements (e.g. lower number of doses or lower dosage to achieve the
desired effect) and/or may produce lower metabolite loads.
A compound of general formula (I) may have multiple potential sites of attack for lism.
To optimize the above-described effects on physicochemical properties and metabolic profile,
deuterium-containing compounds of l formula (I) having a certain pattern of one or more
deuterium-hydrogen exchange(s) can be selected. Particularly, the deuterium atom(s) of
deuterium-containing compound(s) of general formula (I) is/are attached to a carbon atom
and/or is/are located at those positions of the nd of l formula (I), which are sites
of attack for lizing enzymes such as e.g. rome P450.
Where the plural form of the word compounds, salts, polymorphs, hydrates, solvates and the
like, is used , this is taken to mean also a single compound, salt, polymorph, isomer,
hydrate, solvate or the like.
By "stable compound' or "stable structure" is meant a compound that is sufficiently robust to
survive isolation to a useful degree of purity from a reaction mixture, and formulation into an
efficacious therapeutic agent.
The compounds of the present invention optionally contain one or more asymmetric centres,
depending upon the location and nature of the various substituents desired. It is possible that
one or more asymmetric carbon atoms are present in the (R) or (S) configuration, which can
result in racemic mixtures in the case of a single tric , and in diastereomeric
mixtures in the case of multiple asymmetric centres. In certain instances, it is possible that
asymmetry also be present due to cted rotation about a given bond, for example, the
central bond adjoining two substituted aromatic rings of the specified compounds.
Preferred compounds are those which produce the more desirable biological activity.
Separated, pure or partially purified isomers and stereoisomers or racemic or diastereomeric
es of the compounds of the present invention are also included within the scope of the
present invention. The cation and the separation of such materials can be accomplished
by standard techniques known in the art.
Preferred isomers are those which e the more desirable biological activity. These
separated, pure or partially purified isomers or racemic mixtures of the nds of this
invention are also included within the scope of the present ion. The purification and the
separation of such materials can be accomplished by rd techniques known in the art.
The optical isomers can be obtained by resolution of the racemic mixtures according to
conventional processes, for example, by the formation of diastereoisomeric salts using an
optically active acid or base or formation of nt diastereomers. Examples of appropriate
acids are tartaric, yltartaric, ditoluoyltartaric and camphorsulfonic acid. Mixtures of
diastereoisomers can be separated into their individual diastereomers on the basis of their
physical and/or chemical differences by methods known in the art, for example, by
tography or fractional crystallisation. The optically active bases or acids are then
liberated from the ted diastereomeric salts. A different process for separation of optical
isomers involves the use of chiral chromatography (e.g., HPLC columns using a chiral phase),
with or without conventional derivatisation, optimally chosen to maximise the separation of the
enantiomers. Suitable HPLC columns using a chiral phase are commercially available, such as
those manufactured by Daicel, e.g., Chiracel OD and Chiracel OJ, for example, among many
others, which are all routinely selectable. Enzymatic separations, with or t derivatisation,
are also useful. The optically active compounds of the present invention can likewise be
obtained by chiral ses utilizing optically active starting materials.
In order to distinguish different types of isomers from each other reference is made to IUPAC
Rules Section E (Pure Appl Chem 45, 11-30, 1976).
The present invention includes all possible stereoisomers of the compounds of the present
invention as single stereoisomers, or as any mixture of said stereoisomers, e.g. (R)- or (S)-
isomers, in any ratio. Isolation of a single stereoisomer, e.g. a single omer or a single
diastereomer, of a compound of the present invention is achieved by any suitable state of the
art method, such as chromatography, especially chiral chromatography, for example.
Further, it is possible for the compounds of the present invention to exist as tautomers. For
example, any compound of the present invention which contains a substitution pattern
resulting in α-CH-moiety at the quinoline that has an increased C-H-acidity can exist as a 1,4-
dihydroquinoline tautomer, or even a mixture in any amount of the two tautomers, namely:
The present invention es all possible tautomers of the nds of the present
ion as single tautomers, or as any mixture of said tautomers, in any ratio.
Further, the nds of the present invention can exist as N-oxides, which are defined in
that at least one nitrogen of the nds of the present invention is oxidised. The present
invention includes all such possible es.
The present invention also covers useful forms of the compounds of the present invention,
such as metabolites, hydrates, solvates, prodrugs, salts, in particular pharmaceutically
acceptable salts, and/or co-precipitates.
The compounds of the present invention can exist as a hydrate, or as a solvate, wherein the
compounds of the present invention contain polar ts, in particular water, methanol or
ethanol for example, as structural element of the l lattice of the compounds. It is possible
for the amount of polar solvents, in particular water, to exist in a stoichiometric or non-
iometric ratio. In the case of iometric es, e.g. a hydrate, hemi-, (semi-),
mono-, sesqui-, di-, tri-, tetra-, penta- etc. solvates or hydrates, respectively, are possible. The
present invention includes all such hydrates or solvates.
Further, it is possible for the compounds of the present invention to exist in free form, e.g. as a
free base, or as a free acid, or as a zwitterion, or to exist in the form of a salt. Said salt may be
any salt, either an organic or inorganic addition salt, particularly any pharmaceutically
acceptable organic or inorganic addition salt, which is customarily used in pharmacy, or which
is used, for example, for isolating or purifying the compounds of the present invention.
The term “pharmaceutically acceptable salt" refers to an inorganic or organic acid addition salt
of a compound of the present invention. For example, see S. M. Berge, et al. “Pharmaceutical
Salts,” J. Pharm. Sci. 1977, 66, 1-19.
A suitable pharmaceutically acceptable salt of the compounds of the present invention may be,
for example, an acid-addition salt of a compound of the present invention bearing a nitrogen
atom, in a chain or in a ring, for e, which is sufficiently basic, such as an acid-addition
salt with an inorganic acid, or al acid”, such as hydrochloric, hydrobromic, hydroiodic,
sulfuric, ic, bisulfuric, phosphoric, or nitric acid, for example, or with an organic acid,
such as formic, acetic, acetoacetic, pyruvic, trifluoroacetic, nic, c, hexanoic,
heptanoic, undecanoic, , benzoic, salicylic, 2-(4-hydroxybenzoyl)-benzoic, camphoric,
ic, entanepropionic, digluconic, 3-hydroxynaphthoic, nicotinic, ,
pectinic, 3-phenylpropionic, pivalic, 2-hydroxyethanesulfonic, ic, trifluoromethanesulfonic,
dodecylsulfuric, ethanesulfonic, benzenesulfonic, oluenesulfonic, methanesulfonic,
2-naphthalenesulfonic, naphthalinedisulfonic, camphorsulfonic acid, citric, tartaric, stearic,
lactic, oxalic, malonic, succinic, malic, adipic, alginic, maleic, fumaric,
D-gluconic, mandelic, ascorbic, glucoheptanoic, glycerophosphoric, ic, sulfosalicylic, or
thiocyanic acid, for example.
Further, another suitably pharmaceutically acceptable salt of a compound of the present
invention which is sufficiently acidic, is an alkali metal salt, for example a sodium or potassium
salt, an alkaline earth metal salt, for example a calcium, magnesium or strontium salt, or an
aluminium or a zinc salt, or an ammonium salt derived from ammonia or from an organic
primary, secondary or tertiary amine having 1 to 20 carbon atoms, such as ethylamine,
diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine,
triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol,
tris(hydroxymethyl)aminomethane, procaine, ylamine, N-methylmorpholine, arginine,
, hylenediamine, N-methylpiperidine, N-methyl-glucamine, N,N-dimethyl-glucamine,
N-ethyl-glucamine, 1,6-hexanediamine, glucosamine, sarcosine, serinol, o-1,3-
ediol, 3-amino-1,2-propanediol, 4-amino-1,2,3-butanetriol, or a salt with a quarternary
ammonium ion having 1 to 20 carbon atoms, such as tetramethylammonium,
tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-
trimethylammonium, choline or benzalkonium.
Those skilled in the art will further recognise that it is possible for acid on salts of the
claimed compounds to be ed by reaction of the compounds with the appropriate
inorganic or c acid via any of a number of known methods. Alternatively, alkali and
alkaline earth metal salts of acidic compounds of the present invention are prepared by
reacting the compounds of the present invention with the appropriate base via a variety of
known methods.
The present invention includes all possible salts of the compounds of the present invention as
single salts, or as any mixture of said salts, in any ratio.
In the present text, in particular in the Experimental Section, for the synthesis of intermediates
and of examples of the present invention, when a compound is mentioned as a salt form with
the corresponding base or acid, the exact stoichiometric composition of said salt form, as
ed by the respective preparation and/or cation process, is, in most cases, unknown.
Unless specified otherwise, suffixes to chemical names or structural ae relating to salts,
such as "hydrochloride", "trifluoroacetate", m salt", or "x HCl", "x CF3COOH", "x Na+", for
example, mean a salt form, the stoichiometry of which salt form not being specified.
This applies analogously to cases in which synthesis intermediates or example compounds or
salts thereof have been obtained, by the preparation and/or purification processes described,
as es, such as es, with (if defined) unknown stoichiometric composition.
Furthermore, the present invention es all possible crystalline forms, or polymorphs, of the
compounds of the t invention, either as single polymorph, or as a mixture of more than
one polymorph, in any ratio.
Moreover, the present invention also includes prodrugs of the compounds according to the
invention. The term “prodrugs” here designates compounds which themselves can be
biologically active or inactive, but are converted (for example metabolically or hydrolytically)
into compounds according to the invention during their residence time in the body.
In accordance with a second embodiment of the first aspect, the present invention covers
compounds of l formula (I), supra, in which:
A is A1 or A2,
A1 A2
o is 0, 1, 2, 3 or 4,
R is ed from the group consisting of hydrogen, halogen, cyano, nitro, -OH, C1-C4-
alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl, –S(O)-C1-C4-halogenoalkyl and –SO2-C1-C4-halogenoalkyl having 1 to 5
n atoms,
Rp is selected from the group consisting of en, C1-C4-alkyl,
X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9,
wherein at least one of X and Y is CR7R8, or
X, Y form together a ring member selected from the group consisting of -C(O)-O-, -C(O)-
NR9-, -S(O)-NR9-, -SO2-NR9- and -SO2-O-,
R1 is selected from the group consisting of hydrogen, cyano, -CHO, -OH, C1-C4-alkyl, C1-
C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5
halogen atoms, C3-C4-alkenyl, alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-
cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, -NH-C1-C4-alkyl, -N(C1-C4-alkyl)2, NH2-C1-C4-
alkyl-, C1-C4-alkyl-NH-C1-C4-alkyl-, (C1-C4-alkyl)2N-C1-C4-alkyl-, C1-C4-alkyl-C(O)-, C1-
C4-halogenoalkyl-C(O)- having 1 to 5 halogen atoms, C1-C4-alkoxy-C(O)-, benzyloxy-
C(O)-, C1-C4-alkoxy-C1-C4-alkyl-C(O)-, -SO2-C1-C4-alkyl, and –SO2-C1-C4-halogenoalkyl
having 1 to 5 halogen atoms;
phenyl-C1-C4-alkyl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently
selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-halogenoalkyl
having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5
halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-
alkyl, -SO2-C1-C4-alkyl, C4-halogenoalkyl having 1 to 5 n atoms, –S(O)-C1-
ogenoalkyl having 1 to 5 halogen atoms and 1-C4-halogenoalkyl having 1
to 5 halogen atoms;
cyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-
halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms, -NH2, -C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-
C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –
1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl
having 1 to 5 halogen atoms,
R2 is selected from the group consisting of
hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, NH(C1-C4-
alkyl), -C(O)-N(C1-C4-alkyl)2;
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C6-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
-C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents
independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-
alkyl-C(O)-, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -
NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1-
C4-alkyl), -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl
having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms
and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, wherein the cyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, ered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 n atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-
alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –
S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl
having 1 to 5 halogen atoms;
phenyl which is optionally substituted by 1, 2 or 3 substituents independently selected
from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms, cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-
C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle ed from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, ered heteroaryl and 6-
membered heteroaryl, each of which is ally substituted by 1, 2, 3 or 4
substituents independently selected from the group consisting of halogen, cyano,
nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl),
-C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 n atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms,–SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 4- to 10-
membered heterocycloalkyl,
R3 is hydrogen, or C1-C4-alkyl,
R4 is ed from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2,
R5 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2,
R6 is selected from the group consisting of hydrogen, n, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2,
R7 is selected from the group ting of hydrogen, -OH, fluorine, alkyl and C1-C4-
alkoxy,
R8 is selected from the group consisting of hydrogen, -OH, fluorine, C1-C4-alkyl and C1-C4-
alkoxy,
or R7 and R8 together form an oxo group (=O),
R9 is selected from the group consisting of en, C1-C4-alkyl, halogenoalkyl
having 1 to 5 halogen atoms and C1-C4-alkoxy,
R10 is selected from the group consisting of en, -OH, C1-C4-alkyl and C1-C4-alkoxy,
R11 is selected from the group consisting of hydrogen, C1-C4-alkyl and C1-C4-alkoxy,
R12 and R13 are independently ed from the group consisting of
hydrogen, -OH, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(-C(O)-C1-C4-alkyl), C1-
C4-alkoxy;
C1-C4-alkyl, cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
n, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
noalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-
alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, n the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo,
thiono, -COOH, C1-C4-alkoxy-C(O)-, NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
hydroxy-C1-C4-alkyl, halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-
cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -
SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to
halogen atoms;
phenyl, benzo-C5-C6-cycloalkyl, each of which is ally tuted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, cyano,
nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-
alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is
optionally substituted by 1, 2 or 3 substituents ndently selected from the group
consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -
C(O)-NH2, NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
R14 is selected from the group consisting of
-NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 tuents independently ed from the group consisting of
halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-
C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -
NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, –
S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having
1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, n the heterocyclyl subsitutent is selected from the group
consisting of 4- to 10-membered cycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo,
thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
2, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-
cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -
SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to
halogen atoms;
phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected
from the group ting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, halogenoalkoxy having
1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-
C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, 5-membered heteroaryl and ered heteroaryl, each
of which is optionally substituted by 1, 2 or 3 substituents independently selected from
the group ting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-
C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is ally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, NH2, -C(O)-NH(C1-C4-alkyl), -
C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-
C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -
NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –
S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having
1 to 5 halogen atoms and 1-C4-halogenoalkyl having 1 to 5 n atoms;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is ed from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered aryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo,
thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
y-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-
cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, C4-alkyl, -S(O)-C1-C4-alkyl, -
SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to
5 halogen atoms;
phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected
from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, halogenoalkoxy having
1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-
C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each
of which is ally substituted by 1, 2 or 3 substituents independently ed from
the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-
C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, y-C1-C4-alkyl, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
Q is a substituted phenyl ring of the a (Q1)
in which:
Z1, Z2, Z3, Z4, and Z5 are ndently selected from the group consisting of
hydrogen, halogen, SF5, cyano, -CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl
having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-
alkoxy, cyano-C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,
-NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-C4-
alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered
heterocyclyl, which is optionally substituted with 1 or 2 substituents selected
from the group consisting of ne, chlorine, e, methyl and cyano, -CH2-
O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, methyl substituted
with a 4- to ered heterocyclyl which itself is optionally substituted with 1
or 2 substituents selected from the group consisting of fluorine, chlorine,
bromine, methyl and cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-
SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-
(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl)
having 1 to 5 halogen atoms, C1-C4-halogenoalkyl) having 1 to 5 halogen
atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-cycloalkyl), -NHCO(C1-C4-alkyl), -
NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl) having 1 to 5 halogen
atoms, or
Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5- or
6-membered saturated or partially ted heterocyclic ring, a 5-membered
heteroaryl, or a 6-membered heteroaryl, each of which may be optionally
substituted with one or two substituents selected from the group consisting of
methyl, fluorine and oxo, and
Z3, Z4, and Z5 are independently selected from the group consisting of hydrogen,
halogen, SF5, cyano, CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-
C4-alkoxy, C1-C4-alkoxy-C(O)-, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-
C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered
heterocycloalkyl which is ally substituted with 1 or 2 tuents selected
from the group consisting of fluorine, methyl or cyano, -CH2-O-(C1-C4-
alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, methyl substituted with a 4-
to 6-membered heterocycloalkyl which itself is optionally substituted with 1 or 2
substituents selected from the group consisting of fluorine, methyl or
cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -
C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl)
having 1 to 5 n atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen
atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4-
alkyl), C3-C6-cycloalkyl), -NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl),
C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or
Z2 and Z3 form, together with the carbon atoms that they are connected to, a 5- or
6-membered saturated or partially saturated heterocyclic ring, a 5-membered
heteroaryl, or a 6-membered heteroaryl, each of which may be ally
substituted with one or two substituents selected from the group consisting of
methyl, fluorine and oxo, and
Z1, Z4, and Z5 are independently selected from the group consisting of hydrogen,
halogen, SF5, cyano, CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, y, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, C1-
C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl),
C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1-
C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered heterocycloalkyl which is
optionally substituted with 1 or 2 substituents ed from the group consisting
of fluorine, methyl or cyano, -CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-
4-alkyl)2, methyl substituted with a 4- to 6-membered heterocycloalkyl
which itself is optionally substituted with 1 or 2 substituents selected from the
group consisting of fluorine, methyl or cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-
(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-
(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-
C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl)
having 1 to 5 halogen atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-cycloalkyl), -
NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl)
having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q2)
in which:
Z6, Z7, Z8 and Z9 are independently selected from the group consisting of
hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a pyrimidine ring of the formula (Q3)
in which:
Z10, Z11 and Z12 are independently selected from the group ting of
hydrogen, n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-
hydroxyalkyl, NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1-C4-alkyl, and
monocyclic heterocycles selected from the group of 4- to 7-membered
heterocycloalkyl or 5-membered aryls having at least one nitrogen atom
via which the heteroaryl ring is connected to the pyridine ring, each of which is
optionally substituted with 1, 2 or 3 substituents independently selected from the
group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-
alkyl)2, C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -C4-
halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having
1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms,
Q is a pyridine ring of the formula (Q5)
(Q5)
in which:
Z17, Z18, Z19 and Z20 are independently selected from the group ting of
en, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a 5-membered aromatic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and NZ22
, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and wherein
each Z21 is independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic cycle of the formula (Q7)
in which:
U1 – U4 are independently selected from the group consisting of N and C-Z23,
wherein not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,
wherein when Y is O, S or N-R9, none of R7, R8, R10 and R11 is -OH, and n when X is O,
S or N-R9, none of R7 and R8 is -OH,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In ance with a third embodiment of the first aspect, the t invention covers
compounds of general formula (I), supra, in which:
A is A1 or A2,
A1 A2
o is 0, 1 or 2,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
Rp is selected from the group consisting of hydrogen, C1-C4-alkyl,
X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9,
wherein at least one of X and Y is CR7R8,
R1 is selected from the group consisting of hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl, C3-C4-
alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl, C1-
C4-alkyl,
R2 is selected from the group consisting of
hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-
, -C(O)-N(C1-C4-alkyl)2;
–OR14;
-SR15, -S(O)R15, 5;
C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents
independently selected from the group consisting of halogen, -OH, cyano, C1-C4-
alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-
C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl), -
N(C1-C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl), -S-C1-C4-
alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 n atoms; and
a clic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4
substituents independently ed from the group consisting of n, cyano, -OH,
oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, halogenoalkyl having 1 to 5 halogen
atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
C4-alkyl)2, and 4- to 10-membered heterocycloalkyl,
R3 is hydrogen or C1-C4-alkyl,
R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2,
R5 is selected from the group ting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2,
R6 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and C1-C4-alkyl,
or R7 and R8 er form an oxo group (=O),
R9 is C1-C4-alkyl,
R10 is selected from the group consisting of hydrogen, -OH, C1-C4-alkyl and C1-C4-alkoxy,
R11 is hydrogen,
R12 and R13 are independently selected from the group consisting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is ally substituted
by 1, 2 or 3 substituents ndently selected from the group consisting of
n, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 n atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-
alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is ed from the group
consisting of 4- to bered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
phenyl, benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of n, cyano, C1-
C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is
optionally tuted by 1, 2 or 3 substituents independently selected from the group
ting of halogen, cyano, -OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, halogenoalkoxy having 1 to 5 n atoms,
R14 is selected from the group consisting of
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl; and
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl subsitutent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, phenyl-C1-C4-alkyl, each of which is optionally tuted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, -OH, cyano,
C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, n the heterocyclyl substituent is ed from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered aryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group ting of halogen, cyano, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms;
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1, Z2, Z3, Z4, and Z5 are independently selected from the group consisting of
hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, hydroxy, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5
n atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, 4- to 6-membered
heterocyclyl, which is optionally substituted with 1 or 2 substituents selected
from the group consisting of fluorine, ne, e, methyl and cyano, -S-
(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), or
Z1 and Z2 form, together with the carbon atoms that they are ted to, a 5- or
6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered
heteroaryl, each of which may be optionally substituted with one or two
substituents selected from the group consisting of methyl, fluorine and oxo, and
Z3, Z4, and Z5 are independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms,
C1-C4-alkoxy, C1-C4-alkoxy-C(O)-, C1-C4-halogenoalkoxy having 1 to 5 n
atoms, or
Z2 and Z3 form, together with the carbon atoms that they are connected to, a 5- or
6-membered saturated or partially saturated heterocyclic ring, a 5-membered
heteroaryl, or a 6-membered heteroaryl, each of which may be optionally
substituted with one or two tuents selected from the group consisting of
methyl, fluorine and oxo, and
Z1, Z4, and Z5 are independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q2)
in which:
Z6, Z7, Z8 and Z9 are independently selected from the group consisting of hydrogen
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-
alkyl), -N(C1-C4-alkyl)2, or
Q is a pyrimidine ring of the formula (Q3)
in which:
Z10, Z11 and Z12 are ndently selected from the group consisting of
hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a pyridine ring of the a (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of
hydrogen, halogen, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1-
C4-alkyl, and monocyclic heterocycles selected from the group of 4- to 7-
membered cycloalkyl or ered heteroaryls having at least one
nitrogen atom via which the heteroaryl ring is connected to the pyridine ring,
each of which is optionally substituted with 1, 2 or 3 substituents ndently
selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono,
C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-
C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -
NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-
alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-
noalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having
1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q5)
(Q5)
in which:
Z17, Z18, Z19 and Z20 are independently selected from the group ting of
hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a 5-membered ic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and N-
Z22, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and wherein
each Z21 is independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic heterocycle of the formula (Q7)
in which:
U1 – U4 are independently selected from the group consisting of N and C-Z23,
n not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group consisting of hydrogen,
n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy,
wherein when Y is O, S or N-R9, R10 is not -OH,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In accordance with a fourth embodiment of the first aspect, the present invention covers
compounds of general formula (I), supra, in which:
A is A1 or A2,
A1 A2
o is 0, 1 or 2,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy,
Rp is selected from the group consisting of hydrogen, alkyl,
X is selected from the group consisting of CR7R8, O, S, and N-R9,
Y is CR7R8 or O,
R1 is hydrogen or C1-C4-alkyl,
R2 is selected from the group consisting of
hydrogen, halogen, -C(O)-N(C1-C4-alkyl)2;
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl or C3-C6-cycloalkenyl, each of which is
optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the
group consisting of halogen, -OH, cyano, C1-C4-alkoxy-C(O)- and -C(O)-NH2, C1-C4-
alkoxy, -NH2, -N(C1-C4-alkyl)2, -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl); and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, ered heteroaryl, and 6-
membered aryl, each of which is optionally substituted by 1, 2, 3 or 4
substituents independently selected from the group consisting of halogen, -OH,
oxo, -COOH, C1-C4-alkoxy-C(O)-, NH2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4-
alkyl-, -NH2, -N(C1-C4-alkyl)2, and 4- to 10-membered heterocycloalkyl,
R3 is hydrogen or C1-C4-alkyl,
R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -NH2,
R5 is selected from the group consisting of hydrogen, n, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
R6 is selected from the group consisting of hydrogen, n, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group ting of en and C1-C4-alkyl,
or R7 and R8 together form an oxo group (=O),
R9 is C1-C4-alkyl,
R10 is ed from the group consisting of hydrogen, -OH and C1-C4-alkyl,
R11 is hydrogen,
R12 and R13 are independently selected from the group ting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy;
alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents ndently selected from the group consisting of
halogen, -OH, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-N(C1-C4-alkyl)2, -NHC
-C4-alkyl, C1-C4-alkyl, C1-C4-alkoxy, C3-C6-cycloalkyl, -NH2, -N(C1-C4-alkyl)2, -SC1-C4-alkyl
, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, and (C1-C4-alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
ting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy;
phenyl and benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, cyano, C1-
C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 n atoms; and
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl each of which is
optionally substituted by 1, 2 or 3 substituents independently selected from the group
consisting of halogen, -OH, oxo, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, halogenoalkoxy having 1 to 5 n atoms,
R14 is selected from the group consisting of
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally tuted
by 1, 2 or 3 tuents independently selected from the group consisting of
halogen, -OH, C1-C4-alkyl, C1-C4-alkoxy and cycloalkyl; and
4- to 10-membered heterocycloalkyl,
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, which is optionally substituted by 1, 2 or 3 tuents independently
selected from the group consisting of -OH and -COOH; and
a 6-membered heteroaryl,
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of en,
halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkyl having 1 to 5 halogen
atoms
Z2 and Z4 are independently selected from the group ting of hydrogen,
halogen, cyano, -OH, C1-C4-alkyl, C1-C4-alkoxy, -NH(C1-C4-alkyl), -N(C1-C4-
alkyl)2, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -S-(C1-C4-alkyl) and a 4- to 6-membered
heterocycloalkyl, and
Z3 is selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-
alkoxy, halogenoalkoxy having 1 to 5 halogen atoms, and -N(C1-C4-
alkyl)2, or
Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5-
membered heterocycloalkyl or a ered heteroaryl, each of which may be
optionally substituted with one or two substituents selected from the group
consisting of methyl, ne and oxo,
Z3 and Z5 are hydrogen, and
Z4 is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently ed from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4-
, -N(C1-C4-alkyl)2, -NH-CO-C1-C4-alkyl, and monocyclic heterocycles
selected from the group of 4- to 7-membered heterocycloalkyl or 5-membered
heteroaryls having at least one en atom via which the heteroaryl ring is
connected to the pyridine ring, each of which is optionally substituted with 1, 2
or 3 substituents independently selected from the group consisting of halogen,
cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, halogenoalkyl having 1 to 5
halogen atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl,
-S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5
halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-
(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is halogen, or
Q is a 5-membered ic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and NZ22
, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and n
each Z21 is independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
alkoxy, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic heterocycle of the formula (Q7)
in which:
U1 – U4 are independently selected from the group consisting of N and C-Z23,
wherein not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group consisting of hydrogen,
n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy,
and stereoisomers, tautomers, es, hydrates, solvates, and salts thereof, and mixtures of
same.
In accordance with a fifth embodiment of the first aspect, the present invention covers
compounds of general formula (I), supra, in which:
A is selected from the group consisting of
R1 is hydrogen or methyl,
R2 is selected from the group consisting of
hydrogen, chlorine, iodine, -C(O)-N(CH3)2,
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl,
propenyl, cyclopentenyl, cyclohexenyl, each of which is optionally substituted by 1 or 2
substituents independently selected from the group consisting of –OH, cyano, ethoxy-
C(O)-, NH2, methoxy, NH2, N(CH3)2, N(CH3)(C(O)CH3); and
a monocyclic or a bicyclic heterocycle selected from the group consisting of azetidine,
oxetane, pyrrolidine, tetrahydrofurane, pyrazolidine, imidazolidine, 1,2,4-triazolidine,
piperidine, piperazine, tetrahydropyrane, tetrahydropyridine, o-2H-pyrane, 1,2-
idine, 1,2-oxazine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-
dihydro-indole, 1,3-dihydro-isoindoel, oxaazabicyclo[3.3.1]nonane, 6-oxa
azabicyclo[3.1.1]heptane, 8-oxaazabicyclo[3.2.1]octane, thiophene, ole,
le, triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine,
pyrimidine, tetrahydropyrimidine, 4-oxaazaspiro[2.5]octane, each of which is
optionally tuted by 1, 2, 3 or 4 substituents independently selected from the group
consisting of fluorine, chlorine, cyano, -OH, oxo, -COOH, methoxy-C(O)-, ethoxy-C(O)-,
tert-butoxy-C(O)-, -C(O)-NH2, methyl, methyl-C(O)-, romethyl, trifluoromethyl,
hydroxymethyl-, methoxymethyl-, -NH2, -NMe2, pyrrolidine,
R3 is en or methyl,
R4 is selected from the group consisting of hydrogen, fluorine, ne, -OH, cyano,
, methoxy, trifluoromethyl, oromethoxy and NH2,
R5 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano,
methyl, methoxy and trifluoromethyl,
R6 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano,
methyl and methoxy,
R12 and R13 are independently selected from the group consisting of
hydrogen, -NH(-C(O)-methyl), methoxy;
methyl, ethyl, propyl, pyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, 1-
phenylethyl, each of which is optionally substituted by 1, 2 or 3 substituents
ndently selected from the group consisting of fluorine, -OH, -COOH, methoxy-
C(O)-, ethoxy-C(O)-, utoxy-C(O)-, -C(O)-NH2, -C(O)-NMe2, -NH-C(O)-methyl,
methyl, methoxy, cyclopropyl, -NH2, NMe2, S-methyl, S(O)-methyl, SO2-methyl, and
(EtO)2P(=O)-;
heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituent is selected
from the group consisting of oxetane, tetrahydrofurane, tetrahydropyrane pyrrolidine,
morpholine, le, imidazole, 1, 2, 4-oxadiazole, pyridine, each of which is optionally
substituted by 1 substituent independently selected from the group consisting of
fluorine, chlorine, -OH, oxo and ;
phenyl;
2,3-dihydro-1H-indene, and
a monocyclic or a bicyclic heterocycle selected from the group of oxetane, thietane,
pyrrolidine, morpholine, tetrahydropyrane, pyridine and pyrazole, each of which is
optionally substituted by 1 or 2 substituents independently selected from the group
consisting of fluorine, chlorine, -OH, oxo, methyl;
R14 is ed from the group consisting of
methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally
substituted by 1 or 2 substituents independently selected from the group consisting of
fluorine, -OH, , y and cyclopentyl; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of pyrrolidin
and ydropyran,
R15 is selected from the group consisting of
methyl and ethyl, each of which is optionally substituted by 1 substituent independently
selected from the group consisting of -OH and -COOH; and
pyridine,
Q is a substituted phenyl ring of the formula (Q1)
(Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, methyl, oromethyl and methoxy,
Z2 and Z4 are independently ed from the group consisting of hydrogen,
fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2,
oromethyl, methoxy, trifluoromethoxy, -SMe and morpholinyl, and
Z3 is independently selected from the group consisting of hydrogen, fluorine,
chlorine, methyl, methoxy, romethoxy and –NMe2, or
Q is a pyridine ring of the formula (Q4)
(Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of en,
fluorine, chlorine, cyano, methyl, methoxy, ethoxy, isopropoxy, hydroxymethyl,
NH2, -NHMe -NMe2, -NH-C(O)-Me, morpholinyl, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is ne, chlorine, or
Q is selected from the group consisting of
(Q6-1) (Q6-2) (Q6-3) (Q6-4) (Q6-5) (Q6-6)
(Q6-7) (Q6-8) (Q6-9) (Q6-10) (Q6-11) (Q6-12)
(Q6-13) (Q6-14) (Q6-15) (Q6-16) (Q6-17) (Q6-18)
(Q6-19) ) (Q6-21) (Q6-22) (Q6-23) (Q6-24)
(Q6-25) (Q6-26) (Q6-27) ) (Q6-29) (Q6-30)
(Q6-31) (Q6-32) (Q6-33) (Q6-34) (Q6-35) (Q6-36)
(Q6-37) (Q6-38) or (Q6-39)
in which:
each Z21 is independently selected from the group consisting of hydrogen,
fluorine, chlorine, cyano, methyl, trifluoromethyl, methoxy and
Z22 is hydrogen, methyl, or
Q is selected from the group consisting of
(Q7-1) (Q7-2) (Q7-3) (Q7-4) (Q7-5)
(Q7-6) (Q7-7) (Q7-8) (Q7-9)
in which:
each Z23 is ndently selected from the group consisting of hydrogen,
fluorine, ne, cyano, methyl, trifluoromethyl, methoxy, or
Q is selected from the group consisting of
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts f, and mixtures of
same.
In accordance with a sixth ment of the first aspect, the present invention covers
compounds of general formula (I), supra, in which:
A is selected from the group consisting of
R1 is hydrogen or methyl,
R2 is selected from the group consisting of
chlorine, iodine, -C(O)-N(CH3)2,
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, ethenyl, propenyl,
each of which is optionally substituted by 1 or 2 substituents independently selected
from the group ting of –OH, cyano, ethoxy-C(O)-, -C(O)-NH2, methoxy, NH2,
N(CH3)2, N(CH3)(C(O)CH3); and
a monocyclic or a ic heterocycle selected from the group consisting of azetidine,
oxetane, pyrrolidine, tetrahydrofurane, lidine, imidazolidine, 1,2,4-triazolidine,
piperidine, piperazine, tetrahydropyrane, dihydro-2H-pyrane, 1,2-oxazolidine,
morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indoel, 1,3-dihydroisoindole
, 3,9-dioxaazabicyclo[3.3.1]nonane, 6-oxaazabicyclo[3.1.1]heptane, 8-
oxaazabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole, 1,2,3-triazole, 1,2,3,4-
tetrazole, pyridine, dihydropyridine, dine, tetrahydropyrimidine, each of which is
optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group
consisting of ne, -OH, oxo, -COOH, methoxy-C(O)-, ethoxy-C(O)-, tert-butoxy-
C(O)-, -C(O)-NH2, methyl, methyl-C(O)-, difluoromethyl, trifluoromethyl, hydroxymethyl-,
methoxymethyl-, -NH2, -NMe2, pyrrolidine,
R3 is hydrogen or methyl,
R4 is ed from the group consisting of hydrogen, chlorine, fluorine, methyl, methoxy
and trifluoromethyl,
R5 is selected from the group consisting of hydrogen, chlorine, fluorine, -OH, cyano,
methyl, trifluoromethoxy and NH2,
R6 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano,
methyl and methoxy,
R12 and R13 are independently ed from the group consisting of
hydrogen, -NH(-C(O)-methyl), methoxy;
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, 1-
phenylethyl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of fluorine, -OH, -COOH, methoxy-
C(O)-, ethoxy-C(O)-, utoxy-C(O)-, -C(O)-NH2, NMe2, -NH-C(O)-methyl,
, methoxy, cyclopropyl, -NH2, -NMe2, SO2-methyl and (EtO)2P(=O)-;
heterocyclyl-methyl, heterocyclyl-ethyl, n the heterocycyl substituent is selected
from the group consisting of oxetane, tetrahydrofurane, tetrahydropyrane, pyrrolidine,
pyrazole, imidazole, 1, 2, 4-oxadiazole, morpholine, pyridine, each of which is optionally
substituted by 1 substituent independently ed from the group consisting of oxo
and methyl;
phenyl;
2,3-dihydro-1H-indene, and
a monocyclic or a ic cycle selected from the group of oxetane, morpholine,
tetrahydropyrane, pyridine and pyrazole;
R14 is selected from the group consisting of
methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally
tuted by 1 or 2 substituents independently selected from the group consisting of
fluorine, -OH, methyl, methoxy and cyclopentyl; and
a clic or a bicyclic heterocycle selected from the group consisting of pyrrolidin
and tetrahydropyran,
R15 is selected from the group consisting of
methyl and ethyl, each of which is ally substituted by 1 substituent independently
selected from the group consisting of -OH and -COOH; and
pyridine,
Q is a tuted phenyl ring of the formula (Q1)
(Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
ne, chlorine, methyl, methoxy and trifluoromethyl,
Z2 and Z4 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2,
trifluoromethyl, methoxy, trifluoromethoxy, -SMe and morpholinyl, and
Z3 is independently selected from the group consisting of hydrogen, fluorine,
chlorine, methyl, methoxy, difluoromethoxy and –NMe2, or
Q is a pyridine ring of the formula (Q4)
(Q4)
in which:
Z14 and Z15 are independently selected from the group consisting of hydrogen,
ne, chlorine, cyano, methyl, methoxy, ethoxy, isopropoxy, hydroxymethyl,
NH2, morpholinyl and
Z13 and Z16 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, , methoxy, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is fluorine, or
Q is selected from the group consisting of
and isomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In accordance with a seventh embodiment of the first aspect, the present invention covers
nds of general formula (I), supra, in which:
A is selected from the group consisting of
R1 is hydrogen or methyl,
R2 is selected from the group consisting of hydrogen, (1S)-2,3-dihydro-1H-inden
ylamino, (2,3-difluorobenzyl)oxy, (2-acetamidoethyl)amino, nooxoethyl)amino,
(2-aminoethyl)amino, (2-carboxyethyl)sulfanyl, (2-ethoxyoxoethyl)(methyl)amino, (2-
hydroxyethyl)(methyl)amino, (2-hydroxyethyl)amino, ymethyl, methoxymethyl, 2-
hydroxyethyl, (2-hydroxyethyl)oxy, (2-hydroxyethyl)sulfanyl, (2-methoxy
oxoethyl)amino, (3-methoxyoxopropyl)-methylamino, (2-
methoxyethyl)(methyl)amino, (2-methoxyethyl)amino, (2-methoxyethyl)oxy, (2R)
(hydroxymethyl)pyrrolidinyl, (2R)(methoxycarbonyl)pyrrolidinyl, (2R)
(methoxymethyl)pyrrolidinyl, (2R)(tert-butoxycarbonyl)pyrrolidinyl, -
carboxylatopyrrolidinyl, (2R)carboxypyrrolidinyl, )-2,6-
dimethylmorpholinyl, 2-(trifluoromethyl)morpholinyl, (2rac)carboxypyrrolidin
yl, (2S)(ethoxycarbonyl)pyrrolidinyl, (2S)(hydroxymethyl)pyrrolidinyl, (2S)
(methoxycarbonyl)pyrrolidinyl, (2S)(methoxymethyl)pyrrolidinyl, (2S)(tertbutoxycarbonyl
)pyrrolidinyl, (2S)carbamoylpyrrolidinyl, (2S)
carboxypyrrolidinyl, (2S)methyl-2,3-dihydro-1H-indolyl, (2S)
methylmorpholinyl, (2-tert-butoxyoxoethyl)(methyl)amino, (2-tert-butoxy
oxoethyl)amino, 2,2-difluoroethyl(methyl)amino, -trifluoropropyl)amino, (3,3-
ylbutyl)oxy, (3-aminooxopropyl)(methyl)amino, (3-aminooxopropyl)amino,
(3-fluorobenzyl)oxy, (3-methoxymethylbutyl)oxy, hoxybenzyl)oxy, (3R)
(hydroxymethyl)pyrrolidinyl, (3R)(methoxycarbonyl)pyrrolidinyl, (3R)
aminopyrrolidinyl, (3R)carboxypyrrolidinyl, (3R)hydroxypyrrolidinyl, (3R)-
pyrrolidinyloxy, (3rac,4rac)aminofluoropyrrolidinyl, (3S)
(dimethylamino)pyrrolidinyl, (3S)(hydroxymethyl)pyrrolidinyl, (3S)
(methoxycarbonyl)pyrrolidinyl, (3S)hydroxypyrrolidinyl,
(carboxylatomethyl)amino, (carboxymethyl)(methyl)amino, (carboxyethyl)amino,
(cyclopentylmethyl)oxy, (cyclopropylmethyl)(methyl)amino, (pyridinylmethyl)amino,
(rac)hydroxypyrrolidinyl, [(1R,3S)amino-2,2-dimethylcyclopropyl]amino, [(2R)-
oxybutanyl]amino, [(2S)aminooxopropanyl]amino, thyl-1,2,4-
oxadiazolyl)methyl]amino, [(diethoxyphosphoryl)methyl](methyl)amino, [2-(1H-
pyrazolyl)ethyl]amino, 2-(1H-imidazolyl)ethylamino, imidazolyl)ethyl-
methylamino, [2-(cyclopropylamino)ethyl]amino, [2-(dimethylamino)ethyl]amino, [2-
(pyrrolidinyl)ethyl]amino, methylamino)oxopropyl]amino, 1,1-
dioxidothiomorpholinyl, 1,2-oxazolidinyl, 1,3-dihydro-2H-isoindolyl, o
ethoxyoxoethyl, 1H-1,2,3-triazolyl, 1H-imidazolyl, 1H-pyrazolyl, 1H-pyrazol-
4-yl, 1H-pyrazolylamino, 2,2-dimethylmorpholinyl, methylpyrrolidinyl, 2,4-
dimethyl-3,5-dioxo-1,2,4-triazolidinyl, 2-acetylhydrazino, ooxoethyl, 2H-
1,2,3-triazolyl, 1H-tetrazolyl, rolidinyl)azetidinyl, 3,3-difluoroazetidin
yl, 3,3-difluoropyrrolidinyl, 3,4-dihydroisoquinolin-2(1H)-yl, 3,9-dioxa
azabicyclo[3.3.1]nonyl, 3-fluoroazetidinyl, 3-hydroxyazetidinyl, 3-
methylazetidinyl, 3-oxopyrazolidinyl, 1-(difluoromethyl)-1H-pyrazolyl, 4-
(trifluoromethyl)-1H-pyrazolyl, 1-methyl-piperidinyl, 4-fluoropiperidinyl, 4,4-
difluoropiperidinyl, 4-acetylpiperazinyl, 4-oxoimidazolidinyl, 6-oxa
azabicyclo[3.1.1]heptyl, 8-oxaazabicyclo[3.2.1]octyl, amino, anilino, azetidin
yl, benzyl(methyl)amino, bis(2-methoxyethyl)amino, chlorine, iodine, cyanomethyl,
cyclobutyl(methyl)amino, cyclopentyloxy, cyclopropyl, utyl, cyclopentyl,
cyclopropyl(ethyl)amino, cyclopropyl(methyl)amino, cyclopropylamino, diethylamino,
dimethylamino, dimethylaminocarbonyl, aminomethyl, 2-aminoethyl,
(dimethylamino)methyl, 2-(dimethylamino)ethyl, [acetyl(methyl)amino]methyl, ethenyl,
ethyl, ethyl(2-methoxyethyl)amino, ethylamino, ethyloxy, ulfanyl, ethylsulfinyl,
ethylsulfonyl, ethyl(methyl)amino, isobutyl(methyl)amino, isopropyl(methyl)amino,
pyl, isopropyloxy, methoxy(methyl)amino, methoxyamino, methyl, methyl(2-
methylsulfonylethyl)amino, methyl-oxolanyl]methyl]amino, methyl(oxan
ylmethyl)amino, methyl(1-phenylethyl)amino, methyl(2,2,2-trifluoroethyl)amino, oxetan-
3-ylmethylamino, methyl(oxetanyl)amino, methyl(phenyl)amino, methyl[2-(2-
oxopyrrolidinyl)ethyl]amino, methyl[2-(morpholinyl)ethyl]amino, amino,
methyloxy, methylsulfanyl, morpholinyl, morpholinylamino, nitrilomethyl, prop
enyl, propyl, propylamino, pyridinyl, nylsulfanyl, pyridinylamino,
pyrrolidinyl, idinyl, oxetanyl, tetrahydrofuranyl, 3,6-dihydro-2H-pyran
yl, tetrahydropyranyl, tetrahydro-2H-pyranylamino, tetrahydro-2H-pyranyloxy,
2-aminopyrimidinyl, 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidinyl, 3-fluoro-
2-oxo-1,2-dihydropyridinyl, 2-oxo-1,2-dihydropyridinyl, 3-thienyl and
thiomorpholinyl,
R3 is hydrogen or methyl,
R4 is selected from the group consisting of hydrogen, chlorine, fluorine, -OH, cyano,
methyl, methoxy, trifluoromethyl, trifluoromethoxy and NH2,
R5 is ed from the group consisting of hydrogen, chlorine, fluorine, -OH, cyano,
methyl, methoxy and trifluoromethyl,
R6 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano,
methyl and methoxy,
Q is selected from the group consisting of phenyl, 1,3-benzothiazolyl, 1,3-benzothiazol-
7-yl, 1,3-benzoxazolyl, 1H-indolyl, 1-methyl-1H-benzimidazolyl, 2,5-
bis(trifluoromethyl)phenyl, 2,3,4-trifluorophenyl, 2,3,5-trichlorophenyl, 2,3,5-
trifluorophenyl, 2,3,6-trifluorophenyl, 2,3-dichlorophenyl, 2,3-dichlorocyanophenyl,
2,3-dichlorohydroxyphenyl, 2,3-dihydrobenzofuranyl, 2,3-difluorophenyl, 2,4,5-
trifluorophenyl, trifluoromethoxyphenyl, 2,4-difluorohydroxyphenyl, 2,4-
romethoxyphenyl, 2,5-dichlorophenyl, 2-chlorocyanophenyl, 2-chloro
methylphenyl, 2,5-difluoromethoxyphenyl, 2,6-difluorophenyl, 2-chloro
methylpyridinyl, 3-methylpyridinyl, 2,6-dimethylpyridinyl, 2-chloro
fluorophenyl, 2-chloro(dimethylamino)phenyl, 2-chlorofluorophenyl, 2-chloro
fluorophenyl, 2-chlorofluorophenyl, 2-chlorophenyl, 2-chloropyridinyl, 3-
chloropyridinyl, chloropyridinyl, 2,5-dichloropyridinyl, chloropyridin-
4-yl, chloropyridinyl, 2,6-difluoropyridinyl, 3,5-difluoropyridinyl, ro
pyridinyl, 2-cyanopyridinyl, 3-chloromethoxypyridinyl, 5-chloro
methoxypyridinyl, 5-fluoromethoxypyridinyl, 5-fluoroisopropyloxypyridinyl,
2,3-dimethoxypyridinyl, 2,6-dimethoxypyridinyl, 2-fluoromethylphenyl, 3-fluoro-
-methylphenyl, 2-fluoro(trifluoromethoxy)phenyl, 2-fluoro(trifluoromethyl)phenyl,
-fluoro(trifluoromethyl)phenyl, 3-cyanomethylphenyl, 2-fluoropyridinyl, 2-
ethoxyfluoropyridinyl, 2-(hydroxymethyl)pyridinyl, 2-methylypyridinyl, 2-
ypyridinyl, 3-methoxypyridinyl, 2-aminopyridinyl, 2-morpholin
dinyl, ethylamino)-2,4-difluorophenyl, 3-(dimethylamino)phenyl, 3-
(methylamino)phenyl, 3-(trifluoromethyly)phenyl, fluoromethoxy)phenyl, 3,4,5-
trifluorophenyl, 3,4-dichloro(dimethylamino)phenyl, 3,4-dichlorophenyl, 3,4-difluoro-
2-methoxyphenyl, 3,4-difluorophenyl, 3,5-dichloro(dimethylamino)phenyl, 3,5-
dichlorofluorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 4-(difluoromethoxy)-3,5-
difluorophenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 3-tert-butylmethylphenyl, 5-
tert-butylchloromethylphenyl, 3-chlorofluoromethylphenyl, 3-chloro
fluorophenyl, 3-chloromethylphenyl, 3-chloro(dimethylamino)fluorophenyl, 3-
chloro(dimethylamino)phenyl, 3-chlorofluorophenyl, 3-chloromethylphenyl, 3-
(dimethylamino)phenyl, 3-chloro(methylsulfanyl)phenyl, 3-chloro
(morpholinyl)phenyl, 2-chloro(trifluoromethyl)phenyl, 2-methyl
(trifluoromethyl)phenyl, 3-chloro(trifluoromethyl)phenyl, 3-chloroethylphenyl, 3-
chlorofluorophenyl, 3-chloromethoxyphenyl, 3-chloromethylphenyl, 3-
chlorophenyl, 3-fluoromethylphenyl, romethoxyphenyl, 3-fluoro
methylphenyl, 3-fluoropyridinyl, 3-fluoropyridinyl, 4-chloro
(dimethylamino)phenyl, 4-fluoromethoxyphenyl, 5-(methoxycarbonyl)-1,3-
azolyl, 5-chloro-2,4-difluorophenyl, 5-chlorofluoromethylphenyl, 5-
chlorofluoromethylphenyl, 5-chlorofluorophenyl, 5-chloromethoxyphenyl, 5-
fluoromethylphenyl, 5-fluoromethoxyphenyl, 5-chloro-1H-imidazolyl, 3,5-
diethylphenyl, ro-3,5-diethylphenyl, 3-chlorothienyl, rothienyl, 5-
chlorothienyl, 2,5-dichlorothienyl, 5-fluorothienyl, 5-cyanothienyl, 5-cyano
methylthienyl, 5-methylthienyl, 2,5-dimethylthienyl, 5-(trifluoromethyl)thienyl
and 2-methyl-1,3-thiazolyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In accordance with an eigth embodiment of the first aspect, the present invention covers
compounds of general formula (I), supra, in which:
A is A3 or A4
A3 A4
o is 0 or 1,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy,
Rp is selected from the group consisting of hydrogen, alkyl,
X is selected from the group ting of CR7R8, O, S, and N-R9,
Y is CR7R8 or O,
R1 is en or C1-C4-alkyl,
R2 is selected from the group consisting of
hydrogen, halogen, N(C1-C4-alkyl)2;
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl or C3-C6-cycloalkenyl, each of which is
optionally tuted by 1, 2, 3, 4 or 5 substituents independently selected from the
group ting of halogen, -OH, cyano, C1-C4-alkoxy-C(O)- and -C(O)-NH2 C1-C4-
alkoxy, -NH2, -N(C1-C4-alkyl)2, -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl), and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, 5-membered aryl, and 6-
ed heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4
substituents independently selected from the group consisting of halogen, -OH,
oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4-
alkyl-, -NH2, -N(C1-C4-alkyl)2, and 4- to 10-membered heterocycloalkyl,
R3 is hydrogen or alkyl,
R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, NH2,
R5 is ed from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms,
R6 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and C1-C4-alkyl,
or R7 and R8 er form an oxo group (=O),
R9 is C1-C4-alkyl,
R10 is selected from the group ting of hydrogen, -OH and C1-C4-alkyl,
R11 is hydrogen,
R12 and R13 are independently selected from the group consisting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 tuents independently ed from the group consisting of
halogen, -OH, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-N(C1-C4-alkyl)2, -NHC
-C4-alkyl, C1-C4-alkyl, C1-C4-alkoxy, C3-C6-cycloalkyl, -NH2, -N(C1-C4-alkyl)2, -S-
C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, and (C1-C4-alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally tuted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy;
phenyl and benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group ting of halogen, cyano, C1-
C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms; and
a clic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl each of which is
optionally substituted by 1, 2 or 3 substituents independently selected from the group
consisting of halogen, -OH, oxo, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,
R14 is selected from the group ting of
C1-C4-alkyl, cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, C1-C4-alkyl, C1-C4-alkoxy and C3-C6-cycloalkyl; and
4- to 10-membered heterocycloalkyl,
R15 is selected from the group ting of
hydrogen;
C1-C4-alkyl, which is optionally substituted by 1, 2 or 3 substituents independently
selected from the group consisting of -OH and -COOH; and
a 6-membered heteroaryl,
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
halogen, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-halogenoalkyl having 1 to 5
halogen atoms,
Z2 and Z4 are independently ed from the group consisting of hydrogen,
halogen, cyano, -OH, C1-C4-alkyl, C1-C4-alkoxy, -NH(C1-C4-alkyl), -N(C1-C4-
alkyl)2, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -S-(C1-C4-alkyl) and a 4- to 6-membered
heterocycloalkyl, and
Z3 is selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-
, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms and -N(C1-C4-alkyl)2,
Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5-
membered heterocycloalkyl or a 5-membered heteroaryl, each of which may be
optionally substituted with one or two tuents ed from the group
consisting of methyl, fluorine and oxo,
Z3 and Z5 are hydrogen, and
Z4 is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently ed from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4-
alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1-C4-alkyl, and clic heterocycles
ed from the group of 4- to 7-membered heterocycloalkyl or 5-membered
heteroaryls having at least one nitrogen atom via which the heteroaryl ring is
connected to the pyridine ring, each of which is optionally substituted with 1, 2
or 3 substituents independently selected from the group ting of n,
cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl,
-S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5
halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 n atoms, -SO2-
(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is halogen, or
Q is a 5-membered aromatic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and NZ22
, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and wherein
each Z21 is independently selected from the group ting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
alkoxy, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic heterocycle of the formula (Q7)
in which:
U1 – U4 are ndently selected from the group consisting of N and C-Z23,
wherein not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group consisting of hydrogen,
halogen, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy,
and stereoisomers, ers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
Further embodiments of the first aspect of the present invention:
In a further embodiment of the first aspect, the present invention covers nds of formula
(I), supra, in which:
A is A1 or A2,
A1 A2
o is 0, 1 or 2,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
Rp is hydrogen,
X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9,
wherein at least one of X and Y is CR7R8,
R7 is selected from the group ting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R9 is C1-C4-alkyl,
R10 is selected from the group consisting of hydrogen, -OH, C1-C4-alkyl and C1-C4-alkoxy,
R11 is hydrogen,
n when Y is O, S or N-R9, R10 is not -OH,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
A is A1 or A2,
A1 A2
o is 0, 1 or 2,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
Rp is selected from the group consisting of hydrogen, alkyl,
X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9,
wherein at least one of X and Y is CR7R8,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and alkyl,
or R7 and R8 er form an oxo group (=O),
R9 is C1-C4-alkyl,
R10 is selected from the group consisting of hydrogen, -OH, C1-C4-alkyl and C1-C4-alkoxy,
R11 is hydrogen,
wherein when Y is O, S or N-R9, R10 is not -OH,
and stereoisomers, tautomers, N-oxides, es, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of a
(I), supra, in which:
A is A1 or A2,
A1 A2
o is 0, 1 or 2,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano,
halogenoalkyl having 1 to 5 halogen atoms,
Rp is hydrogen,
X, Y are independently selected from the group consisting of CR7R8, O, and S,
wherein at least one of X and Y is CR7R8,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and C1-C4-alkyl,
or R7 and R8 together form an oxo group (=O),
R10 is selected from the group consisting of en, -OH, C1-C4-alkyl and C1-C4-alkoxy,
R11 is hydrogen,
wherein when Y is O, S or N-R9, R10 is not -OH,
and stereoisomers, tautomers, es, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
A is A1 or A2,
A1 A2
o is 0 or 1,
R is selected from the group consisting of halogen, C1-C4-alkyl and alkoxy,
Rp is hydrogen,
X is selected from the group consisting of CR7R8, O, S, and N-R9,
Y is CR7R8,
R7 is selected from the group ting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R9 is C1-C4-alkyl,
R10 is selected from the group consisting of hydrogen, -OH and C1-C4-alkyl, and
R11 is en,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
A is A1 or A2,
A1 A2
o is 0 or 1,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy,
Rp is ed from the group consisting of hydrogen, C1-C4-alkyl,
X is selected from the group consisting of CR7R8, O, S, and N-R9,
Y is CR7R8 or O,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of hydrogen and C1-C4-alkyl,
or R7 and R8 together form an oxo group (=O),
R9 is alkyl,
R10 is selected from the group consisting of hydrogen, -OH and C1-C4-alkyl, and
R11 is hydrogen,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
A is A1 or A2,
A1 A2
o is 0 or 1,
R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy,
Rp is hydrogen,
X is ed from the group consisting of CR7R8, O and S, and N-R9,
Y is CR7R8 or O,
R7 is selected from the group consisting of hydrogen and C1-C4-alkyl,
R8 is selected from the group consisting of en and C1-C4-alkyl,
or R7 and R8 together form an oxo group (=O),
R10 is selected from the group consisting of hydrogen, -OH and C1-C4-alkyl, and
R11 is hydrogen,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first , the present invention covers compounds of a
(I), supra, in which:
A is selected from the group consisting of
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further ment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
A is selected from the group consisting of
and isomers, ers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers nds of formula
(I), supra, in which:
A is selected from the group ting of
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R2 is selected from the group consisting of
hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-
alkyl), -C(O)-N(C1-C4-alkyl)2;
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents
independently selected from the group consisting of halogen, -OH, cyano, C1-C4-
alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-
C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl), -
N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
n atoms and 1-C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4
substituents independently selected from the group consisting of halogen, cyano, -OH,
oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl having 1 to 5 halogen
atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, alkoxy-C1-C4-alkyl-, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, and 4- to 10-membered heterocycloalkyl,
R12 and R13 are independently selected from the group consisting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy;
C1-C4-alkyl, cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, cycloalkyl, -NH2, -NH(C1-C4-alkyl),
C4-alkyl)2, -S-C1-C4-alkyl, C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
noalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-
alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of n, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
phenyl, benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently ed from the group consisting of n, cyano, C1-
C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is
optionally substituted by 1, 2 or 3 substituents ndently selected from the group
consisting of halogen, cyano, -OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,
R14 is selected from the group consisting of
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl; and
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl subsitutent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
ed heteroaryl, each of which is optionally substituted by 1, 2 or 3 tuents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, -OH, cyano,
C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
ed heteroaryl, each of which is ally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms;
and stereoisomers, ers, N-oxides, hydrates, solvates, and salts f, and mixtures of
same.
In a further embodiment of the first , the present invention covers compounds of formula
(I), supra, in which:
R2 is selected from the group consisting of
hydrogen, halogen, cyano, -COOH, alkoxy-C(O)-, NH2, -C(O)-NH(C1-C4-
alkyl), -C(O)-N(C1-C4-alkyl)2;
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
phenyl-C1-C4-alkyl, each of which is ally substituted by 1, 2, 3, 4 or 5 substituents
independently selected from the group consisting of halogen, -OH, cyano, C1-C4-
-C(O)-, NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-
C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl), -
N(C1-C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl), -S-C1-C4-
alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5
n atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-
C4-halogenoalkyl having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4
substituents ndently selected from the group consisting of halogen, cyano, -OH,
oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, NH(C1-C4-alkyl), N(C1-C4-
alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl having 1 to 5 halogen
atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, and 4- to 10-membered heterocycloalkyl,
R12 and R13 are independently ed from the group consisting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -
(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl),
-N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5
halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4-
)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
ting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 tuents
independently selected from the group ting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 n atoms;
phenyl, benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, cyano, C1-
C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle ed from the group of 4- to 10-membered
heterocycloalkyl, ered heteroaryl and 6-membered heteroaryl, each of which is
optionally substituted by 1, 2 or 3 substituents independently selected from the group
consisting of halogen, cyano, -OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms,
R14 is selected from the group consisting of
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 tuents independently selected from the group consisting of
halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl; and
cyclyl-C1-C4-alkyl, wherein the heterocyclyl subsitutent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
noalkoxy having 1 to 5 halogen atoms;
R15 is ed from the group ting of
hydrogen;
C1-C4-alkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, -OH, cyano,
C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, ered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
ndently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, alkoxy, C1-C4-halogenoalkoxy having
1 to 5 halogen atoms;
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a r embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R2 is selected from the group consisting of
hydrogen, halogen,
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C4-alkyl, cycloalkyl, C2-C4-alkenyl or C3-C6-cycloalkenyl, each of which is
optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the
group consisting of halogen, cyano, C1-C4-alkoxy-C(O)- and -C(O)-NH2; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-
membered heteroaryl, each of which is ally tuted by 1, 2, 3 or 4
substituents independently selected from the group consisting of halogen, -OH,
oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4-
alkyl-, -NH2, -N(C1-C4-alkyl)2, and 4- to bered heterocycloalkyl,
R12 and R13 are independently selected from the group consisting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), alkoxy;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
n, -OH, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-N(C1-C4-alkyl)2, -NHC
(O)-C1-C4-alkyl, C1-C4-alkyl, alkoxy, C3-C6-cycloalkyl, -NH2, -N(C1-C4-alkyl)2, -SC1-C4-alkyl
, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, and (C1-C4-alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group
ting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
ndently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy;
phenyl and benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents ndently ed from the group consisting of halogen, cyano, C1-
C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered aryl and 6-membered heteroaryl each of which is
optionally substituted by 1, 2 or 3 substituents ndently ed from the group
consisting of halogen, -OH, oxo, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,
R14 is selected from the group consisting of
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, C1-C4-alkyl, C1-C4-alkoxy and C3-C6-cycloalkyl; and
4- to 10-membered heterocycloalkyl,
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, which is optionally substituted by 1, 2 or 3 substituents independently
selected from the group consisting of -OH and -COOH; and
a 6-membered heteroaryl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first , the present invention covers compounds of a
(I), supra, in which:
R2 is selected from the group consisting of
hydrogen, halogen, -C(O)-N(C1-C4-alkyl)2
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl or C3-C6-cycloalkenyl, each of which is
ally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the
group consisting of halogen, -OH, cyano, C1-C4-alkoxy-C(O)- and -C(O)-NH2, C1-C4-
alkoxy, -NH2, -N(C1-C4-alkyl)2, -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl); and
a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10-
ed heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4
substituents independently ed from the group consisting of halogen, -OH,
oxo, -COOH, alkoxy-C(O)-, -C(O)-NH2, alkyl, C1-C4-alkyl-C(O)-, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4-
alkyl-, -NH2, -N(C1-C4-alkyl)2, and 4- to 10-membered heterocycloalkyl,
R12 and R13 are independently ed from the group consisting of
hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy;
C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently ed from the group consisting of
halogen, -OH, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-N(C1-C4-alkyl)2, -NHC
(O)-C1-C4-alkyl, C1-C4-alkyl, C1-C4-alkoxy, C3-C6-cycloalkyl, -NH2, -N(C1-C4-alkyl)2, -SC1-C4-alkyl
, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, and (C1-C4-alkoxy)2P(=O)-;
heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl tuent is selected from the group
consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-
membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms and C1-C4-alkoxy;
phenyl and C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3
substituents independently selected from the group consisting of halogen, cyano, C1-
C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-
halogenoalkoxy having 1 to 5 halogen atoms; and
a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered
heterocycloalkyl, 5-membered heteroaryl and ered heteroaryl each of which is
optionally substituted by 1, 2 or 3 substituents independently selected from the group
consisting of halogen, -OH, oxo, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms,
R14 is ed from the group consisting of
C1-C4-alkyl, cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted
by 1, 2 or 3 substituents independently selected from the group consisting of
halogen, -OH, C1-C4-alkyl, C1-C4-alkoxy and C3-C6-cycloalkyl; and
4- to 10-membered cycloalkyl,
R15 is selected from the group consisting of
hydrogen;
C1-C4-alkyl, which is optionally substituted by 1, 2 or 3 substituents independently
selected from the group consisting of -OH and -COOH; and
a 6-membered heteroaryl,
and isomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R2 is selected from the group consisting of
hydrogen, ne,
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclohexyl, propenyl, cyclopentenyl,
cyclohexenyl, each of which is optionally substituted by 1 or 2 substituents
independently selected from the group consisting of cyano, ethoxy-C(O)-, and -C(O)-
NH2; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of azetidine,
pyrrolidine, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine,
ydropyridine, dihydro-2H-pyrane, 1,2-oxazolidine, 1,2-oxazine, morpholine,
rpholine, hydroisoquinoline, hydro-indole, 1,3-dihydro-isoindoel, 3,9-
dioxaazabicyclo[3.3.1]nonane, 6-oxaazabicyclo[3.1.1]heptane, 8-oxa
azabicyclo[3.2.1]octane, imidazole, pyrazole, 1,2,4-triazole, 1,2,3-triazole, 4-oxa
ro[2.5]octane, each of which is optionally substituted by 1, 2, 3 or 4 substituents
independently ed from the group consisting of fluorine, chlorine, cyano -OH,
oxo, -COOH, methoxy-C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH2, methyl,
methyl-C(O)-, trifluoromethyl, hydroxymethyl-, methoxymethyl-, -NH2, -NMe2,
pyrrolidine,
R12 and R13 are independently selected from the group consisting of
hydrogen, -NH(-C(O)-methyl), methoxy;
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, , 1-
phenylethyl, each of which is ally substituted by 1, 2 or 3 substituents
independently selected from the group consisting of fluorine, -OH, -COOH, methoxy-
C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH2, -C(O)-NMe2, -NH-C(O)-methyl,
methyl, methoxy, cyclopropyl, -NH2, NMe2, S-methyl, S(O)-methyl, thyl, and
(EtO)2P(=O)-;
heterocyclyl-methyl, heterocyclyl-ethyl, wherein the cyclyl substituent is ed
from the group consisting of pyrrolidine, morpholine, pyrazole, 1, 2, 4-oxadiazole,
ne, each of which is optionally substituted by 1 substituent ndently selected
from the group consisting of fluorine, ne, -OH, oxo and methyl;
phenyl;
2,3-dihydro-1H-indene, and
a monocyclic or a ic heterocycle selected from the group of oxetane, thietane,
pyrrolidine, morpholine, tetrahydropyrane, pyridine and pyrazole, each of which is
optionally substituted by 1 or 2 substituents independently selected from the group
consisting of fluorine, chlorine, -OH, oxo, methyl;
R14 is selected from the group consisting of
methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally
substituted by 1 or 2 substituents independently selected from the group consisting of
fluorine, -OH, methyl, methoxy and cyclopentyl; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of pyrrolidin
and tetrahydropyran,
R15 is ed from the group consisting of
methyl and ethyl, each of which is optionally tuted by 1substituent independently
selected from the group consisting of -OH and -COOH; and
pyridine,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts f, and mixtures of
same.
In a r embodiment of the first aspect, the present invention covers nds of a
(I), supra, in which:
R2 is selected from the group consisting of
hydrogen, chlorine, iodine, -C(O)-N(CH3)2,
–NR12R13;
–OR14;
-SR15, -S(O)R15, -SO2R15;
methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl,
propenyl, cyclopentenyl, cyclohexenyl, each of which is optionally substituted by 1 or 2
substituents ndently selected from the group ting of –OH, cyano, ethoxy-
C(O)-, NH2, methoxy, NH2, N(CH3)2, N(CH3)(C(O)CH3); and
a monocyclic or a bicyclic heterocycle selected from the group consisting of azetidine,
oxetane pyrrolidine, tetrahydrofurane, pyrazolidine, imidazolidine, triazolidine,
piperidine, piperazine, tetrahydropyridine, dihydro-2H-pyrane, 1,2-oxazolidine, 1,2-
oxazine, morpholine, rpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indole, 1,3-
dihydro-isoindoel, 3,9-dioxaazabicyclo[3.3.1]nonane, 6-oxa
azabicyclo[3.1.1]heptane, 8-oxaazabicyclo[3.2.1]octane, thiophene, imidazole,
pyrazole, 1,2,4-triazole, 1,2,3-triazole, 1,2,3,4-tetrazole, pyridine, opyridine
pyrimidine, tetrahydropyrimidine, 4-oxaazaspiro[2.5]octane, each of which is
optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group
ting of fluorine, chlorine, cyano -OH, oxo, -COOH, y-C(O)-, ethoxy-C(O)-,
tert-butoxy-C(O)-, -C(O)-NH2, methyl, methyl-C(O)-, difluoromethyl, trifluoromethyl,
hydroxymethyl-, methoxymethyl-, -NH2, -NMe2, pyrrolidine,
R12 and R13 are independently selected from the group ting of
hydrogen, -NH(-C(O)-methyl), methoxy;
methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, 1-
phenylethyl, each of which is optionally substituted by 1, 2 or 3 substituents
ndently selected from the group consisting of fluorine, -OH, -COOH, methoxy-
C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH2, -C(O)-NMe2, -NH-C(O)-methyl,
methyl, methoxy, cyclopropyl, -NH2, NMe2, S-methyl, S(O)-methyl, SO2-methyl, and
(EtO)2P(=O)-;
heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituent is selected
from the group consisting of oxetane, tetrahydrofurane, tetrahydropyrane pyrrolidine,
morpholine, pyrazole, imidazole, 1, 2, 4-oxadiazole, pyridine, each of which is optionally
substituted by 1 substituent independently selected from the group consisting of
ne, chlorine, -OH, oxo and methyl;
phenyl;
2,3-dihydro-1H-indene, and
a monocyclic or a ic heterocycle selected from the group of oxetane, thietane,
pyrrolidine, morpholine, tetrahydropyrane, pyridine and pyrazole, each of which is
optionally substituted by 1 or 2 substituents independently ed from the group
consisting of fluorine, chlorine, -OH, oxo, methyl;
R14 is selected from the group consisting of
methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is optionally
substituted by 1 or 2 substituents independently selected from the group consisting of
fluorine, -OH, methyl, y and cyclopentyl; and
a monocyclic or a bicyclic heterocycle selected from the group consisting of pyrrolidin
and tetrahydropyran,
R15 is selected from the group consisting of
methyl and ethyl, each of which is optionally substituted by 1substituent independently
selected from the group ting of -OH and -COOH; and
pyridine,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further ment of the first aspect, the present ion covers compounds of formula
(I), supra, in which:
Rp is hydrogen or C1-C4-alkyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
Rp is hydrogen or methyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts f, and mixtures of
same.
In a r embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R3 is hydrogen or C1-C4-alkyl,
and stereoisomers, tautomers, es, hydrates, es, and salts thereof, and es of
same.
In a further embodiment of the first aspect, the present ion covers compounds of formula
(I), supra, in which:
R3 is hydrogen or methyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers nds of formula
(I), supra, in which:
R4 is selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts f, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of a
(I), supra, in which:
R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, NH2,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R4 is selected from the group consisting of hydrogen, chlorine, fluorine, cyano, methyl,
methoxy and trifluoromethyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further ment of the first aspect, the t invention covers compounds of a
(I), supra, in which:
R4 is selected from the group consisting of hydrogen, chlorine, fluorine, -OH, cyano,
methyl, methoxy, trifluoromethyl, trifluoromethoxy and NH2,
and stereoisomers, ers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present ion covers compounds of formula
(I), supra, in which:
R5 is selected from the group consisting of en, halogen, cyano, C1-C4-alkyl, C1-C4-
halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
and stereoisomers, tautomers, N-oxides, es, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R5 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms,
and stereoisomers, ers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R5 is selected from the group consisting of hydrogen, ne, fluorine and methyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the t invention covers compounds of formula
(I), supra, in which:
R5 is selected from the group consisting of hydrogen, chlorine, fluorine, -OH, cyano,
methyl, methoxy and trifluoromethyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and es of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R6 is selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-
noalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy,
and stereoisomers, tautomers, N-oxides, hydrates, es, and salts thereof, and mixtures of
same.
In a further embodiment of the first , the present invention covers compounds of formula
(I), supra, in which:
R6 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl,
C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms,
and stereoisomers, ers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further ment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
R6 is selected from the group consisting of hydrogen, fluorine, chlorine and methyl,
and stereoisomers, tautomers, es, hydrates, solvates, and salts thereof, and es of
same.
In a further embodiment of the first aspect, the present invention covers compounds of a
(I), supra, in which:
R6 is selected from the group consisting of en, fluorine, chlorine, -OH, cyano,
methyl and methoxy,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1, Z2, Z3, Z4, and Z5 are independently selected from the group ting of
hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, hydroxy, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5
halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, 4- to ered
heterocyclyl, which is optionally substituted with 1 or 2 substituents selected
from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -S-
(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), or
Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5- or
6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered
aryl, each of which may be ally substituted with one or two
substituents selected from the group consisting of methyl, fluorine and oxo, and
Z3, Z4, and Z5 are independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-alkoxy-C(O)-, C1-C4-halogenoalkoxy having 1 to 5 n
atoms, or
Z2 and Z3 form, together with the carbon atoms that they are connected to, a 5- or
6-membered ted or partially saturated heterocyclic ring, a 5-membered
heteroaryl, or a 6-membered heteroaryl, each of which may be optionally
tuted with one or two substituents selected from the group consisting of
methyl, fluorine and oxo, and
Z1, Z4, and Z5 are independently selected from the group consisting of en,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q2)
in which:
Z6, Z7, Z8 and Z9 are independently selected from the group consisting of hydrogen
halogen, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-
alkyl), -N(C1-C4-alkyl)2, or
Q is a pyrimidine ring of the formula (Q3)
(Q3)
in which:
Z10, Z11 and Z12 are independently selected from the group consisting of
en, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n
atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of
hydrogen, halogen, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1-
C4-alkyl, and clic heterocycles selected from the group of 4- to 7-
membered heterocycloalkyl or 5-membered heteroaryls having at least one
nitrogen atom via which the heteroaryl ring is connected to the pyridine ring,
each of which is optionally substituted with 1, 2 or 3 substituents independently
selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono,
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-
C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -
NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-
alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-
noalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having
1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, Z19 and Z20 are independently selected from the group consisting of
hydrogen, halogen, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or
Q is a 5-membered aromatic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group ting of N, O, S, C-Z21 and NZ22
, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and wherein
each Z21 is independently selected from the group consisting of en,
halogen, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic cycle of the formula (Q7)
in which:
U1 – U4 are independently selected from the group consisting of N and C-Z23,
wherein not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group consisting of hydrogen,
n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
halogen, C1-C4-alkyl and C1-C4-alkoxy,
Z2 and Z4 are independently selected from the group consisting of hydrogen,
halogen, -OH, C1-C4-alkyl, C1-C4-alkoxy, -C4-alkyl), -N(C1-C4-alkyl)2, C1-
C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkoxy having 1
to 5 halogen atoms, -S-(C1-C4-alkyl) and a 4- to 6-membered heterocycloalkyl,
Z3 is selected from the group ting of hydrogen, halogen, C1-C4-alkyl, C1-C4-
alkoxy and -N(C1-C4-alkyl)2, or
Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5-
membered heterocycloalkyl or a 5-membered heteroaryl, each of which may be
optionally substituted with one or two substituents selected from the group
ting of methyl, fluorine and oxo,
Z3 and Z5 are hydrogen, and
Z4 is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen,
n, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4-
, -N(C1-C4-alkyl)2, -NH-CO-C1-C4-alkyl, and monocyclic heterocycles
selected from the group of 4- to 7-membered heterocycloalkyl or 5-membered
heteroaryls having at least one en atom via which the heteroaryl ring is
connected to the pyridine ring, each of which is optionally substituted with 1, 2
or 3 substituents independently selected from the group consisting of halogen,
cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5
n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen
atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl,
-S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5
n atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-
(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is halogen, or
Q is a 5-membered aromatic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group ting of N, O, S, C-Z21 and NZ22
, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and wherein
each Z21 is independently selected from the group ting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic heterocycle of the formula (Q7)
in which:
U1 – U4 are ndently selected from the group consisting of N and C-Z23,
wherein not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group ting of hydrogen,
halogen, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy,
and stereoisomers, tautomers, es, es, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
halogen, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-halogenoalkyl having 1 to 5
halogen atoms
Z2 and Z4 are independently selected from the group consisting of hydrogen,
halogen, cyano, -OH, C1-C4-alkyl, C1-C4-alkoxy, -NH(C1-C4-alkyl), -N(C1-C4-
alkyl)2, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkoxy
having 1 to 5 halogen atoms, -S-(C1-C4-alkyl) and a 4- to ered
heterocycloalkyl, and
Z3 is ed from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-
alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms and -N(C1-C4-alkyl)2,
or
Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5-
membered heterocycloalkyl or a 5-membered heteroaryl, each of which may be
optionally substituted with one or two substituents selected from the group
consisting of methyl, fluorine and oxo,
Z3 and Z5 are hydrogen, and
Z4 is selected from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-hydroxyalkyl, NH2, -C4-
alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1-C4-alkyl, and monocyclic heterocycles
ed from the group of 4- to 7-membered heterocycloalkyl or 5-membered
heteroaryls having at least one en atom via which the heteroaryl ring is
connected to the pyridine ring, each of which is optionally substituted with 1, 2
or 3 substituents independently selected from the group consisting of n,
cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, halogenoalkyl having 1 to 5
halogen atoms, C1-C4-alkoxy, halogenoalkoxy having 1 to 5 halogen
atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl,
-S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5
halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2halogenoalkyl) having 1 to 5 halogen atoms, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is halogen, or
Q is a 5-membered aromatic heterocycle of the formula (Q6)
in which:
T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and NZ22
, wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is
S, not more than one of T1 – T4 is N-Z22, and wherein
each Z21 is independently selected from the group consisting of hydrogen,
n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy, and
each Z22 is independently selected from the group consisting of hydrogen, C1-C4-
alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6-
cycloalkyl, alkoxy-C1-C4-alkyl, or
Q is a 5-membered aromatic heterocycle of the formula (Q7)
in which:
U1 – U4 are independently selected from the group consisting of N and C-Z23,
wherein not more than three of U1 – U4 are N, and wherein
each Z23 is independently selected from the group consisting of hydrogen,
halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms,
C1-C4-alkoxy,
and stereoisomers, ers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first , the present invention covers compounds of formula
(I), supra, in which:
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of en,
fluorine, chlorine, methyl and y,
Z2 and Z4 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, -OH, methyl, ethyl, -NHMe, -NMe2, trifluoromethyl, methoxy,
trifluoromethoxy, -SMe and morpholinyl, and
Z3 is independently selected from the group consisting of en, fluorine,
chlorine, methyl, methoxy and –NMe2, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, cyano, methyl, methoxy, ethoxy, isopropoxy, hydroxymethyl, NH2, -
NHMe -NMe2, -NH-C(O)-Me, linyl, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is fluorine, chlorine, or
Q is selected from the group consisting of
(Q6-1) (Q6-2) (Q6-3) (Q6-4) (Q6-5) (Q6-6)
(Q6-7) (Q6-8) (Q6-9) (Q6-10) (Q6-11) (Q6-12)
(Q6-13) (Q6-14) (Q6-15) (Q6-16) (Q6-17) (Q6-18)
(Q6-19) (Q6-20) (Q6-21) (Q6-22) (Q6-23) (Q6-24)
(Q6-25) (Q6-26) (Q6-27) (Q6-28) (Q6-29) (Q6-30)
(Q6-31) (Q6-32) ) (Q6-34) (Q6-35) (Q6-36)
) (Q6-38)
in which:
each Z21 is independently selected from the group consisting of hydrogen,
fluorine, chlorine, cyano, methyl, trifluoromethyl, y and
Z22 is hydrogen, methyl, or
Q is selected from the group consisting of
(Q7-1) (Q7-2) (Q7-3) (Q7-4) (Q7-5)
(Q7-6) (Q7-7) (Q7-8) (Q7-9)
in which:
each Z23 is independently selected from the group consisting of hydrogen,
ne, ne, cyano, methyl, trifluoromethyl, methoxy, or
Q is selected from the group consisting of
and isomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first aspect, the present invention covers compounds of formula
(I), supra, in which:
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, , methoxy and trifluoromethyl,
Z2 and Z4 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2,
trifluoromethyl, methoxy, trifluoromethoxy, -SMe and morpholinyl, and
Z3 is independently selected from the group consisting of hydrogen, fluorine,
chlorine, , methoxy, difluoromethoxy and –NMe2, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, cyano, methyl, y, ethoxy, isopropoxy, hydroxymethyl, NH2, -
NHMe -NMe2, O)-Me, morpholinyl, or
Q is a pyridine ring of the formula (Q5)
in which:
Z17, Z18, and Z19 are hydrogen, and
Z20 is fluorine, chlorine, or
Q is ed from the group consisting of
(Q6-1) (Q6-2) (Q6-3) (Q6-4) (Q6-5) (Q6-6)
(Q6-7) (Q6-8) (Q6-9) (Q6-10) (Q6-11) (Q6-12)
(Q6-13) (Q6-14) (Q6-15) (Q6-16) (Q6-17) (Q6-18)
(Q6-19) (Q6-20) (Q6-21) (Q6-22) (Q6-23) (Q6-24)
(Q6-25) (Q6-26) (Q6-27) ) (Q6-29) (Q6-30)
(Q6-31) ) ) (Q6-34) (Q6-35) (Q6-36)
(Q6-37) (Q6-38) or (Q6-39)
in which:
each Z21 is independently selected from the group consisting of hydrogen,
ne, ne, cyano, methyl, trifluoromethyl, methoxy and
Z22 is hydrogen, methyl, or
Q is selected from the group consisting of
(Q7-1) (Q7-2) (Q7-3) (Q7-4) (Q7-5)
(Q7-6) (Q7-7) (Q7-8) (Q7-9)
in which:
each Z23 is independently selected from the group consisting of hydrogen,
fluorine, chlorine, cyano, methyl, trifluoromethyl, y, or
Q is selected from the group consisting of
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further embodiment of the first , the present invention covers compounds of formula
(I), supra, in which:
Q is a substituted phenyl ring of the formula (Q1)
in which:
Z1 and Z5 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, methyl, methoxy and trifluoromethyl,
Z2 and Z4 are independently ed from the group consisting of hydrogen,
fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2,
trifluoromethyl, methoxy, trifluoromethoxy, -SMe and linyl, and
Z3 is independently selected from the group consisting of hydrogen, fluorine,
chlorine, methyl, methoxy, difluoromethoxy and –NMe2, or
Q is a pyridine ring of the formula (Q4)
in which:
Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen,
fluorine, chlorine, cyano, methyl, y, ethoxy, isopropoxy, hydroxymethyl, NH2, -
NHMe -NMe2, -NH-C(O)-Me, morpholinyl, or
Q is selected from the group consisting of
(Q6-1) (Q6-2)
(Q6-13) or (Q6-39)
in which:
each Z21 is independently selected from the group consisting of en,
fluorine, chlorine, cyano, methyl, trifluoromethyl, methoxy and
Z22 is hydrogen, methyl, or
Q is selected from the group consisting of
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a r embodiment of the first aspect, the t invention covers compounds of formula
(I), supra, in which
A is A3 or A4
A3 A4
wherein
Rp is selected from the group consisting of en, alkyl; preferably hydrogen,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
In a further aspect of the present invention in any or all of the embodiments according to the
first to eighth aspect (including the embodiments under the heading “further embodiments of
the first aspect of the present invention”) in the definition of X and/or Y “NR9” as defined supra
is excluded.
In a further aspect of the present invention in any or all of the ments according to the
first to eighth aspect (including the embodiments under the heading “further embodiments of
the first aspect of the present ion”) in the definition of R2 hydrogen is excluded.
In a particular further embodiment of the first aspect, the present invention covers
combinations of two or more of the above mentioned embodiments under the heading “further
embodiments of the first aspect of the present invention”.
The present invention covers any sub-combination within any embodiment or aspect of the
present invention of compounds of general a (I), supra.
The present invention covers the compounds of general a (I) which are disclosed in the
e Section of this text, infra.
The compounds according to the ion of l formula (I) can be prepared according to
the schemes 1a-e, 2, 3 and 4 as shown in the Experimental Section to the present invention
(General ures). The schemes and procedures described illustrate synthetic routes to
the nds of general formula (I) of the invention and are not intended to be limiting. It is
clear to the person skilled in the art that the order of transformations as exemplified in
schemes 1a-e, 2 and 3 can be modified in various ways. The order of transformations
exemplified in these schemes is therefore not intended to be limiting. In addition,
interconversion of any of the tuents, Q, A, R1, R2, R3, R4, R5 or R6 can be achieved
before and/or after the exemplified transformations. These modifications can be such as the
introduction of protecting groups, ge of ting , reduction or oxidation of
functional groups, halogenation, metallation, substitution or other reactions known to the
person skilled in the art. These transformations include those which introduce a functionality
which allows for further interconversion of substituents. Appropriate protecting groups and their
introduction and cleavage are well-known to the person skilled in the art (see for example T.W.
Greene and P.G.M. Wuts in Protective Groups in Organic Synthesis, 3rd edition, Wiley 1999).
Specific examples are described in the subsequent paragraphs.
In the ing, several routes for the preparation of compounds of general formula (I) are
described in schemes 1a-e and 2.
In accordance with a second aspect, the present invention covers methods of preparing
compounds of general formula (I) as defined supra, said methods comprising the step of
ng an intermediate compound of general formula 1N :
in which A, R1, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) as
defined supra,
to react with a compound of general formula 1F :
1F,
in which R2 is NR12R13, OR14, or SR15, each as defined for the compound of general formula (I)
as defined supra,
thereby giving a nd of general formula (I) :
(I),
in which A, R1, R2, R3, R4, R5, R6, and Q are as defined supra.
In ance with an alternative embodiment of the second aspect, the t invention
covers methods of ing compounds of general formula (I) as defined supra, said methods
comprising the step of allowing an intermediate compound of general formula 1T :
6 2
R R O
R A
4 3
R R
in which A, R1, R2, R3, R4, R5 and R6 are as defined for the compound of general formula (I) as
defined supra, and in which Hal is halogen, particularly ne, bromine or iodine,
to react with a compound of general formula 1H :
Q-B(OR)2
in which Q is as defined for the compound of general formula (I) as d supra, and each R
may be individually H or Me or both R are pinacolate,
thereby giving a compound of general formula (I) :
in which A, R1, R2, R3, R4, R5, R6, and Q are as defined supra.
In accordance with an alternative embodiment of the second aspect, the present ion
covers methods of preparing compounds of general formula (I) as defined supra, said methods
comprising the step of allowing an intermediate compound of general formula 1W :
in which Q, R2, R3, R4, R5 and R6 are as defined for the compound of l formula (I) as
defined supra,
to react with a compound of general formula 1M :
in which R1 and A are as defined for the compound of general formula (I) as d supra,
thereby giving a compound of general formula (I) :
in which A, R1, R2, R3, R4, R5, R6, and Q are as defined supra.
In accordance with an alternative embodiment of the second aspect, the present invention
covers methods of preparing compounds of general formula (I) as defined supra, said s
comprising the step of ng an intermediate compound of general formula 1X :
in which Q, A, R1, R3, R4, R5 and R6 are as defined for the compound of l formula (I) as
defined supra,
to react with a compound of general formula 1Y :
in which R2 is OR14 as defined for the nd of general formula (I) as defined supra,
thereby giving a nd of general formula (I) :
in which A, R1, R3, R4, R5, R6, and Q are as defined supra and R2 is C1-C4-alkoxy which is
optionally substituted as defined supra.
In accordance with an alternative embodiment of the second aspect, the present invention
covers methods of preparing compounds of general formula (I) as defined supra, said methods
comprising the step of allowing an intermediate nd of l formula 1N :
in which Q, A, R1, R3, R4, R5 and R6 are as defined for the compound of general formula (I) as
defined supra,
to react with a compound of general formula 2A :
R2Met-X
in which R2 is C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
phenyl-C1-C4-alkyl, each of which is optionally substituted as defined for the compound of
general formula (I) as defined supra, Met is ium or zinc, and X is chlorine, bromine or
iodine,
thereby giving a compound of general formula (I) :
in which A, R1, R3, R4, R5, R6, and Q are as defined supra and R2 is C1-C4-alkyl, C3-C6-
lkyl, alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of
which is ally substituted as defined supra.
In accordance with a third aspect, the present invention covers methods of ing
compounds of general formula (I) as defined supra, said methods comprising the step of
allowing an intermediate compound of l formula 1N :
in which A, R1, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) as
defined supra,
to react with a compound of general formula 1F :
in which R2 is NR12R13, OR14, or SR15, each as defined for the compound of general formula (I)
as defined supra,
thereby giving a compound of general formula (I) :
in which A, R1, R2, R3, R4, R5, R6, and Q are as defined supra,
then optionally converting said compound into solvates, salts and/or solvates of such salts
using the corresponding (i) solvents and/or (ii) bases or acids.
In accordance with an alternative ment of the third aspect, the present invention covers
methods of preparing compounds of l formula (I) as defined supra, said s
comprising the step of allowing an intermediate compound of general formula 1T :
1T,
in which A, R1, R2, R3, R4, R5 and R6 are as defined for the compound of general formula (I) as
defined supra, and in which Hal is halogen, particularly chlorine, e or iodine,
to react with a compound of general formula 1H :
Q-B(OR)2
1H,
in which Q is as defined for the compound of general formula (I) as d supra, and each R
may be individually H or Me or both R are pinacolate,
thereby giving a compound of general formula (I) :
(I),
in which A, R1, R2, R3, R4, R5, R6, and Q are as defined supra,
then ally converting said compound into solvates, salts and/or solvates of such salts
using the corresponding (i) solvents and/or (ii) bases or acids.
In accordance with an alternative embodiment of the third aspect, the present invention covers
methods of preparing compounds of general formula (I) as defined supra, said methods
comprising the step of ng an ediate compound of l formula 1W :
in which Q, R2, R3, R4, R5 and R6 are as defined for the compound of general formula (I) as
defined supra,
to react with a compound of general formula 1M :
in which R1 and A are as defined for the nd of general formula (I) as defined supra,
thereby giving a compound of general formula (I) :
in which A, R1, R2, R3, R4, R5, R6, and Q are as defined supra,
then optionally converting said compound into solvates, salts and/or solvates of such salts
using the corresponding (i) solvents and/or (ii) bases or acids.
In accordance with an alternative ment of the third aspect, the present invention covers
methods of preparing compounds of general formula (I) as defined supra, said methods
comprising the step of allowing an intermediate compound of general formula 1X :
in which Q, A, R1, R3, R4, R5 and R6 are as defined for the compound of general formula (I) as
defined supra,
to react with a compound of general formula 1Y :
in which R2 is OR14 as defined for the nd of general formula (I) as defined supra,
thereby giving a compound of general formula (I) :
in which A, R1, R3, R4, R5, R6, and Q are as d supra and R2 is C1-C4-alkoxy which is
ally substituted as defined supra,
then optionally ting said compound into solvates, salts and/or solvates of such salts
using the corresponding (i) solvents and/or (ii) bases or acids.
In accordance with an alternative embodiment of the third aspect, the present invention covers
methods of preparing compounds of general formula (I) as defined supra, said methods
comprising the step of allowing an intermediate compound of general formula 1N :
1N,
in which Q, A, R1, R3, R4, R5 and R6 are as defined for the compound of l formula (I) as
defined supra,
to react with a nd of general formula 2A :
R2Met-X
in which R2 is C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or
phenyl-C1-C4-alkyl, each of which is optionally substituted as d for the compound of
general formula (I) as defined supra, Met is magnesium or zinc, and X is chlorine, bromine or
iodine,
thereby giving a compound of general formula (I) :
(I),
in which A, R1, R3, R4, R5, R6, and Q are as d supra and R2 is C1-C4-alkyl, C3-C6-
cycloalkyl, C2-C4-alkenyl, cycloalkenyl, C2-C4-alkynyl or -C1-C4-alkyl, each of
which is optionally substituted as defined supra,
then optionally converting said compound into solvates, salts and/or solvates of such salts
using the corresponding (i) solvents and/or (ii) bases or acids.
The present invention covers methods of preparing compounds of the present invention of
general formula (I), said methods comprising the steps as bed in the Experimental
Section herein.
In accordance with a fourth aspect, the present ion covers intermediate compounds
which are useful for the preparation of the compounds of general formula (I), supra.
Particularly, the inventions covers the intermediate compounds of general formula (II) :
(II),
in which
R2 is -OH or as defined for the compound of general formula (I) supra,
R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) supra, and
RA is H or C1-C4-alkyl,
and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of
same.
Particularly, the inventions covers also the intermediate compounds of general formula (III) :
(III),
in which
R2 is -OH or as defined for the compound of general formula (I) supra,
A, R1, R3, R4, R5, and R6 are as defined for the compound of general formula (I) supra, and
Hal is halogen,
and stereoisomers, tautomers, es, hydrates, solvates, and salts thereof, and mixtures of
same.
In accordance with a fifth aspect, the present ion covers the use of said intermediate
compounds for the preparation of a compound of general formula (I) as defined supra.
Particularly, the inventions covers the use of intermediate nds of general formula (II) :
(II),
in which
R2 is -OH or as defined for the compound of general a (I) supra,
R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) supra, and
RA is H or C1-C4-alkyl,
for the preparation of a compound of l formula (I) as defined supra.
Particularly, the inventions covers also the use of intermediate compounds of general formula
(III) :
(III),
in which
R2 is -OH as defined for the compound of general formula (I) supra,
A, R1, R3, R4, R5, and R6 are as defined for the compound of general formula (I) supra, and
Hal is halogen,
for the preparation of a compound of general formula (I) as defined supra.
The present invention covers the intermediate nds which are disclosed in the Example
Section of this text, infra.
The compounds of general formula (I) of the present invention can be converted to any salt,
ably pharmaceutically acceptable salts, as described herein, by any method which is
known to the person skilled in the art. rly, any salt of a compound of general formula (I)
of the present invention can be converted into the free compound, by any method which is
known to the person skilled in the art.
Compounds of general a (I) of the present invention demonstrate a valuable
cological spectrum of action, which could not have been predicted. nds of the
present invention have surprisingly been found to effectively ct with Slo-1 and it is
possible therefore that said compounds be used for the treatment or prevention of diseases,
ably thic infections, particulary of gastro-intestinal and extra-intestinal helminth
infections, more particulary of gastro-intestinal and extra-intestinal infections with nematodes in
humans and animals.
Compounds of the t invention can be utilized to control, treat and/or prevent helminth
infections, in particular gastro-intestinal and extra-intestinal helminth infections. This method
comprises administering to a mammal in need thereof an amount of a nd of this
invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate,
solvate or ester thereof; which is effective to treat the disorder.
In an alternative aspect, this method comprises administering to birds, namely cage birds or in
particular poultry, in need thereof an amount of a compound of this invention, or a
pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester
thereof; which is ive to treat the disorder.
Specifically in the field of veterinary medicine, compounds of the the t invention are
suitable, with favourable toxicity in warm blooded animals, for controlling parasites, in
particular helminths, which occur in animal breeding and animal husbandry in livestock,
breeding, zoo, laboratory, experimental and domestic animals. They are active against all or
specific stages of development of the parasites, in particular of the helminths.
Agricultural ock include, for example, mammals, such as, sheep, goats, horses, donkeys,
camels, buffaloes, rabbits, reindeers, fallow deers, and in ular cattle and pigs; or poultry,
such as turkeys, ducks, geese, and in particular chickens; or fish or crustaceans, e.g. in
aquaculture.
Domestic animals include, for example, mammals, such as hamsters, guinea pigs, rats, mice,
chinchillas, ferrets or in particular dogs, cats; cage birds; reptiles; amphibians or aquarium fish.
The t invention also es methods of treating helminth infections, particularly intestinal
and extra-intestinal helminth infections, more particularly gastro-intestinal and ntestinal
infections with nematodes.
These disorders have been well characterized in animals, and can be treated by administering
pharmaceutical compositions of the present invention.
The term “treating” or “treatment” as used in the present text is used conventionally, e.g., the
management or care of a t for the purpose of combating, alleviating, reducing, relieving,
improving the condition of a disease or disorder, such as a nematode infection. In ular,
and particularly in the animal health or veterinary field, the term “treating” or “treatment”
includes prophylactic, metaphylactic or therapeutical treatment
Helminths pathogenic for humans or animals include, for example, acanthocephala,
nematodes, pentastoma and platyhelmintha (e.g. nea, cestodes and trematodes).
ary helminths include, without any tion:
Monogenea: e.g.: ogyrus spp., Gyrodactylus spp., Microbothrium spp., Polystoma spp.,
Troglocephalus spp.
Cestodes: from the order of the Pseudophyllidea, for example: Bothridium spp.,
lobothrium spp., Diplogonoporus spp., Ichthyobothrium spp., Ligula spp.,
ocephalus spp., Spirometra spp.
from the order of the Cyclophyllida, for example: Andyra spp., Anoplocephala spp., Avitellina
spp., lla spp., Cittotaenia spp., Davainea spp., Diorchis spp., Diplopylidium spp.,
Dipylidium spp., Echinococcus spp., Echinocotyle spp., Echinolepis spp., Hydatigera spp.,
Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp., Paranoplocephala
spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma spp.
Trematodes: from the class of the Digenea, for example: Austrobilharzia spp., Brachylaima
spp., phoron spp., Catatropis spp., Clonorchis spp. Collyriclum spp., Cotylophoron spp.,
Cyclocoelum spp., Dicrocoelium spp., Diplostomum spp., Echinochasmus spp.,
Echinoparyphium spp., Echinostoma spp., Eurytrema spp., Fasciola spp., Fasciolides spp.,
Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp., Gigantobilharzia spp.,
Gigantocotyle spp., phyes spp., Hypoderaeum spp., Leucochloridium spp.,
Metagonimus spp., Metorchis spp., Nanophyetus spp., Notocotylus spp., Opisthorchis spp.,
obilharzia spp., Paragonimus spp., Paramphistomum spp., Plagiorchis spp.,
Posthodiplostomum spp., Prosthogonimus spp., Schistosoma spp., Trichobilharzia spp.,
Troglotrema spp., Typhlocoelum spp.
des: from the order of the Trichinellida, for e: Capillaria spp., Eucoleus spp.,
pillaria spp., Trichinella spp., mosoides spp., Trichuris spp.
from the order of the Tylenchida, for example: Micronema spp., rongyloides spp.,
Strongyloides spp.
from the order of the Rhabditina, for example: Aelurostrongylus spp., Amidostomum spp.,
Ancylostoma spp., Angiostrongylus spp., Bronchonema spp., Bunostomum spp., Chabertia
spp., Cooperia spp., Cooperioides spp., Crenosoma spp., Cyathostomum spp., Cyclococercus
spp., Cyclodontostomum spp., Cylicocyclus spp., Cylicostephanus spp., Cylindropharynx spp.,
Cystocaulus spp., Dictyocaulus spp., Elaphostrongylus spp., Filaroides spp., Globocephalus
spp., Graphidium spp., Gyalocephalus spp., Haemonchus spp., Heligmosomoides spp.,
Hyostrongylus spp., Marshallagia spp., Metastrongylus spp., rius spp., Necator spp.,
Nematodirus spp., Neostrongylus spp., Nippostrongylus spp., Obeliscoides spp.,
Oesophagodontus spp., Oesophagostomum spp., Ollulanus spp.; Ornithostrongylus spp.,
s spp., agia spp., Paracooperia spp., Paracrenosoma spp., Parafilaroides spp.,
Parelaphostrongylus spp., Pneumocaulus spp., Pneumostrongylus spp., ostomum spp.,
Protostrongylus spp., Spicocaulus spp., nurus spp., Strongylus spp., Syngamus spp.,
Teladorsagia spp., Trichonema spp., Trichostrongylus spp., Triodontophorus spp.,
Troglostrongylus spp., Uncinaria spp.
from the order of the Spirurida, for example: ocheilonema spp., Anisakis spp., Ascaridia
spp.; Ascaris spp., Ascarops spp., Aspiculuris spp., Baylisascaris spp., Brugia spp.,
Cercopithifilaria spp., Crassicauda spp., Dipetalonema spp., Dirofilaria spp., Dracunculus spp.;
Draschia spp., Enterobius spp., Filaria spp., Gnathostoma spp., Gongylonema spp.,
Habronema spp., Heterakis spp.; Litomosoides spp., Loa spp., Onchocerca spp., Oxyuris spp.,
onema spp., Parafilaria spp., Parascaris spp., Passalurus spp., Physaloptera spp.,
Probstmayria spp., Pseudofilaria spp., a spp., Skjrabinema spp., Spirocerca spp.,
Stephanofilaria spp., Strongyluris spp., Syphacia spp., Thelazia spp., aris spp.,
Toxocara spp., Wuchereria spp.
Acantocephala: from the order of the Oligacanthorhynchida, for example:
Macracanthorhynchus spp., Prosthenorchis spp.; from the order of the Moniliformida, for
example: formis spp.
from the order of the Polymorphida, for example: Filicollis spp.; from the order of the
Echinorhynchida, for example: Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides
Pentastoma: from the order of the Porocephalida, for example: Linguatula spp.
The compounds of the present ion can be used in particular in therapy and prevention,
i.e. prophylaxis, of helminth infections, particularly gastro-intestinal and extra-intestinal
helminth infections, more particularly -intestinal and extra-intestinal infections with
nematodes.
By using the compounds of the present invention to control animal parasites, in particular
helminths, it is intended to reduce or prevent s, cases of deaths and performance
reductions (in the case of meat, milk, wool, hides, eggs, honey and the like), so that more
ical and simpler animal keeping is made possible and better animal well-being is
achievable.
The term “control” or "controlling", as used herein with regard to the animal health field, means
that the compounds of the present invention are effective in reducing the incidence of the
respective parasite in an animal infected with such parasites to innocuous levels. More
specifically, "controlling", as used , means that the compounds of the t invention
are effective in killing the respective parasite, inhibiting its growth, or inhibiting its proliferation.
In accordance with a further aspect, the present ion covers compounds of l
a (I), as described supra, or stereoisomers, tautomers, N-oxides, es, solvates, and
salts thereof, particularly pharmaceutically able salts thereof, or mixtures of same, for
use in the treatment or prevention of diseases, in particular of helminth infections, ulary of
gastro-intestinal and extra-intestinal helminth infections, more particulary of gastro-intestinal
and extra-intestinal infections with nematodes.
The pharmaceutical activity of the compounds according to the invention can be explained by
their interaction with the Slo-1 ion channel.
In accordance with a further aspect, the present invention covers the use of compounds of
general formula (I), as described supra, or stereoisomers, ers, N-oxides, hydrates,
solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures
of same, for the ent or prevention of es, in particular of helminth infections,
particulary of gastro-intestinal and extra-intestinal helminth infections, more particulary of
gastro-intestinal and extra-intestinal infections with nematodes.
In accordance with a further aspect, the present invention covers the use of compounds of
general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates,
solvates, and salts thereof, ularly pharmaceutically acceptable salts thereof, or es
of same, in a method of treatment or prevention of diseases, in ular of helminth
infections, particulary of gastro-intestinal and extra-intestinal helminth infections, more
ulary of gastro-intestinal and extra-intestinal infections with nematodes.
In accordance with a further aspect, the present invention covers use of a compound of
l formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates,
solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures
of same, for the preparation of a pharmaceutical composition, ably a medicament, for the
prevention or treatment of diseases, in particular of helminth infections, particulary of gastro-
intestinal and extra-intestinal helminth infections, more particulary of gastro-intestinal and
extra-intestinal ions with nematodes.
In accordance with a further aspect, the present invention covers a method of treatment or
prevention of diseases, in particular of helminth infections, particularly of gastro-intestinal and
extra-intestinal helminth infections, more particulary of gastro-intestinal and intestinal
infections with nematodes, using an effective amount of a compound of general formula (I), as
described supra, or stereoisomers, tautomers, N-oxides, es, solvates, and salts thereof,
particularly ceutically acceptable salts thereof, or mixtures of same.
In accordance with a further aspect, the present invention covers compounds of l
formula (I), as bed supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and
salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for
use as an antiendoparasitical agent.
In accordance with a further aspect, the present invention covers compounds of general
formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and
salts thereof, particularly pharmaceutically acceptable salts f, or mixtures of same, for
use as a anthelmintic agent, in particular for use as a nematicidal agent, a platyhelminthicidal
agent, an acanthocephalicidal agent, or a pentastomicidal agent.
In accordance with a further aspect, the present ion covers pharmaceutical
compositions, in particular a veterinary formulation, comprising a compound of general formula
(I), as described supra, or a isomer, a tautomer, an N-oxide, a hydrate, a solvate, a salt
thereof, particularly a ceutically able salt, or a mixture of same, and one or more
excipients), in particular one or more pharmaceutically acceptable excipient(s). Conventional
procedures for preparing such pharmaceutical compositions in appropriate dosage forms can
be ed.
In accordance with a further aspect, the present invention covers a method for preparing a
pharmaceutical composition, in particular a nary formulation, comprising the step of
mixing a compound of general formula (I), as bed supra, or a stereoisomer, a tautomer,
an N-oxide, a hydrate, a solvate, a salt thereof, particularly a pharmaceutically acceptable salt,
or a mixture of same, with one or more excipients), in particular one or more pharmaceutically
acceptable excipient(s).
In accordance with a further aspect, the present invention covers a method of treatment or
prevention of es, in particular of helminth infections, particularly of gastro-intestinal and
extra-intestinal helminth infections, more ulary of -intestinal and extra-intestinal
infections with des, using a pharmaceutical composition, in particular a veterinary
ation, comprising an effective amount of a compound of general formula (I), as
described supra, or isomers, tautomers, N-oxides, hydrates, solvates, and salts thereof,
particularly pharmaceutically acceptable salts thereof, or mixtures of same.
The present invention rmore covers pharmaceutical compositions, in particular veterinary
formulations, which comprise at least one compound according to the invention, conventionally
er with one or more pharmaceutically suitable excipients, and to their use for the above
mentioned purposes.
It is possible for the compounds according to the invention to have systemic and/or local
activity. For this purpose, they can be administered in a suitable manner, such as, for example,
via the oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, , vaginal, dermal,
transdermal, conjunctival, otic route or as an implant or stent. Such administration can be
carried out prophylactically, hylactically or therapeutically.
For these administration routes, it is possible for the compounds according to the invention to
be administered in suitable administration forms.
For oral administration, it is possible to formulate the compounds according to the invention to
dosage forms known in the art that deliver the compounds of the invention rapidly and/or in a
modified manner, such as, for example, tablets (uncoated or coated s, for example with
enteric or controlled release coatings that dissolve with a delay or are insoluble), orallydisintegrating
s, films/wafers, films/lyophylisates, es (for example hard or soft
gelatine capsules), sugar-coated tablets, granules, pellets, chewables (for e soft
chewables), powders, emulsions, suspensions, aerosols or ons. It is possible to
incorporate the compounds according to the invention in crystalline and/or amorphised and/or
dissolved form into said dosage forms.
Parenteral administration can be effected with avoidance of an absorption step (for example
intravenous, intraarterial, ardial, intraspinal or intralumbal) or with inclusion of tion
(for example intramuscular, subcutaneous, intracutaneous, percutaneous or intraperitoneal).
stration forms which are suitable for eral administration are, inter alia,
preparations for injection and infusion in the form of solutions, suspensions, emulsions,
lyophylisates or sterile powders.
Examples which are suitable for other administration routes are pharmaceutical forms for
inhalation [inter alia powder inhalers, nebulizers], nasal drops, nasal solutions, nasal sprays;
tablets/films/wafers/capsules for l, sublingual or buccal administration; suppositories; eye
drops, eye ointments, eye baths, ocular inserts, ear drops, ear sprays, ear powders, earrinses
, ear tampons; vaginal capsules, aqueous sions (lotions, mixturae agitandae),
lipophilic suspensions, emulsions, ointments, creams, ermal therapeutic systems (such
as, for example, patches), milk, pastes, foams, spot-ons, dusting powders, implants or stents.
The compounds according to the ion can be incorporated into the stated stration
forms. This can be effected in a manner known per se by mixing with pharmaceutically suitable
excipients. Pharmaceutically suitable excipients include, inter alia,
• fillers and rs (for example cellulose, microcrystalline cellulose (such as, for
example, ®), lactose, mannitol, starch, calcium phosphate (such as, for example,
Di-Cafos®)),
• ointment bases (for e petroleum jelly, paraffins, triglycerides, waxes, wool wax,
wool wax alcohols, lanolin, hydrophilic ointment, polyethylene s),
• bases for suppositories (for example polyethylene glycols, cacao butter, hard fat),
• solvents (for example water, ethanol, isopropanol, glycerol, propylene glycol, medium
chain-length triglycerides fatty oils, liquid polyethylene glycols, paraffins),
• surfactants, emulsifiers, sants or wetters (for example sodium dodecyl sulfate),
lecithin, phospholipids, fatty ls (such as, for example, Lanette®), sorbitan fatty
acid esters (such as, for example, Span®), polyoxyethylene sorbitan fatty acid esters
(such as, for example, Tween®), polyoxyethylene fatty acid glycerides (such as, for
example, Cremophor®), polyoxethylene fatty acid esters, polyoxyethylene fatty alcohol
ethers, glycerol fatty acid esters, poloxamers (such as, for example, Pluronic®),
• buffers, acids and bases (for example phosphates, carbonates, citric acid, acetic acid,
hydrochloric acid, sodium hydroxide solution, ammonium ate, trometamol,
triethanolamine),
• isotonicity agents (for example glucose, sodium chloride),
• adsorbents (for example highly-disperse silicas),
• ity-increasing agents, gel formers, thickeners and/or binders (for example
polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose
, carboxymethylcellulose-sodium, starch, carbomers, polyacrylic acids (such
as, for example, Carbopol®); alginates, gelatine),
• disintegrants (for example modified starch, carboxymethylcellulose-sodium, sodium
starch glycolate (such as, for example, Explotab®), cross- linked nylpyrrolidone,
croscarmellose-sodium (such as, for example, AcDiSol®)),
• flow regulators, ants, glidants and mould release agents (for example magnesium
stearate, stearic acid, talc, highly-disperse s (such as, for example, Aerosil®)),
• coating als (for example sugar, shellac) and film formers for films or diffusion
membranes which dissolve rapidly or in a modified manner (for example
polyvinylpyrrolidones (such as, for example, Kollidon®), polyvinyl l,
hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, hydroxypropyl-
methylcellulose ate, cellulose acetate, cellulose acetate phthalate, polyacrylates,
polymethacrylates such as, for example, Eudragit®)),
• capsule materials (for example gelatine, hydroxypropylmethylcellulose),
• synthetic polymers (for example polylactides, polyglycolides, polyacrylates,
polymethacrylates (such as, for example, Eudragit®), polyvinylpyrrolidones (such as, for
example, Kollidon®), nyl alcohols, polyvinyl acetates, polyethylene oxides,
polyethylene glycols and their copolymers and blockcopolymers),
• plasticizers (for example polyethylene glycols, propylene glycol, glycerol, triacetine,
triacetyl citrate, dibutyl phthalate),
• penetration enhancers,
• stabilisers (for example antioxidants such as, for example, ic acid, ascorbyl
ate, sodium ascorbate, butylhydroxyanisole, butylhydroxytoluene, propyl e),
• preservatives (for example parabens, sorbic acid, thiomersal, konium chloride,
chlorhexidine acetate, sodium benzoate),
• colourants (for example inorganic pigments such as, for example, iron oxides, um
e),
• flavourings, sweeteners, flavour- and/or odour-masking agents.
The present ion furthermore relates to a pharmaceutical composition which comprise at
least one compound ing to the invention, conventionally together with one or more
pharmaceutically suitable excipient(s), and to their use according to the present invention.
In accordance with another aspect, the present invention covers pharmaceutical combinations,
in particular medicaments, comprising at least one compound of general a (I) of the
present invention and at least one or more further active ingredients, in particular for the
treatment and/or prevention of an endo- and/or ectoparasiticidal infection.
The term “endoparasite” in the t invention is used as known to persons skilled in the art,
and refers in particular to helminths. The term “ectoparasite” in the present invention is used
as known to persons skilled in the art, and refers in ular to arthropods, particularly s
or acarids.
Particularly, the present invention covers a pharmaceutical combination, in particular a
veterinary combination, which comprises:
• one or more first active ingredients, in ular compounds of general formula (I) as
defined supra, and
• one or more further active ingredients, in particular one or more endo- and/or
ectoparasiticides.
The term “combination” in the present invention is used as known to persons skilled in the art,
it being possible for said ation to be a fixed combination, a xed combination or a
kit-of-parts.
A “fixed combination” in the present ion is used as known to persons skilled in the art
and is defined as a combination wherein, for example, a first active ingredient, such as one or
more compounds of general a (I) of the present invention, and a further active ingredient
are t together in one unit dosage or in one single entity. One example of a “fixed
combination” is a pharmaceutical composition wherein a first active ient and a further
active ingredient are present in admixture for simultaneous administration, such as in a
formulation. Another example of a “fixed combination” is a pharmaceutical combination
wherein a first active ingredient and a further active ingredient are present in one unit without
being in admixture.
A non-fixed combination or “kit-of-parts” in the present invention is used as known to persons
skilled in the art and is defined as a combination wherein a first active ingredient and a further
active ingredient are present in more than one unit. One example of a non-fixed combination or
kit-of-parts is a combination wherein the first active ingredient and the further active ingredient
are present separately. It is possible for the components of the xed combination or kit-of-
parts to be administered separately, sequentially, simultaneously, concurrently or
chronologically staggered.
The compounds of the present invention can be administered as the sole pharmaceutical
agent or in combination with one or more other pharmaceutically active ingredients where the
combination causes no unacceptable adverse s. The present invention also covers such
pharmaceutical combinations. For example, the compounds of the present invention can be
combined with known ectoparasiticides and/or endoparasiticides.
The other or further active ingredients specified herein by their common names are known and
described, for example, in the Pesticide Manual (“The Pesticide Manual” 16th Ed., British Crop
Protection Council 2012) or can be searched in the internet (e.g.
http://www.alanwood.net/pesticides). The classification is based on the current IRAC Mode of
Action Classification Scheme at the time of filing of this patent application.
Examples of ectoparasiticides and/or rasiticides are insecticides, acaricides and
nematicides, and include in particular:
(1) Acetylcholinesterase (AChE) inhibitors, such as, for example, carbamates, for example
alanycarb, aldicarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl,
carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb,
methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox,
mate, trimethacarb, XMC and xylylcarb; or organophosphates, for example acephate,
hiphos, azinphos-ethyl, azinphos-methyl, cadusafos, chlorethoxyfos, chlorfenvinphos,
chlormephos, chlorpyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon,
dichlorvos/DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion,
ophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imicyafos,
phos, isopropyl O-(methoxyaminothiophosphoryl) salicylate, isoxathion, malathion,
mecarbam, methamidophos, methidathion, mevinphos, otophos, naled, omethoate,
oxydemeton-methyl, parathion-methyl, phenthoate, e, phosalone, phosmet,
phosphamidon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos,
phenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos,
thiometon, triazophos, triclorfon and vamidothion.
(2) GABA-gated chloride channel blockers, such as, for example, cyclodiene-organochlorines,
for example chlordane and endosulfan or phenylpyrazoles (fiproles), for example ethiprole and
il.
(3) Sodium channel modulators, such as, for e, pyrethroids, e.g. acrinathrin, allethrin, rans
allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin s-cyclopentenyl isomer,
bioresmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin,
gamma-cyhalothrin, cypermethrin, cypermethrin, beta-cypermethrin, cypermethrin,
zeta-cypermethrin, othrin [(1R)-trans-isomer], deltamethrin, empenthrin [(EZ)-(1R)-
], esfenvalerate, prox, fenpropathrin, fenvalerate, hrinate, flumethrin, taufluvalinate
, halfenprox, imiprothrin, kadethrin, momfluorothrin, permethrin, phenothrin [(1R)-
trans-isomer], prallethrin, pyrethrins (pyrethrum), resmethrin, silafluofen, tefluthrin,
ethrin, tetramethrin [(1R)- isomer)], tralomethrin and transfluthrin or DDT or
methoxychlor.
(4) Nicotinic acetylcholine receptor (nAChR) competitive modulators, such as, for example,
neonicotinoids, e.g. acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid
and thiamethoxam or nicotine or sulfoxaflor or flupyradifurone.
(5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators, such as, for example,
spinosyns, e.g. spinetoram and spinosad.
(6) Glutamate-gated chloride channel (GluCl) eric modulators, such as, for example,
avermectins/milbemycins, for example abamectin, emamectin benzoate, lepimectin and
milbemectin.
(7) Juvenile hormone mimics, such as, for example, juvenile hormone analogues, e.g.
hydroprene, ene and methoprene or fenoxycarb or pyriproxyfen.
(9) tors of Chordotonal , such as, for example pymetrozine or flonicamid.
(10) Mite growth inhibitors, such as, for example clofentezine, hexythiazox and diflovidazin or
(12) Inhibitors of mitochondrial ATP se, such as, ATP disruptors such as, for example,
diafenthiuron or organotin compounds, for example azocyclotin, cyhexatin and fenbutatin oxide
or propargite or tetradifon.
(13) Uncouplers of oxidative phosphorylation via disruption of the proton gradient, such as, for
example, chlorfenapyr, DNOC and sulfluramid.
(14) Nicotinic acetylcholine receptor l rs, such as, for e, bensultap, cartap
hydrochloride, thiocylam, and thiosultap-sodium.
(15) Inhibitors of chitin biosynthesis, type 0, such as, for example, bistrifluron, chlorfluazuron,
diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron,
teflubenzuron and muron.
(16) Inhibitors of chitin biosynthesis, type 1, for example buprofezin.
(17) Moulting disruptor (in particular for a, i.e. dipterans), such as, for e,
cyromazine.
(18) Ecdysone receptor agonists, such as, for example, chromafenozide, halofenozide,
methoxyfenozide and tebufenozide.
(19) Octopamine or agonists, such as, for example, amitraz.
(20) Mitochondrial complex III electron transport inhibitors, such as, for example,
hydramethylnone or acequinocyl or ypyrim.
(21) Mitochondrial complex I electron transport inhibitors, such as, for e from the group
of the METI acaricides, e.g. fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad
and tolfenpyrad or rotenone (Derris).
(22) Voltage-dependent sodium channel blockers, such as, for example carb or
metaflumizone.
(23) Inhibitors of acetyl CoA carboxylase, such as, for example, tetronic and tetramic acid
derivatives, e.g. spirodiclofen, spiromesifen and spirotetramat.
(25) Mitochondrial complex II on ort inhibitors, such as, for example, beta-
ketonitrile tives, e.g. cyenopyrafen and cyflumetofen and carboxanilides, such as, for
example, pyflubumide.
(28) Ryanodine receptor modulators, such as, for example, es, e.g. chlorantraniliprole,
cyantraniliprole and flubendiamide,
further active ingredients such as, for example, Afidopyropen, Afoxolaner, Azadirachtin,
Benclothiaz, Benzoximate, Bifenazate, Broflanilide, Bromopropylate, Chinomethionat,
Chloroprallethrin, Cryolite, Cyclaniliprole, Cycloxaprid, diamide, Dicloromezotiaz,
Dicofol, epsilon-Metofluthrin, n-Momfluthrin, Flometoquin, Fluazaindolizine,
Fluensulfone, Flufenerim, Flufenoxystrobin, Flufiprole, Fluhexafon, Fluopyram, Fluralaner,
Fluxametamide, zide, Guadipyr, Heptafluthrin, Imidaclothiz, Iprodione, kappa-Bifenthrin,
kappa-Tefluthrin, Lotilaner, Meperfluthrin, Paichongding, Pyridalyl, Pyrifluquinazon,
Pyriminostrobin, Spirobudiclofen, Tetramethylfluthrin, Tetraniliprole, Tetrachlorantraniliprole,
Tioxazafen, uoximate, Triflumezopyrim and iodomethane; furthermore preparations
based on us firmus (I-1582, BioNeem, Votivo), and also the following compounds: 1-{2-
fluoromethyl[(2,2,2-trifluoroethyl)sulphinyl]phenyl}(trifluoromethyl)-1H-1,2,4-triazole
amine (known from WO2006/043635) (CAS 8850266), {1'-[(2E)(4-chlorophenyl)prop
enyl]fluorospiro[indol-3,4'-piperidin]-1(2H)-yl}(2-chloropyridinyl)methanone (known
from WO2003/106457) (CAS 6373607), 2-chloro-N-[2-{1-[(2E)(4-chlorophenyl)prop
enyl]piperidinyl}(trifluoromethyl)phenyl]isonicotinamide (known from WO2006/003494)
(CAS 8729991), 3-(4-chloro-2,6-dimethylphenyl)hydroxymethoxy-1,8-diazaspiro[4.5]
decenone (known from WO 2010052161) (CAS 12252920), 3-(4-chloro-2,6-
dimethylphenyl)methoxyoxo-1,8-diazaspiro[4.5]decenyl ethyl carbonate (known
from 626) (CAS 14405166) , 4-(butynyloxy)(3,5-dimethylpiperidinyl)
fluoropyrimidine (known from /099160) (CAS 7929140), PF1364 (known from
JP2010/018586) (CAS 12047762), N-[(2E)[(6-chloropyridinyl)methyl]pyridin-2(1H)-
e]-2,2,2-trifluoroacetamide (known from WO2012/029672) (CAS 13634002), (3E)
[1-[(6-chloropyridyl)methyl]pyridylidene]-1,1,1-trifluoro-propanone (known from
WO2013/144213) (CAS 14617436), , N-[3-(benzylcarbamoyl)chlorophenyl]methyl
fluoroethyl)(trifluoromethyl)-1H-pyrazolecarboxamide (known from
WO2010/051926) (CAS 12268890), 5-bromochloro-N-[4-chloromethyl
(methylcarbamoyl)phenyl](3-chloropyridyl)pyrazolecarboxamide (known from
CN103232431) (CAS 14492203), 4-[5-(3,5-dichlorophenyl)-4,5-dihydro(trifluoromethyl)-
3-isoxazolyl]methyl-N-(cisoxidothietanyl)-benzamide, 4-[5-(3,5-dichlorophenyl)-4,5-
dihydro(trifluoromethyl)isoxazolyl]methyl-N-(transoxidothietanyl)-benzamide and
4-[(5S)(3,5-dichlorophenyl)-4,5-dihydro(trifluoromethyl)isoxazolyl]methyl-N-(cis
oxidothietanyl)benzamide (known from
chloro(3-pyridinyl)-1H-pyrazolyl]-N-ethyl[(3,3,3-trifluoropropyl)sulfinyl]-propanamide,
[3-chloro(3-pyridinyl)-1H-pyrazolyl]-N-ethyl[(3,3,3-trifluoropropyl)sulfinyl]-
propanamide and (-)-N-[3-chloro(3-pyridinyl)-1H-pyrazolyl]-N-ethyl[(3,3,3-
trifluoropropyl)sulfinyl]-propanamide (known from
US 2014/0213448 A1) (CAS 14779237), 5-[[(2E)chloropropenyl]amino][2,6-
dichloro(trifluoromethyl)phenyl][(trifluoromethyl)sulfinyl]-1H-pyrazolecarbonitrile
(known from CN 101337937 A) (CAS 11056722), 3-bromo-N-[4-chloromethyl
[(methylamino)thioxomethyl]phenyl](3-chloropyridinyl)-1H-pyrazolecarboxamide,
(Liudaibenjiaxuanan, known from CN 103109816 A) (CAS 12325439); N-[4-chloro[[(1,1-
dimethylethyl)amino]carbonyl]methylphenyl](3-chloropyridinyl)(fluoromethoxy)-1HPyrazolecarboxamide
(known from
1,3,4-thiadiazolyl)chloromethylphenyl]bromo(3-chloropyridinyl)-1H-
pyrazolecarboxamide (known from
dichloro[(3,3-dichloropropenyl)oxy]phenoxy]propoxy]methoxy(trifluoromethyl)-
pyrimidine (known from CN 940 A) (CAS 46); (2E)- and 2(Z)[2-(4-
cyanophenyl)[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]-
hydrazinecarboxamide (known from CN 101715774 A) (CAS 12325439); -
dichloroethenyl)-2,2-dimethyl(1H-benzimidazolyl)phenyl-cyclopropanecarboxylic acid
ester (known from CN 103524422 A) (CAS 15422714); (4aS)chloro-2,5-dihydro
[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]-indeno[1,2-e][1,3,4]
oxadiazine-4a(3H)-carboxylic acid methyl ester (known from CN 102391261 A) (CAS
82); 6-deoxyO-ethyl-2,4-di-O-methyl-, 1-[N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)
phenyl]-1H-1,2,4-triazolyl]phenyl]carbamate]-α-L-mannopyranose (known from
US 2014/0275503 A1) (CAS 11812138); 8-(2-cyclopropylmethoxytrifluoromethyl-
phenoxy)(6-trifluoromethyl-pyridazinyl)aza-bicyclo[3.2.1 ]octane (CAS 12538504),
(8-anti)(2-cyclopropylmethoxytrifluoromethyl-phenoxy)(6-trifluoromethyl-pyridazinyl)
aza-bicyclo[3.2.1 ]octane (CAS 9337987), (8-syn)(2-cyclopropylmethoxy
trifluoromethyl-phenoxy)(6-trifluoromethyl-pyridazinyl)aza-bicyclo[3.2.1 ]octane (known
from WO 2007040280 A1, WO 2007040282 A1) (CAS 9340018), N-[3-chloro(3-
pyridinyl)-1H-pyrazolyl]-N-ethyl[(3,3,3-trifluoropropyl)thio]-propanamide (known from WO
2015/058021 A1,
methyl[(methylamino)carbonyl]phenyl]bromo(3-chloropyridinyl)-1H-pyrazole
carboxamide (known from CN 103265527 A) (CAS 14528777), 5-(1,3-dioxanyl)[[4-
uoromethyl)phenyl]methoxy]-pyrimidine (known from WO 2013/115391 A1) (CAS
14490219), 3-(4-chloro-2,6-dimethylphenyl)hydroxymethoxymethyl-1,8-
piro[4.5]decenone (known from WO 66780 A1,
12290230), 3-(4-chloro-2,6-dimethylphenyl)methoxymethyl-1,8-
diazaspiro[4.5]decane-2,4-dione (known from
(4-chloro-2,6-dimethylphenyl)methoxymethyloxo-1,8-diazaspiro[4.5]decenylcarbonic
acid ethyl ester (known from
), N-[1-[(6-chloropyridinyl)methyl]-2(1H)-pyridinylidene]-2,2,2-trifluoroacetamide
(known from DE 3639877 A1, WO 2012029672 A1) (CAS 13634002), [N(E)]-N-
[1-[(6-chloropyridinyl)methyl]-2(1H)-pyridinylidene]-2,2,2-trifluoro-acetamide, (known from
WO 5276 A1) (CAS 16895667), [N(Z)]-N-[1-[(6-chloropyridinyl)methyl]-2(1H)-
pyridinylidene]-2,2,2-trifluoro-acetamide, (CAS 17023055), 3-endo[2-propoxy
(trifluoromethyl)phenoxy][[5-(trifluoromethyl)pyridinyl]oxy]azabicyclo[3.3.1]nonane
(known from
Active ingredients with unknown or non-specific mode of action, e.g., fentrifanil, fenoxacrim,
cycloprene, benzilate, chlordimeform, flubenzimine, dicyclanil, amidoflumet,
quinomethionate, triarathene, clothiazoben, tetrasul, potassium oleate, petroleum,
metoxadiazone, gossyplure, flutenzin, bromopropylate, cryolite;
Active ingredients from other classes, e.g. butacarb, dimetilan, cloethocarb, phosphocarb,
pirimiphos (-ethyl), parathion l), methacrifos, isopropyl o-salicylate, trichlorfon, sulprofos,
propaphos, s, pyridathion, ate, dichlofenthion, n-S-methylsulphone,
isazofos, cyanofenphos, dialifos, carbophenothion, autathiofos, aromfenvinfos (-methyl),
azinphos l), chlorpyrifos (-ethyl), fosmethilan, iodofenphos, dioxabenzofos, formothion,
fonofos, flupyrazofos, fensulfothion, etrimfos;
organochlorines, e.g. camphechlor, lindane, heptachlor; or phenylpyrazoles, e.g. acetoprole,
pyrafluprole, pyriprole, vaniliprole, sisapronil; or isoxazolines, e.g. ner, afoxolaner,
lotilaner, fluralaner;
pyrethroids, e.g. (cis-, trans-), metofluthrin, profluthrin, flufenprox, flubrocythrinate, fubfenprox,
fenfluthrin, protrifenbute, pyresmethrin, RU15525, terallethrin, cis-resmethrin, heptafluthrin, ,
bioethanomethrin, biopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin, clocythrin,
thrin (lambda-), chlovaporthrin, or halogenated carbonhydrogen compounds (HCHs);
otinoids, e.g. nithiazine;
dicloromezotiaz, triflumezopyrim;
macrocyclic lactones, e.g. nemadectin, ivermectin, latidectin, moxidectin, selamectin,
mectin, doramectin, emamectin benzoate; milbemycin oxime;
ne, epofenonane, diofenolan;
Biologicals, hormones or pheromones, for example natural products, e.g. thuringiensin,
codlemone or neem components;
dinitrophenols, e.g. dinocap, dinobuton, binapacryl;
benzoylureas, e.g. fluazuron, penfluron;
amidine derivatives, e.g. chlormebuform, cymiazole, demiditraz;
Bee hive varroa acaricides, for example organic acids, e.g. formic acid, oxalic acid.
Non-limiting examples of insecticides and acaricides of particular interest for use in animal
health are and include in particular [i.e. Mehlhorn et al Encyclpaedic Reference of Parasitology
4th n (ISBN 9786624)]:
Effectors at arthropod ligand gated de channels: chlordane, hlor, endoculfan.
Dieldrin, bromocyclen, toxaphene, e, fipronil, ole, onil, afoxolaner, fluralaner,
sarolaner, lotilaner, fluxametamide, broflanilide, avermectin, doramectin, eprinomectin,
ivermectin, milbemycin, moxidectin, selamectin;
Modulators of arthropod octopaminergic receptors: amitraz, BTS27271, cymiazole, demiditraz;
ors at arthropod voltage-gated sodium channels: DDT, methoxychlor, metaflumizone,
indoxacarb, cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I, pyrethrin II, allethrin,
ypermethrin, ethrin, betacyfluthrin, cyfluthrin, cyhalothrin, cypermethrin,
deltamethrin, etofenprox, fenvalerate, flucythrinate, flumethrin, halfenprox, permethrin,
phenothrin, resmethrin, tau-fluvalinate, tetramethrin;
Effectors at arthropod nicotinic cholinergic synapses (acetylcholine se, acetylcholine
receptors): bromoprypylate, bendiocarb, carbaryl, methomyl, promacyl, propoxur,
azamethiphos, chlorfenvinphos, chlorpyrifos, coumaphos, cythioate, diazinon, diclorvos,
dicrotophos, dimethoate, ethion, r, fenitrothion, fenthion, heptenophos, malathion,
naled, phosmet, phoxim, phtalofos, propetamphos, temephos, tetrachlorvinphos, trichlorfon,
imidacloprid, nitenpyram, dinotefuran, ad, oram;
Effectors on arthropod development processes: zine, dicyclanil, diflubenzuron,
fluazuron, lufenuron, triflumuron, fenoxycarb, hydroprene, methoprene, pyriproxyfen,
carb, hydroprene, S-methoprene, pyriproxyfen.
ary active ingredients from the group of endoparasiticides, as a further or other active
ingredient in the present invention, include, without limitation, anthelmintically active
compounds and antiprotozoal active compounds.
Anthelmintically active nds, including, without tion, the following nematicidally,
trematicidally and/or cestocidally active compounds:
from the class of macrocyclic lactones, for e: eprinomectin, abamectin, nemadectin,
moxidectin, doramectin, selamectin, lepimectin, ctin, milbemectin, ctin, emamectin,
milbemycin;
from the class of benzimidazoles and probenzimidazoles, for example: oxibendazole,
mebendazole, triclabendazole, thiophanate, dazole, oxfendazole, netobimin,
fenbendazole, febantel, thiabendazole, cyclobendazole, cambendazole, albendazolesulphoxide
, albendazole, flubendazole;
from the class of depsipeptides, preferably cyclic depsipetides, in particular 24-membered
cyclic depsipeptides, for example: side, PF1022A;
from the class of tetrahydropyrimidines, for example: morantel, pyrantel, oxantel;
from the class of imidazothiazoles, for example: butamisole, levamisole, tetramisole;
from the class of aminophenylamidines, for example: amidantel, deacylated amidantel (dAMD),
tribendimidine;
from the class of aminoacetonitriles, for example: monepantel;
from the class of paraherquamides, for e: paraherquamide, ntel;
from the class of salicylanilides, for example: tribromsalan, bromoxanide, brotianide,
clioxanide, closantel, niclosamide, oxyclozanide, rafoxanide;
from the class of substituted phenols, for e: nitroxynil, bithionol, disophenol,
hexachlorophene, niclofolan, meniclopholan;
from the class of organophosphates, for example: trichlorfon, naphthalofos, dichlorvos/DDVP,
crufomate, coumaphos, haloxon;
from the class of piperazinones / quinolines, for example: praziquantel, epsiprantel;
from the class of piperazines, for example: piperazine, hydroxyzine;
from the class of tetracyclines, for example: tetracyclin, chlorotetracycline, clin,
racyclin, rolitetracyclin;
from diverse other classes, for example: bunamidine, niridazole, resorantel, omphalotin,
oltipraz, nitroscanate, nitroxynile, oxamniquine, mirasan, miracil, lucanthone, hycanthone,
hetolin, emetine, diethylcarbamazine, dichlorophen, diamfenetide, clonazepam, bephenium,
nate, clorsulon.
Antiprotozoal active ingredients in the present invention, including, without limitation, the
following active ingredients:
from the class of triazines, for e: diclazuril, ponazuril, letrazuril, toltrazuril;
from the class of polylether ionophore, for example: monensin, salinomycin, maduramicin,
narasin;
from the class of macrocyclic lactones, for e: milbemycin, erythromycin;
from the class of quinolones, for e: enrofloxacin, pradofloxacin;
from the class of quinines, for example: chloroquine;
from the class of dines, for e: pyrimethamine;
from the class of sulfonamides, for example: sulfaquinoxaline, trimethoprim, sulfaclozin;
from the class of thiamines, for example: amprolium;
from the class of lincosamides, for example: clindamycin;
from the class of carbanilides, for example: imidocarb;
from the class of nitrofuranes, for example: nifurtimox;
from the class of quinazolinone ids, for example: halofuginon;
from diverse other s, for example: oxamniquin, paromomycin;
from the class of vaccines or antigenes from rganisms, for example: Babesia canis
rossi, Eimeria tenella, Eimeria praecox, Eimeria necatrix, Eimeria mitis, Eimeria maxima,
Eimeria brunetti, Eimeria acervulina, Babesia canis vogeli, Leishmania infantum, Babesia
canis canis, caulus viviparus.
All named other or further active ingredients in the present invention can, if their functional
groups enable this, ally form salts with suitable bases or acids.
Based upon standard laboratory ques known to evaluate compounds useful for the
ent of helminth infections, by standard toxicity tests and by standard pharmacological
assays for the determination of treatment of the conditions identified above in animals, and by
comparison of these results with the results of known active ingredients or medicaments that
are used to treat these conditions, the effective dosage of the compounds of the present
invention can readily be determined for treatment of each desired indication. The amount of
the active ingredient to be administered in the ent of one of these conditions can vary
widely according to such considerations as the particular compound and dosage unit
ed, the mode of administration, the period of treatment, the age and sex of the subject
treated, and the nature and extent of the condition treated.
The total amount of the active ingredient to be administered will generally range from about
0.001 mg/kg to about 200 mg/kg body weight per day, and preferably from about 0.01 mg/kg to
about 20 mg/kg body weight per day. Clinically useful dosing schedules will range from one to
three times a day dosing to once every four weeks dosing. In addition, it is possible for "drug
holidays", in which a subject is not dosed with a drug for a certain period of time, to be
cial to the overall balance between pharmacological effect and tolerability. rmore,
it is possible to have long-acting treatments, n the subject gets treated once for more
than four weeks. It is possible for a unit dosage to n from about 0.5 mg to about 1500 mg
of active ingredient, and can be administered one or more times per day or less than once a
day. The average daily dosage for administration by injection, including intravenous,
uscular, subcutaneous and parenteral injections, and use of infusion techniques will
preferably be from 0.01 to 200 mg/kg of total body . The average daily rectal dosage
regimen will preferably be from 0.01 to 200 mg/kg of total body weight. The average daily
vaginal dosage regimen will preferably be from 0.01 to 200 mg/kg of total body . The
average daily topical dosage regimen will preferably be from 0.1 to 200 mg administered
between one to four times daily. The transdermal concentration will preferably be that required
to maintain a daily dose of from 0.01 to 200 mg/kg. The average daily inhalation dosage
regimen will preferably be from 0.01 to 100 mg/kg of total body weight.
Of course the specific initial and continuing dosage regimen for each subject will vary
according to the nature and severity of the condition as determined by the attending
diagnostician, the activity of the specific nd employed, the age and l condition of
the subject, time of administration, route of administration, rate of excretion of the drug, drug
combinations, and the like. The desired mode of treatment and number of doses of a
compound of the present invention or a pharmaceutically acceptable salt or ester or
composition thereof can be ascertained by those skilled in the art using conventional treatment
tests.
EXPERIMENTAL SECTION
Abbreviations:
aq. s
DMF dimethylformamide
DMSO dimethylsulfoxide
MTBE methyl-t.-butylether
THF ydrofurane
The various aspects of the invention described in this application are rated by the
following examples which are not meant to limit the ion in any way.
The example testing experiments described herein serve to illustrate the t invention and
the invention is not limited to the examples given.
EXPERIMENTAL SECTION - GENERAL PART
All ts, for which the synthesis is not described in the experimental part, are either
commercially available, or are known compounds or may be formed from known compounds
by known methods by a person skilled in the art.
The compounds and intermediates produced according to the methods of the invention may
require purification. Purification of organic nds is well known to the person skilled in the
art and there may be several ways of purifying the same compound. In some cases, no
purification may be necessary. In some cases, the compounds may be purified by
crystallization. In some cases, ties may be stirred out using a suitable solvent. In some
cases, the compounds may be purified by chromatography, particularly flash column
chromatography, using for example prepacked silica gel cartridges, e.g. Biotage SNAP
ges KP-Sil® or KP-NH® in combination with a Biotage autopurifier system (SP4® or
Isolera Four®) and s such as gradients of hexane/ethyl acetate or
dichloromethane/methanol. In some cases, the compounds may be purified by preparative
HPLC using for example a Waters autopurifier equipped with a diode array detector and/or online
electrospray ionization mass spectrometer in combination with a suitable prepacked
reverse phase column and s such as gradients of water and acetonitrile which may
contain additives such as trifluoroacetic acid, formic acid or aqueous ammonia.
In some cases, purification methods as described above can provide those compounds of the
present invention which possess a sufficiently basic or acidic functionality in the form of a salt,
such as, in the case of a compound of the present ion which is sufficiently basic, a
trifluoroacetate or e salt for example, or, in the case of a compound of the present
invention which is sufficiently acidic, an ammonium salt for example. A salt of this type can
either be ormed into its free base or free acid form, respectively, by various methods
known to the person skilled in the art, or be used as salts in subsequent biological assays. It is
to be understood that the specific form (e.g. salt, free base etc.) of a compound of the present
invention as isolated and as described herein is not necessarily the only form in which said
compound can be applied to a biological assay in order to quantify the specific biological
activity.
ICAL AND CHROMATOGRAPHY METHODS
Analytical and preparative liquid tography
Analytical (UP)LC-MS was performed by means of different equipments as described below.
The masses (m/z) are reported from the positive mode electrospray ionisation unless the
negative mode is indicated (ESI-).
Method L0:
Measurement of logP values was performed according to EEC directive 79/831 Annex V.A8 by
HPLC (High Performance Liquid Chromatography) on reversed phase columns with the
following methods:
[a] logP value is determined by ement of LC-UV, in an acidic range, with 0.1% formic
acid in water and acetonitrile as eluent (linear gradient from 10% acetonitrile to 95%
acetonitrile).
[b] logP value is determined by measurement of LC-UV, in a l range, with 0.001 molar
ammonium acetate solution in water and acetonitrile as eluent (linear gradient from 10%
acetonitrile to 95% acetonitrile).
Calibration was done with straight-chain alkanones (with 3 to 16 carbon atoms) with known
logP values rement of logP values using retention times with linear interpolation
between sive alkanones). Lambda-max-values were determined using UV-spectra from
200 nm to 400 nm and the peak values of the chromatographic signals.
M+1 (or M+H) means the molecular ion peak, plus or minus 1 a.m.u. (atomic mass unit)
tively, as observed in mass spectroscopy by electrospray ionization (ESI + or -).
Method L1:
Instrument type: Waters ACQUITY SQD UPLC system; column: Waters Acquity UPLC HSS T3
1.8 µ 50 x 1 mm; eluent A: 1 l water + 0.25 ml formic acid, eluent B: 1 l acetonitrile + 0.25 ml
formic acid; gradient: 0.0 min 90% A → 1.2 min 5% A → 2.0 min 5% A oven: 50°C; flow: 0.40
ml/min; UV-detection: 208 – 400 nm.
Method L2:
MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLC instrument type:
t Technologies 1260 Infinity; column: Waters XSelect (C18, 50x2.1mm, 3.5μ); flow: 0.8
mL/min; column temp: 35°C; eluent A: 0.1% formic acid in acetonitrile; eluent B: 0.1% formic
acid in water; lin. gradient: t=0 min 5% A, t=3.5 min 98% A, t=6 min 98% A; detection: DAD
(220-320 nm); detection: MSD (ESI pos/neg) mass range: 100 – 800; detection: ELSD (PL-
ELS 2100): gas flow 1.2 mL/min, gas temp: 70°C, neb: 50°C.
Method L3:
MS instrument type: Agilent Technologies LC/MSD SL; HPLC instrument type: Agilent
Technologies 1100 Series; column: Waters XSelect (C18, 50x2.1mm, 3.5μ; flow: 0.8 mL/min;
column temp: 25°C; eluent A: 95% itrile + 5% 10 mM ammoniumbicarbonate in water;
eluent B: 10 mM ammoniumbicarbonate in water pH=9.0; lin. gradient: t=0 min 5% A, t=3.5 min
98% A, t=6 min 98% A; detection: DAD (220-320 nm); ion: MSD (ESI pos/neg) mass
range: 100-800.
Method L4:
Instrument type: Waters ACQUITY SQD UPLC System; : Waters Acquity UPLC HSS
T3 1.8 µ 50 x 1 mm; eluent A: 1 l water + 0.25 ml 99%ige formic acid , Eluent B: 1 l acetonitrile
+ 0.25 ml 99%ige formic acid; gradient: 0.0 min 95% A → 6.0 min 5% A → 7.5 min 5% A
oven: 50°C; flow: 0.35 ml/min; UV-detection: 210 – 400 nm.
Method L5:
MS instrument type: Waters SQD; Instrument HPLC: Waters UPLC; column: Zorbax SB-Aq
(Agilent), 50 mm x 2.1 mm, 1.8 µm; eluent A: water + 0.025% formic acid, eluent B: acetonitrile
(ULC) + 0.025% formic acid; gradient: 0.0 min 98%A - 0.9 min 25%A – 1.0 min 5%A - 1.4 min
5%A – 1.41 min 98%A – 1.5 min 98%A; oven: 40°C; flow: 0.600 ml/min; UV-detection: DAD;
210 nm.
Method L6:
MS instrument type: Thermo Scientific FT-MS; HPLC instrument type: Thermo Scientific
UltiMate 3000; column: Waters, HSST3, 2.1 x 75 mm, C18 1.8 µm; eluent A: 1 l water + 0.01%
formic acid; eluent B: 1 l acetonitril + 0.01% formic acid; nt: 0.0 min 10% B → 2.5 min
95% B → 3.5 min 95% B; Ofen: 50°C; Fluss: 0.90 ; UV-Detektion: 210 nm / optimum
integration path 210-300 nm:
Method L7:
MS instrument type: Waters (Micromass) Quattro Micro; HPLC instrument type: Waters UPLC
Acquity; column: Waters BEH C18 1.7 µ 50 x 2.1 mm; eluent A: 1 l water + 0.01 mol
ammoniumformiate, eluent B: 1 l acetonitril; gradient: 0.0 min 95% A → 0.1 min 95% A → 2.0
min 15% A → 2.5 min 15% A→ 2.51 min 10% A → 3.0 min 10% A; oven: 40°C; flow: 0.5
ml/min; UV-detection: 210 nm.
Method L8:
MS instrument type: Waters SQD2; ment HPLC: Waters UPLC; column: Zorbax SB-Aq
(Agilent), 50 mm x 2.1 mm, 1.8 µm; eluent A: water + 0.025% formic acid, eluent B: acetonitrile
(ULC) + 0.025% formic acid; gradient: 0.0 min 98%A - 0.9 min 25%A – 1.0 min 5%A - 1.4 min
%A – 1.41 min 98%A – 1.5 min 98%A; oven: 40°C; flow: 0.600 ml/min; UV-detection: DAD;
210 nm.
Method L9:
MS instrument type: t Technologies LC/MSD SL; HPLC instrument type: Agilent
logies 1100 Series; column: Waters XSelect (C18, 50x2.1mm, 3.5μ; flow: 0.8 ;
column temp: 25°C; eluent A: 95% itrile + 5% ammoniumbicarbonate in water; eluent B:
10mmM ammoniumbicarbonate in water pH=9.0; lin. gradient: t=0 min 5% A, t=3.5min 98% A,
t=6 min 98% A; detection: DAD (220-320 nm); detection: MSD (ESI pos/neg) mass range: 100-
Method L10:
MS instrument type: Agilent Technologies 6130 Quadrupole LC-MS; HPLC instrument type:
Agilent Technologies 1260 Infinity; column: Waters XSelect (C18, 30x2.1mm, 3.5μ); flow: 1
mL/min; column temp: 35°C; eluent A: 0.1% formic acid in itrile; eluent B: 0.1% formic
acid in water; lin. gradient: t=0 min 5% A, t=1.6min 98% A, t=3 min 98% A; detection: DAD
(220-320 nm); detection: MSD (ESI pos/neg) mass range: 100 – 800; detection: ELSD (PL-
ELS 2100): gas flow 1.2 mL/min, gas temp: 70°C, neb: 50°C.
Method L11:
MS instrument type: Agilent Technologies LC/MSD SL; HPLC instrument type: t
Technologies 1100 Series; column: Phenomenex Gemini NX (C18, 50x2.0mm), 3.0μ; flow: 0.8
mL/min; column temp: 25°C; eluent A: 95% acetonitrile + 5% 10mM ammoniumbicarbonate in
water in acetonitrile ; eluent B: 10 mM ammoniumbicarbonate in water pH=9.0; lin.
gradient: t=0 min 5% A, t=3.5 min 98% A, t=6 min 98% A; detection: DAD (220-320 nm);
detection: MSD (ESI pos/neg) mass range: 100-800.
Method L12:
MA ment: Agilent MS Quad 6150; HPLC instrument: Agilent 1290; column: Waters
Acquity UPLC HSS T3 1.8 µm 50 x 2.1 mm; eluent A: 1 l water + 0.25 ml 99% formic acid ,
Eluent B: 1 l acetonitril + 0.25 ml 99% formic acid ; gradient: 0.0 min 90% A → 0.3 min 90% A
→ 1.7 min 5% A → 3.0 min 5% A oven: 50°C; flow: 1,20 ml/min; UV-detection: 205 – 305
Method M1:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear gradient was
d, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 1.80 min with a total run time of 2.10 min. The column temperature was at 45 °C
with the flow rate of 1.20 mL/min.
Method M2:
The column used was an EVO, 2.6 µm, 3.0 × 50 mm. A linear nt was applied, starting at
90% A (A: 0.1% FA in water) and ending at 95% B (B: 0.1% FA in MeCN) over 4.20 min with a
total run time of 4.50 min. The column temperature was at 40 °C with the flow rate of 1.00
mL/min.
Method M3:
The column used was a CORTECS C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 95% A (A: 0.09% FA in water) and ending at 100% B (B: 0.1% FA in MeCN) over
1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C with the flow
rate of 1.00 mL/min.
Method M4:
The column used was a CORTECS C18+, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN) over
1.70 min with a total run time of 2.00 min. The column temperature was at 45 °C with the flow
rate of 1.00 mL/min.
Method M5:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear nt was
applied, starting at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN)
over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C with the
flow rate of 1.00 mL/min.
Method M6:
The column used was a CORTECS C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 95% A (A: 0.09% FA in water) and ending at 100% B (B: 0.1% FA in MeCN) over
2.60 min with a total run time of 3.00 min. The column temperature was at 40 °C with the flow
rate of 1.00 mL/min.
Method M7:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 2.80 min with a total run time of 3.30 min. The column temperature was at 45 °C
with the flow rate of 1.20 mL/min.
Method M8:
The column used was a CORTECS C18+, 2.7 µm, 2.1 × 50 mm. A linear nt was applied,
starting at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN) over
1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C with the flow
rate of 1.00 mL/min.
Method M9:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.1% FA in water) and ending at 95% B (B: 0.1% FA in MeCN)
over 4.20 min with a total run time of 4.50 min. The column temperature was at 40 °C with the
flow rate of 1.00 mL/min.
Method M10:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear gradient was
applied, ng at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN)
over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C with the
flow rate of 1.00 mL/min.
Method M11:
The column used was a CORTECS C18+, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 90% A (A: 0.1% FA in water) and ending at 95% B (B: 0.1% FA in MeCN) over 2.70
min with a total run time of 3.00 min. The column temperature was at 40 °C with the flow rate
of 1.00 mL/min.
Method M12:
The column used was an Ascentis Express C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.09% FA in water) and ending at 100% B (B: 0.1% FA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.50 mL/min.
Method M13:
The column used was an Ascentis Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M14:
The column used was an Ascentis Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, ng at 95% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 2.70 min with a total run time of 3.00 min. The column ature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M15:
The column used was an Ascentis Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 70% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 2.70 min with a total run time of 3.00 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M16:
The column used was a CORTECS C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was d,
starting at 95% A (A: 0.09% FA in water) and ending at 100% B (B: 0.1% FA in MeCN) over
1.70 min with a total run time of 2.00 min. The column ature was at 40 °C with the flow
rate of 1.00 mL/min.
Method M17:
The column used was a CORTECS C18+ 100A, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN)
over 1.60 min with a total run time of 2.00 min. The column temperature was at 40 °C with the
flow rate of 1.00 mL/min.
Method M18:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.09% FA in water) and ending at 100% B (B: 0.1% FA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M19:
The column used was a Kinetex EVO C18 100A, 2.6 µm, 3.0 × 50 mm. A linear gradient was
applied, ng at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN)
over 1.60 min with a total run time of 2.00 min. The column temperature was at 40 °C with the
flow rate of 1.00 mL/min.
Method M20:
The column used was an Ascentis Express C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.50 mL/min.
Method M21:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.09% FA in water) and ending at 100% B (B: 0.1% FA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.50 mL/min.
Method M22:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear nt was
applied, starting at 90% A (A: 0.09% FA in water) and ending at 95% B (B: 0.1% FA in MeCN)
over 2.70 min with a total run time of 3.00 min. The column temperature was at 40 °C with the
flow rate of 1.50 mL/min.
Method M23:
The column used was an Ascentis Express C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.09% FA in water) and ending at 95% B (B: 0.1% FA in MeCN)
over 2.70 min with a total run time of 3.00 min. The column temperature was at 40 °C with the
flow rate of 1.50 mL/min.
Method M24:
The column used was an Ascentis Express C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was
d, starting at 95% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 2.70 min with a total run time of 3.00 min. The column ature was at 40 °C
with the flow rate of 1.50 mL/min.
Method M25:
The column used was a Kinetex EVO C18, 2.6 µm, 4.6 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 5mMNH4HCO3 in water) and ending at 95% B (B: MeCN) over
1.75 min with a total run time of 2.00 min. The column temperature was at 40 °C with the flow
rate of 1.80 mL/min.
Method M26:
The column used was an Ascentis Express C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 4.90 min with a total run time of 5.30 min. The column temperature was at 45 °C
with the flow rate of 1.50 mL/min.
Method M27:
The column used was an ell HPH-C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN)
over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C with the
flow rate of 1.00 mL/min.
Method M28:
The column used was a CORTECS C18+, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
ng at 90% A (A: 0.1% FA in water) and ending at 95% B (B: 0.1% FA in MeCN) over 2.70
min with a total run time of 3.00 min. The column temperature was at 45 °C with the flow rate
of 1.00 mL/min.
Method M29:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 4.60 min with a total run time of 5.30 min. The column ature was at 40 °C
with the flow rate of 1.20 mL/min.
Method M30:
The column used was a ack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 2.80 min with a total run time of 3.30 min. The column temperature was at 45 °C
with the flow rate of 1.20 mL/min.
Method M31:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 4.70 min with a total run time of 5.00 min. The column temperature was at 45 °C
with the flow rate of 1.20 mL/min.
Method M32:
The column used was a CORTECS C18+, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 90% A (A: 0.1% FA in water) and ending at 95% B (B: 0.1% FA in MeCN) over 5.20
min with a total run time of 5.70 min. The column temperature was at 45 °C with the flow rate
of 1.00 mL/min.
Method M33:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 2.20 min with a total run time of 2.60 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M34:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear nt was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.20 mL/min.
Method M35:
The column used was a CORTECS C18+, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 95% A (A: 0.09% FA in water) and ending at 95% B (B: 0.1% FA in MeCN) over
2.70 min with a total run time of 3.00 min. The column temperature was at 40 °C with the flow
rate of 1.00 mL/min.
Method M36:
The column used was a CORTECS C18+ 100A, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 0.1% FA in water) and ending at 100% B (B: 0.1% FA in MeCN)
over 2.60 min with a total run time of 3.00 min. The column temperature was at 40 °C with the
flow rate of 1.00 .
Method M37:
The column used was a CORTECS C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was d,
starting at 95% A (A: 0.09% FA in water) and ending at 95% B (B: 0.1% FA in MeCN) over
2.60 min with a total run time of 3.00 min. The column temperature was at 40 °C with the flow
rate of 1.00 .
Method M38:
The column used was a CORTECS C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was applied,
starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in MeCN)
over 1.80 min with a total run time of 2.00 min. The column temperature was at 45 °C with the
flow rate of 1.00 mL/min.
Method M39:
The column used was an is Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 70% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 5.70 min with a total run time of 6.50 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M40:
The column used was an Ascentis Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 60% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 2.70 min with a total run time of 3.00 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M41:
The column used was a Kinetex EVO C18, 2.6 µm, 3.0 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 5 mM NH4HCO3 in water) and ending at 95% B (B: MeCN) over
1.80 min with a total run time of 2.00 min. The column temperature was at 45 °C with the flow
rate of 1.50 mL/min.
Method M42:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear nt was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 1.70 min with a total run time of 2.00 min. The column temperature was at 40 °C
with the flow rate of 1.20 mL/min.
Method M43:
The column used was a Kinetex EVO C18 100A, 2.6 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 90% A (A: 5 mM 3 in water) and ending at 95% B (B: MeCN) over
2.60 min with a total run time of 3.00 min. The column temperature was at 40 °C with the flow
rate of 1.00 mL/min.
Method M44:
The column used was a HPH-C18, 2.7 µm, 3.0 × 50 mm. A linear gradient was applied,
starting at 90% A (A: 5 mM NH4HCO3 in water) and ending at 100% B (B: MeCN) over 2.60
min with a total run time of 3.00 min. The column ature was at 40 °C with the flow rate
of 1.50 mL/min.
Method 45:
The column used was an Ascentis Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 3.10 min with a total run time of 3.60 min. The column temperature was at 40 °C
with the flow rate of 1.00 .
Method M46:
The column used was an Ascentis Express C18, 2.7 µm, 2.1 × 50 mm. A linear gradient was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 100% B (B: 0.05% TFA in
MeCN) over 2.10 min with a total run time of 2.60 min. The column temperature was at 40 °C
with the flow rate of 1.00 mL/min.
Method M47:
The column used was an Ascentis Express C18, 2.7 µm, 3.0 × 50 mm. A linear nt was
applied, starting at 95% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 4.20 min with a total run time of 4.50 min. The column temperature was at 40 °C
with the flow rate of 1.50 mL/min.
Method M48:
The column used was a Shim-pack XR-ODS, 2.2 µm, 3.0 × 50 mm. A linear nt was
applied, starting at 80% A (A: 0.05% TFA in water) and ending at 95% B (B: 0.05% TFA in
MeCN) over 5.00 min with a total run time of 5.60 min. The column temperature was at 45 °C
with the flow rate of 1.20 mL/min.
1H-NMR Data
1H-NMR data were determined with a Bruker Avance 400 (equipped with a flow cell (60 μl
volume), or with a Bruker AVIII 400 equipped with 1.7 mm cryo CPTCI probe head, or with a
Bruker AVIII 400 (400.13MHz) equipped with a 5 mm probe head, or with a Bruker AVII 600
(600.13 MHz) equipped with a 5 mm cryo TCI probe head, or with a Bruker AVIII 600 (601.6
MHz) equipped with a 5 mm cryo CPMNP probe head, or with a Bruker AVIII 500 (500.13MHz)
ed with a 5 mm broadband head or a 5 mm Prodigy™ probe head, with
tetramethylsilane as reference (0.0) and the solvents CD3CN, CDCl3 or D6-DMSO. Alternative
1H- and 13C-NMR instrument types: Bruker DMX300 (1H-NMR: 300 MHz; 13C NMR: 75 MHz),
Bruker Avance III 400 (1H-NMR: 400 MHz; 13C NMR: 100 MHz) or Bruker 400 Ultrashield (1H-
NMR: 400 MHz; 13C NMR: 100 MHz).
Chemical shifts (δ) are displayed in parts per million [ppm]; the following abbreviations are
used: s = singlet, d = doublet, t = t, q = quartet, m = multiplet, br. = broad; coupling
constants are displayed in Hertz [Hz].
EXPERIMENTAL SECTION - GENERAL PROCEDURES
The synthesis of the compounds of the formula (I) can be performed ing to or in analogy
to the following schemes (Scheme 1a-e, Scheme 2 and Scheme 3).
Scheme 1a
EtOH or MeOH high boiling t
1A 1B 1C
POCl3 1F: R2H
(base)
1D 1E 1G
2-Halogen-substituted anilines 1A (Hal = iodine, bromine, chlorine) are commercial available
and can be readily converted with (alkoxymethylen)malonates 1B dissolved the corresponding
alcohol solvent, preferably under boiling conditions into nomethylene)malonates 1C as
described in Monatshefte fuer Chemie, 2015, , 291-302 or without any solvent as
described in WO 2002004444. The ring e is performed in high boiling solvents,
preferably in diphenylether or xylol, to achieve hydroxy quinolines 1D as described in WO
2013118071. The hydroxy quinolines 1D can be easily converted into the corresponding
chlorine compounds 1E with a chlorination t, preferably refluxing POCl3 as described in
WO 2013118071.
Dependend on the nature of the nucleophile R2H 1F, the chloro ines 1E reacts with 1F in
the presence of a base, e.g. sodium ethylate, sodium methylate, potassium t-butylate,
ylamine N,N-diisopropyl ethylamine, diazabicycloundecan, sodium hydride, lithium
hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, cesium carbonate,
or the like to obtain ester intermediates 1G.
Scheme 1b
Coupling
Saponification
1H: Q-B(OR)2
1D 1I 1J
1F: R2H
(base)
POCl3
(base)
1N (I)
Hydrolysis 1M
Amide formation
Alternatively, a Suzuki cross coupling reaction of intermediates 1D with boronic acids or
boronic esters 1H Q-B(OR)2 (R=H; R = Me or R,R = pinacolate) as described in Chem. Soc.
Rev. 2014, 43, 412-443 or in Tetrahedron 2002, 58 (48), 9633-9695 to ester ediates 1I.
Subsequently, the ester intermediates 1I can be smoothly saponified e.g. with lithium
hydroxide resulting in the corresponding carboxylic acids 1J, which can be easily ted
into the corresponding chloro carboxylic chlorides 1K with a chlorination reagent, ably
refluxing POCl3 as described in WO 2013096151. Intermediates 1K react under hydrolytic
conditions to yield one carboxylic acids 1L, which are combined with commercial
available amines 1M via an amide formation and dehydration reagents, e.g. N-(3-dimethylaminoisopropyl
)-N'-ethylcarbodiimide-hydrochloride (EDC) to give amides 1N. Similar
syntheses are described in Journal of Medicinal Chemistry 2012, 55, 3563-3567 for example.
Intermediates 1K can directly form the amides 1N as the carboxylic acid chlorides 1K are
ed with amines 1M under basic ions, e.g. pyridine, triethylamine or N,N-
diisopropyl ethylamine as bed in Chemical Biology & Drug Design 2015, 85(5), 549-564.
Dependend on the nature of the nucleophile R2H 1F, the chloro ines 1N reacts with 1F in
the presence of a base, e.g. sodium ethylate, sodium methylate, potassium t-butylate,
triethylamine N,N-diisopropyl ethylamine, diazabicycloundecan, sodium hydride, lithium
hydroxide, sodium hydroxide, ium hydroxide, ium carbonate, cesium carbonate,
or the like to obtain the target compounds of formula (I).
Scheme 1c
6 6
R Cl O 6
R Cl O Hydrolysis R Cl O
5 (acid) 5
R Saponification R R
OEt, OMe O– M+ OH
4 3 3
R N 4 4
R 3
R N R R N R
Hal Hal Hal
1E 1O 1P
A Amide
Coupling 1M HN1
R formation
1H: Q-B(OR)2
6 6
R Cl O 6 R Cl O
Saponification R Cl O
5
R 5 R A
OEt, OMe N
4 3 3 R
R N R 4 3 R N R
R N R
Q Hal
1Q Q
1R 1S
1M HN Amide 1F: R2H
R ion (base)
6 6 2
R Cl O R R O
5
R A R A
N N
1 1
4 3 R 4 3 R
R N R R N R
Q 1N Hal 1T
1H: Q-B(OR)2
1F: R2H
(base) 6 2
R R O
R A
4 3 R
R N R
Q (I)
Chloro quinolines 1E can be smoothly saponified e.g. with lithium hydroxide resulting in the
corresponding carboxylates 1O, obtained e.g. as lithium salt, or resulting in the carboxylic
acids 1P after acid hydrolysis. Subsequently, the intermediate carboxamides 1S are ed
by amide ng conditions, e.g. via carboxylic acid chlorides formed from 1P which are
combined with amines 1M under basic conditions, e.g. pyridine, triethylamine or N,N-
diisopropyl ethylamine or via amide formation from the carboxylic acids 1P which are
combined with amines 1M and dehydration reagents, e.g. N-(3-dimethylaminoisopropyl)-N'-
arbodiimide-hydrochloride (EDC). Similar syntheses are described in Journal of
Medicinal Chemistry 2012, 55, 3563-3567 for example. Dependend on the nature of the
nucleophile R2H 1F, the chloro quinolines 1S react with 1F in the presence of a base, e.g.
sodium ethylate, sodium methylate, potassium t-butylate, triethylamine N,N-diisopropyl
ethylamine, diazabicycloundecan, sodium hydride, lithium hydroxide, sodium hydroxide,
ium hydroxide, potassium carbonate, cesium carbonate, or the like to obtain the
intermediate carboxamides 1T. A Suzuki cross coupling reaction of intermediate carboxamides
1T with boronic acids or boronic esters 1H Q-B(OR)2 (R=H; R = Me or R,R = pinacolate) as
described in Chem. Soc. Rev. 2014, 43, 412-443 or in Tetrahedron 2002, 58 (48), 9633-9695
leads to the final products of formula (I).
Alternatively, chloro quinolines 1E react via a Suzuki cross coupling reaction with boronic acids
or boronic esters 1H Q-B(OR)2 (R=H; R = Me or R,R = pinacolate) as bed in Chem. Soc.
Rev. 2014, 43, 3 or in Tetrahedron 2002, 58 (48), 9633-9695 to e quinoline
carboxylic esters 1Q, which can be ly saponified e.g. with lithium hydroxide resulting in
the corresponding quinoline carboxylic acid 1R. Subsequently, the intermediate carboxamides
1N are obtained by amide ng conditions, e.g. via carboxylic acid chlorides formed from
1R which are combined with amines 1M under basic conditions, e.g. pyridine, triethylamine or
N,N-diisopropyl ethylamine or via amide formation from the carboxylic acids 1R which are
combined with amines 1M and dehydration reagents, e.g. N-(3-dimethylaminoisopropyl)-N'-
ethylcarbodiimide-hydrochloride (EDC). Similar syntheses are described in Journal of
nal Chemistry 2012, 55, 3563-3567 for example. Dependend on the nature of the
nucleophile R2H 1F, the chloro quinolines 1N react with 1F in the presence of a base, e.g.
sodium ethylate, sodium methylate, potassium t-butylate, triethylamine N,N-diisopropyl
ethylamine, diazabicycloundecan, sodium hydride, m hydroxide, sodium hydroxide,
potassium ide, potassium carbonate, cesium carbonate, or the like to obtain the the final
products of formula (I) as well.
Scheme 1d
Coupling
1H: Q-B(OR)2
1G 1U
Saponification Saponification
Coupling
1H: Q-B(OR)2
1V 1W
1M Amide ion 1M Amide formation
Coupling
1H: Q-B(OR)2
1T (I)
Quinoline carboxylic esters 1G can be converted via a Suzuki cross coupling reaction with
boronic acids or boronic esters 1H Q-B(OR)2 (R=H; R = Me or R,R = late) as described
in Chem. Soc. Rev. 2014, 43, 412-443 or in Tetrahedron 2002, 58 (48), 9633-9695 to provide
quinoline carboxylic esters 1U, which can be smoothly saponified e.g. with lithium hydroxide
resulting in the corresponding quinoline carboxylic acid 1W. Subsequently, the final products of
formula (I) are ed by amide ng conditions, e.g. via carboxylic acid chlorides formed
from 1W which are combined with amines 1M under basic conditions, e.g. pyridine,
triethylamine or N,N-diisopropyl ethylamine or via amide ion from the carboxylic acids
1W which are combined with amines 1M and dehydration reagents, e.g. N-(3-dimethylamino-
isopropyl)-N'-ethylcarbodiimide-hydrochloride (EDC). Similar syntheses are described in
Journal of Medicinal Chemistry 2012, 55, 3563-3567 for example.
Alternatively, quinoline carboxylic esters 1G can be saponified first and then converted via a
Suzuki cross coupling on with c acids or boronic esters 1H Q-B(OR)2 (R=H; R =
Me or R,R = late) into quinoline carboxylic acids 1W or transformed into quinoline
carboxamides 1T by means of amide coupling conditions, e.g. via quinoline carboxylic acid
chlorides formed from 1V which are combined with amines 1M under basic conditions, e.g.
pyridine, triethylamine or N,N-diisopropyl ethylamine or via amide formation from the quinolone
carboxylic acids 1V which are combined with amines 1M and dehydration reagents, e.g. N-(3-
dimethylaminoisopropyl)-N'-ethylcarbodiimide-hydrochloride (EDC). Finally, quinoline
carboxamides 1T can be converted via a Suzuki cross coupling on with boronic acids or
boronic esters 1H Q-B(OR)2 (R=H; R = Me or R,R = pinacolate) as described in Chem. Soc.
Rev. 2014, 43, 412-443 or in Tetrahedron 2002, 58 (48), 9633-9695 into final products of
formula (I).
Scheme 1d’
halogenation
1G 1G'
nuclophilic
substitution
1G'' 1V''
A subgroup of 1G, where R2 is an alkyl group, such as methyl (R30 = H) can be halogenated,
e.g. brominated by brominating agents such as bromine, N-bromo-succinimide, pyridinium
tribromide or phenyltrimethylammonium tribromide to bromoalkylderivatives 1G’ as described
e.g. in J. Heterocl. Chem. 1981, vol. 18, 925 – 928, J. Med. Chem., 2009, vol. 52, 3047 –
3062 or J. Am. Chem. Soc., 1948, 70, 417–418. Such bromoalkyl compounds 1G‘ can be
substituted by nucleophiles such as amines, alkohols or thiols or their salts, occasionally in
presence of base according to standard procedures to furnish substituted alkyl-quinolines 1G’’.
Under the reaction conditions of the nucleophilic substitution the esters 1G’’ can be further
converted to the corresponding acids 1V’’ or they can be isolated and converted in a te
hydrolysis step to the acids 1V’’. Then, the final products (I) can be obtained from the acids
1V’’ by amide formation and coupling of the group Q by the methods described in scheme 1d.
Scheme 1e (R2 = optionally tuted alkoxy)
1M 1Y: R2H (alcohols)
nobu"
Amide
formation (I)
1J 1X
Hydroxy quinolones 1X are obtained by amide coupling conditions, e.g. via carboxylic acid
chlorides formed from 1J which are combined with amines 1M under basic ions, e.g.
pyridine, triethylamine or isopropyl ethylamine or via amide formation from the carboxylic
acids 1J which are combined with amines 1M and dehydration reagents, e.g. i-
methylaminoisopropyl)-N'-ethylcarbodiimide-hydrochloride (EDC). Similar syntheses are
described in Journal of Medicinal Chemistry 2012, 55, 3563-3567 for example.The final
ts of formula (I) are obtained by a Mitsunobu on of hydroxy quinolones 1X with
alcohols 1Y (R2 = C1-C4-alkoxy, optionally substituted) in the presence of dehydrating
reagents, e.g. diisopropyl-(E)-diazene-1,2-dicarboxylate and nylphosphine as described
in Organic & Biomolecular Chemistry 2012, 10(32), 6537-6546.
Scheme 2 (R2 = C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl
or phenyl-C1-C4-alkyl, each of which is optionally substituted as defined for the compound of
general formula (I) as defined supra)
6 6 2
R Cl O R R O
5
R R
OEt, OMe OEt, OMe
2A: R2Met-X
4 3 4 3
R N R R N R
Q Q
1Q 2B
Saponification Saponification
R Cl O 6 2
R R O
R 5
OH OH
4 3
R N R 4 3
R N R
1R Q
A A
1N HN 1N HN
Amide formation
1 1 Amide formation
R R
R Cl O 6 2
R R O
R A 5
2A: R2Met-X A
N N
4 3 R 1
R N R 4 3 R
R N R
Q
1N I-a
Quinoline carboxylic ester ediates 1Q or quinolone carboxamide intermediates 1N can
be converted with certain Grignard- or metal organic compounds 2A: C1-C4-alkyl-Met-X, C3-C6-
cycloalkyl-Met-X, C2-C4-alkenyl-Met-X, C3-C6-cycloalkenyl-Met-X, alkynyl-Met-X or
phenyl-C1-C4-alkyl-Met-X (Met = Mg, Zn; X = I, Br, Cl) introducing C1-C4-alkyl, C3-C6-cycloalkyl,
C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of which is
optionally substituted as defined for the compound of general a (I) as d supra,as
described in Tetrahedron Letters, 2000, 41(33), 6387-6391 for example, into ester
intermediates 2B or final compounds I-a.
Scheme 3 (R3 = C1-C4-alkyl)
see Scheme 1a-e, 2
high boiling sovent
3A 3B 3C
R3 = C1-C4-alkyl
An alternative route to obtain hydroxyl ester 3C (R3 = alkyl, RA = methyl, ethyl or yl)
uses commercial available 2H-3,1-oxazine-2,4(1H)-diones 3A (Hal = iodine, bromine, chlorine)
in a decarboxylation reaction with ketoesters 3B (R3 = C1-C4-alkyl, RA = methyl, ethyl or t.-
butyl) in the presence of a base, e.g. sodium hydride in polar high boiling solvents, e.g. N,N-
dimethyl acetamide as described in US 20080306048. The following steps can be performed
according to Scheme 1a-e or Scheme 2.
Scheme 4
3A: R2-X
1N I-a
Quinolone carboxamide intermediates 1N can be converted by photoredox catalysis with
certain alkyl, clycloalkyl and hetercyclooalkyl halides or carboxylic acids 3A: C1-C4-alkyl-X, C3-
C6-cycloalkyl-X, C3-C6-cycloalkenyl-X, heterocycloalkyl-X (X = Br, COOH) introducing C1-C4-
alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkenyl, cycloalkyl each of which is optionally
substituted as defined for the compound of general formula (I) as defined supra,as bed
in J. Org. Chem., 2016, 81 (16), pp 6898–6926 or Chem. Rev., 2013, 113 (7), pp 5322–5363.
EXPERIMENTAL SECTION – EXAMPLES
Synthesis of 8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]
inolinecarboxamides les 135, 137, 150, 188, 189, 243, 261, 264, 273).
Step 1
8-(3,5-dichlorophenyl)hydroxyquinolinecarboxylic acid
Under argon atmosphere a flask was charged with ethyl 8-bromohydroxy-quinoline
carboxylate (15.0 g, 50.7 mmol) (Gharat, al.,
acid (11.6 g, 60.8 mmol), potassium carbonate (14.0 g, 101 mmol) 1,1'-
bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.24 g,
1.52 mmol) and a degassed 5:1 mixture of dioxan and water (190 ml). The suspension was
stirred overnight at 70°C. Then an aqueous solution of sodium hydroxide (5 M, 101 ml, 505
mmol) was added and the dark mixture was refluxed for 6 h. Subsequently, hot water (110 ml),
methanol (70 ml) and charcoal (2.5 g) were added and refluxing continued for a few minutes.
The e was filtered hot and the filter cake washed with methanol / water (1:1). 5 M acetic
acid (150 ml, 750 mmol) was added slowly under stirring to the hot filtrate to achieve a pH
range of 6-7. Further 90 ml of water were added and the solvents were partially removed under
reduced pressure. The suspension was cooled under stirring to RT and lateron to 0°C. The
itate was filtered off, washed with methanol / water (2:1), stirred in MTBE, filtered off
again and dried in vacuo.
Yield: 17.5 g (92 % purity, 95 % of th.)
LC-MS (Method L1): Rt = 1.02 min; MS (ESIpos): m/z = 334 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.06), 0.008 (0.98), 1.909 ,
2.524 (1.24), 2.670 (0.41), 3.162 (0.87), 3.175 (0.89), 3.568 (5.51), 7.609 , 7.628 (3.44),
7.650 (15.61), 7.654 (16.00), 7.769 (2.83), 7.773 (4.62), 7.778 , 7.788 (3.38), 7.791
(3.46), 7.806 (2.84), 7.809 (2.66), 7.874 (0.44), 7.879 (0.42), 7.948 (0.51), 7.952 (0.48), 8.364
(3.52), 8.368 (3.54), 8.385 , 8.388 (3.26), 8.603 (10.14), 12.202 (1.00).
Step 2
4-chloro(3,5-dichlorophenyl)quinolinecarbonyl chloride
To a suspension of 8-(3,5-dichlorophenyl)hydroxyquinolinecarboxylic acid (step 1) (8.10
g, 24.2 mmol) in chloroform (48 ml) under strirring were added DMF (4 drops) and
oxalylchloride (40 ml, 460 mmol) slowly during 1 h at ambient temperature, causing significant
gas evolution. Then, the e was slowly heated to reflux and stirred at reflux temperature
for 3.5 h. The les were evaporated under reduced pressure and the residue was coevaporated
twice with dry dichloromethane and once with dry THF. The crude product (9.0 g,
100%) was used in the next step.
1H-NMR (400MHz, CHLOROFORM-d): δ [ppm]= 9.42 (s, 1H), 8.53 (dd, 1H), 7.89 - 7.95 (m,
1H), 7.80 - 7.87 (m, 1H), 7.53 (d, 2H), 7.46 (t, 1H).
Step 3
ro(3,5-dichlorophenyl)quinolinecarboxylic acid
4-chloro(3,5-dichlorophenyl)quinolinecarbonyl chloride (step 2) (5.40 g, 14.6 mmol) was
suspended in THF (100 ml). Water (25 ml) and sodium hydrogencarbonate (2.0 g, 23.8 mmol)
were added until a pH 5 is maintained and the reaction mixture was stirred overnight at
ambient temperature. The THF was largely removed under reduced pressure at a bath
temperature not ing 40°C. Acetonitril (20 ml) was added and the organic solvents were
removed again under reduced pressure. This procedure was repeated and the suspension
was cooled to 0°C. The precipitate was filtered off, washed with little volumes of acetonitrile /
water (2:1) and petrolether and dried in vacuo.
Yield: 5.10 g (93 % purity, 92 % of th.)
LC-MS (Method L1): Rt = 1.16 min; MS (ESIpos): m/z = 352 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.29), 0.008 (1.20), 1.760 (0.44),
2.329 (0.64), 2.367 (0.44), 2.524 (2.38), 2.671 (0.63), 2.711 (0.43), 3.601 (0.50), 7.654 ,
7.660 (4.30), 7.664 (6.77), 7.669 (16.00), 7.673 (7.64), 7.804 (1.91), 7.823 (3.49), 7.843 (3.22),
7.887 (3.53), 7.890 (3.71), 7.904 (2.79), 8.354 (3.04), 8.357 (3.11), 8.375 (2.85), 8.378 (2.73),
8.907 (6.32).
Step 4a
4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinolinecarboxamide
(example 4)
To a solution of 4-chloro(3,5-dichlorophenyl)quinolinecarboxylic acid (step 3) (7.60 g,
21.6 mmol) in THF (110 ml) were added under stirring hromanamine hydrochloride
(4.4 g, 23.7 mmol), triethylamine (12 ml, 86 mmol) and after 10 min at ambient temperature a
solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide in ethylacetate (19 ml,
50 % t, 32 mmol), whereafter the temperature of the mixture was raised to 36°C. After
stirring overnight at ambient temperature further (4S)-chromanamine hydrochloride (0.8 g,
4.3 mmol), triethylamine (3 ml, 21.5 mmol) and a solution of 2,4,6-tripropyl-1,3,5,2,4,6-
trioxatriphosphinane 2,4,6-trioxide in ethylacetate (3.85 ml, 50 % content, 6.5 mmol) were
added and stirring ued at ambient temperature for r night. Then water was added
and most of the c solvents evaporated under reduced pressure. The formed precipitate
was filtered off and washed with petrolether and was dried in vacuo.
Yield: 10.0 g (94 % , 90 % of th.)
LC-MS (Method L1): Rt = 1.35 min; MS s): m/z = 483 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 1.356 (1.31), 1.743 (2.45), 1.752 (3.18), 1.759
(6.79), 1.768 (3.21), 1.776 , 1.988 (0.51), 2.059 (0.99), 2.066 (1.07), 2.076 (1.22), 2.084
(1.26), 2.093 (1.57), 2.100 (1.38), 2.209 (1.45), 2.221 , 2.229 (1.27), 2.242 (0.90), 2.366
(0.47), 3.585 (2.47), 3.601 (5.93), 3.617 (2.49), 4.221 (0.89), 4.241 (2.24), 4.249 (1.82), 4.262
(2.18), 4.270 (2.80), 4.279 (2.21), 4.287 (1.82), 4.296 (1.93), 4.315 (0.75), 5.267 , 5.282
(2.01), 5.301 (2.05), 5.315 , 6.791 (3.63), 6.811 (4.03), 6.917 (1.84), 6.936 (3.82), 6.955
(2.20), 7.161 (2.03), 7.179 (3.22), 7.199 (1.53), 7.380 (3.39), 7.399 (3.19), 7.680 (16.00), 7.879
(0.46), 7.893 (2.16), 7.912 (3.99), 7.932 (3.43), 8.009 (4.26), 8.026 (2.94), 8.389 (3.75), 8.410
(3.33), 8.962 (9.97), 9.251 , 9.272 (3.16).
Step 4b
4-chloro(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-indenyl]quinolinecarboxamide
(example 3)
To a stirred mixture of 4-chloro(3,5-dichlorophenyl)quinolinecarbonyl de (step 2)
(480 mg, 1.29 mmol) in DMF (4 ml) was added triethylamine (0.36 ml, 2.6 mmol) and then
dropwise a solution of ndanamine (0.18 ml, 2.6 mmol) in dichloromethane (1.2 ml) at
0°C. The reaction mixture was stirred 1 h at 0°C, then warmed to ambient temperature and the
pH adjusted to 5-6 with 1 M acetic acid followed by on of water and tion with
dichloromethane. The organic phases were separated and ated under reduced
pressure and the residue was purified by column chromatography on silica (100 g), eluent:
cyclohexane / ethyl acetate (9 – 40%).
Yield: 149 mg (25 % of th.)
LC-MS (Method L1): Rt = 1.37 min; MS (ESIpos): m/z = 467 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.33), 1.234 (2.20), 1.397 (0.85), 1.924
(1.63), 1.935 (0.83), 1.946 (1.76), 1.956 (1.90), 1.967 (0.79), 1.977 (1.84), 1.998 (0.66), 2.524
(2.18), 2.567 (0.88), 2.575 (0.77), 2.838 , 2.859 (1.28), 2.878 (2.28), 2.898 (2.50), 2.918
(1.19), 2.951 (1.54), 2.959 (1.64), 2.973 (1.71), 2.980 (1.81), 2.990 (0.99), 2.999 (0.88), 3.012
(0.86), 3.020 (0.74), 3.070 (1.91), 5.542 (1.02), 5.562 (2.83), 5.582 (2.79), 5.602 (0.92), 7.223
, 7.232 (4.00), 7.240 (4.95), 7.246 (5.24), 7.254 (7.15), 7.263 (2.96), 7.271 (3.67), 7.281
(2.50), 7.293 , 7.435 (2.55), 7.446 (2.61), 7.456 (2.00), 7.635 , 7.665 (0.98), 7.678
(13.08), 7.681 (16.00), 7.686 (7.10), 7.689 (3.73), 7.695 (1.37), 7.700 (0.80), 7.895 (2.06),
7.913 (4.25), 7.934 , 8.004 (4.66), 8.008 (3.27), 8.022 (3.28), 8.026 (2.07), 8.393 (4.14),
8.396 (2.75), 8.414 (3.73), 8.417 (2.39), 8.962 (10.00), 9.118 (3.31), 9.139 (3.23).
Step 5
4-(azetidinyl)(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinoline
carboxamide (example 135)
N O O
Cl Cl
In a walled microwave vessel triethylamine (84 µl, 0.6 mmol) and azetidine (40 µl, 0.6
mmol) were added to a solution of 4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-
chromenyl]quinolinecarboxamide (step 4a) (145 mg, 0.3 mmol) in N-methyl pyrrolidon.
The vessel was capped and heated under stirring to 100°C for 2.5 h. 5 M formic acid (180 µl,
0.9 mmol) and little DMSO were added to the dark mixture and the solution purified by prep.
HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile).
Yield: 93 mg (62 % of th.)
LC-MS (Method L1): Rt = 0.89 min; MS (ESIpos): m/z = 504 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (6.30), 0.008 (2.98), 2.004 (1.02),
2.014 (0.94), 2.026 (1.43), 2.041 (1.28), 2.126 (1.31), 2.141 (1.56), 2.373 (2.15), 2.394 (2.92),
2.412 (2.16), 2.433 (1.25), 2.519 (4.80), 2.523 (4.67), 4.243 (3.28), 4.255 (4.75), 4.261 (3.01),
4.270 (2.58), 4.427 (5.50), 4.446 (8.06), 4.466 (4.62), 5.160 (0.92), 5.174 (1.75), 5.194 (1.64),
.754 (2.42), 6.781 (3.04), 6.785 (3.14), 6.802 (3.39), 6.805 (3.26), 6.887 (1.73), 6.890 (1.66),
6.906 (3.30), 6.909 , 6.924 (1.93), 6.927 (1.70), 7.142 (1.75), 7.146 (1.77), 7.163 (2.63),
7.180 (1.31), 7.185 (1.20), 7.291 (2.83), 7.311 (2.52), 7.434 (2.40), 7.452 (3.13), 7.455 (2.90),
7.473 (2.61), 7.592 (2.65), 7.597 (4.87), 7.602 , 7.611 (16.00), 7.616 , 7.698 (3.62),
7.701 (3.63), 7.716 , 7.719 , 8.058 (3.06), 8.061 (3.05), 8.080 (2.76), 8.083 ,
8.430 (11.34), 8.946 (2.94), 8.966 (2.74).
ethyl N-{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromenylcarbamoyl]quinolinyl}-
N-methylglycinate (example 137)
O O CH3
N O O
Cl Cl
Under argon atmosphere a thick-walled microwave vessel was charged with 1,4-
diazabicyclo(2.2.2)octane (56 mg, 0.5 mmol), ethyl-N-methylglycinatehydrochloride (1:1) (154
mg, 1.0 mmol), N,N-diisopropylethylamine (350 µl, 2.0 mmol), yl pyrrolidon (0.8 ml) and
4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinolinecarboxamide
(step 4a) (242 mg, 0.5 mmol). The vessel was capped and the mixture heated under stirring at
100°C for 3 h. Further amounts of ethyl-N-methylglycinatehydrochloride (1:1) (77 mg, 0.5
mmol), isopropylethylamine (170 µl, 1.0 mmol) were added and heating continued for 2
h. 5 M formic acid (0.7 ml, 3.5 mmol) and DMSO (3 ml) were added and the solution purified
by prep. HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile).
Yield: 150 mg (98 % purity, 52 % of th.)
LC-MS (Method L1): Rt = 1.38 min; MS (ESIpos): m/z = 564 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.78), 0.008 (0.70), 1.199 (4.33),
1.217 , 1.234 , 1.356 , 2.063 (0.43), 2.073 (0.48), 2.084 (0.47), 2.099 ,
2.107 (0.59), 2.114 (0.45), 2.193 (0.49), 2.205 (0.59), 2.216 (0.59), 2.227 (0.52), 2.523 (0.52),
3.049 (12.82), 4.052 (6.68), 4.134 (1.34), 4.152 (4.12), 4.170 (4.04), 4.187 (1.27), 4.255 (1.01),
4.267 (1.21), 4.278 (1.65), 4.282 (1.70), 4.293 (0.97), 5.257 (0.42), 5.271 (0.95), 5.291 (0.95),
.305 (0.42), 6.792 (1.74), 6.812 (1.94), 6.901 (0.87), 6.919 (1.84), 6.937 (1.07), 7.154 (0.86),
7.157 (0.93), 7.175 (1.47), 7.193 (0.70), 7.196 , 7.362 (1.56), 7.380 (1.46), 7.645 (16.00),
7.688 (1.26), 7.707 (1.75), 7.728 (1.59), 7.840 (1.89), 7.842 (2.05), 7.857 (1.58), 7.860 (1.56),
8.354 (1.72), 8.357 , 8.376 (1.63), 8.379 (1.60), 8.757 (6.02), 9.197 (1.69), 9.217 (1.64).
N-{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromenylcarbamoyl]quinolinyl}-N-
methylglycine (example 150)
O OH
N O O
Cl Cl
Ethyl N-{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromenylcarbamoyl]quinolinyl}-
N-methylglycinate (from example 137) (35 mg, 62 µmol) was stirred in THF (0.3 ml), l
(0.3 ml) and 5 M aq. sodium hydroxide (50 µl, 250 µmol) for 1.5 h at ambient temperature. The
reaction mixture was acidified to pH 3 by addition of 5 M formic acid and part of the solvents
evaporated under reduced re. The formed precipitate was filtered off, washed with water
and dried in vacuo.
Yield: 27 mg (81 % of th.)
LC-MS (Method L1): Rt = 1.11 min; MS (ESIpos): m/z = 536 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 2.132 (1.28), 2.205 (1.37), 2.328 (0.59), 3.040
(16.00), 3.931 (0.61), 3.975 (4.59), 3.984 (4.71), 4.281 (3.48), 5.309 (1.69), 5.326 (1.68), 6.779
(2.78), 6.799 (3.08), 6.883 (1.42), 6.901 , 6.920 (1.72), 7.140 (1.56), 7.159 (2.50), 7.175
(1.25), 7.348 (2.66), 7.365 (2.47), 7.643 (14.76), 7.660 , 7.678 (2.82), 7.699 (1.88), 7.820
, 7.835 (2.42), 8.139 (1.05), 8.304 (2.56), 8.326 (2.33), 8.755 (6.56).
8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](1H-1,2,3-triazolyl)quinoline-
3-carboxamide (example 188)
8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](2H-1,2,3-triazolyl)quinoline-
3-carboxamide (example 189)
A thick-walled microwave vessel was charged with 4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-
dihydro-2H-chromenyl]quinolinecarboxamide (step 4a) (145 mg, 0.3 mmol), 1,2,3-triazol
(62 mg, 0.9 mmol), N-methyl pyrrolidon (0.5 ml), ylamine (84 µl, 0.6 mmol) and caesium
carbonate (98 mg, 0.3 mmol). The vessel was capped and the mixture heated under stirring at
100°C for 2 h. 5 M formic acid (240 µl, 1.2 mmol) and water (1.5 ml) were added and the
precipitate ed off and discarded. The filtrate was purified by prep. HPLC (C18, gradient:
0.1% aq. formic acid / acetonitrile).
Yield (example 188): 23 mg (15 % of th.)
LC-MS (Method L1): Rt = 1.18 min; MS (ESIneg): m/z = 514 [M-H]-
1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.23 (s, 1H), 9.12 (d, 1H), 8.65 (d, 1H), 8.14 (d, 1H),
8.06 (dd, 1H), 7.80 - 7.88 (m, 1H), 7.68 - 7.76 (m, 3H), 7.39 - 7.46 (m, 1H), 7.10 - 7.20 (m, 1H),
7.06 (d, 1H), 6.82 - 6.92 (m, 1H), 6.76 (d, 1H), 4.98 - 5.09 (m, 1H), 4.18 (td, 1H), 4.00 - 4.12
(m, 1H), 2.02 (br dd, 1H), 1.73 - 1.86 (m, 1H).
Yield (example 189): 73 mg (97% purity, 46 % of th.)
LC-MS (Method L1): Rt = 1.27 min; MS (ESIpos): m/z = 516 [M+H]-
1H-NMR z, DMSO-d6): Shift [ppm]= 9.12 - 9.22 (m, 2H), 8.35 (s, 2H), 8.03 (dd, 1H),
7.87 - 7.96 (m, 1H), 7.78 - 7.87 (m, 1H), 7.66 - 7.76 (m, 2H), 7.25 (d, 1H), 7.10 - 7.19 (m, 1H),
6.88 - 6.98 (m, 1H), 6.76 (d, 1H), 4.98 - 5.14 (m, 1H), 4.07 - 4.29 (m, 2H), 2.02 - 2.14 (m, 1H),
1.94 (dtd, 1H).
tert-butyl 1-{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromenylcarbamoyl] quinolin
yl}-L-prolinate (example 243)
According to the procedure of example 137 the title compound was synthesized from 4-chloro-
8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinolinecarboxamide (step 4a)
(242 mg, 0.5 mmol) and tert-butyl L-prolinate (171 mg, 1.0 mmol) by heating at 100°C for 3 h.
Yield: 185 mg (60 % of th.)
LC-MS (Method L1): Rt = 1.39 min; MS (ESIpos): m/z = 618 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 1.198 (16.00), 1.918 (0.63), 1.932 (0.85),
1.945 , 4.260 (0.44), 6.788 (0.61), 6.808 (0.69), 6.939 (0.64), 7.186 (0.52), 7.394 (0.55),
7.412 , 7.638 (5.73), 7.655 (0.62), 7.676 (0.53), 7.815 (0.70), 7.832 , 8.315 (0.60),
8.334 (0.55), 8.684 (2.06), 9.236 (0.58), 9.257 (0.57).
1-{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromenylcarbamoyl]quinolinyl}-L-
proline (example 261)
N O O
Cl Cl
A solution of hydrogen chloride in dioxan (1 ml, 4 M) was added to a on of utyl 1-{8-
ichlorophenyl)[(4S)-3,4-dihydro-2H-chromenylcarbamoyl]quinolinyl}-L-prolinate
(from example 243) (155 mg, 0.25 mmol) in DICHLOROMETHANE (0.8 ml) and stirred
overnight at ambient temperature. The volatiles were removed under reduced pressure and
the residue stirred with dichloromethane and water. The separated water phase was extracted
with dichloromethane, the combined organic phases dried and evaporated. The residue was
purified by prep. HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile).
Yield: 52 mg (37 % of th.)
LC-MS d L1): Rt = 0.91 min; MS (ESIpos): m/z = 562 [M+H]+
¹H-NMR Peaklist (500 MHz, DMSO-d6) δ [ppm]: -0.007 (3.09), 0.006 (1.99), 1.907 ,
2.028 (0.58), 2.033 (0.60), 2.044 (0.71), 2.056 (0.83), 2.166 (0.52), 2.175 (0.71), 2.185 (0.75),
2.193 (0.77), 2.204 (0.50), 2.358 (0.89), 2.361 (1.22), 2.365 (0.93), 2.369 (0.58), 2.392 (0.70),
2.407 (0.71), 2.514 (3.50), 2.518 (3.01), 2.522 (2.34), 2.631 (0.87), 2.635 (1.14), 2.639 (0.81),
3.866 (0.46), 3.878 (1.06), 3.895 (0.91), 4.183 (0.43), 4.188 (0.44), 4.205 (1.12), 4.224 ,
4.229 , 4.243 (0.75), 4.250 (1.08), 4.262 (0.91), 4.277 (0.46), 4.638 (0.83), 4.649 (1.02),
4.654 (1.33), 4.665 (1.06), 5.254 (0.54), 5.264 (1.14), 5.280 (1.10), 5.291 (0.50), 6.786 (2.22),
6.788 (2.18), 6.802 (2.42), 6.804 (2.32), 6.919 (1.16), 6.921 , 6.933 (2.26), 6.935 (2.11),
6.948 (1.31), 6.950 (1.18), 7.169 (1.12), 7.172 (1.16), 7.186 , 7.200 (0.93), 7.203 (0.89),
7.388 , 7.403 (1.70), 7.629 (1.72), 7.634 (4.02), 7.637 (8.89), 7.639 (16.00), 7.642 (4.87),
7.652 (2.18), 7.654 (1.91), 7.669 (1.82), 7.806 (2.51), 7.809 (2.42), 7.821 (2.05), 7.823 (1.86),
8.303 (1.86), 8.320 (1.72), 8.680 (8.25), 12.586 (0.91).
8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl][(2-hydroxyethyl)sulfanyl]
quinolinecarboxamide (example 264)
A thick-walled vessel was d with 4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-
2H-chromenyl]quinolinecarboxamide (step 4a) (121 mg, 250 µmol), DMSO (0.3 ml), 2-
ylethanol (39 mg, 500 µmol) and ylamine (87 µl, 630 µmol), capped and heated 2h
at 100°C. After cooling to ambient temperature 5 M formic acid (300 µl, 1.5 mmol) was added,
the mixture dissolved by adding acetonitrile and purified by prep. HPLC (C18, gradient: 0.1%
aq. formic acid / acetonitrile).
Yield: 95 mg (72 % of th.)
LC-MS (Method L1): Rt = 1.28 min; MS (ESIpos): m/z = 525 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.66), 0.008 , 2.119 (1.04),
2.128 (0.86), 2.366 (0.82), 2.710 (0.82), 3.060 (2.72), 3.077 (6.64), 3.093 (3.50), 3.287 (2.70),
3.438 (1.04), 3.454 (2.48), 3.468 (3.16), 3.481 (2.10), 3.497 (0.89), 4.254 (1.46), 4.263 (1.26),
4.273 (2.24), 4.282 (2.43), 4.297 (1.35), 4.946 (2.06), 4.960 (4.56), 4.974 (1.99), 5.291 (1.28),
.310 (1.31), 6.781 (2.41), 6.784 (2.61), 6.802 (2.74), 6.805 (2.88), 6.910 (1.33), 6.913 (1.46),
6.928 (2.63), 6.932 (2.57), 6.947 (1.59), 6.950 (1.53), 7.151 (1.31), 7.156 (1.35), 7.173 (2.21),
7.190 , 7.194 (1.13), 7.448 (2.17), 7.465 (2.06), 7.627 (1.00), 7.632 (1.04), 7.658 (5.73),
7.662 (16.00), 7.666 (6.68), 7.669 (3.41), 7.675 (1.22), 7.838 (1.93), 7.856 (2.97), 7.859 (2.35),
7.877 (2.92), 7.929 (3.21), 7.932 (3.50), 7.946 , 7.950 (2.06), 8.624 (2.97), 8.627 (2.97),
8.645 (2.70), 8.649 (2.50), 8.881 (10.45), 9.155 (2.48), 9.175 (2.37).
8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]methoxyquinolinecarboxamide
(example 373)
Under argon atmosphere a solution of sodium ate in methanol (140 µl, 5.4 M, 780 µmol)
was added dropwise to a solution of 4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-
chromenyl]quinolinecarboxamide (step 4a) (150 mg, 310 µmol) in N-methyl pyrrolidon (1
ml) and the mixture d at ambient temperature for 40 min. Acetic acid (250 µl, 5.0 M, 1.2
mmol) was added and the mixture purified by prep. HPLC (C18, gradient: 0.1% aq. formic acid
/ acetonitrile).
Yield: 94 mg (63% of th.)
LC-MS (Method L1): Rt = 1.39 min; MS (ESIpos): m/z = 479 [M+H]+
¹H-NMR Peaklist (400 MHz, 6) δ [ppm]: 4.172 (16.00), 4.245 (0.90), 4.254 ,
4.269 (1.49), 4.273 (1.51), 4.283 (0.86), 5.274 , 5.293 (0.83), 5.754 (12.35), 6.793 (1.40),
6.796 (1.53), 6.814 (1.59), 6.816 (1.66), 6.909 (0.74), 6.912 (0.74), 6.928 (1.55), 6.930 (1.54),
6.946 , 6.949 , 7.159 (0.76), 7.163 (0.82), 7.180 (1.29), 7.363 (1.33), 7.380 (1.25),
7.650 (0.88), 7.655 (2.07), 7.659 (2.33), 7.670 (7.40), 7.675 (4.39), 7.702 (1.20), 7.720 (1.66),
7.723 (1.57), 7.741 (1.47), 7.886 (1.69), 7.890 (1.80), 7.904 , 7.908 (1.42), 8.296 (1.61),
8.299 (1.63), 8.317 , 8.320 , 8.811 (5.57), 9.192 (1.36), 9.212 (1.34).
Synthesis of 4-chloro(3,5-dimethylphenyl)-N-[(1S)-1,2,3,4-tetrahydronaphthalen
yl]quinolinecarboxamide (example 1).
Step 1
ethylchloro(3,5-dimethylphenyl)quinolinecarboxylate
Under argon atmosphere a flask was charged with ethyl ochloroquinoline
carboxylate (330 mg, 1.05 mmol) (Zask, al. Bioorganic and Medicinal Chemistry Letters, 2003 ,
1487 – 1490; Laxmikant, al. US2013/210844), 3,5-dimethylbenzene boronic acid (189 mg,
1.26 mmol) and a degassed mixture of dioxan (6.6 ml) and water 1.3 ml). Then potassium
ate (290 mg, 2.10 mmol) and 1,1'-bis(diphenylphosphino)ferrocenepalladium
(II)dichloride romethane complex (42.8 mg, 52.5 µmol) were added and the
mixture d overnight at 50°C. The reaction mixture was filtered through celite and washed
with ethyl acetate and water. The organic phase of the filtrate was washed with water and
brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was
purified by prep. HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile) and silica gel
chromatography (cyclohexane / ethyl acetate - 5:1).
Yield: 77.0 mg (21 % of th.)
LC-MS d L1): Rt = 1.43 min; MS (ESIpos): m/z = 340 [M+H]+
NMR: 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.13 (s, 1H), 8.42 (dd, 1H), 7.87 - 7.96 (m, 2H),
7.20 (s, 2H), 7.07 (s, 1H), 4.44 (q, 2H), 2.35 (s, 6H), 1.38 (t, 3H).
Step 2
4-chloro(3,5-dimethylphenyl)quinolinecarboxylic acid
To ethylchloro(3,5-dimethylphenyl)quinolinecarboxylate (step 1) (84.0 mg, 247 µmol)
in 0.5 ml ethanol and 0.5 ml THF was added an aqueous solution of sodium hydroxide (5 M,
150 µl, 740 µmol) and the mixture stirred overnight at ambient temperature. The solvents were
removed under reduced pressure, the residue was dissolved in DMSO and 5 M formic acid
and purified via prep. HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile) yielding an offwhite
solid.
Yield: 75.0 mg (97 % of th).
LC-MS (Method L1): Rt = 1.15 min; MS (ESIpos): m/z = 312 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 2.346 (16.00), 7.062 (1.52), 7.189 (3.52),
7.884 (1.52), 7.895 (1.68), 7.902 (3.49), 8.396 (0.99), 8.403 (0.92), 8.414 (0.88), 8.421 (0.87),
9.116 .
Step 3
4-chloro(3,5-dimethylphenyl)-N-[(1S)-1,2,3,4-tetrahydronaphthalenyl]quinoline
carboxamide (example 1)
4-Chloro(3,5-dimethylphenyl)quinolinecarboxylic acid (step 2) (71.0 mg, 228 µmol) in 1.2
ml THF was treated with (1S)-1,2,3,4-tetrahydronaphthalenamine (36.9 mg, 251 µmol) and
triethylamine (190 µl, 1.4 mmol) and d at 60°C for 10 min. Then a solution of 2,4,6-
tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide in cetate (200 µl, 50 % t,
340 µmol) was added, the heating removed and the e stirred overnight at ambient
temperature. Water and 5 M formic acid (0.6 ml) were added and the solvents removed under
reduced re. The residue was purified by prep. HPLC (C18, gradient: 0.1% aq. formic
acid / acetonitrile).
Yield: 20.0 mg (20 % of th)
LC-MS (Method L1): Rt = 1.42 min; MS (ESIpos): m/z = 441 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (4.41), 0.008 (4.06), 2.342 (16.00),
2.759 (1.07), 7.059 (1.60), 7.111 , 7.128 (1.05), 7.183 (4.61), 7.195 (1.69), 7.202 (0.82),
7.207 (0.96), 7.422 (0.89), 7.438 (0.75), 7.855 (4.02), 7.865 (2.24), 7.869 (2.26), 8.303 (1.26),
8.314 (1.10), 8.317 (1.07), 8.328 (1.10), 8.874 (5.11), 9.102 (0.96), 9.123 .
Synthesis of -dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](morpholin-
4-yl)quinolinecarboxamide le 52).
Step 1
8-bromochloroquinolinecarboxylic acid
To a sion of ethylbromochlorquinolinecarboxylate (9.44 g, 30.0 mmol) in THF
(65 ml) was added an aqueous sodiumhydroxid solution (12 ml, 10 M, 120 mmol) and the
mixture stirred vigorously at ambient temperature. After 5 hours, water (12 ml) was added and
the mixture stirred overnight at ambient temperature. The atant was decanted from the
amorphous precipitate which had formed on the wall of the flask and discarded. The precipitate
was dried in vacuo, yielding the sodium salt of the title compound.
LC-MS (Method L1): Rt = 0.70 min; MS (ESIpos): m/z = 285 [M+H]+
1H-NMR (400MHz, DMSO-d
6): δ [ppm] = 8.98 (s, 1H), 8.29 (dd, 1H), 8.16 - 8.23 (m, 1H), 7.64
(t, 1H).
The remaining wet solid was dissolved in water (250 ml) at 60°C and formic acid (57 ml, 5.0 M,
280 mmol) was added under vigorous stirring resulting in a pH value of 3 and formation of a
precipitate. The mixture was cooled to ambient temperature, the precipitate filtered off, washed
with water and dried in vacuo at 40°C.
Yield: 7.0 g (98 % purity, 80 % of th.)
LC-MS (Method L1): Rt = 0.70 min; MS (ESIpos): m/z = 285 [M+H]+
1H-NMR (400MHz, DMSO-d
6): δ [ppm] = 14.12 (br s, 1H), 9.25 (s, 1H), 8.42 (d, 1H), 8.36 (d,
1H), 7.75 (t, 1H).
Step 2
8-bromochloro-N-[(4S)-3,4-dihydro-2H-chromenyl]quinolinecarboxamide
8-Bromochloroquinolinecarboxylic acid (step 1) (7.00 g, 24.4 mmol) was dissolved in THF
by stirring in an oilbath of 50°C for 10 min. The heating was removed, (4S)-chromanamine
hydrochloride (5.44 g, 29.3 mmol), N,N-diisopropyl-ethyl-amine (17 ml, 98 mmol) and a
solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide in ethyl acetate (23 ml,
50 % content, 39 mmol) were added, which caused an se in temperature to 45°C.
Stirring was continued for 30 min and water (300 ml) was added under continuous stirring to
support itation of a solid. The precipitate was collected, washed with water and dried in
vacuo.
Yield: 9.50 g (93 % of th.)
LC-MS (Method L1): Rt = 1.01 min; MS (ESIneg): m/z = 417 [M+H]-
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 2.047 (0.74), 2.054 , 2.063 (1.54), 2.070
(1.66), 2.081 (1.85), 2.088 (1.86), 2.097 (2.49), 2.104 (2.18), 2.113 (1.49), 2.120 (1.08), 2.197
(1.06), 2.206 (1.61), 2.218 (2.41), 2.231 (2.17), 2.239 (2.10), 2.252 (1.56), 2.264 (1.01), 2.273
(0.71), 2.328 (0.42), 2.670 (0.47), 4.205 (1.18), 4.212 , 4.233 (3.76), 4.240 (2.80), 4.253
, 4.261 (2.42), 4.277 (2.42), 4.285 (3.12), 4.293 (2.75), 4.302 (3.10), 4.313 (1.33), 4.321
, 4.329 (1.04), 5.266 (1.51), 5.281 (3.35), 5.300 (3.35), 5.315 , 6.793 (5.60), 6.814
(6.35), 6.922 (2.99), 6.940 (6.44), 6.959 (3.78), 7.162 (3.04), 7.165 (3.11), 7.183 (5.15), 7.201
(2.48), 7.382 (5.42), 7.401 (5.04), 7.713 (4.62), 7.733 (8.03), 7.754 , 8.312 (6.79), 8.324
(8.26), 8.327 (8.69), 8.345 (6.64), 9.042 (16.00), 9.264 , 9.285 (4.67).
Step 3
8-bromo-N-[(4S)-3,4-dihydro-2H-chromenyl](morpholinyl)quinolinecarboxamide
To a suspension of 8-bromochloro-N-[(4S)-3,4-dihydro-2H-chromenyl]quinoline
amide (step 2) (9.50 g, 22.7 mmol) in THF (70 ml), morpholine (6.0 ml, 68 mmol) and
azabicyclo[2.2.2]octane (2.55 g, 22.7 mmol) were added and stirred for 1.5 h at 80°C
bath temperature. Water was added (30 ml) and the THF evaporated under reduced pressure.
More water was added and the suspension stirred first at 50°C then at ambient ature.
The precipitate was filtered off, washed with water and dried in vacuo.
Yield: 10.5 g (98 % of th.)
LC-MS (Method L1): Rt = 0.92 min; MS (ESIneg): m/z = 466 [M-H]-
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.41), -0.008 (4.42), 0.008 (3.18),
2.041 (0.54), 2.048 (0.76), 2.056 (1.13), 2.063 (1.19), 2.076 (1.30), 2.091 (1.80), 2.098 ,
2.106 (1.11), 2.197 (0.74), 2.206 (1.17), 2.218 (1.70), 2.231 (1.59), 2.240 (1.58), 2.253 ,
2.262 (0.74), 2.274 (0.52), 2.327 (0.60), 2.366 (0.49), 2.523 (2.30), 2.669 , 2.710 (0.48),
3.217 (0.69), 3.228 (1.18), 3.248 (4.71), 3.258 (11.00), 3.269 (11.28), 3.279 (5.00), 3.842
(8.92), 3.853 (14.13), 3.864 (8.07), 4.214 , 4.221 (1.01), 4.242 (2.68), 4.249 (2.03), 4.263
(2.41), 4.271 (2.08), 4.276 (2.00), 4.286 (2.44), 4.293 (2.07), 4.302 (2.18), 4.314 (0.86), 4.321
(0.96), 4.329 (0.65), 5.245 (1.10), 5.259 (2.45), 5.279 (2.44), 5.292 (1.06), 6.797 (4.29), 6.815
(4.84), 6.927 (2.26), 6.929 , 6.946 (4.75), 6.964 (2.87), 7.164 (2.33), 7.167 (2.40), 7.185
(3.85), 7.202 , 7.206 (1.79), 7.385 (4.05), 7.403 (3.77), 7.499 (3.74), 7.518 (5.40), 7.538
(4.06), 8.123 (4.80), 8.125 (5.04), 8.142 (4.71), 8.144 (4.51), 8.197 (4.92), 8.199 (4.64), 8.218
(4.71), 8.753 (16.00), 9.177 (3.99), 9.197 (3.89).
Step 4
8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](morpholinyl)quinoline
carboxamide (example 52)
Under argon atmosphere potassium carbonate (1.29 g, 9.31 mmol) was ved in a
degassed 5:1 mixture of dioxan and water (21 ml) by sonification. 1,1'-
bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane x (190 mg,
0.23 mmol) and o-N-[(4S)-3,4-dihydro-2H-chromenyl](morpholinyl)quinoline
carboxamide (step 3) (2.18 g, 4.65 mmol) were added, ed by 2,3-dichlorobenzene
boronic acid (977 mg, 5.12 mmol). The vessel was closed and stirred at 80°C bath
temperature for 2.5 h. Water was added and the mixture extracted with ethyl acetate. The
organic phases were dried and evaporated under d pressure. The residue was purified
by column-chromatography on silica (10 g), eluent: cyclohexane / ethyl acetate (15-35%). The
obtained solid was stirred in a mixture of MTBE (30 ml) and methanol (1.5 ml), filtered off an
dried in vacuo.
Yield: 2.03 g (82 % of th.)
LC-MS d L1): Rt = 1.13 min; MS (ESIpos): m/z = 534 [M+H]+
¹H-NMR Peaklist (600 MHz, DMSO-d6) δ [ppm]: 2.056 , 2.199 (0.43), 2.208 (0.44), 2.214
(0.44), 3.269 (0.65), 3.280 (1.04), 3.289 (1.15), 3.300 (1.36), 3.307 (1.17), 3.321 (0.61), 3.335
), 4.233 (0.78), 4.237 (0.53), 4.247 (0.59), 4.251 (0.49), 4.261 (0.49), 4.267 (0.62), 4.272
(0.54), 4.278 (0.63), 5.239 (0.42), 5.246 (0.54), 5.260 (0.42), 6.781 (1.24), 6.794 (1.32), 6.911
(0.70), 6.915 (0.74), 6.928 (0.40), 7.150 (0.59), 7.162 (0.96), 7.175 (0.49), 7.310 (0.47), 7.312
(0.47), 7.323 (0.59), 7.324 (0.57), 7.336 (0.53), 7.338 (0.53), 7.348 (0.71), 7.350 (0.72), 7.357
, 7.370 (0.95), 7.420 (0.46), 7.432 (1.04), 7.445 (1.07), 7.457 (0.42), 7.664 (0.76), 7.676
(1.51), 7.690 (2.57), 7.693 (1.60), 7.704 (2.49), 7.716 (0.68), 8.281 (1.15), 8.283 (1.14), 8.295
(1.07), 8.297 (1.02), 8.588 (1.70), 8.595 (1.82), 9.166 (0.54), 9.180 (1.03), 9.195 (0.56).
Synthesis of hlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](dimethylamino
)fluoroquinolinecarboxamide (example 141).
Step 1
ethyl 8-bromofluorohydroxyquinolinecarboxylate
A mixture of 2-bromofluoroaniline (24.89 g, 131 mmol) and diethyl
ethoxymethylenemalonate (28.33 g, 131 mmol, 26 mL) was stirred at room temperature for 16
h. Stirring was continued at 250°C under vacuo (60 mbar) for 6 h. The on mixture was
allowed to cool to room tempearture. The solid residue was stirred in refluxing ethyl acetate
(400 mL). The precipitate was filtered off and washed with ethyl acetate. The solid was stirred
in a refluxing mixture of ethanol (400 mL) and methanol (40 mL). The hot suspension was
filtered off. The solid was washed with ethanol and dried on air.
Yield: 28.60 g (83 mmol, 63% of th.)
LC-MS (Method L2): Rt = 1.73 min, m/z = 314/316 (M+H)+
1H-NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 8.45 (s, 1H), 8.22 (m, 1H), 7.50 - 7.39 (m, 1H),
4.23 (d, J = 7.1 Hz, 2H), 1.28 (t, J = 7.1 Hz, 3H).
Step 2
ethyl ochlorofluoroquinolinecarboxylate
To stirring phosphorus oxychloride (38.4 g, 250 mmol, 23 mL) was added ethyl 8-bromo
fluorohydroxyquinolinecarboxylate (step 1) (23.6 g, 75 mmol). The resulting suspension
was d at 80ºC for 1 h. The mixture was allowed to cool to room temperature and was
poured out into vigorously stirred ice-water (100 mL). The ing mixture was left standing
for two days at room temperature. The precipitate was collected by filtration and was washed
with water until the filtrate was neutral. Solids were triturated in a mixture of diethyl ether and
diisopropyl ether (1:1; 1 L). Solids were ed off. The filtrate was concentrated in vacuo at
°C. After co-evaporation of the residue with toluene 21.3 g (64 mmol, 85% of theory) of the
title compound were obtained.
Yield: 21.3 g (64 mmol, 85% of th.)
LC-MS (Method L2): Rt = 2.18 min, m/z = 332/334 (M+H)+
Step 3
ethyl 8-bromo(dimethylamino)fluoroquinolinecarboxylate
To a solution of ethyl 8-bromochlorofluoroquinolinecarboxylate (step 2) (14.31 g, 43
mmol) in dry tetrahydrofuran (150 mL) were added triethyl amine (8.71 g, 86 mmol, 12 mL) and
dimethylamine (2 M in tetrahydrofuran; 48 mmol, 24 mL). The reaction e was d for
16 h at room temperature. Solids were filtered off and washed with tetrahydrofuran. The filtrate
was concentrated in vacuo to afford the title compound.
Yield: 12.66 g (37 mmol, 86% of th.)
LC-MS (Method L2): Rt = 1.75 min, m/z = 341/343 (M+H)+
1H-NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.28 (dd, J = 9.4, 6.1 Hz, 1H), 7.63 (dd, J = 9.4,
8.2 Hz, 1H), 4.39 (q, J = 7.1 Hz, 2H), 3.07 (s, 6H), 1.36 (t, J = 7.1 Hz, 3H).
Step 4
ethyl 8-bromo(dimethylamino)fluoroquinolinecarboxylate hydrochloride
To a solution of ethyl 8-bromo(dimethylamino)fluoroquinolinecarboxylate (step 3) (14.0
g, 41 mmol) in tetrahydrofuran (100 mL) was added a solution of lithiumhydroxide
monohydrate (11.5 g, 274 mmol) in water (100 mL). The mixture was d for 16 h at 75ºC
and was allowed to cool to room temperature. Layers were separated and the s layer
was extracted with tetrahydrofuran (2x150 mL). Combined organic layers were concentrated in
vacuo and hydrochloric acid (4 M; 100 mL) was added. The solid was filtered off, washed with
water and diethyl ether and was dried on air to afford the title compound.
Yield: 10.6 g (30 mmol, 74% of th.)
LC-MS (Method L2): Rt = 1.21 min, m/z = 313/315 (M+H)+
1H-NMR (400 MHz, 6) δ 8.73 (s, 1H), 8.41 (dd, J = 9.4, 5.7 Hz, 1H), 7.66 (dd, J = 9.4,
8.1 Hz, 1H), 3.35 (s, 6H) [acidic protons were not detected].
Step 5
8-bromo-N-[(4S)-3,4-dihydro-2H-chromenyl](dimethylamino)fluoroquinoline
carboxamide
To a solution of 8-bromo(dimethylamino)fluoroquinolinecarboxylic acid hydrochloride
(step 4) (2.00 g, 5.7 mmol) in N,N-dimethylformamide (50 mL) were added 1-
[bis(dimethylamino)-methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate
(2.18 g, 5.7 mmol) and N,N-diisopropylethylamine (4.21 g, 32.6 mmol, 5.7 mL). The mixture
was stirred at room temperature for 1 h. (4S)-Chromanamine hydrochloride (1.06 g, 5.7
mmol) was added. The on mixture was stirred for 16 h at room temperature. The mixture
was poured out into water (200 mL). Solids were filtered off, washed with water and were dried
in vacuo. After co-evaporation with toluene and ethyl acetate the title compound was obtained.
Yield: 1.90 g (4.3 mmol, 75% of th.)
LC-MS (Method L2): Rt = 1.78 min, m/z = 444/446 (M+H)+
1H-NMR (400 MHz, 6) δ 9.12 (d, J = 8.1 Hz, 1H), 8.70 (s, 1H), 8.23 (dd, J = 9.4, 6.1
Hz, 1H), 7.59 (dd, J = 9.3, 8.3 Hz, 1H), 7.37 (d, J = 6.8 Hz, 1H), 7.22 - 7.14 (m, 1H), 6.98 -
6.90 (m, 1H), 6.81 (dd, J = 8.2, 1.0 Hz, 1H), 5.29 - 5.20 (m, 1H), 4.34 - 4.19 (m, 2H), 3.06 (s,
6H), 2.27 - 2.15 (m, 1H), 2.11 - 2.00 (m, 1H).
Step 6
8-(3-chlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](dimethyl-amino)fluoroquinoline-
3-carboxamide (example 141)
In an 8 mL screw capped vial, to a degassed (1 min, nitrogen) mixture of o-N-[(4S)-3,4-
dihydro-2H-chromenyl](dimethylamino)fluoroquinolinecarboxamide (100 mg, 0.225
mmol), (3-chlorophenyl)boronic acid (42 mg, 0.270 mmol) and sodium carbonate (72 mg,
0.675 mmol) in a mixture of tetrahydrofuran (1.30 mL) and water (0.25 mL) was added 1,1'-
bis(diphenylphosphino)ferrocenepalladium(II) dichloride (3 mg, 0.005 mmol). The reaction
mixture was stirred for 16 h at 60°C and was cooled to room temperature. Water (5 mL) was
added and the aqueous layer was extracted with dichloromethane (3x3 mL) by phase
separator. ts were removed in vacuo. Purification by flash column chromatography
(heptane, 5%-35% ethyl acetate) afforded the title compound.
Yield: 56 mg (0.118 mmol, 52% of th.)
LC-MS (Method L2): Rt = 3.03 min, m/z = 476 (M+H)+
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.58 (s, 1H), 8.27 (dd, J = 9.4, 6.2
Hz, 1H), 7.60 (t, J = 9.3 Hz, 1H), 7.55 - 7.45 (m, 3H), 7.43 - 7.31 (m, 2H), 7.20 - 7.12 (m, 1H),
6.95 - 6.88 (m, 1H), 6.83 - 6.76 (m, 1H), 5.28 - 5.19 (m, 1H), 4.32 - 4.19 (m, 2H), 3.07 (s, 6H),
2.25 - 2.14 (m, 1H), 2.09 - 1.98 (m, 1H).
sis of 8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl][methyl
(oxetanyl)amino]quinolinecarboxamide (example 331).
Step 1
ethyl 8-bromo[methyl(oxetanyl)amino]quinolinecarboxylate
N O
A flask was charged with ethyl 8-bromochloroquinolinecarboxylate (1.26 g, 4 mmol)
(Zask, al. Bioorganic and Medicinal Chemistry Letters, 2003 , 1487 – 1490; Laxmikant, al.
US2013/210844), 1-methyloxetanamine (0.42 g, 4 mmol), N,N-diisopropyl-ethylamin (0.62
g, 4.8 mmol) in 40 mL Acetonitril. The reaction mixture was ed for 24 hours. Then the
solvent was removed under reduced pressure and the remaining material was dissolved in
ethyl acetate and washed twice with water. The organic phase was separated, dried over
calcium sulfate, filtered and the filtrate was removed under reduced pressure. The resulting
residue was purified by reverse phase column chromatography (eluent water / acetonitrile
gradient).
Yield: 1.2 g (3.2 mmol, 82% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.20 (d, 1H), 8.14 (d, 1H), 7.55 (dd, 1H), 4.72 –
4.62 (m, 5H, oxetanyl), 4.43 – 4.38 (q, 2H), 3.10 (s, 3H), 1.37 (t, 3H).
Step 2
ethyl 8-(2,3-dichlorophenyl)[methyl(oxetanyl)amino]quinolinecarboxylate
In an microwave vial, to a degassed (1 min, argon) mixture of ethyl o[methyl(oxetan-
3-yl)amino]quinolinecarboxylate (step 1) (500 mg, 1.37 mmol), (2,3-dichlorophenyl)boronic
acid (261 mg, 1.37 mmol), an s solution of cesium carbonate (2M, 1.37 mL, 2.74 mmol)
and dioxane (12.5 mL) was added 1,1'-bis(diphenylphosphino)ferrocenepalladium(II) dichloride
(111 mg, 0.14 mmol). The reaction e was treated in a e microwave oven for 25
minutes at 100 °C. The reaction mixture was filtered via a sodium sulfate / silica gel cartridge
and purified by reverse phase column chromatography t water / acetonitrile gradient).
Yield: 600 mg (98% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.21 (t, 1H), 7.74 (d, 2H), 7.71 (d, 1H), 7.45 (t,
1H), 7.36 (d, 1H), 4.76 – 4.65 (m, 5H, oxetanyl), 4.40 – 4.34 (q, 2H), 3.14 (s, 3H), 1.34 (t, 3H).
Step 3
8-(2,3-dichlorophenyl)[methyl(oxetanyl)amino]quinolinecarboxylic acid
Ethyl 8-(2,3-dichlorophenyl)[methyl(oxetanyl)amino]quinolinecarboxylate (step 2) (580
mg, 1.34 mmol) was dissolved in 20 mL dioxane and mixed with LiOH (35.4 mg, 1.48 mmol) in
5 mL water. The n mixture was heated for 16 hours at 60 °C. The dioxane was removed
under reduced pressure, the remaining solution was taken into a mixture of ethyl acetate and
water. The aqueous phase was separated and treated with 1N HCl until pH 5. This acidified
on was extracted twice with ethyl acetate, the combined extracts were dried, filtered and
the solvent was removed under reduced re. The obtained compound was used in the
next step without r purification.
Yield: 570 mg (99% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H, COOH), 8.73 (s, 1H), 8.24 – 8.22 (dd, 1H),
7.23 – 7.68 (m, 3H), 7.44 (t, 1H), 7.37 – 7.35 (dd, 1H), 4.76 – 4.65 (m, 5H, oxetanyl), 3.13 (s,
Step 4
8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl][methyl(oxetanyl)amino]-
quinolinecarboxamide (example 331)
A flask was charged with 8-(2,3-dichlorophenyl)[methyl(oxetanyl)amino]quinoline
carboxylic acid (step 3) (260 mg, 0.645 mmol), (4S)-chromanamine hydrochloride (131.7
mg, 0.71 mmol), isopropyl ethylamine (250 mg, 1.93 mmol), -dimethylamino)
pyridine (39.4 mg, 0.32 mmol), 1-hydroxy-1H-benzotriazole (43.5 mg, 0.32 mmol) and l-
3-(3-dimethylaminopropyl)carbodiimide hydrochloride (123.6 mg, 0.645 mmol) in 10 mL
dichloromethane. The reaction mixture was stirred at ambient temperature overnight, then
mixed with water, the dichloromethane phase was separated, dried via a sodium sulfate / silica
gel cartridge and the solvent was removed under reduced pressure. The residue was purified
by reverse phase column chromatography t water / acetonitrile gradient) to obtain the
title compound.
Yield: 130 mg (0.24 mmol, 37% of th.)
1H-NMR Peaklist (399,9532 MHz, DMSO): δ= 9.1403 (1.94); 9.1288 (2); 9.1208 ; 9.1103
(1.85); 8.6012 ); 8.4715 (0.58); 8.3155 (1.57); 8.2143 (2.25); 8.1975 (2.56); 8.1729
(1.06); 7.7323 (2.07); 7.7127 (5.31); 7.6894 (10.46); 7.6737 (1.95); 7.4635 (1.67); 7.4521
(1.74); 7.4433 (2.94); 7.4332 (2.77); 7.4235 (2.08); 7.4143 ; 7.3824 (1.86); 7.3618 (4.63);
7.3428 (4.44); 7.3225 (1.63); 7.1895 (1.81); 7.171 (3.64); 7.1535 (2.27); 6.9433 (2.6); 6.9255
; 6.9084 (2.02); 6.8059 (4.77); 6.7848 (4.45); 6.5782 (0.9); 5.2488 (1.97); 5.237 (2);
4.725 (1.91); 4.697 (7.04); 4.6722 (5.48); 4.6575 (5.6); 4.5955 (1.22); 4.5844 (1.61); 4.2921
(2.17); 4.2752 (3.94); 4.2675 (3.64); 4.2552 (2.23); 4.2471 (2.41); 4.2281 (0.89); 3.3183
(319.34); 3.2701 (0.87); 3.2496 (0.61); 3.1747 (0.71); 3.081 (16); 3.0759 (15.54); 2.9497
(1.08); 2.6703 ; 2.5893 (0.63); 2.5051 (1239.6); 2.5012 (1583.24); 2.4971 (1204.24);
2.3276 (9.3); 2.2832 (0.88); 2.2475 (1.34); 2.2286 (1.72); 2.2205 (1.78); 2.1313 (0.96); 2.074
(5.92); 2.0168 (0.96); 1.2694 (0.87); 1.169 (4.47); 1.0034 (0.71); 0.9887 (0.75); 0.1463 (2.93); -
0.0001 (642.47); -0.0792 (0.67); 7 (3.13); -3.3083 (0.55).
sis of 8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-indenyl]ethoxyquinoline
carboxamide (example 134).
Step 1
8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-indenyl]hydroxyquinolinecarboxamide
A on of 8-(3,5-dichlorophenyl)hydroxyquinolinecarboxylic acid (5.50 g, 16.5 mmol)
in THF was treated stirred with (1S)-indanamine (2.5 ml, 20 mmol) and trimethylamine (9.2
ml, 66 mmol) for 10 min at ambient temperature. Then a solution of 2,4,6-tripropyl-1,3,5,2,4,6-
triphosphinane trioxide in ethylacetate (19.6 ml, 50 % content, 33 mmol) was added
an stirred overnight at ambient temperature. Water (100 ml) was added and the THF
evaporated under reduced pressure. More water and ethyl acetate were added and the
mixture cleared by filtration. The aqueous phase was ted with ethyl acetate and the
combined organic phases dried and evaporated under reduced pressure. The residue was
purified by column chromatography on silica (340 g) with cyclohexane / ethyl acetate (15-
40%). Two fractions were isolated:
Yield: 3.0 g (98 % purity, 40 % of th.) and 0.69 g (94 % purity, 9 % of th.)
LC-MS (Method L1): Rt = 1.27 min; MS (ESIneg): m/z = 447 [M+H]-
¹H-NMR st (400 MHz, DMSO-d6) δ [ppm]: 1.849 (1.87), 1.868 (2.39), 1.880 (2.59), 1.900
(2.50), 1.921 (1.16), 2.578 , 2.588 (3.08), 2.841 (1.03), 2.862 (1.82), 2.882 (2.65), 2.902
(3.54), 2.922 (2.00), 2.977 (2.56), 2.990 (2.71), 2.999 (2.71), 3.029 (1.74), 5.474 (1.16), 5.493
, 5.512 (3.77), 5.531 (1.67), 7.197 (1.27), 7.214 (3.91), 7.233 (6.17), 7.256 (5.56), 7.280
(7.00), 7.298 (9.89), 7.316 (4.52), 7.521 (2.83), 7.540 (5.61), 7.560 (4.06), 7.626 (14.53), 7.631
(16.00), 7.695 (5.87), 7.713 (5.06), 7.804 (5.42), 8.297 (4.58), 8.318 (4.68), 8.611 , 8.624
, 10.285 (4.44), 10.304 (4.72), 11.637 (3.53).
Step 2
8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-indenyl]ethoxyquinolinecarboxamide
(example 134)
8-(3,5-dichlorophenyl)-N-[(1S)-2,3-dihydro-1H-indenyl]hydroxyquinolinecarboxamide
(step 1) (70.0 mg, 156 µmol), ethanol (27 µl, 470 µmol), triphenylphosphine (61.3 mg, 234
µmol) and diisopropyl-(E)-diazene-1,2-dicarboxylate (46 µl, 230 µmol) were stirred in THF (1
ml) at ambient temperature for 6 h. 5 M formic acid (93 µl, 470 µmol) was added, the solvent
evaporated and the residue ed by prep. HPLC (C18, gradient: 0.1% aq. formic acid /
acetonitrile).
Yield: 40 mg (92 % purity, 49 % of th.)
LC-MS (Method L7): Rt = 2.60 min; MS (ESIpos): m/z = 477 [M+H]+
¹H-NMR (Peaklist) (500 MHz, DMSO-d6) δ [ppm]: -0.007 (4.15), 0.007 (3.67), 1.235 ,
1.395 (7.56), 1.409 (16.00), 1.423 (7.72), 1.950 (1.18), 1.966 (1.28), 1.975 (1.34), 1.991 (1.30),
2.522 (1.98), 2.853 (1.24), 2.869 (1.51), 2.885 (1.92), 2.901 (0.85), 2.981 (1.03), 2.989 (1.09),
2.999 (1.11), 3.006 (1.07), 3.013 (0.81), 3.286 (5.84), 4.352 , 4.354 (1.53), 4.366 (4.56),
4.368 (4.83), 4.380 (4.46), 4.383 (4.79), 4.394 (1.38), 4.396 (1.51), 5.533 (0.78), 5.549 (2.29),
5.564 (2.27), 5.580 (0.78), 5.754 (0.91), 7.227 , 7.231 (3.49), 7.238 (4.46), 7.245 (4.52),
7.249 (3.34), 7.260 (1.11), 7.278 , 7.290 , 7.294 (1.20), 7.400 (2.19), 7.406 (2.33),
7.417 (2.00), 7.654 (2.35), 7.658 (5.35), 7.661 (4.98), 7.674 (15.77), 7.678 (10.55), 7.714
(2.52), 7.729 , 7.731 (3.32), 7.745 (2.97), 7.889 (3.47), 7.891 (3.80), 7.903 (3.01), 7.906
(3.03), 8.304 (3.32), 8.307 (3.57), 8.321 (3.16), 8.324 (3.16), 8.842 (11.93), 8.998 (2.83), 9.015
(2.77).
Synthesis of 8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]ethyl quinolinecarboxamide
(example 350).
A on of diethylzinc in heptane (400 µl, 1.0 M, 400 µmol) was added dropwise to a mixture
of 4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinoline
carboxamide (step 4, example 4) (97 mg, 200 µmol) and 1,1'-bis(diphenylphosphino)ferrocene-
palladium(II)dichloride dichloromethane complex (32.7 mg, 40.0 µmol) in dioxan (2 ml) and
stirred at 90°C overnight under an argon atmosphere. 5 M formic acid (160 µl, 5.0 M, 800
µmol) and DMSO (1 ml) were added and the filtered mixture was ed twice by ative
HPLC (C18, nt: 0.1% aq. formic acid / acetonitrile).
Yield: 52 mg (98 % purity, 53 % of th.)
LC-MS (Method L1): Rt = 1.35 min; MS (ESIpos): m/z = 477 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: 1.303 (2.43), 1.322 (5.61), 1.341 (2.50), 3.252
(2.09), 3.271 (2.06), 4.250 (1.06), 4.259 (1.62), 4.268 (1.95), 4.275 (1.54), 4.284 (1.06), 5.305
(0.92), 5.325 (0.92), 6.783 (1.53), 6.785 (1.66), 6.803 (1.75), 6.806 (1.83), 6.911 (0.78), 6.914
(0.83), 6.930 (1.72), 6.932 (1.71), 6.948 (1.03), 6.951 (1.00), 7.149 (0.86), 7.153 (0.89), 7.170
(1.43), 7.350 (1.48), 7.370 (1.41), 7.652 (16.00), 7.752 (1.09), 7.770 (1.68), 7.791 (1.47), 7.871
, 7.874 (2.04), 7.889 (1.44), 7.892 (1.42), 8.319 (1.50), 8.322 (1.58), 8.340 (1.43), 8.343
, 8.839 (5.77), 9.102 (1.60), 9.123 .
Isolation of 8-(3-chloroethylphenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]
ethylquinolinecarboxamide (example 351).
The preparative HPLC separation described in example 350 yielded the title compound as a
by-product.
Yield: 12 mg (100% purity, 13% of th.)
LC-MS (Method L1): Rt = 1.36 min; MS (ESIpos): m/z = 471 [M+H]+
1H-NMR (400MHz, DMSO-d
6): δ [ppm]= 9.10 (d, 1H), 8.81 (s, 1H), 8.29 (dd, 1H), 7.72 - 7.83
(m, 2H), 7.46 (t, 1H), 7.31 - 7.40 (m, 3H), 7.17 (t, 1H), 6.93 (td, 1H), 6.79 (dd, 1H), 5.27 - 5.35
(m, 1H), 4.22 - 4.31 (m, 2H), 3.21 - 3.29 (m, 2H) superimpose by water signal, 2.64 - 2.73 (m,
2H), 2.16 - 2.26 (m, 1H), 2.01 - 2.11 (m, 1H), 1.32 (t, 3H), 1.23 (t, 3H).
Synthesis of 8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](propen
yl)quinolinecarboxamide (example 317)
Under argon atmosphere and uos sonication potassium carbonate (571 mg, 4.13 mmol)
was dissolved in a thick-walled vessel in a 5:1 degassed mixture of dioxan and water (7.0 ml).
1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (84.4
mg, 103 µmol) and 4-chloro(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen
yl]quinolinecarboxamide (step 4, example 4) (1.00 g, 2.07 mmol) were added, followed by
4,4,5,5-tetramethyl(propenyl)-1,3,2-dioxaborolane (0.49 ml, 4.1 mmol). The vessel
was capped and stirred at 80°C for 4 h. 5 M formic acid (1.3 ml) and water were added and the
mixture extracted with ethyl e. The organic phases were dried and evaporated under
reduced pressure. The e was purified by column tography on silica (50 g), eluent:
cyclohexane / ethyl acetate (7-16%).
Yield: 885 mg (87 % of th.)
LC-MS (Method L1): Rt = 1.39 min; MS (ESIpos): m/z = 489 [M+H]+
1H-NMR (400MHz, DMSO-d6): Shift [ppm] = 8.88 - 9.00 (m, 2H), 8.04 (dd, 1H), 7.90 (dd, 1H),
7.76 (dd, 1H), 7.67 (s, 3H), 7.32 (br d, 1H), 7.11 - 7.22 (m, 1H), 6.92 (t, 1H), 6.78 (dd, 1H),
5.54 (s, 1H), 5.18 - 5.30 (m, 1H), 5.03 (br s, 1H), 4.16 - 4.33 (m, 2H), 2.12 - 2.26 (m, 4H), 1.95
- 2.06 (m, 1H).
Synthesis of 8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]isopropylquinolinecarboxamide
(example 359)
H3C CH3
O O
Cl Cl
Under argon atmosphere 8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](prop-
1-enyl)quinolinecarboxamide (from example 317) (150 mg, 306 µmol) was dissolved in
ethyl acetate (7 ml) and ethanol (3.5 ml). Pd on charcoal (44 mg, 10%) was added and the
mixture hydrogenated under normal pressure at t ature for 1.5 h. The catalyst
was filtered off through Celite, washed with an ethyl acetate/ethanol mixture (2:1) and the
filtrate evaporated under reduced pressure. The residue was ed two times by prep. HPLC
(C18, gradient: 0.1% aq. formic acid / acetonitrile).
Yield: 64 mg (42 % of th.)
LC-MS (Method L1): Rt = 1.41 min; MS (ESIpos): m/z = 491 [M+H]+
1H-NMR (400MHz, DMSO-d6): Shift [ppm] = 9.12 (d, 1H), 8.76 (s, 1H), 8.45 (d, 1H), 7.85 (d,
1H), 7.74 (t, 1H), 7.61 - 7.66 (m, 3H), 7.36 (d, 1H), 7.17 (t, 1H), 6.93 (t, 1H), 6.79 (d, 1H), 5.25
- 5.31 (m, 1H), 4.21 - 4.31 (m, 2H), 3.82 - 3.92 (m, 1H), 2.21 (td, 1H), 2.06 (ddd, 1H), 1.56 (br
d, 3H), 1.53 (br d, 3H).
Synthesis of ethyl cyano{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromen
ylcarbamoyl]quinolinyl}acetate (example 354)
Under argon atmosphere sodium hydride (165 mg, 60 % content, 4.13 mmol) was added at
0°C to a on of ethyl-cyanoacetate (0.44 ml, 4.1 mmol) in dry N-methyl pyrrolidon, stirred
at t temperature for 15 min until the evolution of gas had ceased. Then 4-chloro(3,5-
dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinolinecarboxamide (1.00 g, 2.07
mmol) was added and the mixture stirred at 70°C for 3 h. After cooling to t temperature
M formic acid (1.2 ml, 6.2 mmol) and water were added and the mixture extracted two times
with ethyl acetate. The combined organic phases were dried and evaporated under reduced
pressure. The e was purified by column chromatography on silica (100g) with
cyclohexane / ethyl acetate (5 - 50 %).
Yield: 650 mg (96 % purity, 54 % of th.)
LC-MS d L6): Rt = 2.46 min; MS (ESIpos): m/z = 560 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.55), 0.008 (3.23), 0.146 (0.40),
0.890 (0.44), 1.157 (2.49), 1.175 (7.53), 1.188 (4.41), 1.193 , 1.205 (8.20), 1.211 (4.25),
1.215 , 1.223 (4.21), 1.233 (2.01), 1.245 (1.50), 1.250 (2.12), 1.264 (0.77), 1.268 (1.05),
1.988 (9.00), 2.083 (0.45), 2.092 (0.48), 2.104 (0.46), 2.116 (0.65), 2.129 (0.70), 2.163 (1.14),
2.176 (1.60), 2.187 (1.26), 2.327 (0.47), 2.366 (0.41), 2.523 (1.67), 2.669 , 2.710 (0.46),
3.998 (2.03), 4.002 (0.89), 4.021 (2.14), 4.038 (2.14), 4.056 (0.79), 4.133 (0.51), 4.151 (0.98),
4.168 (0.93), 4.175 (0.83), 4.186 (0.84), 4.193 (1.11), 4.202 (2.21), 4.210 , 4.219 (4.66),
4.228 (3.20), 4.236 (4.66), 4.246 (3.73), 4.254 (2.15), 4.263 (1.53), 4.272 (0.85), 4.287 (1.21),
4.298 (1.72), 4.309 (1.16), 5.226 , 5.245 (0.83), 5.266 (0.79), 5.285 , 6.794 (1.56),
6.804 (5.05), 6.815 (1.91), 6.826 (4.30), 6.837 (0.92), 6.856 (1.42), 6.866 (0.52), 6.875 (0.87),
6.917 (0.71), 6.936 (1.45), 6.955 (0.86), 7.142 (0.96), 7.145 (0.95), 7.163 (1.28), 7.173 (0.83),
7.177 (0.93), 7.194 , 7.212 (0.58), 7.387 (1.34), 7.408 (1.79), 7.429 (1.14), 7.599 (0.99),
7.603 (1.04), 7.683 (16.00), 7.702 (0.43), 7.875 (1.05), 7.879 (1.00), 7.897 (2.37), 7.914 (1.62),
7.918 (1.55), 8.002 (3.30), 8.019 (2.41), 8.408 (1.18), 8.423 (1.48), 8.443 (1.15), 9.112 (4.72),
9.124 (4.29), 9.517 (1.49), 9.525 , 9.537 (1.51), 9.544 (1.34).
Synthesis of nomethyl)(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen
yl]quinolinecarboxamide (example 355)
O O
Cl Cl
A solution of ethyl cyano{8-(3,5-dichlorophenyl)[(4S)-3,4-dihydro-2H-chromen
ylcarbamoyl]quinolinyl}acetate (example 354) (300 mg, 0.54 mmol) in DMSO (2.4 ml) was
treated with sodium chloride (63 mg, 1.1 mmol) and water (0.24 ml) and heated under stirring
overnight at 90°C. Water (2.5 ml) was added, the precipitate filtered off, washed with water and
dried in vacuo.
Yield: 250 mg (99 % purity, 95 % of th.)
LC-MS (Method L1): Rt = 1.24 min; MS (ESIpos): m/z = 488 [M+H]+
¹H-NMR Peaklist (400 MHz, 6) δ [ppm]: 2.099 (0.43), 2.136 (0.80), 2.145 (0.69), 2.205
(0.64), 2.224 (0.67), 2.239 (0.54), 4.266 (1.68), 4.277 (2.29), 4.711 , 5.278 (0.45), 5.294
(1.03), 5.312 (1.04), 5.326 (0.45), 6.798 (2.04), 6.818 (2.30), 6.899 (1.01), 6.917 (2.07), 6.936
, 7.163 (1.04), 7.182 (1.68), 7.200 (0.79), 7.387 (1.76), 7.405 (1.62), 7.677 (16.00), 7.883
(1.06), 7.903 , 7.922 (1.56), 7.988 (2.46), 8.006 (1.65), 8.417 (1.93), 8.437 (1.73), 9.029
(5.73), 9.379 (1.69), 9.399 (1.68).
Synthesis of minooxoethyl)(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-
chromenyl]quinolinecarboxamide (example 360)
A suspension of 4-(cyanomethyl)(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromen
yl]quinolinecarboxamide (example 355) (150 mg, 307 µmol) in conc. hloric acid (0.77
ml, 37%) and dioxan (0.5 ml) was stirred 3 days at ambient temperature. The solid was filtered
off, washed with dioxan and dried in vacuo.
Yield: 90 mg (92 % purity, 53 % of th.)
LC-MS (Method L1): Rt = 1.13 min; MS (ESIpos): m/z = 506 [M+H]+
¹H-NMR Peaklist (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.40), 0.008 (3.42), 2.068 (0.55),
2.085 (0.61), 2.095 (0.80), 2.208 (0.74), 2.220 (0.70), 2.229 (0.68), 2.242 (0.51), 2.327 (0.61),
2.366 (0.61), 2.670 (0.57), 2.710 (0.54), 2.794 (0.77), 3.568 (2.60), 4.179 (0.56), 4.197 (0.56),
4.216 (3.94), 4.225 , 4.238 (1.19), 4.264 (1.32), 4.283 (1.00), 5.270 (0.46), 5.285 (1.06),
.304 (1.07), 5.319 (0.51), 6.779 (1.94), 6.800 (2.15), 6.883 (0.98), 6.899 , 6.918 (1.20),
7.147 (1.02), 7.164 (1.67), 7.185 (0.81), 7.349 (2.28), 7.369 (1.67), 7.659 (16.00), 7.764 (1.23),
7.782 (1.93), 7.803 (1.67), 7.894 (2.35), 7.910 , 7.989 (1.55), 8.349 (1.83), 8.368 (1.68),
8.949 (6.32), 9.468 (1.76), 9.488 (1.75).
The filtrate was adjusted to pH 6 by addition of aqueous sodiumbicarbonate (7 ml, 1.5 M) and
extracted with ethyl acetate. The combined organic phases were dried, evaporated and the
residue purified by prep. HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile) yielding a
second crop (40 mg, 100% purity, 26% of th.)
Synthesis of 4-cyano(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]
quinolinecarboxamide (example 362)
O O
Cl Cl
Under argon atmosphere a thick-walled microwave vessel was charged with 4-chloro(3,5-
dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]quinolinecarboxamide (1.00 g, 2.07
mmol), (I)cyanide (185 mg, 2.07 mmol), sodiumcarbonate (219 mg, 2.07 mmol), 1,1'-
bis(diphenylphosphino)ferrocene-palladium(II)dichloride romethane complex (169 mg,
0.21 mmol) and N-methyl pyrrolidon (7.2 ml), capped and heated overnight under ng at
120°C. The reaction mixture was added to a 3 :1 mixture of saturated aq. ammoniumchloride /
conc. aqueous ammonia (120 ml) and ethyl acetate, stirred for 30 min and filtered through
celite. The phases were separated, the organic phase washed three times with a 3 :1 mixture
of ted aq. ammoniumchloride / conc. aq. ammonia, then brine and dried. The residue
(1.06 g) was purified by column chromatography on silica (100g) with cyclohexane / ethyl
acetate (3 - 30 %).
Yield: 760 mg (93 % purity, 72 % of th.)
LC-MS (Method L1): Rt = 1.44 min; MS (ESIpos): m/z = 474 [M+H]+
¹H-NMR Peaklist (400 MHz, 6) δ [ppm]: -0.008 (0.70), 0.008 (0.49), 1.398 (16.00),
1.988 , 2.519 , 6.790 (0.48), 6.849 (0.44), 6.851 (0.45), 6.870 (0.51), 6.872 (0.48),
6.966 (0.40), 7.673 , 7.696 (4.12), 7.933 , 7.951 (0.60), 7.953 (0.54), 7.972 (0.53),
8.054 (0.67), 8.057 (0.62), 8.071 (0.49), 8.075 (0.41), 9.279 (0.96), 9.311 (0.50).
Synthesis of 8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl]
(dimethylamino)methylquinolinecarboxamide (example 481).
Step 1
tert-butyl 8-bromohydroxymethylquinolinecarboxylate
A three-necked flask was charged with sodium hydride (910 mg, 22.7 mmol, 60% dispersion in
mineral oil) and dry DMF (50 mL). oisatoic anhydride (5 g, 20.6 mmol) was added
slowly (0.42 g, 4 mmol), followed by dropwise addition of tert-butyl 3-oxobutanoate (3.6 g, 22.7
mmol) ved in 50 mL DMF at room ature. The reaction mixture was heated to 120
°C for 10 minutes. Then the solvent was removed under reduced pressure and the remaining
material was dispersed in water and extracted twice with dichloromethane. The combined
organic layers were dried over sodium sulfate, filtered and reduced in vacuo. The resulting
residue was purified by silica gel flash chromatography (eluent cyclohexane/ethyl acetate
gradient).
Yield: 1.05 g (2.96 mmol, 15% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 10.48 (s, 1H), 8.10 – 8.08 (d, 1H), 8.02 – 7.99 (d, 1H), 7.31 –
7.27 (t, 1H), methyl singulett under DMSO signal, 1.51 (s, 9H).
Step 2
8-bromochloromethylquinolinecarbonyl chloride
A necked flask was d with tert-butyl 8-bromohydroxymethylquinoline
carboxylate (1.2 g, 3,54 mmol)) and phosphorus oxychloride (42 g, 274 mmol) and heated to
reflux for 16 h. The reaction e was reduced in vacuo and used as such in the next step.
Step 3
8-bromochloro-N-[(4S)-3,4-dihydro-2H-chromenyl]methylquinolinecarboxamide
8-Bromochloromethylquinolinecarbonyl de (raw t from step 2) (1 g, 3,13
mmol) was dissolved in 60 mL acetonitril and mixed with (4S)-chromanamine hydrochloride
(582 mg, 3,13 mmol) and triethylamine (951 mg, 9,4 mmol) at 0 °C. The rection e was
allowed to warm to room temperature and stirred until complete conversion. The solvent was
removed under reduced pressure; the remaining solution was extracted twice with
dichloromethane. The combined organic layers were dried over sodium e, filtered and
reduced in vacuo. The resulting residue was purified by silica gel flash chromatography (eluent
cyclohexane/ethyl acetate gradient).
Yield: 766 mg (1.77 mmol, 55% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 9.29 (d, 1H, NH), 8.26 – 8.22 (t, 2H), 7.66 – 7.62 (dd, 1H),
7.38 – 7.36 (d, 1H), 7.20 – 7.16 (t, 1H), 6.97 – 6.93 (t, 1H), 6.82 – 6.80 (d, 1H), 5.32 – 5.28 (m,
1H), 4.34 – 4.29 (m, 1H), 4.23 – 4.17 (m, 1H), 2.71 (s, 3H), 2.28 -2.22 (m, 1H), 2.10 – 2.03 (m,
Step 4
8-bromo-N-[(4S)-3,4-dihydro-2H-chromenyl](dimethylamino)methylquinoline
carboxamide
8-Bromochloro-N-[(4S)-3,4-dihydro-2H-chromenyl]methylquinolinecarboxamide
(step 3) (766 mg, 1.77 mmol) in 30 mL dioxane were distributed to three microwave flasks (20
mL volume). Each of it was charged with 3.7 mL aqueous dimethylamine solution (40%,
combined 8.87 mmol). The reaction es were heated in a microwave oven (Anton Paars
Monowave 400) to 100 °C for 40 minutes. The reaction mixtures were combined and the
solvent was removed under reduced pressure. The ing residue was purified by silica gel
flash chromatography (eluent cyclohexane/ethyl acetate nt).
Yield: 625 mg (1.42 mmol, 73% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 9.07 (d, 1H, NH), 8.08 – 8.02 (2d, 2H), 7.41 – 7.37 (t, 1H),
7.32 – 7.31 (d, 1H), 7.20 – 7.16 (t, 1H), 6.96 – 6.92 (t, 1H), 6.82 – 6.79 (d, 1H), 5.28 – 5.26 (m,
1H), 4.35 – 4.27 (m, 1H), 4.23 – 4.16 (m, 1H), 3.01 (s, 6H), 2.61 (s, 3H), 2.28 – 2.19 (m, 1H),
2.10 – 2.02 (m, 1H).
Step 5
8-(2,3-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](dimethylamino)
methylquinolinecarboxamide (Example 481)
To a degassed (1 min, argon) mixture of o-N-[(4S)-3,4-dihydro-2H-chromenyl]
(dimethylamino)methylquinolinecarboxamide (step 4) (200 mg, 0.45 mmol), (2,3-
dichlorophenyl)boronic acid (130 mg, 0.68 mmol), potassium carbonate (125.5 mg, 0.90
mmol), water (3,5 mL) and dioxane (12 mL) was added 1,1'-
bis(diphenylphosphino)ferrocenepalladium(II) dichloride (18.5 mg, 0.02 mmol). The reaction
mixture was d for 16 h at 85 °C, then cooled down to room temperature, d with water
and extracted twice with dichloromethane. The combined organic layers were dried over
sodium sulfate, filtered and reduced in vacuo. The resulting residue was purified by silica gel
flash chromatography (eluent cyclohexane/ethyl acetate gradient) to obtain the title compound.
Yield: 159 mg (0.31 mmol, 66% of th.)
1H-NMR (400 MHz, DMSO-d6) δ 9.06 (d, 1H, NH), 8.17 – 8.15 (d, 1H), 7.68 – 7.66 (d, 1H),
7.58 – 7.55 (m, 2H), 7.42 – 7.42 (m, 1H), 7.32 – 7.30 (m, 2H), 7.17 – 7.15 (t, 1H), 6.93 – 6.91
(t, 1H), 6.80 – 6.78 (d, 1H), 5.28 – 5.24 (m, 1H), 4.32 – 4.27 (m, 1H), 4.23 – 4.17 (m, 1H), 3.04
(s, 6H), methyl singulett under DMSO signal, 2.24 – 2.18 (m, 1H), 2.08 – 2.02 (m, 1H).
Synthesis of 8-(3,5-dichlorophenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](tetrahydro-
2H-pyranyl)quinolinecarboxamide (Example 539).
Under argon atmosphere 8-(3,5-dichlorphenyl)-N-[(4S)-3,4-dihydro-2H-chromenyl](3,6-
dihydro-2H-pyranyl)chinolincarboxamide (60.0 mg, 113 µmol) was dissolved in ethyl
acetate/ethanol (2:1, 6 ml). The catalyst, 10% palladium on charcoal (20 mg), was added,
argon replaced by hydrogen and the e d under atmospheric pressure of hydrogen
for 4.5 h. More 10% palladium on charcoal (20 mg) was added under argon and
hydrogenation ued under atmospheric pressure for 6 h. The reaction mixture was filtered
over celite, rinsed with ethyl acetate and concentrated in vacuo. The residue (66 mg) was
purified by prep. HPLC (C18, gradient: 0.1% aq. formic acid / acetonitrile).
Yield: 11 mg (18 % of th.)
LC-MS (Method L1): Rt = 1.28 min; MS (ESIpos): m/z = 533 [M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.51), 1.235 , 1.676 (1.54), 1.713 (2.60),
1.751 (1.67), 2.057 (0.97), 2.072 (1.11), 2.085 (1.87), 2.218 (1.33), 2.231 (1.31), 2.240 (1.26),
2.252 (0.92), 2.327 (0.56), 2.366 (0.60), 2.429 , 2.460 (2.25), 2.670 (0.69), 2.710 (0.67),
3.464 (1.07), 3.493 (1.97), 3.520 (2.14), 3.546 (2.15), 3.575 (1.18), 3.738 (1.26), 4.010 ,
4.023 , 4.038 (2.85), 4.219 (0.82), 4.240 (2.21), 4.247 (1.78), 4.260 , 4.268 (2.70),
4.279 (2.21), 4.295 (1.97), 5.293 (0.94), 5.307 (2.08), 5.327 (2.08), 5.342 (0.90), 5.754 (5.00),
6.785 (3.97), 6.804 (4.38), 6.918 , 6.937 (4.07), 6.956 (2.40), 7.158 (2.10), 7.176 (3.37),
7.193 (1.61), 7.405 (3.52), 7.423 (3.20), 7.613 (13.15), 7.617 (16.00), 7.648 (4.20), 7.653
(5.68), 7.748 (2.29), 7.766 (3.65), 7.787 (3.20), 7.856 (4.95), 7.874 , 8.510 (3.43), 8.531
(3.17), 8.777 (12.63), 9.140 (3.54), 9.161 (3.54).
Synthesis of N-[(4S)-3,4-dihydro-2H-chromenyl](methoxymethyl)(2,3,5-
trifluorophenyl)quinolinecarboxamide (Example 686).
Step 1
ethyl 8-bromomethylquinolinecarboxylate
To a solution of ethyl 8-bromohydroxy-quinolinecarboxylate (3.00 g, 9.54 mmol) (Gharat,
g, 9.54 mmol). The mixture was warmed in an oil bath of 60°C, dimethylzink (solution in
toluene, 1.9 ml, 2.0 M, 3.8 mmol) was added dropwise and stirred at this temperature for 1 h.
During a period of 4.5 h more ylzink (solution in toluene, 6.2 ml, 2.0 M, 12.4 mmol) was
added at this temperature in l portions until almost all starting material was consumed
(HPLC monitoring). The mixture was poured into water (250 ml), containing acetic acid (1.8
ml), the organic solvents largely evaporated under diminished pressure and the aqueous
phase extracted with ethylacetate. The combined organic phases were dried and evaporated
to s. The residue (3.1 g) was was purified by column chromatography on silica (100 g),
eluent: cyclohexane / ethyl acetate (3 - 10%) yielding the titel nd (1.25 g, 45% of
theory)
LC-MS (Method L4): Rt = 3.06 min; MS (ESIpos): m/z = 294 [M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.369 (4.76), 1.387 (9.98), 1.405 , 2.934 (16.00),
4.393 (1.57), 4.411 (4.77), 4.429 (4.71), 4.447 (1.51), 7.615 (1.30), 7.634 (2.23), 7.655 (1.46),
8.253 (1.85), 8.271 (1.76), 8.340 , 8.361 (1.99), 9.185 (3.32).
Step 2
ethyl 8-bromo(bromomethyl)quinolinecarboxylate
Ethylbromomethylquinolinecarboxylate (1.50 g, 5.10 mmol) was dissolved in THF (23
ml). Phenyltrimethylammonium tribromide (3.07 g, 8.16 mmol,) and acetic acid (1.5 ml, 25
mmol) were added and the mixture stirred at ambient temperature.
More phenyltrimethylammonium tribromide (0.96 g, 2.5 mmol) was added and stirred for 3 d at
ambuient temperature. Another portion of phenyltrimethylammonium mide (0.96 g, 2.5
mmol) and acetic acid (0.9 ml, 15,3 mmol) were added and stirring continued ght. The
on mixture was diluted with water and romethane. The aqueous phase was
extracted with dichloromethane and the combined organic layers were washed with an
aqueous sodium hydrogencarbonate solution, dried and concentrated in vacuo at 30°C.
The residue was stirred for 1 h in MTBE (80 ml ). The solid was filtered off, washed with MTBE
and dried in vacuo. The crude (3.23 g) was purified by column chromatography, eluent
cyclohexane/ethyl acetate (3 – 22 %).
Yield: 985 mg (90.5 % purity, 47 % of th.)
LC-MS (Method L1): Rt = 1.11 min; MS (ESIpos): m/z = 371 [M+H]+
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.401 (7.41), 1.415 (16.00), 1.429 , 1.435 (0.41),
4.441 (2.26), 4.455 (7.12), 4.470 (6.98), 4.484 (2.13), 5.479 (11.96), 5.758 (1.31), 7.721 (2.28),
7.736 (2.76), 7.738 (2.62), 7.753 (2.43), 8.311 (2.94), 8.314 (3.02), 8.326 (2.85), 8.329 (2.69),
8.446 (2.62), 8.448 (2.54), 8.463 (2.57), 8.465 (2.29), 9.311 .
Step 3
8-bromo(methoxymethyl)quinolinecarboxylic acid
A suspension of ethyl 8-bromo(bromomethyl)quinolinecarboxylate (1.14 g, 3.06 mmol) in
methanol (15 ml) was treated dropwise with sodium methoxide (solution in methanol, 5.4 M) at
t temperature during which dissolution occurred and later a solid precipitated. After 1.5
h THF (5 ml) and water (3 ml) were added and stirring continued over night at ambient
ature. The solution was then diluted with 20 mL of water and the pH was adjusted to 4
by addition of acetic acid (5 M). After concentration in vacuo to remove most of the organic
ts the remaining mixture was distributed between ethyl acetate and water. The aqueous
layer was extracted several times with ethyl acetate and the combined organic layers were
dried and trated in vacuo. This material (363 mg, 91% purity, 37% of theory) was
suitable for further use. The aqueous phase war concentrated to a small volume under
reduced pressure, diluted with DMSO and purified by prep. HPLC (C18, gradient: 0.1% aq.
formic acid / acetonitrile) yielding a second crop (270 mg, 100% purity, 30% of ).
LC-MS (Method L1): Rt = 0.69 min; MS (ESIpos): m/z = 296 [M+H]+
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.221 , 3.184 (0.52), 5.199 (16.00), 7.611 (3.54),
7.627 (5.28), 7.643 (3.76), 8.238 (4.81), 8.252 (4.56), 8.351 (4.61), 8.367 (4.38), 9.215 (10.02).
Step 4
8-bromo-N-[(4S)-3,4-dihydro-2H-chromenyl](methoxymethyl)quinolinecarboxamide
A solution of 8-bromo(methoxymethyl)quinolinecarboxylic acid (360 mg, 1.22 mmol) in
THF (6 ml) was treated with (4S)-chromanamine hloride (1:1) and trimethylamine
(680 µl, 4.9 mmol). The mixture was warmed to 45°C, 2,4,6-tripropyl-1,3,5,2,4,6-
trioxatriphosphinane 2,4,6-trioxide (solution in ethyl acetate, 23 ml, 50 % t, 39 mmol)
was added, the heating removed and the mixture stirred at ambient temperature overnight.
After dilution with water (pH 8-9) the THF was removed in vacuo. The precipitate was filtered
off and dissolved in approx. 10 ml of warm acetone. Warm water was added (10 mL) and the
mixture was d to cool to RT. The solid was filtered off, washed with acetone/water (1:2)
and dried in vacuo.
Yield: 391 mg (95 % purity, 72 % of th.)
LC-MS (Method L1): Rt = 0.96 min; MS (ESIpos): m/z = 427 [M+H]+
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.235 (0.52), 2.090 (2.20), 2.230 (2.15), 3.287 (16.00),
4.241 (2.66), 4.293 (2.83), 4.998 (8.92), 5.314 (2.68), 6.800 , 6.811 (3.13), 6.943 (3.04),
7.183 (3.03), 7.397 (3.01), 7.612 (3.03), 8.211 (2.99), 8.221 (3.08), 8.311 (2.87), 8.324 (2.94),
8.998 (4.49), 9.207 (2.80).
Step 5
N-[(4S)-3,4-dihydro-2H-chromenyl](methoxymethyl)(2,3,5-trifluorophenyl)quinoline
carboxamide (Example 686)
Under argon a vessel was charged with 8-bromo-N-[(4S)-3,4-dihydro-2H-chromenyl]
(methoxymethyl)quinolinecarboxamide (90 mg, 211 µmol), 2,3,5-trifluorobenzene boronic
acid (55.6 mg, 316 µmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride
dichloromethane complex (8.60 mg, 10.5 µmol), potassium carbonate (58.2 mg, 421 µmol) and
with a degassed 5:1 mixture of dioxan and water (0.73 ml). The mixture was stirred overnight
at 70°C. It was diluted with ethyl acetate, filtered through a sodium sulfate plug and
trated in vacuo. The crude was purified by prep. HPLC (C18, gradient: 0.1% aq. formic
acid / acetonitrile.
Yield: 31 mg (31 % of th.)
LC-MS (Method L1): Rt = 1.14 min; MS (ESIpos): m/z = 479 [M+H]+
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 (1.04), 2.043 (0.47), 2.048 , 2.053 (0.96),
2.058 (1.04), 2.065 (1.12), 2.069 (1.07), 2.077 (1.37), 2.081 (1.20), 2.087 (2.11), 2.092 (0.63),
2.193 (0.58), 2.199 , 2.202 (0.81), 2.207 (1.32), 2.213 (0.97), 2.216 (1.31), 2.221 (1.32),
2.230 (0.99), 2.236 (0.64), 2.239 (0.62), 2.244 (0.46), 2.793 (0.55), 3.345 (8.00), 4.220 (0.71),
4.225 (0.87), 4.234 , 4.239 (2.32), 4.244 (1.61), 4.253 (1.77), 4.258 (1.47), 4.268 (1.42),
4.273 , 4.279 (1.58), 4.285 , 4.292 (0.78), 4.298 (0.84), 4.303 (0.65), 5.037 (16.00),
.287 (0.91), 5.297 (1.95), 5.310 (1.96), 5.320 , 6.790 (3.66), 6.791 (3.76), 6.803 (4.00),
6.804 (3.99), 6.917 (1.85), 6.918 (1.84), 6.929 (3.75), 6.931 (3.68), 6.942 (2.14), 6.943 (2.05),
7.159 (1.78), 7.161 , 7.173 (3.01), 7.184 (1.56), 7.187 (1.49), 7.259 (1.51), 7.267 (1.49),
7.274 , 7.376 (3.08), 7.388 (2.95), 7.609 (0.49), 7.614 , 7.619 (0.75), 7.624 (1.18),
7.628 (1.14), 7.633 (1.23), 7.638 (1.18), 7.642 (1.18), 7.646 , 7.651 (0.65), 7.657 (0.56),
7.800 (2.66), 7.812 (3.85), 7.814 (3.18), 7.826 (3.61), 7.873 (4.17), 7.875 , 7.885 (3.06),
7.887 (2.94), 8.416 (3.61), 8.418 (3.65), 8.430 (3.48), 8.432 (3.27), 8.890 (12.74), 9.184 (3.52),
9.197 (3.43).
Synthesis of )-3,4-dihydro-2H-chromenyl](oxetanyl)(2,3,5-
trifluorophenyl)quinolinecarboxamide (example 660).
In a 100 mL round bottom flask, a mixture of ro-N-[(4S)-3,4-dihydro-2H-chromenyl]
(2,3,5-trifluorophenyl)quinolinecarboxamide (500 mg, 1.066 mmol), anhydrous m
hydroxide (51 mg, 2.133 mmol), 3-bromooxetane (0.133 mL, 1.600 mmol), [4,4′-bis(1,1-
dimethylethyl)-2,2′-bipyridine-N1,N1′]bis[3,5-difluoro[5-(trifluoromethyl)pyridinyl-N]phenyl-
C] iridium(III) hexafluorophosphate (24 mg, 0.021 mmol) and tris(trimethylsilyl)silane (0.329
mL, 1.066 mmol) in 1,2-dimethoxyethane (20 mL) was degassed by purging with argon. In a
50 mL round bottom flask, a mixture of nickel(II) chloride ethylene glycol dimethyl ether
complex (14 mg, 0.064 mmol) and 4,4'-di-tert-butyl-2,2'-bipyridine (17 mg, 0.064 mmol) in 1,2-
dimethoxyethane (10 mL) was gently warmed with a heatgun, purged with argon and stirred for
five minutes. By syringe half of this nickel-catalyst mixture (5 mL) was added to the reaction
mixture. The resulting suspension was purged with argon for five minutes and was
subsequently stirred under irradiation with blue LED light for 18 h while cooling with a fan. The
reaction mixture was diluted with dichloromethane (30 mL). Water (10 mL) was added and the
layers were separated. The aqueous layer was extracted with dichloromethane (2x10 mL).
ed organic layers were dried with sodium sulfate and solvents were removed in vacuo.
Purification by flash column chromatography (80 g; heptane, 10%-60% ethyl acetate) and
preparative HPLC (Method 11) afforded 0.054 g (0.110 mmol; 10% of theory) of the title
compound.
LC-MS d 2): Rt = 3.65 min; m/z = 491 (M+H)+
1H-NMR (400 MHz, DMSO-d
6) δ 9.26 (d, J = 8.1 Hz, 1H), 8.87 (s, 1H), 7.91 – 7.87 (m, 1H),
7.84 – 7.73 (m, 2H), 7.70 – 7.57 (m, 1H), 7.35 (d, J = 7.8 Hz, 1H), 7.30 – 7.23 (m, 1H), 7.19 (t,
J = 7.8 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 5.31 – 5.11 (m, 4H), 4.84 –
4.70 (m, 2H), 4.34 – 4.21 (m, 2H), 2.25 – 2.15 (m, 1H), 2.08 – 2.01 (m, 1H).
TABLE 1: Examples
Number R1 R2 R3 R4 R5 R6 Q A
(1S)-1,2,3,4-
1 H chloro H H H H tetrahydronaphth
dimethylphenyl
(1S)-1,2,3,4-
2 H chloro H H H H tetrahydronaphth
dichlorophenyl
alenyl
3,5- (1S)-2,3-dihydro-
3 H chloro H H H H
dichlorophenyl 1H-indenyl
3,5- (4S)-3,4-dihydro-
4 H chloro H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
H chloro H H H H rophenyl
2H-chromenyl
(1S)-2,3-dihydro-
6 H chloro H H H H 3-chlorophenyl
1H-indenyl
2,3- (4S)-3,4-dihydro-
7 H chloro H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
8 H dimethylamino H H H H
dichlorophenyl 2H-chromenyl
3,5- (1S)-2,3-dihydro-
9 H dimethylamino H H H H
dichlorophenyl 1H-indenyl
2-chloro (4S)-3,4-dihydro-
H dimethylamino H H H H
phenyl 2H-chromenyl
3,5- (1S)-2,3-dihydro-
11 H ylamino H H methyl H
dichlorophenyl enyl
3,5- (4S)-3,4-dihydro-
12 H dimethylamino H H methyl H
dichlorophenyl 2H-chromenyl
3,5-dichloro (4S)-3,4-dihydro-
13 H dimethylamino H H H H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
14 H pyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
H dimethylamino H H H H
ylphenyl 2H-chromenyl
(1S)-1,2,3,4-
16 H dimethylamino H H H H tetrahydronaphth
rophenyl
alenyl
3,5- (4S)-3,4-dihydro-
17 H morpholinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
18 H dimethylamino H methyl H H
dichlorophenyl omenyl
3,5- ,3-dihydro-
19 H dimethylamino H methyl H H
dichlorophenyl 1H-indenyl
(1S)-1,2,3,4-
H linyl H H H H tetrahydronaphth
dichlorophenyl
alenyl
3,5- (1S)-2,3-dihydro-
21 H dimethylamino H fluoro H H
dichlorophenyl enyl
3,5- (4S)-3,4-dihydro-
22 H dimethylamino H fluoro H H
dichlorophenyl 2H-chromenyl
3,5-dichloro (4S)-3,4-dihydro-
23 H methylamino H H H H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
24 H methylamino H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
H morpholinyl H H H H 3-chlorophenyl
2H-chromenyl
3,5- (4S)-3,4-dihydro-
26 H 1H-imidazolyl H H H H
rophenyl 2H-chromenyl
(1S)-2,3-dihydro-1H-inden (1S)-2,3-dihydro-
27 H H H H H 3-chlorophenyl
ylamino 1H-indenyl
(1S)-2,3-dihydro-1H-inden 2,3- (1S)-2,3-dihydro-
28 H H H H H
ylamino dichlorophenyl 1H-indenyl
2-chloro (4S)-3,4-dihydro-
29 H dimethylamino H H H H
fluorophenyl 2H-chromenyl
3,4- (4S)-3,4-dihydro-
H dimethylamino H H H H
difluorophenyl 2H-chromenyl
4-fluoro (4S)-3,4-dihydro-
31 H dimethylamino H H H H
methoxyphenyl 2H-chromenyl
2,4-difluoro ,4-dihydro-
32 H dimethylamino H H H H
methoxyphenyl 2H-chromenyl
3-fluoro (4S)-3,4-dihydro-
33 H dimethylamino H H H H
methylphenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
34 H dimethylamino H H H H
dichlorophenyl 2H-chromenyl
(1S)-2,3-dihydro-
H morpholinyl H H H H 3-chlorophenyl
1H-indenyl
3-chloro (4S)-3,4-dihydro-
36 H dimethylamino H H H H
methylphenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
37 H dimethylamino H H H H
fluorophenyl 2H-chromenyl
2,4,6-trifluoro (4S)-3,4-dihydro-
38 H ylamino H H H H
methoxyphenyl 2H-chromenyl
3-chloro
(4S)-3,4-dihydro-
39 H ylamino H H H H (trifluoromethyl)
2H-chromenyl
phenyl
3,5- (4S)-3,4-dihydro-
40 H dimethylamino H H fluoro H
dichlorophenyl 2H-chromenyl
3,5-dichloro (4S)-3,4-dihydro-
41 H dimethylamino H H fluoro H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
42 H morpholinyl H H fluoro H
rophenyl 2H-chromenyl
3,5-dichloro (4S)-3,4-dihydro-
43 H morpholinyl H H fluoro H
fluorophenyl 2H-chromenyl
3-chloro ,4-dihydro-
44 H ylamino H H H H
methylphenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
45 H dimethylamino H H H H
phenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
46 H dimethylamino H H H H
fluorophenyl 2H-chromenyl
3,4,5- (4S)-3,4-dihydro-
47 H dimethylamino H H H H
trifluorophenyl omenyl
2-fluoro
(4S)-3,4-dihydro-
48 H dimethylamino H H H H (trifluoromethox
2H-chromenyl
y)phenyl
3,5- (4S)-3,4-dihydro-
49 H dimethylamino H H H H
difluorophenyl 2H-chromenyl
2-fluoro
(4S)-3,4-dihydro-
50 H dimethylamino H H H H (trifluoromethyl)
2H-chromenyl
phenyl
3-chloro (4S)-3,4-dihydro-
51 H dimethylamino H H H H
phenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
52 H morpholinyl H H H H
dichlorophenyl 2H-chromenyl
2,4-difluoro (4S)-3,4-dihydro-
53 H morpholinyl H H H H
methoxyphenyl 2H-chromenyl
chloro (4S)-3,4-dihydro-
54 H morpholinyl H H H H
fluorophenyl 2H-chromenyl
3-fluoro (4S)-3,4-dihydro-
55 H dimethylamino H H H H
methoxyphenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
56 H dimethylamino H H H H
methylphenyl 2H-chromenyl
2,4,5- (4S)-3,4-dihydro-
57 H dimethylamino H H H H
trifluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
58 H amino H H H H
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
59 H benzyl(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
60 H dimethylamino H H H H
fluorophenyl 2H-chromenyl
ro ,4-dihydro-
61 H dimethylamino H H H H
methylphenyl 2H-chromenyl
3-fluoropyridin- (4S)-3,4-dihydro-
62 H dimethylamino H H H H
2-yl 2H-chromenyl
2-fluoropyridin- (4S)-3,4-dihydro-
63 H dimethylamino H H H H
4-yl 2H-chromenyl
,4-dihydro-
64 H dimethylamino H H H H methoxypyridin-
2H-chromenyl
2-chloropyridin- (4S)-3,4-dihydro-
65 H dimethylamino H H H H
4-yl 2H-chromenyl
(4S)-3,4-dihydro-
66 H dimethylamino H H H H dimethylpyridin-
2H-chromenyl
3,5- (4S)-3,4-dihydro-
67 H lamino H H H H
dichlorophenyl 2H-chromenyl
4-(trifluoromethyl)-1H- 3,5- (4S)-3,4-dihydro-
68 H H H H H
pyrazolyl dichlorophenyl 2H-chromenyl
3,5- ,3-dihydro-
69 H 1H-pyrazolylamino H H H H
dichlorophenyl 1H-indenyl
(4S)-3,4-dihydro-
70 H dimethylamino H H H H (dimethylamino)
2H-chromenyl
phenyl
1-methyl-1H-
(4S)-3,4-dihydro-
71 H dimethylamino H H H H benzimidazol
2H-chromenyl
3,5- (4S)-3,4-dihydro-
72 H 1H-pyrazolyl H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
73 H ylamino H H H H 1H-indolyl
2H-chromenyl
3,5- (4S)-3,4-dihydro-
74 H (2-hydroxyethyl)amino H H H H
dichlorophenyl 2H-chromenyl
(2- 3,5- (4S)-3,4-dihydro-
75 H H H H H
methoxyethyl)(methyl)amino dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
76 H (2-methoxyethyl)amino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
77 H 4-oxoimidazolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
78 H bis(2-methoxyethyl)amino H H H H
rophenyl 2H-chromenyl
3,5- ,3-dihydro-
79 H pyrrolidinyl H H H H
dichlorophenyl enyl
3,5- (1S)-2,3-dihydro-
80 H (2S)carboxypyrrolidinyl H H H H
dichlorophenyl 1H-indenyl
2,3,4- (4S)-3,4-dihydro-
81 H dimethylamino H H H H
trifluorophenyl 2H-chromenyl
2,3,4- (4S)-3,4-dihydro-
82 H morpholinyl H H H H
trifluorophenyl 2H-chromenyl
2-fluoro
(4S)-3,4-dihydro-
83 H morpholinyl H H H H (trifluoromethox
2H-chromenyl
y)phenyl
3,5- (1S)-2,3-dihydro-
84 H (3R)aminopyrrolidinyl H H H H
dichlorophenyl 1H-indenyl
3,4-dihydroisoquinolin-2(1H)- 3,5- (1S)-2,3-dihydro-
85 H H H H H
yl dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
86 H anilino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
87 H isobutyl(methyl)amino H H H H
rophenyl 1H-indenyl
[2- 3,5- ,3-dihydro-
88 H H H H H
hylamino)ethyl]amino dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
89 H (2-methoxyethyl)amino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
90 H ethyl(2-methoxyethyl)amino H H H H
dichlorophenyl 1H-indenyl
(2S)
3,5- (1S)-2,3-dihydro-
91 H (methoxymethyl)pyrrolidin H H H H
dichlorophenyl 1H-indenyl
(2R)
3,5- (1S)-2,3-dihydro-
92 H (methoxymethyl)pyrrolidin H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
93 H methoxyethyl)amino H H H H
rophenyl 1H-indenyl
(3S)
3,5- ,3-dihydro-
94 H (dimethylamino)pyrrolidin H H H H
dichlorophenyl 1H-indenyl
tetrahydro-2H-pyran 3,5- (1S)-2,3-dihydro-
95 H H H H H
ylamino dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
96 H [2-(pyrrolidinyl)ethyl]amino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
97 H -trifluoropropyl)amino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
98 H morpholinylamino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
99-1 H (pyridinylmethyl)amino H H H H
dichlorophenyl 1H-indenyl
[(2R)hydroxybutan 3,5- (1S)-2,3-dihydro-
99-2 H H H H H
no dichlorophenyl enyl
3,5- (1S)-2,3-dihydro-
100 H (2-hydroxyethyl)amino H H H H
dichlorophenyl 1H-indenyl
3,5- ,3-dihydro-
101 H (3R)hydroxypyrrolidinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
102 H 3-hydroxyazetidinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
103 H rolidinyl)azetidinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
104 H cyclopropyl(ethyl)amino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
105 H cyclobutyl(methyl)amino H H H H
dichlorophenyl 1H-indenyl
(cyclopropylmethyl)(methyl)a 3,5- (1S)-2,3-dihydro-
106 H H H H H
mino dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
107 H 2,2-dimethylmorpholinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
108 H 1,2-oxazolidinyl H H H H
dichlorophenyl 1H-indenyl
(2S)methyl-2,3-dihydro- 3,5- (1S)-2,3-dihydro-
109 H H H H H
olyl dichlorophenyl 1H-indenyl
(2,2,2- 3,5- (1S)-2,3-dihydro-
110 H H H H H
trifluoroethyl)amino dichlorophenyl enyl
3,5- (1S)-2,3-dihydro-
111 H 1,3-dihydro-2H-isoindolyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
112 H 3,3-difluoropyrrolidinyl H H H H
dichlorophenyl 1H-indenyl
-carbamoylpyrrolidin 3,5- (1S)-2,3-dihydro-
113 H H H H H
yl dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
114 H methyl(1-phenylethyl)amino H H H H
rophenyl 1H-indenyl
(3-amino 3,5- (1S)-2,3-dihydro-
115 H H H H H
oxopropyl)(methyl)amino dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
116 H 4-acetylpiperazinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
117 H 1,1-dioxidothiomorpholinyl H H H H
rophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
118 H benzyl(methyl)amino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
119 H 3-fluoroazetidinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
120 H 3-methylazetidinyl H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
121 H 3,3-difluoroazetidinyl H H H H
dichlorophenyl enyl
[3-(dimethylamino) 3,5- (1S)-2,3-dihydro-
122 H H H H H
oxopropyl]amino dichlorophenyl 1H-indenyl
[(5-methyl-1,2,4-oxadiazol 3,5- (1S)-2,3-dihydro-
123 H H H H H
yl)methyl]amino dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
124 H (3-aminooxopropyl)amino H H H H
dichlorophenyl 1H-indenyl
[2-(1H-pyrazol 3,5- (1S)-2,3-dihydro-
125 H H H H H
yl)ethyl]amino dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
126 H (2-acetamidoethyl)amino H H H H
dichlorophenyl 1H-indenyl
[(2S)aminooxopropan- 3,5- (1S)-2,3-dihydro-
127 H H H H H
2-yl]amino dichlorophenyl 1H-indenyl
3,5- ,3-dihydro-
128 H (2-methoxyoxoethyl)amino H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
129 H (2-aminooxoethyl)amino H H H H
dichlorophenyl 1H-indenyl
(4S)-3,4-dihydro-
130 H dimethylamino H H H H 3-chlorophenyl
2H-chromenyl
3,5- (4S)-3,4-dihydro-
131 H methoxyamino H H H H
dichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
132 H dimethylamino H H H H
trichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
133 H morpholinyl H H H H
trichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
134 H methylamino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
135 H azetidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
136 H pyridinylamino H H H H
dichlorophenyl 2H-chromenyl
(2-ethoxy 3,5- (4S)-3,4-dihydro-
137 H H H H H
oxoethyl)(methyl)amino dichlorophenyl 2H-chromenyl
(2- 3,5- (4S)-3,4-dihydro-
138 H H H H H
hydroxyethyl)(methyl)amino dichlorophenyl omenyl
3,4- (4S)-3,4-dihydro-
139 H dimethylamino H fluoro H H
dichlorophenyl 2H-chromenyl
3,4- (4S)-3,4-dihydro-
140 H dimethylamino H fluoro H H
difluorophenyl omenyl
,4-dihydro-
141 H ylamino H fluoro H H 3-chlorophenyl
2H-chromenyl
3,5- (4S)-3,4-dihydro-
142 H morpholinyl H fluoro H H
difluorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
143 H morpholinyl H fluoro H H
fluorophenyl 2H-chromenyl
3,4- (4S)-3,4-dihydro-
144 H morpholinyl H H fluoro H
dichlorophenyl omenyl
3,4- ,4-dihydro-
145 H dimethylamino H H fluoro H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
146 H dimethylamino H H fluoro H
dichlorophenyl 2H-chromenyl
(4S)methoxy-
147 H ylamino H H H H 3,4-dihydro-2H-
dichlorophenyl
chromenyl
(1S)methoxy-
148 H dimethylamino H H H H 2,3-dihydro-1H-
dichlorophenyl
methyl[2-(morpholin 3,5- (4S)-3,4-dihydro-
149 H H H H H
yl)ethyl]amino dichlorophenyl 2H-chromenyl
xymethyl)(methyl) 3,5- (4S)-3,4-dihydro-
150 H H H H H
amino dichlorophenyl 2H-chromenyl
(dimethylamino) (4S)-3,4-dihydro-
151 H dimethylamino H H H H
-2,4- 2H-chromenyl
difluorophenyl
(4S)fluoro-3,4-
152 H dimethylamino H H H H dihydro-2H-
dichlorophenyl
chromenyl
3,5- (4S)-3,4-dihydro-
153 H ethylamino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
154 H 2-acetylhydrazino H H H H
rophenyl 2H-chromenyl
3-chloro ,4-dihydro-
155 H morpholinyl H fluoro H H
fluorophenyl 2H-chromenyl
3,4- (4S)-3,4-dihydro-
156 H morpholinyl H fluoro H H
dichlorophenyl 2H-chromenyl
3,4- (4S)-3,4-dihydro-
157 H morpholinyl H fluoro H H
difluorophenyl 2H-chromenyl
3,4- (4S)-3,4-dihydro-
158 H morpholinyl H H fluoro H
difluorophenyl omenyl
(4S)-3,4-dihydro-
159 H morpholinyl H H fluoro H 3-chlorophenyl
2H-chromenyl
3-chloro (4S)-3,4-dihydro-
160 H morpholinyl H H fluoro H
fluorophenyl omenyl
ro (4S)-3,4-dihydro-
161 H morpholinyl H H fluoro H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
162 H morpholinyl H H fluoro H
difluorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
163 H morpholinyl H H fluoro H
fluorophenyl 2H-chromenyl
-chloro ,4-dihydro-
164 H morpholinyl H H fluoro H
fluorophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
165 H morpholinyl H H fluoro H
fluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
166 H morpholinyl H H fluoro H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
167 H morpholinyl H fluoro H H 3-chlorophenyl
2H-chromenyl
3,5- (4S)-3,4-dihydro-
168 H dimethylamino H fluoro H H
difluorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
169 H ylamino H fluoro H H
fluorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
170 H morpholinyl H fluoro H H
fluorophenyl 2H-chromenyl
3-chloro ,4-dihydro-
171 H dimethylamino H fluoro H H
fluorophenyl omenyl
2-chloro (4S)-3,4-dihydro-
172 H dimethylamino H fluoro H H
fluorophenyl omenyl
3,4- (4S)-3,4-dihydro-
173 H dimethylamino H H fluoro H
difluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
174 H dimethylamino H H fluoro H 3-chlorophenyl
omenyl
3-chloro (4S)-3,4-dihydro-
175 H dimethylamino H H fluoro H
fluorophenyl 2H-chromenyl
2-chloro ,4-dihydro-
176 H dimethylamino H H fluoro H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
177 H dimethylamino H H fluoro H
rophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
178 H dimethylamino H H fluoro H
fluorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
179 H dimethylamino H H fluoro H
fluorophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
180 H dimethylamino H H fluoro H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
181 H rpholinyl H H H H
dichlorophenyl omenyl
(2-tert-butoxy 3,5- (4S)-3,4-dihydro-
182 H H H H H
oxoethyl)amino dichlorophenyl 2H-chromenyl
(2-tert-butoxy 3,5- (4S)-3,4-dihydro-
183 H H H H H
oxoethyl)(methyl)amino dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
184 H propylamino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
185 H (2-aminoethyl)amino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
186 H (3R)hydroxypyrrolidinyl H H H H
rophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
187 H (3S)hydroxypyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
188 H ,3-triazolyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
189 H 2H-1,2,3-triazolyl H H H H
dichlorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
190 H morpholinyl H H H H
fluorophenyl 2H-chromenyl
-chloro-2,4- (4S)-3,4-dihydro-
191 H morpholinyl H H H H
difluorophenyl omenyl
3,5- (4S)-3,4-dihydro-
192 H morpholinyl H fluoro H H
dichlorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin chloro (4S)-3,4-dihydro-
193 H H H H H
yl fluorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 2,3- (4S)-3,4-dihydro-
194 H H H H H
yl dichlorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 5-chloro-2,4- (4S)-3,4-dihydro-
195 H H H H H
yl difluorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 3-chloro (4S)-3,4-dihydro-
196 H H H H H
yl fluorophenyl 2H-chromenyl
-chloro-2,4- (4S)-3,4-dihydro-
197 H dimethylamino H H H H
difluorophenyl 2H-chromenyl
meth 3,5- (4S)-3,4-dihydro-
198 dimethylamino H H H H
yl dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
199 H methyl(phenyl)amino H H H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
200 H morpholinyl H fluoro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
201 H 3,3-difluoropyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
202 H 3-oxopyrazolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
203 H 1,1-dioxidothiomorpholinyl H H H H
dichlorophenyl 2H-chromenyl
2,3-dihydro ,4-dihydro-
204 H linyl H H H H
benzofuranyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
205 H linyl H chloro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
206 H morpholinyl H chloro H H
dichlorophenyl 2H-chromenyl
2,3- ,4-dihydro-
207 H dimethylamino H chloro H H
dichlorophenyl omenyl
3,5- (4S)-3,4-dihydro-
208 H dimethylamino H chloro H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
209 H morpholinyl H H H fluoro
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
210 H morpholinyl H H H fluoro
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
211 H linyl H H chloro H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
212 H morpholinyl H H chloro H
rophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
213 H dimethylamino H H chloro H
dichlorophenyl omenyl
2,3- (4S)-3,4-dihydro-
214 H morpholinyl H H H methyl
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
215 H morpholinyl H H H methyl
dichlorophenyl 2H-chromenyl
(methoxycarbo (4S)-3,4-dihydro-
216 H morpholinyl H H H H
nyl)-1,3- 2H-chromenyl
benzoxazolyl
3,5- (4S)-3,4-dihydro-
217 H ylamino H H H methyl
dichlorophenyl 2H-chromenyl
2,3- ,4-dihydro-
218 H dimethylamino H H H methyl
dichlorophenyl 2H-chromenyl
2,4-difluoro (4S)-3,4-dihydro-
219 H dimethylamino H H H H
hydroxyphenyl 2H-chromenyl
3-fluoro (4S)-3,4-dihydro-
220 H morpholinyl H H H H
methylphenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
221 H linyl H H H H
fluorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
222 H morpholinyl H H H H
trifluorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 5-chloro (4S)-3,4-dihydro-
223 H H H H H
yl fluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
224 H morpholinyl H H H H benzothiazol
2H-chromenyl
3-fluoro (4S)-3,4-dihydro-
225 H morpholinyl H H H H
methylphenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
226 H morpholinyl H H H H
fluorophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
227 H morpholinyl H H H H
fluorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
228 H morpholinyl H H H H
methoxyphenyl 2H-chromenyl
(4S)-3,4-dihydro-
229 H methylamino H H H H 3-chlorophenyl
2H-chromenyl
2,5-difluoro (4S)-3,4-dihydro-
230 H morpholinyl H H H H
methoxyphenyl omenyl
ro
(4S)-3,4-dihydro-
231 H morpholinyl H H H H fluoro
2H-chromenyl
methylphenyl
3,4-difluoro (4S)-3,4-dihydro-
232 H morpholinyl H H H H
methoxyphenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
233 H morpholinyl H trifluoromethyl H H
rophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
234 H morpholinyl H H H H
difluorophenyl 2H-chromenyl
3-chloro
(4S)-3,4-dihydro-
235 H morpholinyl H H H H (trifluoromethyl)
2H-chromenyl
phenyl
3-chloro (4S)-3,4-dihydro-
236 H methylamino H H H H
phenyl omenyl
2,3,5- (4S)-3,4-dihydro-
237 H amino H H H H
trichlorophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
238 H linyl H H H H
fluorophenyl 2H-chromenyl
-chloro
(4S)-3,4-dihydro-
239 H morpholinyl H H H H
2H-chromenyl
methylphenyl
3-chloro
(4S)-3,4-dihydro-
240 H morpholinyl H H H H fluoro
2H-chromenyl
methylphenyl
(2S)(tert-
3,5- (1S)-2,3-dihydro-
241 H butoxycarbonyl)pyrrolidin H H H H
dichlorophenyl 1H-indenyl
(2S)(tert-
3,5- (4S)-3,4-dihydro-
242 H butoxycarbonyl)pyrrolidin H H H H
dichlorophenyl 2H-chromenyl
(2R)(tert-
3,5- ,4-dihydro-
243 H butoxycarbonyl)pyrrolidin H H H H
rophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 3-fluoro (4S)-3,4-dihydro-
244 H H H H H
yl methylphenyl 2H-chromenyl
hydroxypyrrolidin 3,4-difluoro (4S)-3,4-dihydro-
245 H H H H H
yl methoxyphenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 2,5-difluoro (4S)-3,4-dihydro-
246 H H H H H
yl methoxyphenyl 2H-chromenyl
2,3,6- (4S)-3,4-dihydro-
247 H ylamino H H H H
trifluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
248 H methoxy(methyl)amino H H H H 2-chlorophenyl
2H-chromenyl
2,3- (4S)-3,4-dihydro-
249 H methoxy(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
250 H methoxy(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
251 H morpholinyl H H H H benzothiazol
2H-chromenyl
(4S)-3,4-dihydro-
252 H cyclopropyl(methyl)amino H H H H 2-chlorophenyl
2H-chromenyl
2,3- (4S)-3,4-dihydro-
253 H cyclopropyl(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
254 H cyclopropyl(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
255 H (methoxycarbonyl)pyrrolidin- H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
256 H dimethylamino H trifluoromethyl H H
dichlorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 3,5- (4S)-3,4-dihydro-
257 H H H H H
yl difluorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 2-chloro (4S)-3,4-dihydro-
258 H H H H H
yl fluorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 2-chloro (4S)-3,4-dihydro-
259 H H H H H
yl phenyl 2H-chromenyl
(3rac)hydroxypyrrolidin (4S)-3,4-dihydro-
260 H H H H H 3-chlorophenyl
yl 2H-chromenyl
hydroxypyrrolidin 3-chloro (4S)-3,4-dihydro-
261 H H H H H
yl methoxyphenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 3-chloro (4S)-3,4-dihydro-
262 H H H H H
yl phenyl omenyl
(2R)
3,5- (4S)-3,4-dihydro-
263 H (methoxycarbonyl)pyrrolidin- H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
264 H 2,2-dimethylpyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
265 H ethylamino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
266 H (2S)carboxypyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
267 H morpholinyl H H H H
methoxyphenyl 2H-chromenyl
-fluoro (4S)-3,4-dihydro-
268 H morpholinyl H H H H
methoxyphenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 5-chloro (4S)-3,4-dihydro-
269 H H H H H
yl methoxyphenyl 2H-chromenyl
hydroxypyrrolidin 5-fluoro ,4-dihydro-
270 H H H H H
yl methoxyphenyl 2H-chromenyl
3-chloro
(3rac)hydroxypyrrolidin (4S)-3,4-dihydro-
271 H H H H H (trifluoromethyl)
yl 2H-chromenyl
phenyl
-chloro
(3rac)hydroxypyrrolidin (4S)-3,4-dihydro-
272 H H H H H fluoro
yl 2H-chromenyl
methylphenyl
3,5- (4S)-3,4-dihydro-
273 H cyclopropylamino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
274 H (2R)carboxypyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3-chloro
(3rac)hydroxypyrrolidin (4S)-3,4-dihydro-
275 H H H H H fluoro
yl 2H-chromenyl
methylphenyl
3,5- (4S)-3,4-dihydro-
276 H (carboxylatomethyl)amino H H H H
dichlorophenyl omenyl
2,6- (4S)-3,4-dihydro-
277 H ylamino H H H H
difluorophenyl 2H-chromenyl
2,6- (4S)-3,4-dihydro-
278 H morpholinyl H fluoro H H
difluorophenyl 2H-chromenyl
2,6- (4S)-3,4-dihydro-
279 H dimethylamino H fluoro H H
difluorophenyl 2H-chromenyl
nzoxazol- ,4-dihydro-
280 H morpholinyl H H H H
7-yl 2H-chromenyl
(3S)
3,5- (4S)-3,4-dihydro-
281 H (methoxycarbonyl)pyrrolidin- H H H H
rophenyl 2H-chromenyl
(3R)
3,5- (4S)-3,4-dihydro-
282 H (methoxycarbonyl)pyrrolidin- H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
283 H (3R)hydroxypyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
284 H (3S)hydroxypyrrolidinyl H H H H
dichlorophenyl omenyl
[(diethoxyphosphoryl)methyl] 3,5- (4S)-3,4-dihydro-
285 H H H H H
(methyl)amino dichlorophenyl 2H-chromenyl
[2-(cyclopropylamino)ethyl] 3,5- (4S)-3,4-dihydro-
286 H H H H H
amino dichlorophenyl 2H-chromenyl
(2R)
3,5- (4S)-3,4-dihydro-
287 H (hydroxymethyl)pyrrolidin H H H H
dichlorophenyl 2H-chromenyl
(2S)
3,5- (4S)-3,4-dihydro-
288 H (hydroxymethyl)pyrrolidin H H H H
dichlorophenyl omenyl
[(1R,3S)amino-2,2- 3,5- (4S)-3,4-dihydro-
289 H H H H H
dimethylcyclopropyl]amino dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
290 H (2S)methylmorpholinyl H H H H
dichlorophenyl 2H-chromenyl
(3rac,4rac)amino 3,5- (4S)-3,4-dihydro-
291 H H H H H
fluoropyrrolidinyl dichlorophenyl 2H-chromenyl
(2rac)carboxypyrrolidin 3,5- (1S)-2,3-dihydro-
292 H H H H H
yl dichlorophenyl enyl
3,4-dichloro
(4S)-3,4-dihydro-
293 H dimethylamino H H H H (dimethylamino)
2H-chromenyl
phenyl
3-chloro
(4S)-3,4-dihydro-
294 H dimethylamino H H H H hylamino)
2H-chromenyl
phenyl
-chloro
(3rac)hydroxypyrrolidin (4S)-3,4-dihydro-
295 H H H H H fluoro
yl 2H-chromenyl
methylphenyl
,4-dihydro-
296 H dimethylamino H H H H phenyl
2H-chromenyl
3,5- (1S)-2,3-dihydro-
297 H (2-hydroxyethyl)amino H H H H
rophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
298 H (2-methoxyethyl)amino H H H H
dichlorophenyl 1H-indenyl
(2R)carboxylatopyrrolidin- 3,5- (1S)-2,3-dihydro-
299 H H H H H
1-yl dichlorophenyl 1H-indenyl
6-oxa 3,5- (4S)-3,4-dihydro-
300 H H H H H
azabicyclo[3.1.1]heptyl dichlorophenyl 2H-chromenyl
3,9-dioxa 3,5- (4S)-3,4-dihydro-
301 H H H H H
azabicyclo[3.3.1]nonyl rophenyl 2H-chromenyl
8-oxaazabicyclo[3.2.1]oct- 3,5- (4S)-3,4-dihydro-
302 H H H H H
3-yl rophenyl 2H-chromenyl
(2R,6S)-2,6- 3,5- (4S)-3,4-dihydro-
303 H H H H H
dimethylmorpholinyl difluorophenyl 2H-chromenyl
(2R,6S)-2,6- 2,3- (4S)-3,4-dihydro-
304 H H H H H
dimethylmorpholinyl dichlorophenyl omenyl
(2R,6S)-2,6- 2,3- (1S)-2,3-dihydro-
305 H H H H H
dimethylmorpholinyl dichlorophenyl 1H-indenyl
(2R,6S)-2,6- 3,5- (1S)-2,3-dihydro-
306 H H H H H
dimethylmorpholinyl difluorophenyl 1H-indenyl
4-chloro
(4S)-3,4-dihydro-
307 H ylamino H H H H (dimethylamino)
2H-chromenyl
phenyl
3,5-dichloro
,4-dihydro-
308 H dimethylamino H H H H (dimethylamino)
2H-chromenyl
phenyl
2,3- (4S)-3,4-dihydro-
309 H morpholinyl H methyloxy H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
310 H morpholinyl H methyloxy H H
dichlorophenyl 2H-chromenyl
3-chloro
(4S)-3,4-dihydro-
311 H dimethylamino H H H H (dimethylamino)
2H-chromenyl
phenyl
(4S)-3,4-dihydro-
312 H ylamino H H H H (methylamino)p
2H-chromenyl
henyl
2,6- (4S)-3,4-dihydro-
313 H morpholinyl H H H H
rophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
314 H morpholinyl H trifluoromethyl H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
315 H dimethylamino H trifluoromethyl H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
316 H dimethylamino H H chloro H
dichlorophenyl 2H-chromenyl
(3rac)hydroxypyrrolidin 3,5- (4S)-3,4-dihydro-
317 H H H H H
yl dichlorophenyl 2H-chromenyl
(3S)
3,5- (4S)-3,4-dihydro-
318 H (hydroxymethyl)pyrrolidin H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
319 H morpholinyl H H H H rophenyl
2H-chromenyl
3,5- (4S)-3,4-dihydro-
320 H (ethoxycarbonyl)pyrrolidin H H H H
dichlorophenyl 2H-chromenyl
2,4-dimethyl-3,5-dioxo-1,2,4- 2,3- (4S)-3,4-dihydro-
321 H H H H H
triazolidinyl dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
322 H morpholinyl H H H H uoromethox
2H-chromenyl
y)phenyl
3-chloro
(4S)-3,4-dihydro-
323 H dimethylamino H H H H (morpholin
2H-chromenyl
yl)phenyl
ro
(4S)-3,4-dihydro-
324 H dimethylamino H H H H (dimethylamino)
2H-chromenyl
phenyl
3-chloro
(4S)-3,4-dihydro-
325 H dimethylamino H H H H (dimethylamino)
2H-chromenyl
orophenyl
2,3- (4S)-3,4-dihydro-
326 H dimethylamino H methyloxy H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
327 H dimethylamino H methyloxy H H
rophenyl 2H-chromenyl
methyl[2-(2-oxopyrrolidin 3,5- (4S)-3,4-dihydro-
328 H H H H H
yl)ethyl]amino dichlorophenyl 2H-chromenyl
(3R)
3,5- (4S)-3,4-dihydro-
329 H (hydroxymethyl)pyrrolidin H H H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
330 H dimethylamino H fluoro H H
dichlorophenyl omenyl
2,3- (4S)-3,4-dihydro-
331 H methyl(oxetanyl)amino H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
332 H (3R)carboxypyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5-dichloro (4S)-3,4-dihydro-
333 H methyloxy H H H H
fluorophenyl omenyl
3,5- (1S)-2,3-dihydro-
334 H ethyloxy H H H H
dichlorophenyl enyl
3,5- (4S)-3,4-dihydro-
335 H pyloxy H H H H
dichlorophenyl omenyl
3,5- (1S)-2,3-dihydro-
336 H isopropyloxy H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
337 H cyclopentyloxy H H H H
dichlorophenyl 1H-indenyl
3,5- (4S)-3,4-dihydro-
338 H (2-methoxyethyl)oxy H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
339 H tetrahydro-2H-pyranyloxy H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
340 H (2-hydroxyethyl)oxy H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
341 H ethyloxy H H H H
dichlorophenyl omenyl
3,5- (1S)-2,3-dihydro-
342 H (3,3-dimethylbutyl)oxy H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
343 H (3-fluorobenzyl)oxy H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
344 H (2,3-difluorobenzyl)oxy H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
345 H (3-methoxybenzyl)oxy H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
346 H yrrolidinyloxy H H H H
dichlorophenyl 1H-indenyl
(3-methoxy 3,5- (1S)-2,3-dihydro-
347 H H H H H
methylbutyl)oxy dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
348 H pentylmethyl)oxy H H H H
dichlorophenyl 1H-indenyl
3,5- (1S)-2,3-dihydro-
349 H isopropyloxy H H H H
dichlorophenyl 1H-indenyl
3,5- (4S)-3,4-dihydro-
350 H ethyl H H H H
dichlorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
351 H ethyl H H H H
ethylphenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
352 H methyl H H H H
methylphenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
353 H methyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
354 H 1-cyanoethoxyoxoethyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
355 H cyanomethyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
356 H propyl H H H H
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
357 H propenyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
358 H cyclopropyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
359 H isopropyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
360 H 2-aminooxoethyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
361 H nitrilomethyl H H H H
rophenyl 2H-chromenyl
3,5- (1S)-2,3-dihydro-
362 H (2-hydroxyethyl)sulfanyl H H H H
dichlorophenyl enyl
3,5- (4S)-3,4-dihydro-
363 H pyridinylsulfanyl H H H H
rophenyl 2H-chromenyl
3,5- ,4-dihydro-
364 H (2-hydroxyethyl)sulfanyl H H H H
dichlorophenyl 2H-chromenyl
3-chloro
(4S)-3,4-dihydro-
365 H methylsulfanyl H H H H (methylsulfanyl)
2H-chromenyl
phenyl
2,3- (4S)-3,4-dihydro-
366 H ethylsulfanyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
367 H ethylsulfanyl H H H H
dichlorophenyl 2H-chromenyl
2,3- ,4-dihydro-
368 H ethylsulfinyl H H H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
369 H ethylsulfonyl H H H H
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
370 H ethylsulfinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
371 H ethylsulfonyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
372 H boxyethyl)sulfanyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
373 H methyloxy H H H H
dichlorophenyl 2H-chromenyl
Number R1 R2 R3 R4 R5 R6 Q A
(2rac)
3,5- (4S)-3,4-dihydro-
374 H (trifluoromethyl)morpho H H H H
dichlorophenyl 2H-chromenyl
linyl
(2-methoxy 3,5- (4S)-3,4-dihydro-
375 H H H H H
oxoethyl)amino rophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
376 H H H H H H
dichlorophenyl 2H-chromenyl
-fluoro
(4S)-3,4-dihydro-
377 H dimethylamino H H H H methoxypyridin-
omenyl
2-cyanopyridin- (4S)-3,4-dihydro-
378 H dimethylamino H H H H
4-yl 2H-chromenyl
2-aminopyridin- (4S)-3,4-dihydro-
379 H dimethylamino H H H H
4-yl 2H-chromenyl
(4S)-3,4-dihydro-
380 H dimethylamino H H H H methylpyridin-
2H-chromenyl
(4S)-3,4-dihydro-
381 H dimethylamino H H H H methylpyridin-
2H-chromenyl
3-chloropyridin- ,4-dihydro-
382 H dimethylamino H H H H
4-yl 2H-chromenyl
3-fluoropyridin- (4S)-3,4-dihydro-
383 H dimethylamino H H H H
4-yl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
384 H methylamino H H H H
dichlorophenyl omenyl
2,3,5- ,4-dihydro-
385 H methylamino H H H H
trifluorophenyl 2H-chromenyl
2,3,5- ,4-dihydro-
386 H isopropyl H H H H
trichlorophenyl 2H-chromenyl
-cyano (4S)-3,4-dihydro-
387 H dimethylamino H H H H
methylthienyl 2H-chromenyl
methyl (4S)-3,4-dihydro-
388 H dimethylamino H H H H
thienyl 2H-chromenyl
-cyano (4S)-3,4-dihydro-
389 H dimethylamino H H H H
thienyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
390 H dimethylamino H H H H
thienyl 2H-chromenyl
-methyl (4S)-3,4-dihydro-
391 H dimethylamino H H H H
thienyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
392 H 3-fluoroazetidinyl H H H H
dichlorophenyl omenyl
3,5- (4S)-3,4-dihydro-
393 H 4-fluoropiperidinyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
394 H 3,3-difluoroazetidinyl H H H H
rophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
395 H methylamino H fluoro H H
dichlorophenyl omenyl
3,5- (4S)-3,4-dihydro-
396 H pyridinyl H H H H
dichlorophenyl 2H-chromenyl
2-oxo-1,2- 3,5- (4S)-3,4-dihydro-
397 H H H H H
dihydropyridinyl dichlorophenyl 2H-chromenyl
4,4-difluoropiperidin 3,5- (4S)-3,4-dihydro-
398 H H H H H
yl dichlorophenyl 2H-chromenyl
2-morpholin (4S)-3,4-dihydro-
399 H dimethylamino H H H H
dinyl 2H-chromenyl
-chloro
(4S)-3,4-dihydro-
400 H dimethylamino H H H H methoxypyridin-
2H-chromenyl
(4S)-3,4-dihydro-
401 H dimethylamino H H H H methoxypyridin-
2H-chromenyl
,4-dihydro-
402 H dimethylamino H H H H (hydroxymethyl
2H-chromenyl
)pyridinyl
,4-dihydro-
403 H dimethylamino H H H H difluoropyridin-
2H-chromenyl
3,5- (4S)-3,4-dihydro-
404 H cyclobutyl H H H H
rophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
405 H 2-hydroxyethylamino H H H H
dichlorophenyl omenyl
(4S)-3,4-dihydro-
406 H isopropyl H H H H 3-chlorophenyl
2H-chromenyl
(4S)-3,4-dihydro-
407 H isopropyl H H H H (trifluoromethox
2H-chromenyl
y)phenyl
2-fluoro
(4S)-3,4-dihydro-
408 H isopropyl H H H H (trifluoromethyl)
2H-chromenyl
phenyl
3-chloro (4S)-3,4-dihydro-
409 H isopropyl H H H H
fluorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
410 H pyl H H H H
fluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
411 H isopropyl H H H H (trifluoromethyl)
2H-chromenyl
phenyl
3,5- (4S)-3,4-dihydro-
412 H 2-aminopyrimidinyl H H H H
rophenyl 2H-chromenyl
(4S)-3,4-dihydro-
413 H dimethylamino H H H H difluoropyridin-
2H-chromenyl
2-chloro
(4S)-3,4-dihydro-
414 H dimethylamino H H H H fluoropyridin
2H-chromenyl
(4S)-3,4-dihydro-
415 H dimethylamino H H H H dichloropyridin-
2H-chromenyl
-fluoro
,4-dihydro-
416 H dimethylamino H H H H isopropyloxypyr
2H-chromenyl
idinyl
2-ethoxy
(4S)-3,4-dihydro-
417 H dimethylamino H H H H fluoropyridin
2H-chromenyl
2-chloro (4S)-3,4-dihydro-
418 H pyl H H H H
fluorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
419 H isopropyl H H H H
fluorophenyl 2H-chromenyl
2-chloro
(4S)-3,4-dihydro-
420 H isopropyl H H H H (trifluoromethyl)
2H-chromenyl
phenyl
2-chloro (4S)-3,4-dihydro-
421 H isopropyl H H H H
fluorophenyl 2H-chromenyl
2,5-dimethyl (4S)-3,4-dihydro-
422 H isopropyl H H H H
thienyl 2H-chromenyl
2,5-dichloro (4S)-3,4-dihydro-
423 H isopropyl H H H H
thienyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
424 H oethyl H H H H
rophenyl omenyl
2,5-dimethyl (4S)-3,4-dihydro-
425 H isopropyl H fluoro H H
thienyl 2H-chromenyl
2,5-dichloro (4S)-3,4-dihydro-
426 H isopropyl H fluoro H H
thienyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
427 H methoxy(methyl)amino H H H H
trifluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
428 H dimethylamino H H cyano H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
429 H dimethylamino H H hydroxy H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
430 H isopropyl H H H H
difluorophenyl 2H-chromenyl
3-chloro
(4S)-3,4-dihydro-
431 H isopropyl H H H H (trifluoromethyl)
2H-chromenyl
phenyl
3,5- (4S)-3,4-dihydro-
432 H hylamino)methyl H H H H
dichlorophenyl omenyl
(4S)-3,4-dihydro-
433 H dimethylamino H H H H ifluoromet
2H-chromenyl
hyl)phenyl
-fluoro
(4S)-3,4-dihydro-
434 H dimethylamino H H H H (trifluoromethyl)
2H-chromenyl
phenyl
2-chloro (4S)-3,4-dihydro-
435 H dimethylamino H H H H
cyanophenyl 2H-chromenyl
-fluoro ,4-dihydro-
436 H dimethylamino H H H H
methylphenyl 2H-chromenyl
2-fluoro (4S)-3,4-dihydro-
437 H dimethylamino H H H H
methylphenyl 2H-chromenyl
3,5-dichloro (4S)-3,4-dihydro-
438 H isopropyl H H H H
phenyl 2H-chromenyl
3-fluorooxo-1,2- 3,5- (4S)-3,4-dihydro-
439 H H H H H
dihydropyridinyl dichlorophenyl omenyl
2,3- (4S)-3,4-dihydro-
440 H amino H H H H
dichlorophenyl 2H-chromenyl
2,5-dichloro ,4-dihydro-
441 H morpholinyl H H H H
thienyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
442 H morpholinyl H H H H
thienyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
443 H morpholinyl H H H H
l 2H-chromenyl
3-chloro
(4S)-3,4-dihydro-
444 H isopropyl H H H H fluoro
2H-chromenyl
methylphenyl
2,3- (4S)-3,4-dihydro-
445 H 1,2-oxazolidinyl H H H H
dichlorophenyl omenyl
3-chloro (4S)-3,4-dihydro-
446 H isopropyl H H H H
fluorophenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
447 H isopropyl H H H H
dimethylphenyl 2H-chromenyl
3-fluoro (4S)-3,4-dihydro-
448 H isopropyl H H H H
methylphenyl 2H-chromenyl
3,4,5- ,4-dihydro-
449 H isopropyl H H H H
trifluorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
450 H isopropyl H H H H
trifluorophenyl 2H-chromenyl
2-methyl
(4S)-3,4-dihydro-
451 H isopropyl H H H H (trifluoromethyl)
2H-chromenyl
phenyl
2,3,5- (1S)-2,3-dihydro-
452 H methoxy(methyl)amino H H H H
trifluorophenyl 1H-indenyl
2,5- (4S)-3,4-dihydro-
453 H isopropyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
454 H 1H-pyrazolyl H H H H
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
455 H isopropyl H fluoro H H
rophenyl 2H-chromenyl
2-methyl-1,3- (4S)-3,4-dihydro-
456 H ylamino H H H H
thiazolyl 2H-chromenyl
4-chloro (4S)-3,4-dihydro-
457 H dimethylamino H H H H
thienyl 2H-chromenyl
(4S)-3,4-dihydro-
458 H dimethylamino H H H H (trifluoromethyl)
2H-chromenyl
thienyl
-fluoro (4S)-3,4-dihydro-
459 H dimethylamino H H H H
thienyl 2H-chromenyl
(4S)-3,4-dihydro-
460 H dimethylamino H H H H dichloropyridin-
2H-chromenyl
(4S)-3,4-dihydro-
461 H morpholinyl H H H H bis(trifluoromet
2H-chromenyl
hyl)phenyl
2,5- (4S)-3,4-dihydro-
462 H morpholinyl H H H H
dichlorophenyl 2H-chromenyl
-fluoro
(4S)-3,4-dihydro-
463 H morpholinyl H H H H uoromethyl)
2H-chromenyl
phenyl
2-chloro (4S)-3,4-dihydro-
464 H linyl H H H H
cyanophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
465 H morpholinyl H H H H
methylphenyl omenyl
-fluoro (4S)-3,4-dihydro-
466 H morpholinyl H H H H
phenyl 2H-chromenyl
ro (4S)-3,4-dihydro-
467 H morpholinyl H H H H
methylphenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
468 H morpholinyl H H H H
dimethylphenyl 2H-chromenyl
2,5- ,4-dihydro-
469 H dimethylamino H H H H
dichlorophenyl omenyl
2-chloro (4S)-3,4-dihydro-
470 H dimethylamino H H H H
methylphenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
471 H dimethylamino H H H H
dimethylphenyl omenyl
(4S)-3,4-dihydro-
472 H dimethylamino H H H H dimethoxypyridi
2H-chromenyl
nyl
2-chloro
(4S)-3,4-dihydro-
473 H dimethylamino H H H H methylpyridin-
2H-chromenyl
(4S)-3,4-dihydro-
474 H dimethylamino H H H H dimethoxypyridi
2H-chromenyl
nyl
3-chloro
(4S)-3,4-dihydro-
475 H dimethylamino H H H H methoxypyridin-
2H-chromenyl
(4S)-3,4-dihydro-
476 H dimethylamino H H H H dichloropyridin-
2H-chromenyl
2,3- ,4-dihydro-
477 H isopropyl H fluoro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
478 H vinyl H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
479 H pyl H fluoro H H (trifluoromethox
omenyl
y)phenyl
2,5-dimethyl (4S)-3,4-dihydro-
480 H morpholinyl H H H H
thienyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
481 H linyl methyl H H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
482 H difluoroethyl(methyl)am H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
483 H morpholinyl methyl H H H
dichlorophenyl 2H-chromenyl
oxetan 2,3- (4S)-3,4-dihydro-
484 H H H H H
ylmethylamino dichlorophenyl 2H-chromenyl
3,5- ,3-dihydro-
485 H linyl H fluoro H H
dichlorophenyl 1H-indenyl
(4S)-3,4-dihydro-
486 H morpholinyl H fluoro H H benzothiazol
2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
487 H isopropyl H fluoro H H
trifluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
488 H isopropyl H fluoro H H (trifluoromethyl)
omenyl
phenyl
3,5- (4S)-3,4-dihydro-
489 H 3-thienyl H H H H
dichlorophenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
490 H morpholinyl H fluoro H H
dimethylphenyl 2H-chromenyl
2,3- (1S)-2,3-dihydro-
491 H morpholinyl H fluoro H H
dichlorophenyl 1H-indenyl
(1S)-1,2,3,4-
492 H linyl H fluoro H H tetrahydronaphth
dichlorophenyl
(3rac)-2,3-
3,5- o
493 H dimethylamino H H H H
dichlorophenyl benzothiophen
3,5- (4S)-3,4-dihydro-
494 H cyclopentyl H H H H
dichlorophenyl 2H-chromenyl
2,3-dichloro (4S)-3,4-dihydro-
495 H morpholinyl H H H H
hydroxyphenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
496 H linyl H H H methoxy
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
497 H morpholinyl H H H methoxy
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
498 H morpholinyl H H methoxy H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
499 H morpholinyl H H methoxy H
dichlorophenyl 2H-chromenyl
-chloro ,4-dihydro-
500 H morpholinyl H H methoxy H
fluorophenyl 2H-chromenyl
3,5- ,4-dihydro-
501 H dimethylamino H H methoxy H
dichlorophenyl 2H-chromenyl
2,3- ,4-dihydro-
502 H ylamino H H methoxy H
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
503 H dimethylamino H H methoxy H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
504 H dimethylamino H H H methoxy
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
505 H dimethylamino H H H methoxy
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
506 H dimethylamino H H H methoxy
fluorophenyl 2H-chromenyl
3,5- ,4-dihydro-
507 H dimethylamino H H H chloro
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
508 H dimethylamino H H H chloro
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
509 H ylamino H H H chloro
fluorophenyl 2H-chromenyl
trifluoro- 2,3- (4S)-3,4-dihydro-
510 H dimethylamino H H H
methyl dichlorophenyl 2H-chromenyl
trifluoro- 5-chloro (4S)-3,4-dihydro-
511 H dimethylamino H H H
methyl fluorophenyl omenyl
trifluoro- 3,5- (4S)-3,4-dihydro-
512 H morpholinyl H H H
methyl dichlorophenyl 2H-chromenyl
trifluoro- 2,3- (4S)-3,4-dihydro-
513 H morpholinyl H H H
methyl dichlorophenyl 2H-chromenyl
trifluoro- 5-chloro (4S)-3,4-dihydro-
514 H morpholinyl H H H
methyl fluorophenyl 2H-chromenyl
methyl(oxan 2,3- (4S)-3,4-dihydro-
515 H H H H H
ylmethyl)amino rophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
516 H methoxy(methyl)amino H fluoro H H
trifluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
517 H morpholinyl H H hydroxy H
dichlorophenyl 2H-chromenyl
oxetan 3,5- ,4-dihydro-
518 H H H H H
ylmethylamino dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
519 H (3rac)-pyrrolidinyl H H H H
dichlorophenyl 2H-chromenyl
1-(difluoromethyl)-1H- 3,5- (4S)-3,4-dihydro-
520 H H H H H
pyrazolyl dichlorophenyl 2H-chromenyl
chloro (4S)-3,4-dihydro-
521 H morpholinyl H H hydroxy H
hydroxyphenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
522 H dimethylamino methyl H H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
523 H dimethylamino methyl H H H
dichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
524 H dimethylamino methyl H H H
trifluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
525 H ethyl(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
526 H isopropyl(methyl)amino H H H H
rophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
527 H ethyl(methyl)amino H H H H
rophenyl 2H-chromenyl
-chloro ,4-dihydro-
528 H dimethylamino H amino H H
phenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
529 H dimethylamino H amino H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
530 H morpholinyl H H H methoxy
dichlorophenyl 2H-chromenyl
-chloro ,4-dihydro-
531 H morpholinyl H H H chloro
fluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
532 H morpholinyl H H H chloro
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
533 H morpholinyl H H H chloro
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
534 H isopropyl(methyl)amino H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
535 H methoxy(methyl)amino H chloro H H dichloropyridin-
2H-chromenyl
-chloro (4S)-3,4-dihydro-
536 H morpholinyl H amino H H
fluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
537 H linyl H amino H H
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
538 H linyl H amino H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
539 H oxanyl H H H H
dichlorophenyl 2H-chromenyl
3,4,5- (4S)-3,4-dihydro-
540 H morpholinyl H fluoro H H
trifluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
541 H methylamino H fluoro H H
dichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
542 H methylamino H fluoro H H
trifluorophenyl 2H-chromenyl
chloro (4S)-3,4-dihydro-
543 H linyl H fluoro H H
thienyl 2H-chromenyl
2,5-dimethyl (4S)-3,4-dihydro-
544 H morpholinyl H fluoro H H
thienyl 2H-chromenyl
,4-dihydro-
545 H methylamino H fluoro H H dichloropyridin-
2H-chromenyl
(difluoromethox (4S)-3,4-dihydro-
546 H morpholinyl H fluoro H H
y)-3,5- 2H-chromenyl
difluorophenyl
(difluoromethox (4S)-3,4-dihydro-
547 H methylamino H fluoro H H
y)-3,5- omenyl
difluorophenyl
2,3- ,4-dihydro-
548 H morpholinyl H fluoro H H
difluorophenyl 2H-chromenyl
2,3,4- (4S)-3,4-dihydro-
549 H morpholinyl H fluoro H H
trifluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
550 H morpholinyl H fluoro H H dichloropyridin-
2H-chromenyl
2,3- (4S)-3,4-dihydro-
551 H dimethylamino H amino H H
dichlorophenyl 2H-chromenyl
2,3- ,4-dihydro-
552 H methyl H H H H
dichlorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
553 H morpholinyl H chloro H H dichloropyridin-
2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
554 H methyl H H H H
trifluorophenyl 2H-chromenyl
(1rac)methyl-
555 H dimethylamino H H H H 3,4-dihydro-2H-
dichlorophenyl
naphthalenyl
3,5- (4S)-3,4-dihydro-
556 H morpholinyl H chloro H H
difluorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
557 H morpholinyl H chloro H H
fluorophenyl omenyl
(4S)-3,4-dihydro-
558 H linyl H chloro H H (trifluoromethyl)
2H-chromenyl
phenyl
-chloro (4S)-3,4-dihydro-
559 H dimethylamino H hydroxy H H
fluorophenyl omenyl
2,3- (4S)-3,4-dihydro-
560 H dimethylamino H hydroxy H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
561 H dimethylamino H hydroxy H H
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
562 H midazolidinyl H H H H
dichlorophenyl 2H-chromenyl
2,3,5- ,4-dihydro-
563 H 4-oxoimidazolidinyl H H H H
trichlorophenyl 2H-chromenyl
3-chloro (4S)-3,4-dihydro-
564 H morpholinyl H chloro H H
fluorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
565 H morpholinyl H chloro H H
fluorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
566 H 2-hydroxyethylamino H H H H
trichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
567 H 2-hydroxyethylamino H H H H
trifluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
568 H 2-hydroxyethylamino H H H H dichloropyridin-
2H-chromenyl
(4S)-3,4-dihydro-
569 H 4-oxoimidazolidinyl H H H H uoromethox
2H-chromenyl
y)phenyl
(4S)-3,4-dihydro-
570 H ethyl H H H H (trifluoromethox
omenyl
y)phenyl
(4S)-3,4-dihydro-
571 H methyl H H H H (trifluoromethox
2H-chromenyl
y)phenyl
2,3,5- (4S)-3,4-dihydro-
572 H methyl H H H H
trichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
573 H ethyl H H H H
trichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
574 H dimethylamino H H H H
diethylphenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
575 H ethyl H H H H
dichlorophenyl omenyl
2,3,5- (4S)-3,4-dihydro-
576 H morpholinyl H chloro H H
trifluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
577 H 2-hydroxyethylamino H fluoro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
578 H 2-hydroxyethylamino H fluoro H H
dichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
579 H 2-hydroxyethylamino H fluoro H H
trifluorophenyl 2H-chromenyl
(4rac)
580 H dimethylamino H H H H hroman
dichlorophenyl
(4rac)-3,4-
581 H ylamino H H H H dihydro-1H-
dichlorophenyl
isochromenyl
ro-3,5- (4S)-3,4-dihydro-
582 H dimethylamino H H H H
diethylphenyl 2H-chromenyl
2-chloro-3,5- (4S)-3,4-dihydro-
583 H morpholinyl H H H H
diethylphenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
584 H linyl H hydroxy H H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
585 H dimethylaminocarbonyl H H H H
dichlorophenyl 2H-chromenyl
3-tert-butyl (4S)-3,4-dihydro-
586 H dimethylamino H H H H
methylphenyl 2H-chromenyl
3-tert-butyl ,4-dihydro-
587 H morpholinyl H H H H
methylphenyl omenyl
3,5- (4S)-3,4-dihydro-
588 H morpholinyl H H H H
diethylphenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
589 H hydroxyethyl(methyl)a H H H H
dichlorophenyl omenyl
2,3,5- (4S)-3,4-dihydro-
590 H yethyl(methyl)a H H H H
trichlorophenyl 2H-chromenyl
2- 2,6-
(4S)-3,4-dihydro-
591 H hydroxyethyl(methyl)a H H H H dichloropyridin-
2H-chromenyl
mino 4-yl
3,5- (4S)-3,4-dihydro-
592 H hydroxymethyl H H H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
593 H 2-hydroxyethyl H H H H
rophenyl 2H-chromenyl
3-cyano (4S)-3,4-dihydro-
594 H morpholinyl H H H H
phenyl 2H-chromenyl
methyl-[[ -(3rac)-
2,3- (4S)-3,4-dihydro-
595 H oxolan H fluoro H H
dichlorophenyl omenyl
yl]methyl]amino
2-(1H-pyrazol 2,3,5- (4S)-3,4-dihydro-
596 H H fluoro H H
yl)ethylamino trifluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
597 H 2-hydroxyethylamino H fluoro H H dichloropyridin-
2H-chromenyl
3-cyano (4S)-3,4-dihydro-
598 H dimethylamino H H H H
methylphenyl 2H-chromenyl
2-(1H-imidazol 2,3- (4S)-3,4-dihydro-
599 H H fluoro H H
yl)ethylamino dichlorophenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
600 H methyl H H H H
fluorophenyl 2H-chromenyl
-butyl
(4S)-3,4-dihydro-
601 H dimethylamino H H H H chloro
2H-chromenyl
methylphenyl
2-chloro ,4-dihydro-
602 H 4-oxoimidazolidinyl H H H H
fluorophenyl 2H-chromenyl
2-chloro ,4-dihydro-
603 H ethyl H H H H
fluorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
604 H 4-oxoimidazolidinyl H H H H
fluorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
605 H methyl H H H H
fluorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
606 H hydroxyethyl(methyl)a H H H H
trifluorophenyl 2H-chromenyl
-tert-butyl
,4-dihydro-
607 H morpholinyl H H H H chloro
2H-chromenyl
methylphenyl
2,3-dichloro (4S)-3,4-dihydro-
608 H morpholinyl H H H H
cyanophenyl 2H-chromenyl
trifluoro- 5-chloro (4S)-3,4-dihydro-
609 H morpholinyl H H H
methoxy fluorophenyl 2H-chromenyl
trifluoro- 2,3- (4S)-3,4-dihydro-
610 H morpholinyl H H H
y dichlorophenyl 2H-chromenyl
trifluoro- 3,5- (4S)-3,4-dihydro-
611 H morpholinyl H H H
methoxy dichlorophenyl 2H-chromenyl
trifluoro- 5-chloro (4S)-3,4-dihydro-
612 H dimethylamino H H H
methoxy fluorophenyl omenyl
trifluoro- 2,3- (4S)-3,4-dihydro-
613 H dimethylamino H H H
methoxy dichlorophenyl 2H-chromenyl
trifluoro- 3,5- (4S)-3,4-dihydro-
614 H dimethylamino H H H
methoxy dichlorophenyl 2H-chromenyl
2,3- ,4-dihydro-
615 H morpholinyl H y H H
dichlorophenyl omenyl
3,5- (4S)-3,4-dihydro-
616 H morpholinyl H hydroxy H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
617 H dimethylamino H cyano H H
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
618 H dimethylamino H H hydroxy H
phenyl 2H-chromenyl
2,3- ,4-dihydro-
619 H dimethylamino H H hydroxy H
dichlorophenyl omenyl
(4rac)
620 H dimethylamino H H H H fluorochroman
dichlorophenyl
(4rac)-6,8-
621 H dimethylamino H H H H dichlorochromandichlorophenyl
(4rac)
622 H dimethylamino H H H H chlorochroman
dichlorophenyl
(4rac)
623 H dimethylamino H H H H fluorochroman
rophenyl
2,3-dichloro ,4-dihydro-
624 H dimethylamino H H H H
cyanophenyl 2H-chromenyl
2-(1H-imidazol 3,5- (4S)-3,4-dihydro-
625 H H H H H
yl)ethylamino dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
626 H morpholinyl H H hydroxy H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
627 H morpholinyl H H hydroxy H
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
628 H ethyl H H H H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
629 H methylamino H chloro H H
rophenyl 2H-chromenyl
(1rac)-3,3-
630 H morpholinyl H chloro H H dimethylindan
dichlorophenyl
[acetyl(methyl)amino]m 3,5- (4S)-3,4-dihydro-
631 H H H H H
ethyl dichlorophenyl omenyl
(4rac)
632 H dimethylamino H H H H chlorochroman
dichlorophenyl
(4rac)-6,8-
633 H dimethylamino H H H H difluorochromandichlorophenyl
(4rac)
634 H dimethylamino H H H H bromochroman
dichlorophenyl
3,5- (1rac)
635 H morpholinyl H chloro H H
dichlorophenyl oxoindanyl
2,3,5- (4S)-3,4-dihydro-
636 H methylamino H chloro H H
trifluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
637 H ethylamino H fluoro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
638 H ethylamino H fluoro H H
dichlorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
639 H ethylamino H fluoro H H
trifluorophenyl 2H-chromenyl
(4S)-3,4-dihydro-
640 H mino H fluoro H H dichloropyridin-
2H-chromenyl
2,3- (4S)-3,4-dihydro-
641 H yloxyethylamino H H H H
dichlorophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
642 H morpholinyl H cyano H H
fluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
643 H 2-(dimethylamino)ethyl H H H H
dichlorophenyl 2H-chromenyl
2-(1H-imidazol 3,5- (4S)-3,4-dihydro-
644 H H fluoro H H
yl)ethyl-methylamino dichlorophenyl 2H-chromenyl
ro (4S)-3,4-dihydro-
645 H methyl H H H H
methylphenyl 2H-chromenyl
2-chloro (4S)-3,4-dihydro-
646 H ethyl H H H H
methylphenyl 2H-chromenyl
methyl(2-
3,5- (4S)-3,4-dihydro-
647 H methylsulfonylethyl)ami H fluoro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
648 H 3-fluoroazetidinyl H fluoro H H
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
649 H hydroxyethyl(methyl)a H fluoro H H
rophenyl 2H-chromenyl
(3-methoxy
3,5- (4S)-3,4-dihydro-
650 H oxopropyl)- H fluoro H H
dichlorophenyl 2H-chromenyl
methylamino
-chloro (4S)-3,4-dihydro-
651 H morpholinyl H H H cyano
fluorophenyl omenyl
3,5- (4S)-3,4-dihydro-
652 H morpholinyl H cyano H H
dichlorophenyl 2H-chromenyl
3,6-dihydro-2H-pyran- 2,3- (4S)-3,4-dihydro-
653 H H H H H
4-yl dichlorophenyl 2H-chromenyl
1,3-dimethyl-2,4-dioxo-
3,5- (4S)-3,4-dihydro-
654 H 1,2,3,4- H H H H
rophenyl 2H-chromenyl
ydropyrimidinyl
2,3,5- (4S)-3,4-dihydro-
655 H ethyl H H H H
trifluorophenyl 2H-chromenyl
-chloro-1H- (4S)-3,4-dihydro-
656 H dimethylamino H H H H
imidazolyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
657 H morpholinyl H H H cyano
rophenyl 2H-chromenyl
-chloro (4S)-3,4-dihydro-
658 H dimethylamino H H H cyano
fluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
659 H dimethylamino H H H cyano
dichlorophenyl omenyl
2,3,5- (4S)-3,4-dihydro-
660 H oxetanyl H H H H
trifluorophenyl 2H-chromenyl
methyl(2- 2,6-
(4S)-3,4-dihydro-
661 H sulfonylethyl)ami H fluoro H H dichloropyridin-
2H-chromenyl
no 4-yl
2,3,5- (4S)-3,4-dihydro-
662 H iodo H H H H
trifluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
663 H morpholinyl H H H cyano
rophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
664 H dimethylamino H H H cyano
dichlorophenyl 2H-chromenyl
(4rac)fluoro-
665 H dimethylamino H H H H 3,4-dihydro-1H-
dichlorophenyl
isochromenyl
3,5- (1S)-2,3-dihydro-
666 H hydroxyethyl(methyl)a H fluoro H H
dichlorophenyl 1H-indenyl
3,5- (1rac)
667 H dimethylamino H H H H
dichlorophenyl oxoindanyl
(4S)-3,4-dihydro-
668 H dimethylamino H chloro H H ropyridin-
2H-chromenyl
3,5- (4S)-3,4-dihydro-
669 H dimethylamino H chloro H H
difluorophenyl 2H-chromenyl
3-tert-butyl (4S)-3,4-dihydro-
670 H dimethylamino H chloro H H
methylphenyl omenyl
(4S)-3,4-dihydro-
671 H dimethylamino H chloro H H (trifluoromethyl)
2H-chromenyl
phenyl
3,5- (4S)-3,4-dihydro-
672 H ylamino H chloro H H
ylphenyl 2H-chromenyl
pyrazol (4S)-3,4-dihydro-
673 H H fluoro H H dichloropyridinyl
)ethylamino 2H-chromenyl
3,5- (4S)-3,4-dihydro-
674 H hydroxyethyl(methyl)a H chloro H H
dichlorophenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
676 H ethyl H H H H
dimethylphenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
677 H (3rac)-pyrrolidinyl H H H H
trifluorophenyl 2H-chromenyl
(3rac)-tetrahydrofuran- 2,3,5- (4S)-3,4-dihydro-
678 H H H H H
3-yl trifluorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
679 H 1-methyl-piperidinyl H H H H
trifluorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
680 H morpholinyl H H H y
dichlorophenyl 2H-chromenyl
3,5- ,4-dihydro-
681 H morpholinyl H H H hydroxy
rophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
682 H dimethylamino H H H hydroxy
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
683 H dimethylamino H H H hydroxy
rophenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
684 H isopropyl H fluoro H H
dimethylphenyl 2H-chromenyl
2,5- (4S)-3,4-dihydro-
685 H methyl H H H H
dimethylphenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
686 H methoxymethyl H H H H
trifluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
687 H ethyl H H H H
difluorophenyl 2H-chromenyl
2,3,4- (4S)-3,4-dihydro-
688 H ethyl H H H H
orophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
689 H morpholinyl H fluoro H fluoro
trifluorophenyl 2H-chromenyl
2,3,5- (4S)-3,4-dihydro-
690 H dimethylamino H fluoro H fluoro
trifluorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
691 H linyl H fluoro H fluoro
dichlorophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
692 H dimethylamino H fluoro H fluoro
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
693 H morpholinyl H fluoro H fluoro
dichlorophenyl 2H-chromenyl
2,3- (4S)-3,4-dihydro-
694 H dimethylamino H fluoro H fluoro
rophenyl 2H-chromenyl
3,5- (4S)-3,4-dihydro-
695 H methyl H H H H
difluorophenyl 2H-chromenyl
TABLE 2: LC-MS and NMR data
NMR peak forms are stated as they appear in the spectra, possible higher order effects have
not been considered.
NMR peak lists
1H-NMR data of selected examples are n in form of 1H-NMR peak lists. To each signal
peak are listed the δ-value in ppm and the signal intensity in round brackets. Between the δvalue
– signal intensity pairs are semicolons or commas as delimiters.
The peak list of an example has therefore the form:
δ1 (intensity1); δ2 (intensity2);……..; δi (intensityi);……; δn (intensityn) or
δ1 (intensity1), δ2 (intensity2),……..; δi sityi),……, δn sityn)
Intensity of sharp signals correlates with the height of the signals in a printed example of a
NMR spectrum in cm and shows the real ons of signal intensities. From broad signals
l peaks or the middle of the signal and their relative ity in comparison to the most
intensive signal in the spectrum can be shown.
For calibrating chemical shift for 1H spectra, we use tetramethylsilane and/or the chemical shift
of the solvent used, especially in the case of spectra measured in DMSO. Therefore in NMR
peak lists, tetramethylsilane peak can occur but not necessarily.
The 1H-NMR peak lists are similar to classical 1H-NMR prints and contains ore usually all
peaks, which are listed at classical NMR-interpretation.
Additionally they can show like classical 1H-NMR prints signals of solvents, stereoisomers of
the target compounds, which are also object of the invention, and/or peaks of impurities.
To show compound signals in the delta-range of solvents and/or water the usual peaks of
solvents, for example peaks of DMSO in DMSO-D6 and the peak of water are shown in our 1H-
NMR peak lists and have usually on average a high intensity .
The peaks of isomers of the target compounds and/or peaks of impurities have usually
on average a lower intensity than the peaks of target compounds (for example with a purity
>90%).
Such stereoisomers and/or impurities can be typical for the specific preparation process.
Therefore their peaks can help to recognize the reproduction of our preparation process via
“side-products-fingerprints”.
An expert, who ates the peaks of the target compounds with known s (MestreC,
ACD-simulation, but also with empirically evaluated expectation values) can isolate the peaks
of the target compounds as needed optionally using additional ity filters. This isolation
would be similar to relevant peak picking at classical 1H-NMR interpretation.
Further details of NMR-data description with peak lists you find in the publication “Citation of
NMR Peaklist Data within Patent Applications” of the ch Disclosure Database Number
564025.
Example logP LC-MS
NMR or NMR Peaklist
N° (Method L0) [a] (Method L2-L5)
LC-MS (Method L1): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (4.41), 0.008 (4.06), 2.342 (16.00), 2.759 (1.07), 7.059 , 7.111 (0.66), 7.128
1 1.42 min; MS (ESIpos): m/z = (1.05), 7.183 (4.61), 7.195 (1.69), 7.202 (0.82), 7.207 , 7.422 (0.89), 7.438 (0.75), 7.855 , 7.865 (2.24), 7.869 (2.26),
440 [M+H]+ 8.303 (1.26), 8.314 (1.10), 8.317 (1.07), 8.328 (1.10), 8.874 (5.11), 9.102 (0.96), 9.123 (0.96).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.38), 1.805 , 1.836 (2.05), 1.854 (1.44), 1.862 (1.41), 1.867 (1.25), 1.879
, 1.887 (1.60), 1.910 (1.44), 1.932 (1.44), 1.946 (1.07), 1.960 (0.93), 2.045 (1.14), 2.069 (1.54), 2.080 (1.05), 2.088 (1.03),
LC-MS (Method L1): Rt = 2.746 (1.96), 2.760 , 2.771 (3.46), 2.787 (1.53), 3.289 (3.24), 5.230 (0.89), 5.248 (1.82), 5.265 (1.70), 5.281 (0.81), 7.111
2 1.47 min; MS (ESIpos): m/z = (2.30), 7.128 , 7.161 (1.10), 7.166 (1.44), 7.179 (3.34), 7.184 (3.63), 7.190 (3.11), 7.196 (4.53), 7.202 (2.62), 7.208 (2.92),
481 [M+H]+ 7.212 (2.70), 7.226 (0.95), 7.422 (3.20), 7.439 (2.63), 7.444 (2.24), 7.675 (7.89), 7.679 (16.00), 7.683 (9.38), 7.687 (5.20), 7.692
(1.77), 7.889 (2.30), 7.907 (3.45), 7.909 (4.06), 7.928 (3.18), 7.999 , 8.002 (4.95), 8.017 (2.68), 8.020 (3.30), 8.383 (3.21),
8.386 (4.14), 8.404 (2.94), 8.407 (3.59), 8.940 (10.21), 9.119 (3.46), 9.141 .
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 0.008 (1.33), 1.234 (2.20), 1.397 (0.85), 1.924 (1.63), 1.935 (0.83), 1.946 (1.76), 1.956
(1.90), 1.967 (0.79), 1.977 (1.84), 1.998 (0.66), 2.524 (2.18), 2.567 (0.88), 2.575 (0.77), 2.838 (0.77), 2.859 (1.28), 2.878 (2.28),
2.898 (2.50), 2.918 (1.19), 2.951 (1.54), 2.959 (1.64), 2.973 (1.71), 2.980 (1.81), 2.990 (0.99), 2.999 , 3.012 (0.86), 3.020
LC-MS (Method L1): Rt =
3 (0.74), 3.070 (1.91), 5.542 , 5.562 (2.83), 5.582 (2.79), 5.602 (0.92), 7.223 (0.96), 7.232 (4.00), 7.240 , 7.246 (5.24),
1.37 min; MS (ESIpos): m/z =
7.254 (7.15), 7.263 (2.96), 7.271 (3.67), 7.281 (2.50), 7.293 (1.17), 7.435 (2.55), 7.446 (2.61), 7.456 , 7.635 , 7.665
467 [M+H]+
(0.98), 7.678 (13.08), 7.681 (16.00), 7.686 (7.10), 7.689 (3.73), 7.695 (1.37), 7.700 (0.80), 7.895 (2.06), 7.913 (4.25), 7.934 ,
8.004 (4.66), 8.008 , 8.022 (3.28), 8.026 (2.07), 8.393 (4.14), 8.396 (2.75), 8.414 (3.73), 8.417 (2.39), 8.962 (10.00), 9.118
(3.31), 9.139 (3.23).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 0.008 (2.60), 0.833 (1.52), 0.839 (3.28), 0.855 (3.89), 0.859 (2.26), 0.871 (1.10), 0.876
(0.82), 1.106 , 1.157 , 1.175 (2.15), 1.193 (1.15), 1.988 (3.86), 2.058 (0.88), 2.066 (0.96), 2.076 (1.10), 2.086 (2.40),
2.093 , 2.100 (1.27), 2.109 (0.88), 2.196 (0.93), 2.208 (1.32), 2.221 (1.22), 2.229 (1.16), 2.243 (0.82), 3.076 (2.73), 3.288
LC-MS (Method L1): Rt = (3.01), 4.021 (0.91), 4.038 (0.91), 4.221 (0.77), 4.241 (2.10), 4.249 (1.66), 4.261 (2.02), 4.270 (2.60), 4.279 (2.07), 4.287 ,
4 1.33 min; MS (ESIpos): m/z = 4.296 (1.82), 5.266 (0.85), 5.281 , 5.301 (1.91), 5.315 (0.88), 6.789 , 6.791 (3.20), 6.809 (3.59), 6.812 (3.55), 6.916
483 [M+H]+ (1.71), 6.918 (1.65), 6.934 (3.51), 6.937 (3.37), 6.953 (2.16), 6.956 (1.99), 7.157 (1.74), 7.162 (1.79), 7.179 (2.96), 7.196 (1.43),
7.200 (1.40), 7.379 (3.11), 7.398 (2.90), 7.676 (7.53), 7.680 (16.00), 7.685 (7.22), 7.688 (4.08), 7.694 (1.49), 7.893 (2.34), 7.911
(3.81), 7.914 (3.22), 7.932 (3.47), 8.006 (4.05), 8.010 (4.08), 8.024 (3.07), 8.027 , 8.387 (3.53), 8.390 (3.48), 8.408 (3.33),
8.411 (3.06), 8.962 (10.68), 9.251 (3.18), 9.272 (3.11).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.48), 0.008 (3.53), 1.157 (0.87), 1.175 , 1.192 (0.90), 1.988 (2.96), 2.058
(0.97), 2.066 (1.02), 2.075 (1.14), 2.082 (1.14), 2.093 (1.62), 2.100 , 2.108 (0.97), 2.196 (1.00), 2.209 (1.44), 2.222 (1.34),
2.231 (1.27), 3.289 (3.14), 4.021 (0.70), 4.038 (0.70), 4.221 (0.87), 4.241 (2.39), 4.249 (1.84), 4.261 (2.26), 4.269 (2.89), 4.279
LC-MS (Method L1): Rt = (2.24), 4.287 (1.79), 4.296 (2.04), 5.268 (0.95), 5.282 (2.07), 5.302 (2.07), 5.318 (0.95), 6.788 (3.63), 6.791 (4.03), 6.809 (4.26),
1.24 min; MS (ESIpos): m/z = 6.811 (4.43), 6.915 (2.02), 6.918 (2.07), 6.934 (4.08), 6.937 (4.13), 6.952 (2.54), 6.956 (2.41), 7.157 (2.04), 7.161 , 7.178
449 [M+H]+ (3.28), 7.196 (1.67), 7.200 (1.59), 7.378 (3.31), 7.398 (3.16), 7.491 (1.37), 7.496 (1.05), 7.506 (3.83), 7.510 (10.25), 7.515 (4.63),
7.529 (6.47), 7.549 (2.34), 7.572 (3.11), 7.577 (5.20), 7.581 (2.86), 7.589 (1.84), 7.593 (2.59), 7.598 (1.67), 7.675 (2.91), 7.679
(6.05), 7.684 (3.38), 7.887 (2.84), 7.905 (4.85), 7.908 , 7.926 (5.13), 7.958 (5.28), 7.962 (5.82), 7.976 (3.31), 7.979 (2.86),
8.362 (4.30), 8.366 (4.45), 8.383 (4.11), 8.387 (3.83), 8.934 (16.00), 9.244 (3.56), 9.265 (3.46).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.23), 0.008 (3.14), 0.853 (0.88), 1.175 (2.40), 1.235 (4.21), 1.925 (1.92), 1.934
(0.91), 1.945 (1.99), 1.956 , 1.967 (0.92), 1.976 (2.11), 1.998 (0.79), 2.517 (2.33), 2.525 (2.38), 2.568 (0.89), 2.859 (1.26),
2.878 (1.91), 2.899 (2.60), 2.919 (1.22), 2.951 , 2.959 (1.75), 2.973 (1.77), 2.981 (1.65), 2.990 (0.94), 2.999 (0.87), 3.287
LC-MS (Method L1): Rt = (2.04), 5.544 (1.02), 5.564 (3.03), 5.584 (3.00), 5.604 (0.98), 5.754 (7.31), 6.510 (1.69), 7.232 (5.18), 7.241 (5.18), 7.246 (6.49),
6 1.31 min; MS (ESIpos): m/z = 7.255 , 7.264 (2.87), 7.272 (3.87), 7.281 , 7.285 (1.99), 7.294 (1.18), 7.434 (2.78), 7.447 (2.68), 7.456 (2.20), 7.488
433 [M+H]+ , 7.492 (1.58), 7.497 (1.25), 7.507 , 7.512 (9.71), 7.515 (6.13), 7.517 (5.24), 7.531 (6.56), 7.551 , 7.574 (3.40),
7.579 (5.63), 7.584 (3.06), 7.592 (1.94), 7.596 (2.78), 7.601 (1.72), 7.676 (3.20), 7.678 (3.96), 7.680 , 7.685 (3.54), 7.889
(3.03), 7.907 (5.37), 7.910 (3.81), 7.928 (5.57), 7.957 (5.81), 7.961 (6.39), 7.975 (3.50), 7.979 (2.97), 8.368 (4.68), 8.372 (4.77),
8.389 (4.45), 8.393 (4.06), 8.935 (16.00), 9.113 (3.64), 9.134 (3.51).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 0.008 (3.31), 0.852 (0.82), 1.142 (0.91), 1.157 (1.29), 1.172 (2.28), 1.175 (2.52), 1.192
, 1.234 (5.59), 1.394 (15.65), 1.398 ), 1.985 (3.80), 1.988 (4.30), 2.039 (2.93), 2.046 (3.13), 2.057 (3.86), 2.064 (3.92),
2.074 (5.03), 2.082 (7.46), 2.086 , 2.090 (3.57), 2.098 (2.57), 2.185 (3.22), 2.196 (4.56), 2.207 (4.45), 2.218 (4.15), 2.230
, 2.242 (2.40), 2.251 (1.61), 2.365 , 2.707 (0.88), 3.288 (5.56), 4.020 (1.05), 4.038 (1.02), 4.204 (2.11), 4.232 (5.79),
LC-MS (Method L1): Rt = 4.259 (7.69), 4.268 , 4.276 (6.03), 4.285 (6.49), 4.296 (2.90), 4.304 (2.52), 4.312 (1.99), 5.251 (2.66), 5.266 (6.52), 5.285
7 1.24 min; MS (ESIpos): m/z = (7.14), 5.300 (3.71), 6.781 (12.26), 6.788 (2.84), 6.801 (13.54), 6.809 (3.01), 6.903 (5.41), 6.922 (11.79), 6.940 (7.05), 6.953 (1.43),
483 [M+H]+ 7.150 (6.38), 7.170 (10.21), 7.189 (4.94), 7.363 (10.65), 7.383 ), 7.403 (10.71), 7.456 (7.17), 7.475 (11.58), 7.495 (5.62), 7.511
(3.80), 7.528 , 7.548 (0.88), 7.573 (1.93), 7.590 , 7.677 (2.72), 7.720 (7.52), 7.723 (13.02), 7.727 (7.34), 7.740 (6.82),
7.743 (11.14), 7.747 (6.20), 7.845 (5.00), 7.849 (8.98), 7.852 (5.56), 7.863 (9.83), 7.866 (15.94), 7.870 (9.04), 7.883 (1.11), 7.898
(8.89), 7.902 (9.54), 7.919 (13.05), 7.923 (10.44), 7.937 (5.59), 7.940 (5.21), 7.958 (2.72), 7.976 (1.43), 8.362 (2.05), 8.383 (2.05),
8.397 (12.37), 8.418 (11.26), 8.854 (13.98), 8.860 (14.48), 8.932 (4.65), 9.245 (6.76), 9.254 (6.38), 9.266 (7.08), 9.275 (5.79).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.11), 0.008 (1.00), 3.066 (16.00), 3.071 (4.46), 3.287 , 3.926 (1.28), 4.269
LC-MS (Method L6): Rt =
8 2,53 , 6.785 (0.90), 6.788 (0.97), 6.805 (1.03), 6.808 (1.03), 6.925 (0.97), 6.928 (0.93), 6.944 (0.61), 6.947 (0.58), 7.171 ,
2.06 min; MS s): m/z =
7.359 (0.80), 7.378 (0.74), 7.629 (1.51), 7.634 ), 7.647 , 7.650 (0.96), 7.668 , 7.790 (1.13), 7.793 (1.20), 7.807
492 [M+H]+
(0.93), 7.811 (0.88), 8.229 (1.01), 8.233 (1.03), 8.251 (0.94), 8.254 (0.89), 8.632 (3.95), 9.084 , 9.105 (0.84).
LC-MS (Method L1): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (2.94), 0.008 (2.72), 2.323 (0.52), 2.710 (0.57), 3.070 (16.00), 3.286 (4.49), 3.567
9 1.04 min; MS s): m/z = (0.42), 5.534 (0.73), 7.220 (1.05), 7.235 (1.05), 7.242 (1.91), 7.267 (0.89), 7.630 (1.27), 7.636 (12.76), 7.648 (1.00), 7.670 (0.93),
476 [M+H]+ 7.788 (1.11), 7.792 , 7.806 (0.97), 8.232 (1.08), 8.253 (0.95), 8.638 (4.07), 8.941 (0.86), 8.962 (0.79).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.60), 0.008 (1.51), 2.326 (13.07), 3.055 (16.00), 3.288 (3.31), 6.784 ,
LC-MS (Method L6): Rt =
6.787 (0.96), 6.804 (1.02), 6.807 , 6.922 (0.96), 6.925 (0.93), 6.940 (0.61), 6.943 (0.58), 7.009 (1.28), 7.147 (3.19), 7.584
1.69 min; MS (ESIpos): m/z =
(0.61), 7.601 (1.16), 7.604 (0.75), 7.622 (1.25), 7.640 (1.28), 7.645 , 7.658 (0.73), 8.150 (0.99), 8.154 (0.99), 8.170 (0.93),
476 [M+H]+
8.175 (0.84), 8.581 (4.01), 9.069 (0.84), 9.090 .
1H-NMR (500 MHz, DMSO-d6) delta [ppm]: -0.007 (1.04), 0.007 (1.04), 2.568 (6.31), 3.046 (16.00), 3.286 (1.53), 5.532 (0.72), 5.548
LC-MS (Method L7): Rt =
11 (0.72), 7.220 (1.16), 7.224 (0.84), 7.228 (1.19), 7.233 (1.07), 7.238 (1.68), 7.266 (0.89), 7.403 (0.73), 7.623 (0.69), 7.627 (1.62),
2.58 min; MS (ESIpos): m/z =
7.631 (1.75), 7.641 (5.09), 7.645 (3.28), 7.664 (1.62), 7.667 (1.70), 8.012 (1.49), 8.014 (1.50), 8.016 (1.25), 8.578 (3.50), 8.934
490 [M+H]+
, 8.951 (0.93).
LC-MS (Method L6): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.00), 0.008 (2.59), 2.566 (6.36), 3.042 (16.00), 3.287 (1.44), 4.270 (0.90), 5.754
12 2.18 min; MS (ESIpos): m/z = (4.48), 6.785 (1.08), 6.806 (1.12), 6.923 (1.03), 6.942 (0.64), 7.168 (0.84), 7.351 (0.82), 7.371 (0.78), 7.621 (0.71), 7.626 (1.60),
506 [M+H]+ 7.630 (2.09), 7.639 (6.13), 7.644 (3.08), 7.665 (1.73), 7.670 (1.76), 8.012 (1.45), 8.572 (3.85), 9.076 (0.91), 9.096 (0.91).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.31), 0.008 (1.23), 3.065 (16.00), 4.270 (0.87), 6.785 (0.94), 6.788 (1.04), 6.806
LC-MS (Method L1): Rt =
13 (1.05), 6.809 (1.12), 6.926 , 6.929 (0.96), 6.944 (0.62), 7.171 (0.78), 7.377 (0.73), 7.628 (0.81), 7.646 (1.07), 7.650 ,
1.05 min; MS (ESIpos): m/z =
7.668 (1.02), 7.802 (4.91), 7.806 , 7.818 (4.35), 7.824 , 8.227 (1.02), 8.231 (1.06), 8.249 , 8.252 (0.89), 8.636
510 [M+H]+
(4.18), 9.087 (0.78), 9.108 (0.78).
1H-NMR (400 MHz, CHLOROFORM-d) delta [ppm]: -0.008 (1.09), 0.008 (1.14), 1.562 (5.12), 2.082 (1.48), 2.090 , 2.098 (3.67),
LC-MS (Method L7): Rt =
14 2.107 (2.27), 2.116 (1.78), 2.588 (16.00), 4.031 (2.54), 4.248 (1.04), 4.259 (1.53), 4.270 (1.04), 6.783 (0.82), 7.213 (0.97), 7.232
2.39 min; MS (ESIpos): m/z =
(0.93), 7.348 (4.36), 7.353 (5.19), 7.377 (0.81), 7.525 (1.06), 7.530 (1.97), 7.535 (1.20), 7.571 (0.87), 7.590 (1.42), 7.611 (1.29),
518 [M+H]+
7.676 , 7.679 (1.69), 7.694 (1.17), 7.697 (1.10), 8.088 (1.16), 8.171 (1.22), 8.193 (1.14).
1H-NMR (400 MHz, 6) delta [ppm]: -0.008 (1.60), 0.008 (1.51), 2.326 (13.07), 3.055 (16.00), 3.288 (3.31), 6.784 (0.87),
LC-MS (Method L6): Rt =
6.787 (0.96), 6.804 , 6.807 (1.05), 6.922 (0.96), 6.925 , 6.940 (0.61), 6.943 (0.58), 7.009 (1.28), 7.147 (3.19), 7.584
1.55 min; MS (ESIpos): m/z =
(0.61), 7.601 (1.16), 7.604 (0.75), 7.622 (1.25), 7.640 , 7.645 (1.45), 7.658 (0.73), 8.150 (0.99), 8.154 (0.99), 8.170 (0.93),
452 [M+H]+
8.175
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 2.756 (0.89), 2.770 (0.83), 3.070 (16.00), 7.124 (0.88), 7.173 , 7.177 (0.86), 7.190
LC-MS (Method L6): Rt =
16 (1.17), 7.202 (0.75), 7.207 (0.69), 7.389 (0.77), 7.627 (1.23), 7.632 (11.18), 7.645 (1.08), 7.648 , 7.666 (0.97), 7.783 ,
2.26 min; MS (ESIpos): m/z =
7.787 (1.17), 7.801 (0.91), 7.805 , 8.228 (1.01), 8.232 (1.03), 8.250 (0.94), 8.253 , 8.608 (3.86), 8.972 (0.87), 8.993
490 [M+H]+
(0.85).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.02), 0.008 (0.92), 1.169 (0.67), 3.268 (1.80), 3.280 (4.39), 3.287 (5.64), 3.865
(3.30), 3.877 (5.67), 3.889 (3.15), 4.244 (1.15), 4.252 (0.88), 4.265 (1.45), 4.276 (1.35), 4.283 (0.98), 4.292 (0.96), 5.255 (1.02),
LC-MS (Method L1): Rt =
17 5.275 (1.02), 6.786 (1.88), 6.789 (2.08), 6.807 (2.18), 6.810 (2.27), 6.915 (1.06), 6.918 , 6.934 (2.10), 6.937 (2.04), 6.952
1.24 min; MS (ESIpos): m/z =
(1.32), 6.955 (1.28), 7.153 (1.06), 7.158 (1.11), 7.175 (1.66), 7.192 (0.85), 7.196 (0.84), 7.380 (1.77), 7.399 (1.67), 7.633 (2.13),
534 [M+H]+
7.636 (4.66), 7.639 (16.00), 7.643 (3.34), 7.682 (1.63), 7.699 (2.18), 7.703 (1.97), 7.721 , 7.830 (2.42), 7.834 (2.58), 7.848
(2.01), 7.851 (1.90), 8.276 (2.01), 8.280 (2.07), 8.297 , 8.301 (1.76), 8.699 (8.76), 9.164 , 9.184 (1.86).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (2.30), 0.008 (2.10), 2.037 (0.83), 2.168 (0.72), 2.180 (0.72), 2.262 (16.00), 3.070
LC-MS (Method L6): Rt =
18 (2.04), 4.217 (0.95), 4.243 (1.45), 4.252 (1.36), 4.259 (1.09), 4.268 (1.06), 5.207 (0.94), 5.226 (0.92), 6.779 (1.82), 6.800 ,
1.77 min; MS (ESIpos): m/z =
6.881 (1.11), 6.884 (1.13), 6.900 (2.29), 6.903 (2.22), 6.919 (1.39), 6.922 (1.31), 7.140 (0.97), 7.144 (1.05), 7.161 (1.67), 7.179
506 [M+H]+
(0.84), 7.183 (0.82), 7.323 , 7.343 (1.95), 7.569 (0.80).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.93), 0.008 (1.79), 1.879 (0.89), 1.899 , 1.908 (1.37), 1.930 (1.00), 2.261
LC-MS (Method L6): Rt =
19 (16.00), 2.832 (0.71), 2.851 (0.96), 2.871 , 2.940 , 2.949 (0.89), 2.962 (0.93), 2.971 (0.90), 3.081 (2.10), 5.500 (1.37),
1.81 min; MS (ESIpos): m/z =
.520 (1.38), 7.201 (1.33), 7.207 (2.03), 7.215 (3.05), 7.223 , 7.230 (2.32), 7.243 , 7.248 (0.89), 7.258 (2.20), 7.274
490 [M+H]+
(1.48), 7.280 (1.39), 7.361 (1.57), 7.368 (1.60), 7.383 (1.37), 7.546 , 7.568 (1.01).
LC-MS (Method L1): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 1.149 (1.09), 1.837 (2.38), 2.069 (1.99), 2.757 (4.80), 3.878 (12.72), 5.231 (2.34), 7.125
1.32 min; MS (ESIpos): m/z = , 7.180 (3.90), 7.197 (4.92), 7.213 (3.63), 7.411 (3.59), 7.428 (3.24), 7.636 (16.00), 7.680 (2.42), 7.698 (3.79), 7.718 (2.69),
532 [M+H]+ 7.826 (4.25), 7.842 (3.43), 8.280 , 8.300 (3.40), 8.673 (8.04), 9.047 (3.28), 9.067 (3.16).
LC-MS (Method L1): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 3.071 (16.00), 5.515 (0.74), 5.535 (0.74), 7.213 (1.11), 7.222 (1.33), 7.230 , 7.234
21 1.20 min; MS (ESIpos): m/z = , 7.261 (0.99), 7.381 (0.72), 7.389 (0.77), 7.495 (2.53), 7.500 (2.65), 7.584 (0.68), 7.607 (1.36), 7.630 (0.72), 7.679 ,
494 [M+H]+ 7.684 (1.25), 7.689 (0.68), 8.280 (0.72), 8.295 (0.78), 8.304 , 8.319 (0.70), 8.607 (3.29), 8.927 (0.97), 8.948 (0.95).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 3.067 (16.00), 4.249 (0.91), 4.258 (0.94), 6.779 (0.92), 6.782 (1.01), 6.800 (1.06), 6.803
LC-MS (Method L6): Rt =
22 (1.10), 6.912 (1.02), 6.915 (1.03), 6.931 (0.61), 7.165 (0.86), 7.339 (0.87), 7.358 (0.82), 7.494 , 7.499 (2.71), 7.584 (0.72),
2.26 min; MS (ESIpos): m/z =
7.607 , 7.630 (0.77), 7.677 (0.88), 7.682 (1.54), 7.687 (0.82), 8.278 (0.75), 8.294 (0.81), 8.302 , 8.318 (0.73), 8.600
510 [M+H]+
, 9.066 (0.94), 9.087 (0.93).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 , -0.008 (15.27), 0.008 (13.12), 0.146 (1.58), 2.154 (1.98), 2.367 (2.04),
LC-MS (Method L1): Rt = 0:8/
23 2.709 (1.98), 3.054 (12.95), 3.067 (11.82), 3.288 (8.82), 4.260 (5.48), 5.250 (2.09), 6.782 (4.01), 6.803 (4.13), 6.895 (1.92), 6.910
min; MS (ESIpos): m/z = 496
(3.67), 6.928 (2.37), 7.160 (2.83), 7.308 (3.11), 7.325 (2.94), 7.517 (2.49), 7.535 (3.73), 7.556 (3.00), 7.732 (4.18), 7.746 (3.45),
[M+H]+
7.784 (14.53), 7.801 (16.00), 8.339 (3.17), 8.360 (3.05), 8.453 (11.82), 8.966 (3.17), 8.987 (3.22).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.23), -0.008 ), 0.008 (11.29), 0.146 (1.26), 0.850 (1.36), 0.868 (0.82),
2.046 (1.11), 2.061 (1.08), 2.140 (1.17), 2.154 , 3.055 (9.80), 3.067 (9.17), 3.287 , 4.246 (2.43), 4.259 (4.02), 4.274
LC-MS (Method L1): Rt = , 5.230 (1.36), 5.250 , 6.778 (2.53), 6.781 (2.78), 6.799 (2.91), 6.802 (3.04), 6.891 (1.39), 6.894 (1.42), 6.909 ,
24 0:86 min; MS (ESIpos): m/z = 6.912 (2.81), 6.928 (1.71), 6.931 , 7.140 (1.36), 7.144 (1.49), 7.161 (2.21), 7.179 (1.14), 7.183 (1.17), 7.305 (2.15), 7.324
478 [M+H]+ , 7.516 (2.06), 7.534 (2.62), 7.537 (2.50), 7.555 (2.43), 7.595 (1.71), 7.599 (3.98), 7.604 (4.93), 7.615 (16.00), 7.620 (9.01),
7.713 , 7.716 (3.35), 7.730 (2.69), 7.734 (2.59), 7.792 (1.55), 7.805 (1.49), 8.336 (2.21), 8.340 (2.40), 8.358 (2.25), 8.362
(2.18), 8.446 (9.01), 8.968 (2.50), 8.989 (2.43).
LC-MS (Method L1): Rt =
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 3.282 (1.79), 3.293 (1.98), 3.311 (16.00), 6.807 (0.71), 6.932 (0.68), 7.468 (0.89), 7.474
1.08 min; MS (ESIpos): m/z =
(0.85), 7.493 (0.76), 7.540 (0.71), 7.643 (0.98), 7.780 (0.75), 8.673 (1.65).
500 [M+H]+
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (4.85), 0.008 (4.19), 1.234 (0.78), 1.710 (0.76), 1.740 (0.93), 1.986 (1.09), 1.999
(1.07), 2.007 , 2.021 (0.85), 2.072 (1.71), 2.366 (0.62), 2.709 (0.62), 3.287 (4.75), 3.971 (0.74), 3.977 (0.87), 3.999 (1.86),
LC-MS (Method L1): Rt = 4.006 (1.18), 4.021 (1.22), 4.027 (0.93), 4.132 (0.93), 4.139 (1.24), 4.149 (1.14), 4.158 (1.40), 4.168 (0.85), 4.176 , 4.185
26 1.07 min; MS (ESIpos): m/z = (0.68), 5.041 , 5.055 (1.65), 5.074 (1.65), 5.088 (0.72), 6.741 (3.06), 6.761 (3.39), 6.837 (1.45), 6.840 (1.45), 6.856 (3.14),
515 [M+H]+ 6.874 (1.94), 7.020 (2.31), 7.039 (1.88), 7.122 (1.63), 7.126 (1.53), 7.142 (2.64), 7.160 (1.30), 7.164 (1.22), 7.264 (5.35), 7.499
(5.93), 7.502 (6.65), 7.519 (3.45), 7.523 (3.34), 7.700 (5.90), 7.703 (16.00), 7.802 (2.44), 7.820 (3.22), 7.841 (2.46), 7.917 (3.72),
8.008 (3.14), 8.011 (3.53), 8.027 , 8.030 (2.85), 8.962 (2.87), 8.982 , 9.152 (10.38).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 12.73 (br s, 1H), 9.01 (d, 1H), 8.69 (s, 1H), 8.46 (d, 1H), 8.30 (br d, 1H), 8.13 (s, 1H), 7.75
27 1.06 min; MS (ESIpos): m/z = (d, 1H), 7.69 (s, 1H), 7.41 - 7.62 (m, 4H), 7.07 - 7.36 (m, 8H), 5.39 - 5.60 (m, 2H), 2.90 - 3.07 (m, 2H), 2.73 - 2.88 (m, 2H), 2.57 -
530 [M+H]+ 2.69 (m, 1H), 2.53 - 2.71 (m, 13H), 2.30 - 2.44 (m, 1H), 2.09 (dq, 1H), 1.93 (dq, 1H).
LC-MS (Method L1): Rt =
28 1.09 min; MS (ESIpos): m/z =
564 [M+H]+
LC-MS (Method L1): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 3.072 (16.00), 3.287 (1.21), 5.754 (0.68), 6.774 (0.89), 6.777 (0.93), 6.794 (1.01), 6.797
29 0.88 min; MS (ESIpos): m/z = (0.99), 6.905 (0.97), 6.908 (0.91), 6.923 (0.62), 7.303 (0.79), 7.311 , 7.324 (0.64), 7.332 (1.23), 7.579 (0.65), 7.633 (3.39),
476 [M+H]+ 7.641 (1.60), 7.651 (1.51), 8.240 (1.01), 8.247 (0.94), 8.258 (0.82), 8.265 (0.85), 8.531 (4.23), 9.073 (0.80), 9.093 (0.77).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (0.71), 3.063 (16.00), 4.262 (0.82), 4.270 (0.92), 6.784 (0.87), 6.787 (0.95), 6.805
LC-MS (Method L1): Rt =
(1.03), 6.808 (1.04), 6.924 (0.98), 6.927 (0.96), 6.943 (0.63), 6.946 , 7.171 (0.79), 7.351 (0.81), 7.370 (0.78), 7.496 (0.70),
0.88 min; MS (ESIpos): m/z =
7.523 (0.72), 7.620 , 7.637 (1.13), 7.641 (1.00), 7.659 (1.13), 7.751 (1.16), 7.754 , 7.768 (0.93), 7.772 (0.86), 8.201
460 [M+H]+
(1.03), 8.205 (1.05), 8.222 (0.98), 8.226 (0.90), 8.613 , 9.077 (0.87), 9.097 (0.85).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 3.059 (16.00), 3.287 (0.75), 3.855 (10.21), 4.263 (0.81), 4.271 (0.92), 6.785 (0.89), 6.788
LC-MS (Method L1): Rt = (1.00), 6.806 (1.02), 6.808 (1.10), 6.923 , 6.926 (1.02), 6.942 (0.60), 7.143 (0.67), 7.149 (1.06), 7.154 (1.00), 7.171 (0.85),
31 0.83 min; MS (ESIpos): m/z = 7.244 , 7.265 (0.76), 7.273 (0.99), 7.294 (0.73), 7.344 (0.93), 7.349 (1.64), 7.366 (1.32), 7.370 (1.57), 7.607 (0.73), 7.625
472 [M+H]+ (1.04), 7.628 (0.92), 7.646 (1.00), 7.731 (1.12), 7.735 (1.21), 7.749 (0.87), 7.752 , 8.176 (0.99), 8.180 (1.04), 8.197 (0.93),
8.201 (0.91), 8.600 (3.83), 9.082 (0.91), 9.103 (0.89).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.08), 0.008 (1.10), 3.069 (16.00), 3.944 , 4.253 (0.96), 4.262 (1.04), 6.777
LC-MS (Method L1): Rt = (1.03), 6.781 (1.18), 6.798 (1.20), 6.801 (1.26), 6.894 (0.57), 6.897 (0.59), 6.912 (1.14), 6.915 (1.14), 6.931 (0.70), 6.934 (0.68),
32 0.87 min; MS (ESIpos): m/z = 7.116 (0.62), 7.131 (0.71), 7.134 , 7.146 (0.75), 7.163 (0.92), 7.186 (0.84), 7.213 (0.89), 7.339 (0.92), 7.358 (0.88), 7.623
490 [M+H]+ (0.67), 7.641 (1.36), 7.643 , 7.661 , 7.675 (1.33), 7.679 (1.50), 7.692 (0.67), 8.235 (1.06), 8.239 (1.07), 8.255 (1.01),
8.260 (0.92), 8.549 (4.05), 9.070 (1.00), 9.091 (0.97).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 1.819 , 1.835 (1.55), 3.072 (16.00), 4.248 (0.89), 4.257 (0.93), 6.777 (0.92), 6.798
LC-MS (Method L1): Rt =
33 (1.00), 6.904 (0.81), 7.160 (1.13), 7.181 (0.99), 7.184 (0.91), 7.328 (0.83), 7.347 (0.76), 7.558 (0.73), 7.562 , 7.576 (1.27),
0.84 min; MS (ESIpos): m/z =
7.579 , 7.618 (1.09), 7.635 (0.76), 7.639 (1.15), 7.656 (0.69), 8.216 (1.00), 8.220 (1.05), 8.237 (0.92), 8.241 (0.89), 8.521
456 [M+H]+
(3.83).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (0.91), 0.008 (0.91), 3.074 (16.00), 3.287 (1.06), 4.248 (0.91), 4.255 , 6.771
LC-MS (Method L1): Rt =
34 (1.09), 6.774 (1.20), 6.792 (1.29), 6.795 (1.32), 6.903 (1.12), 6.922 (0.67), 7.140 (0.60), 7.156 (0.93), 7.324 (1.17), 7.328 (1.10),
0.93 min; MS (ESIpos): m/z =
7.343 (1.08), 7.347 (1.14), 7.426 (0.79), 7.437 (0.86), 7.628 (1.83), 7.632 (3.18), 7.651 (1.79), 7.669 (0.69), 7.675 (1.55), 7.679
492 [M+H]+
(1.60), 7.695 (1.35), 7.699 (1.26), 8.240 (1.22), 8.246 (1.24), 8.259 (1.08), 8.265 (1.09), 8.520 (2.86).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.10), 0.008 (2.86), 1.147 (0.97), 1.920 (1.70), 1.930 (0.91), 1.940 (1.83), 1.952
(1.95), 1.961 (0.97), 1.971 (1.89), 1.993 (0.73), 2.366 (2.43), 2.525 (6.69), 2.566 (2.62), 2.710 (2.49), 2.831 (0.79), 2.852 (1.52),
2.871 (2.01), 2.891 (2.68), 2.911 (1.22), 2.963 (1.58), 2.972 (1.70), 2.985 (1.70), 2.994 (1.64), 3.002 , 3.012 (0.91), 3.024
LC-MS (Method L1): Rt = (0.91), 3.033 (0.79), 3.288 ), 3.297 (13.02), 3.859 (8.40), 3.871 (12.35), 3.882 , 5.524 (1.03), 5.543 (3.04), 5.563 (3.04),
1.12 min; MS (ESIpos): m/z = 5.582 , 7.226 , 7.234 (5.60), 7.240 (6.14), 7.248 (9.06), 7.258 (2.62), 7.270 (4.02), 7.279 (2.43), 7.292 , 7.420
484 [M+H]+ (2.92), 7.429 (2.92), 7.442 (2.56), 7.451 (2.31), 7.456 , 7.466 (3.71), 7.471 (6.39), 7.476 (4.68), 7.479 (4.87), 7.497 (6.69),
7.516 (3.10), 7.538 (3.41), 7.542 , 7.547 , 7.556 (1.89), 7.560 , 7.565 (1.64), 7.640 (4.26), 7.644 (6.69), 7.649
(3.89), 7.675 (2.92), 7.693 (4.50), 7.696 (3.83), 7.714 (4.26), 7.777 (5.05), 7.781 (5.23), 7.795 (3.71), 7.799 (3.35), 8.255 ,
8.258 (4.14), 8.276 (3.95), 8.279 (3.65), 8.675 (16.00), 9.020 (4.02), 9.041 (3.89).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.70), -0.008 (6.82), 0.008 (6.40), 0.146 (0.83), 1.147 (1.53), 1.926 (4.03), 1.947
LC-MS d L1): Rt =
36 (3.76), 2.328 , 2.366 (2.09), 2.665 (1.11), 2.670 (1.25), 2.710 (2.09), 3.072 (16.00), 3.289 (10.16), 4.248 , 5.225 (0.56),
0.86 min; MS (ESIpos): m/z =
6.775 (1.11), 6.796 (1.25), 6.903 (0.83), 7.131 (1.11), 7.159 (1.11), 7.263 (0.83), 7.328 (0.97), 7.346 (0.83), 7.461 (1.25), 7.481
472 [M+H]+
(0.97), 7.564 (0.97), 7.578 (1.39), 7.582 , 7.619 (1.11), 7.640 (1.25), 7.658 (0.70), 8.216 (1.11), 8.518 (4.31), 9.058 (0.56).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.91), 0.008 (3.78), 1.147 (0.96), 2.019 (0.89), 2.028 (1.03), 2.047 (0.96), 2.055
(1.51), 2.062 (1.30), 2.070 , 2.170 (0.96), 2.182 (1.30), 2.194 (1.30), 2.204 (1.17), 2.327 (0.69), 2.366 (1.44), 2.665 (0.55),
2.669 (0.76), 2.674 (0.55), 2.710 (1.51), 3.081 (16.00), 4.212 (0.69), 4.232 (2.20), 4.240 (1.85), 4.252 (3.50), 4.261 (3.64), 4.268
LC-MS (Method L1): Rt =
37 (2.06), 4.277 (1.99), 4.295 (0.69), 5.218 (0.89), 5.232 (1.92), 5.252 (1.85), 5.266 (0.82), 6.778 (3.50), 6.781 (3.85), 6.799 (4.05),
0.90 min; MS (ESIpos): m/z =
6.802 (4.26), 6.894 (2.06), 6.897 (2.06), 6.912 , 6.915 , 6.931 (2.61), 6.934 (2.40), 7.143 (1.99), 7.147 (2.06), 7.164
476 [M+H]+
(3.09), 7.182 (1.65), 7.186 (1.58), 7.319 (1.65), 7.341 (6.59), 7.364 (4.74), 7.480 (1.51), 7.487 , 7.495 , 7.502 (2.27),
7.518 (1.72), 7.528 (1.30), 7.540 (1.30), 7.636 (2.33), 7.654 (3.71), 7.657 (2.95), 7.675 (3.57), 7.730 (3.16), 7.745 (2.06), 8.257
(2.47), 8.277 (2.33), 8.550 (5.15), 9.077 (2.61), 9.097 .
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.49), -0.008 ), 0.008 (12.78), 0.146 (1.49), 1.147 (1.73), 2.199 (0.78),
LC-MS (Method L6): Rt =
38 2.327 (1.25), 2.366 (1.88), 2.669 (1.41), 2.710 (1.88), 3.043 (1.65), 3.079 (16.00), 3.287 (12.86), 3.611 (0.63), 3.906 (4.16), 3.922
1.80 min; MS (ESIpos): m/z =
, 4.249 (0.78), 5.247 (0.71), 6.777 (1.10), 6.798 (1.18), 6.911 (0.94), 7.160 (0.86), 7.355 (1.18), 7.651 (0.71), 7.669 ,
508 [M+H]+
7.690 (1.18), 7.752 (1.25), 8.280 (1.02), 8.302 (0.94), 8.544 (4.00).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (0.97), 0.008 (0.99), 3.043 (0.70), 3.071 ), 3.289 (2.25), 4.241 , 4.250
LC-MS (Method L1): Rt = (0.99), 6.769 (1.02), 6.772 (1.12), 6.789 , 6.792 (1.24), 6.877 (0.58), 6.896 (1.12), 6.914 (0.70), 7.137 (0.61), 7.154 (0.92),
39 0.94 min; MS (ESIpos): m/z = 7.318 (0.87), 7.339 (1.14), 7.361 (0.68), 7.374 (0.75), 7.394 (0.75), 7.597 (1.38), 7.604 (2.28), 7.624 (1.55), 7.641 (0.61), 7.776
526 [M+H]+ (0.75), 7.894 (0.85), 7.899 (0.85), 7.904 (0.85), 7.910 (0.73), 8.233 , 8.239 (1.09), 8.253 (0.97), 8.258 (0.95), 8.473 (2.47),
8.476 (2.79), 9.074 (0.75), 9.094 (0.70).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.20), 0.008 (1.12), 3.036 ), 3.287 (1.15), 4.256 (0.82), 4.265 (0.81), 6.785
LC-MS d L1): Rt =
40 (0.91), 6.788 (1.01), 6.805 (1.04), 6.808 (1.09), 6.923 (0.98), 6.926 (0.95), 6.942 (0.61), 7.171 (0.77), 7.355 (0.79), 7.374 (0.75),
1.28 min; MS (ESIpos): m/z =
7.674 (1.45), 7.677 (3.02), 7.681 (6.87), 7.684 (2.17), 7.687 (1.35), 7.794 (0.76), 7.801 , 7.816 (0.76), 7.823 (0.93), 7.884
510 [M+H]+
(0.86), 7.892 , 7.910 (0.84), 7.917 (0.75), 8.627 (3.52), 9.120 (0.88), 9.140 (0.86).
LC-MS (Method L1): Rt = 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 3.035 (16.00), 3.287 (1.06), 4.256 (0.95), 4.266 , 6.788 (1.08), 6.808 (1.19), 6.924
41 1.29 min; MS (ESIpos): m/z = (1.08), 7.173 (0.90), 7.355 (0.95), 7.374 (0.86), 7.810 (0.67), 7.817 (0.87), 7.833 (0.70), 7.840 (0.82), 7.861 (3.09), 7.878 (3.15),
528 [M+H]+ 7.884 (0.99), 7.891 (0.79), 7.910 (0.83), 7.917 (0.71), 8.631 (3.37), 9.121 , 9.142 (0.97).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 2.084 (0.98), 2.091 (0.83), 2.207 (0.87), 2.219 (0.85), 2.229 (0.81), 3.239 (2.45), 3.250
(5.46), 3.261 (5.61), 3.272 (2.65), 3.288 (1.94), 3.860 (4.44), 3.872 (7.25), 3.883 (4.20), 4.238 , 4.245 (1.11), 4.259 (1.49),
LC-MS (Method L1): Rt =
42 4.266 (1.84), 4.275 (1.47), 4.281 (1.19), 4.290 (1.20), 5.250 (1.36), 5.269 (1.34), 6.787 (2.49), 6.807 (2.79), 6.913 (1.30), 6.916
1.31 min; MS (ESIpos): m/z =
(0.97), 6.932 (2.70), 6.950 (1.60), 7.154 , 7.175 (2.09), 7.193 (1.03), 7.377 (2.28), 7.395 (2.06), 7.684 (12.45), 7.686 (16.00),
552 [M+H]+
7.839 (1.47), 7.843 (1.61), 7.846 (1.80), 7.861 (1.53), 7.869 (1.65), 7.892 , 7.899 (1.55), 7.917 (1.79), 7.924 , 8.694
(6.98), 9.201 , 9.221 (2.33).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.62), -0.008 (6.95), 0.008 (6.61), 0.146 (0.77), 1.146 (1.05), 1.235 (0.81), 2.085
(1.58), 2.208 (1.53), 2.327 (0.77), 2.366 , 2.670 (0.91), 2.709 (1.39), 3.249 (9.34), 3.260 (9.68), 3.287 (9.96), 3.861 (7.43),
LC-MS (Method L1): Rt =
43 3.872 (12.12), 3.883 (7.23), 4.238 (2.40), 4.266 (3.02), 4.275 (2.49), 4.292 (2.01), 5.250 (2.25), 5.269 , 6.790 (4.07), 6.808
1.31 min; MS (ESIpos): m/z =
(4.50), 6.916 (2.01), 6.932 (4.26), 6.954 (2.49), 7.159 (2.20), 7.176 (3.50), 7.197 (1.72), 7.377 (3.69), 7.396 (3.50), 7.856 (2.83),
570 [M+H]+
7.863 (5.37), 7.868 (13.51), 7.884 (16.00), 7.891 (4.55), 7.898 (2.97), 7.916 (3.26), 7.923 (2.54), 8.700 (13.03), 9.202 (3.83), 9.222
(3.78).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (2.21), 0.008 , 2.301 (2.93), 2.377 (7.46), 3.062 (16.00), 4.263 (0.86), 4.270
LC-MS (Method L1): Rt = (0.99), 6.785 (1.06), 6.788 (1.15), 6.805 (1.22), 6.808 (1.26), 6.905 (0.56), 6.908 (0.59), 6.924 (1.13), 6.927 (1.11), 6.943 (0.70),
44 0.90 min; MS (ESIpos): m/z = 6.946 (0.67), 7.153 (0.60), 7.170 , 7.286 (1.86), 7.333 (1.69), 7.335 (1.73), 7.358 , 7.374 (0.87), 7.417 (1.07), 7.421
472 [M+H]+ (1.60), 7.610 (0.86), 7.627 (1.27), 7.631 , 7.648 (1.23), 7.712 (1.31), 7.716 (1.44), 7.730 (0.99), 7.734 (0.91), 8.169 (2.71),
8.193 (1.12), 8.196 (1.15), 8.214 (1.07), 8.218 (1.00), 8.609 (4.09), 9.077 (0.98), 9.098 (0.96).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (2.87), 0.008 (2.38), 3.066 (16.00), 4.242 (0.72), 4.261 (1.05), 4.269 , 6.785
(1.14), 6.788 (1.20), 6.805 (1.30), 6.808 , 6.906 , 6.909 , 6.924 (1.28), 6.928 (1.24), 6.943 (0.82), 6.946 (0.75),
LC-MS (Method L1): Rt =
45 7.149 (0.62), 7.153 (0.66), 7.171 (1.01), 7.352 (0.99), 7.371 (1.02), 7.477 (0.90), 7.498 (1.55), 7.521 (1.34), 7.580 (0.77), 7.586
0.89 min; MS (ESIpos): m/z =
(0.81), 7.593 (0.84), 7.598 (0.88), 7.602 (0.64), 7.607 (0.63), 7.614 (0.57), 7.622 (1.17), 7.639 (1.40), 7.643 , 7.661 (1.36),
476 [M+H]+
7.754 (1.52), 7.758 (1.56), 7.772 , 7.776 (1.13), 7.788 (1.17), 7.794 (1.08), 7.807 (1.15), 7.812 (1.07), 8.205 (1.23), 8.208
(1.27), 8.226 , 8.230 (1.10), 8.278 (0.69), 8.614 (3.82), 9.077 (1.08), 9.098 (1.06).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.83), -0.008 , 0.008 (6.79), 0.146 (0.83), 2.033 (0.69), 2.041 (0.72), 2.053
(0.69), 2.068 (1.10), 2.076 (0.89), 2.083 (0.66), 2.176 (0.69), 2.189 (0.92), 2.201 (0.92), 2.211 (0.83), 2.236 (0.60), 2.366 ,
2.710 (1.04), 3.074 (16.00), 4.241 (1.55), 4.249 (1.37), 4.261 (2.38), 4.269 (2.62), 4.285 (1.40), 5.226 (0.60), 5.241 (1.40), 5.260
LC-MS (Method L1): Rt = (1.40), 5.275 (0.63), 6.785 (2.53), 6.788 (2.68), 6.806 (2.92), 6.809 (2.95), 6.906 (1.43), 6.909 (1.46), 6.924 (2.86), 6.928 (2.74),
46 0.94 min; MS s): m/z = 6.943 (1.82), 6.946 (1.67), 7.150 (1.52), 7.154 (1.49), 7.171 (2.23), 7.189 (1.16), 7.193 (1.13), 7.356 (2.32), 7.374 (2.20), 7.429
476 [M+H]+ (1.13), 7.432 (1.46), 7.435 , 7.438 (2.26), 7.446 (1.31), 7.453 (2.06), 7.457 (2.41), 7.459 , 7.463 (2.86), 7.468 (1.43),
7.473 (1.61), 7.478 (1.13), 7.515 (3.04), 7.519 (4.35), 7.523 (2.26), 7.625 (0.72), 7.631 , 7.649 (2.86), 7.652 (2.59), 7.670
(2.77), 7.790 (2.95), 7.794 (3.10), 7.809 (2.47), 7.812 (2.32), 8.232 (2.15), 8.235 (2.18), 8.253 , 8.256 (1.97), 8.418 (1.28),
8.623 (3.81), 9.088 (2.12), 9.108 (2.06).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.98), -0.011 (6.35), -0.008 ), 0.008 (8.04), 0.146 (1.09), 1.147 (0.63),
2.033 (1.06), 2.041 (1.06), 2.052 (1.09), 2.068 (1.50), 2.075 (1.28), 2.083 (0.90), 2.176 (1.09), 2.189 , 2.201 (1.31), 2.211
(1.20), 2.669 (0.60), 3.079 (16.00), 4.220 , 4.240 (2.37), 4.249 (2.02), 4.260 , 4.269 (3.60), 4.275 (2.15), 4.285 (1.88),
LC-MS (Method L1): Rt =
47 4.304 (0.65), 5.228 (0.95), 5.240 (1.99), 5.261 (1.91), 5.275 (0.82), 6.787 , 6.790 (3.68), 6.807 (4.17), 6.810 (3.93), 6.906
0.92 min; MS (ESIpos): m/z =
(2.15), 6.909 (2.07), 6.924 (4.01), 6.928 (3.68), 6.943 (2.53), 6.947 (2.18), 7.152 (2.07), 7.156 (2.10), 7.173 (3.11), 7.190 (1.58),
478 [M+H]+
7.194 (1.53), 7.352 (3.08), 7.371 , 7.558 (4.31), 7.575 (4.63), 7.581 (5.34), 7.599 , 7.608 (0.93), 7.632 (2.81), 7.650
(3.84), 7.653 (3.35), 7.671 , 7.791 (4.03), 7.795 (4.09), 7.809 (3.35), 7.813 , 8.233 (2.78), 8.254 (2.40), 8.444 (1.55),
8.617 (4.03), 9.093 (2.64), 9.113 (2.53).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.64), -0.008 (16.00), 0.008 (12.95), 0.146 (1.58), 1.147 (1.58), 2.025 (1.87),
2.033 (2.09), 2.045 (2.32), 2.060 (3.17), 2.068 (2.71), 2.169 (2.04), 2.181 (2.94), 2.195 (2.83), 2.203 (2.83), 2.217 (1.87), 2.327
LC-MS (Method L1): Rt = (1.02), 2.366 (2.15), 2.669 (1.30), 2.709 (2.20), 3.193 (6.61), 4.195 (1.58), 4.216 (4.24), 4.237 (3.56), 4.253 (3.34), 4.262 (4.35),
48 0.98 min; MS (ESIpos): m/z = 4.269 (3.79), 4.278 (3.96), 4.289 (1.70), 4.297 (1.92), 5.198 (1.70), 5.212 (3.84), 5.232 (3.84), 6.786 (7.41), 6.789 (7.75), 6.807
526 [M+H]+ (8.54), 6.810 (8.59), 6.888 (4.13), 6.891 (4.18), 6.907 (8.65), 6.910 (8.37), 6.925 (5.37), 6.928 (4.98), 7.149 (4.18), 7.153 (4.35),
7.171 (6.78), 7.188 , 7.192 (3.39), 7.341 (7.24), 7.360 (6.90), 7.446 (3.39), 7.466 (2.77), 7.516 (4.01), 7.681 (4.47), 7.699
(5.88), 7.720 , 7.798 (2.94), 8.345 (2.37), 8.479 (3.11), 9.124 (3.00), 9.144 (3.05).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 , -0.008 (16.00), 0.008 (13.79), 0.146 (1.77), 1.147 (1.47), 2.040 (1.77),
2.067 (2.73), 2.073 (2.21), 2.189 (2.43), 2.201 (2.36), 2.211 (2.29), 2.327 (1.40), 2.366 (2.73), 2.669 (1.40), 2.710 (2.65), 3.179
LC-MS (Method L1): Rt = (6.34), 4.207 (1.25), 4.228 (3.47), 4.249 (3.02), 4.259 (3.32), 4.270 (3.61), 4.276 (3.02), 4.286 , 4.304 (1.33), 5.225 (3.17),
49 0.86 min; MS (ESIpos): m/z = 5.245 (3.10), 6.420 (0.59), 6.443 (0.59), 6.792 (6.34), 6.795 (6.64), 6.813 (7.37), 6.816 (7.30), 6.900 (3.39), 6.903 , 6.918
460 [M+H]+ (6.93), 6.922 (6.78), 6.937 (4.50), 6.940 , 7.156 (3.54), 7.160 (3.61), 7.178 (5.46), 7.195 (3.24), 7.199 (2.80), 7.217 (0.66),
7.241 (1.11), 7.265 (0.74), 7.319 (9.07), 7.324 (9.73), 7.345 (12.90), 7.366 (6.05), 7.377 (1.84), 7.382 (1.92), 7.398 (1.62), 7.404
, 7.653 (3.10), 7.671 (4.87), 7.692 (3.76), 7.820 (4.87), 7.836 , 8.132 (1.25), 8.280 (2.36), 8.538 (1.62), 9.132 .
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.73), -0.008 (16.00), 0.008 (14.73), 0.146 (1.80), 1.147 (1.73), 2.033 (2.47),
2.045 (2.87), 2.060 (3.80), 2.075 (2.47), 2.167 (2.47), 2.180 (3.53), 2.192 (3.47), 2.201 (3.33), 2.214 (2.40), 2.327 (1.33), 2.366
LC-MS (Method L1): Rt = (2.40), 2.669 (1.53), 2.710 (2.40), 3.162 (9.07), 4.196 (1.80), 4.217 (5.20), 4.238 (4.73), 4.250 (4.93), 4.260 , 4.267 (4.60),
50 0.96 min; MS (ESIpos): m/z = 4.275 (4.67), 4.295 (2.07), 5.197 (2.00), 5.213 (4.67), 5.232 (4.67), 5.245 (2.20), 6.784 (9.40), 6.786 (10.33), 6.804 ), 6.807
510 [M+H]+ (11.13), 6.887 (5.20), 6.890 (5.40), 6.906 (10.73), 6.909 (10.67), 6.924 (6.47), 6.928 (6.20), 7.147 (5.13), 7.151 (5.33), 7.168 ,
7.185 (4.13), 7.189 (4.07), 7.347 (8.87), 7.363 (8.33), 7.540 , 7.680 (3.40), 7.698 (6.33), 7.719 , 7.790 (8.33), 7.878
(3.47), 8.132 (1.13), 8.342 (3.00), 8.498 , 9.120 (3.87), 9.138 (3.87).
1H-NMR (400 MHz, 6) delta [ppm]: -0.149 (1.69), -0.008 (16.00), 0.008 (14.14), 0.146 (1.86), 1.147 (1.52), 2.032 (1.78),
2.060 , 2.183 (2.37), 2.196 (2.29), 2.205 (2.20), 2.218 , 2.328 (1.27), 2.332 , 2.366 (2.88), 2.670 (1.44), 2.710
LC-MS (Method L1): Rt =
51 (3.05), 3.203 (4.99), 4.196 (1.27), 4.217 (3.30), 4.237 , 4.263 (3.56), 4.271 (3.05), 4.280 (3.13), 5.211 (3.13), 5.231 (3.13),
0.89 min; MS s): m/z =
6.787 (6.26), 6.790 (6.52), 6.808 (7.20), 6.811 (7.11), 6.889 (3.64), 6.892 (3.64), 6.908 (7.53), 6.911 (6.94), 6.927 (4.49), 6.930
476 [M+H]+
(4.23), 7.151 (3.56), 7.155 (3.56), 7.172 (5.59), 7.189 (2.79), 7.193 (2.96), 7.346 (7.28), 7.364 (8.30), 7.436 (3.30), 7.697 ,
7.718 (4.06), 7.778 (2.46), 8.132 , 8.336 (1.86), 8.478 (2.12), 9.127 (2.37).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.150 (0.80), -0.008 (7.08), 0.008 (6.23), 0.146 (0.85), 1.147 (0.94), 1.234 (1.04), 1.401
(0.66), 2.061 (1.98), 2.184 (1.46), 2.196 (1.94), 2.208 , 2.218 (1.84), 2.327 , 2.366 (1.32), 2.669 (0.76), 2.710 (1.37),
3.288 (16.00), 3.336 (2.41), 3.866 (9.35), 3.876 (15.01), 3.888 (8.54), 4.211 , 4.231 (3.26), 4.239 , 4.252 (4.48), 4.262
LC-MS (Method L6): Rt =
52 (4.25), 4.270 (2.78), 4.279 (2.83), 4.298 (0.94), 5.241 (2.45), 5.256 (2.41), 5.754 (5.00), 6.777 (5.57), 6.794 (5.95), 6.797 (6.14),
2.17 min; MS s): m/z =
6.893 (2.17), 6.912 (4.63), 6.930 (2.69), 7.140 (2.64), 7.161 (4.58), 7.178 (2.08), 7.304 (1.84), 7.307 (1.98), 7.323 (2.88), 7.327
534 [M+H]+
(3.59), 7.333 (2.45), 7.352 (7.69), 7.370 , 7.413 , 7.424 (2.55), 7.432 (3.73), 7.444 (4.11), 7.451 (2.08), 7.463 (2.03),
7.655 (2.12), 7.659 (2.93), 7.672 (7.74), 7.677 (7.17), 7.684 (14.35), 7.687 (8.73), 7.704 (12.93), 7.707 (7.46), 7.722 (3.26), 8.277
(5.38), 8.282 (5.47), 8.297 (4.91), 8.302 (4.67), 8.583 (8.50), 8.590 (9.39), 9.143 (2.27), 9.158 (3.16), 9.178 (2.55).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.011 (3.43), -0.008 (7.74), 0.008 (4.34), 0.146 (0.57), 1.157 (2.48), 1.175 (4.93), 1.193
, 1.988 (8.75), 2.057 (0.67), 2.072 , 2.080 (0.75), 2.204 (0.82), 2.216 (0.77), 2.225 (0.77), 3.272 (2.97), 3.285 (6.13),
3.297 (8.04), 3.863 (4.09), 3.875 (6.63), 3.887 (3.55), 3.945 (16.00), 4.003 (0.72), 4.021 (2.03), 4.038 (2.03), 4.056 (0.67), 4.236
(1.36), 4.244 (1.09), 4.257 (1.56), 4.270 (1.44), 4.277 (1.09), 4.286 (1.09), 5.250 (1.24), 5.269 (1.16), 6.780 (2.31), 6.783 (2.38),
LC-MS (Method L1): Rt =
53 6.800 (2.55), 6.803 (2.50), 6.902 , 6.906 (1.27), 6.921 , 6.924 (2.23), 6.940 (1.54), 6.943 (1.36), 7.100 (0.70), 7.115
1.02 min; MS (ESIpos): m/z =
(1.01), 7.121 (1.41), 7.128 , 7.137 (1.63), 7.140 (1.61), 7.146 (1.99), 7.151 (1.98), 7.156 (1.37), 7.166 , 7.168 (2.40),
532 [M+H]+
7.186 (1.12), 7.190 (1.14), 7.195 (1.44), 7.199 (1.34), 7.216 (1.04), 7.221 (2.01), 7.226 (1.29), 7.243 (0.85), 7.247 , 7.353
(0.64), 7.356 (0.82), 7.361 (2.01), 7.374 (1.09), 7.377 (1.11), 7.381 (1.86), 7.391 (0.57), 7.465 (0.90), 7.485 (0.60), 7.676 ,
7.694 , 7.714 (4.29), 7.717 (3.84), 7.722 (3.60), 7.734 (1.24), 7.739 (0.70), 8.095 (0.60), 8.278 (2.26), 8.283 (2.09), 8.298
(2.13), 8.303 (1.81), 8.615 (10.00), 9.154 , 9.175 (2.11).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.29), -0.008 (12.61), 0.008 (10.72), 0.146 (1.29), 1.147 (0.91), 1.235 (0.73),
1.988 (0.80), 2.087 (1.68), 2.210 (1.47), 2.231 (1.33), 2.366 , 2.710 (1.40), 3.267 (4.16), 3.278 (9.96), 3.287 (15.97), 3.864
LC-MS (Method L1): Rt = (7.30), 3.876 (12.16), 3.888 (7.06), 4.224 (0.73), 4.244 (2.38), 4.252 (1.92), 4.265 (3.14), 4.276 (3.00), 4.292 (2.06), 5.255 (2.20),
54 1.24 min; MS (ESIpos): m/z = 5.275 (2.24), 6.789 (4.37), 6.810 (4.72), 6.916 , 6.919 (2.06), 6.934 (4.26), 6.953 (2.59), 7.154 (2.24), 7.158 , 7.175
552 [M+H]+ (3.49), 7.192 (1.71), 7.381 (3.70), 7.399 (3.42), 7.681 , 7.699 (4.19), 7.702 (3.95), 7.720 (3.84), 7.806 (14.46), 7.822 (14.43),
7.843 (4.61), 7.846 (4.93), 7.861 , 7.864 (3.67), 8.273 (3.95), 8.277 (4.12), 8.295 (3.81), 8.298 (3.67), 8.704 (16.00), 9.165
(3.98), 9.186 (3.91).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.58), 0.008 (1.48), 3.056 (16.00), 3.065 (1.61), 3.289 (1.47), 3.903 (10.43),
LC-MS (Method L6): Rt = 3.909 , 4.271 (0.85), 6.785 (0.92), 6.788 (1.00), 6.805 (1.06), 6.808 (1.08), 6.926 (1.03), 6.929 (0.97), 6.945 (0.63), 7.171
55 1.44 min; MS (ESIpos): m/z = (0.82), 7.220 (0.62), 7.242 (1.22), 7.264 , 7.354 (0.82), 7.374 (1.35), 7.376 (1.39), 7.382 (0.75), 7.475 (0.94), 7.480 (0.83),
472 [M+H]+ 7.507 (0.90), 7.513 (0.86), 7.597 (0.76), 7.615 (1.05), 7.618 (0.89), 7.636 (1.04), 7.717 (1.17), 7.721 (1.25), 7.735 (0.90), 7.739
(0.84), 8.156 (1.01), 8.160 (1.04), 8.177 (0.96), 8.181 (0.89), 8.608 (4.20), 9.075 (0.90), 9.096 (0.86).
1H-NMR (500 MHz, DMSO-d6) delta [ppm]: 2.403 (6.76), 3.060 (16.00), 3.164 (0.79), 3.174 (0.80), 4.261 , 6.787 (0.91), 6.789
LC-MS (Method L6): Rt =
56 (0.97), 6.803 (1.01), 6.806 (1.01), 6.925 , 6.927 (0.92), 6.940 , 7.170 (0.76), 7.355 , 7.370 (0.74), 7.431 (1.71),
1.79 min; MS (ESIpos): m/z =
7.447 (1.38), 7.451 (1.32), 7.614 (0.78), 7.629 (1.13), 7.631 (1.04), 7.636 , 7.639 (1.64), 7.646 (1.03), 7.721 (1.15), 7.724
472 [M+H]+
(1.19), 7.735 (0.90), 7.738 (0.83), 8.185 (1.00), 8.188 (1.01), 8.202 (0.95), 8.205 (0.87), 8.601 (3.95), 9.077 (0.87), 9.094 (0.83).
1H-NMR (500 MHz, 6) delta [ppm]: 3.070 (16.00), 6.781 (0.93), 6.783 (1.06), 6.797 (1.06), 6.799 (1.13), 6.915 (0.96), 6.917
LC-MS (Method L1): Rt =
57 (1.03), 6.932 (0.60), 7.165 , 7.344 (0.86), 7.358 , 7.637 (0.80), 7.652 (1.06), 7.654 (0.90), 7.669 (1.03), 7.716 (1.03),
0.92 min; MS (ESIpos): m/z =
7.718 (1.16), 7.730 (0.77), 7.732 (0.77), 8.251 (0.96), 8.254 (1.06), 8.268 , 8.271 (0.93), 8.559 , 9.074 (0.90), 9.090
478 [M+H]+
(0.86).
1H-NMR(399,9532 MHz, DMSO): δ= 8.8706 (0.51); 8.8451 (2.08); 8.4185 (0.68); 8.4155 (0.7); 8.3974 (0.66); 8.3942 (0.64); 8.3138
(0.34); 7.7984 (0.62); 7.7955 (0.67); 7.7805 (0.77); 7.7776 (0.75); 7.664 (3.27); 7.6592 (3.77); 7.602 (0.98); 7.5971 (1.58); 7.5922
(0.8); 7.5884 (0.66); 7.5699 ; 7.5674 (0.69); 7.5491 (0.53); 7.2426 (0.53); 7.2249 ; 7.1558 (0.53); 7.1387 (0.34); 6.8988
58 2,11 (0.39); 6.896 (0.43); 6.8801 (0.66); 6.8773 (0.7); 6.8616 (0.34); 6.8587 (0.35); 6.806 (0.78); 6.8035 (0.77); 6.7857 (0.73); 6.7829
(0.66); 5.3292 (0.33); 4.3233 (0.33); 4.2445 (0.35); 3.315 ); 2.6749 (0.48); 2.6702 (0.67); 2.6656 (0.48); 2.5236 (1.77); 2.5187
(2.78); 2.5102 (37.2); 2.5056 (77.48); 2.501 (107.64); 2.4965 (79.14); 2.492 (37.03); 2.3325 (0.44); 2.3279 (0.63); 2.3234 (0.47);
1.9882 (0.43); 1.398 (16); 0.008 ; -0.0001 (52.5); 5 (1.57)
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.35), 0.008 (3.16), 2.093 (0.79), 2.366 (0.71), 2.710 (0.67), 2.925 (16.00), 3.287
(2.93), 4.247 (1.14), 4.254 (1.00), 4.266 (1.71), 4.274 (1.91), 4.289 (1.02), 4.422 (6.70), 5.298 (1.04), 5.319 (1.04), 6.784 (2.02),
6.787 (2.18), 6.804 (2.31), 6.807 (2.37), 6.889 (1.10), 6.893 (1.06), 6.908 (2.16), 6.911 (2.08), 6.927 (1.37), 6.930 (1.31), 7.145
LC-MS (Method L1): Rt =
59 (1.10), 7.150 (1.10), 7.167 (1.66), 7.184 (0.83), 7.188 (0.85), 7.302 (0.69), 7.319 (1.89), 7.333 (0.81), 7.337 , 7.341 (0.81),
1.42 min; MS (ESIpos): m/z =
7.389 , 7.405 (3.56), 7.408 (5.68), 7.421 , 7.427 (4.85), 7.444 (4.93), 7.461 (2.10), 7.465 , 7.642 (1.14), 7.646
568 [M+H]+
(2.04), 7.647 (2.98), 7.651 (5.53), 7.656 (14.31), 7.660 , 7.690 (1.73), 7.708 (2.27), 7.711 (1.98), 7.729 (2.16), 7.835 (2.54),
7.838 (2.66), 7.853 (2.02), 7.857 (1.91), 8.318 (2.18), 8.321 (2.23), 8.339 (2.06), 8.343 (1.85), 8.752 (9.09), 9.153 (2.02), 9.174
(1.98).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.988 (0.48), 2.044 , 2.085 (0.43), 3.066 (2.26), 3.075 (16.00), 3.169 (2.25), 4.230
LC-MS d L1): Rt = (0.60), 4.249 (0.92), 4.257 (1.04), 4.271 (0.62), 5.227 (0.50), 5.244 (0.54), 6.775 (1.07), 6.793 (1.18), 6.884 (0.51), 6.903 (1.06),
60 0.85 min; MS (ESIpos): m/z = 6.922 (0.68), 7.141 (0.56), 7.158 (0.91), 7.175 (0.50), 7.214 (0.55), 7.331 (0.84), 7.351 (0.82), 7.438 (1.23), 7.449 (1.52), 7.460
476 [M+H]+ (1.03), 7.467 (1.28), 7.625 (0.51), 7.638 (2.53), 7.642 (1.75), 7.657 (1.45), 7.674 (0.45), 8.228 (0.46), 8.248 (0.96), 8.254 (0.96),
8.266 (0.84), 8.273 , 8.522 (3.66), 9.072 (0.54), 9.091 (0.52).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (4.15), 0.008 (3.77), 2.366 , 2.386 (6.43), 2.710 (1.00), 3.060 (16.00), 3.287
LC-MS (Method L6): Rt =
61 (5.91), 3.681 (0.59), 4.270 (0.79), 6.787 (0.97), 6.805 (1.00), 6.808 , 6.923 (0.93), 6.942 (0.66), 7.187 (0.86), 7.221 ,
1.62 min; MS (ESIpos): m/z =
7.355 , 7.372 (0.76), 7.608 (0.76), 7.626 (1.07), 7.629 (0.93), 7.647 (1.04), 7.717 (1.14), 7.720 (1.21), 7.734 (0.90), 7.738
456 [M+H]+
(0.79), 8.188 (1.00), 8.192 (1.04), 8.210 (0.93), 8.214 , 8.606 (3.97), 9.077 (0.83), 9.097 (0.79).
¹H-NMR (500 MHz, DICHLOROMETHANE-d2) δ [ppm]: 3.078 (16.00), 4.203 (0.84), 5.308 (0.97), 5.320 (1.31), 5.341 (0.74), 5.356
LC-MS (Method L6): Rt =
62 (0.72), 6.815 (1.16), 6.831 (1.27), 6.913 (1.20), 6.927 (0.69), 7.165 (0.71), 7.179 (1.10), 7.297 (0.77), 7.305 (0.99), 7.315 (1.75),
1.27 min; MS (ESIpos): m/z =
7.331 (1.10), 7.446 (0.67), 7.463 (1.09), 7.554 (0.91), 7.569 (1.18), 7.571 (1.18), 7.586 (0.87), 7.726 (1.17), 7.728 (1.20), 7.740
443 [M+H]+
, 7.741 (1.01), 8.152 (1.65), 8.166 , 8.673 (2.52).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 2.362 (0.64), 2.635 (0.64), 3.075 (16.00), 6.787 (0.94), 6.790 (1.04), 6.804 (1.04), 6.806
LC-MS (Method L6): Rt =
63 (1.09), 6.925 (0.94), 6.927 (0.99), 6.942 (0.59), 7.171 (0.79), 7.355 (0.84), 7.369 (0.79), 7.422 (1.78), 7.603 (0.74), 7.612 (0.79),
1.57 min; MS (ESIpos): m/z =
7.670 (0.79), 7.684 (0.99), 7.687 (0.99), 7.702 (0.89), 7.857 (1.04), 7.859 (1.19), 7.871 (0.99), 7.873 (1.04), 8.279 (0.99), 8.282
443 [M+H]+
(1.09), 8.296 (0.99), 8.301 (1.88), 8.311 (1.39), 8.626 (3.76), 9.094 (0.84), 9.110 (0.84).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.17), 3.065 (16.00), 3.909 (9.18), 4.260 (0.93), 4.268 (0.99), 5.752 (2.29), 6.786
LC-MS d L6): Rt = (1.02), 6.803 (1.15), 6.806 (1.15), 6.923 (1.06), 6.941 (0.64), 7.014 (1.90), 7.016 (2.04), 7.169 (0.88), 7.194 (1.22), 7.197 (1.12),
64 1.48 min; MS (ESIpos): m/z = 7.207 (1.15), 7.210 (1.10), 7.349 (0.91), 7.368 (0.83), 7.632 (0.74), 7.650 (1.07), 7.653 (0.90), 7.671 (0.98), 7.768 (1.17), 7.772
455 [M+H]+ (1.15), 7.785 (0.90), 7.789 (0.83), 8.205 (1.69), 8.218 (1.63), 8.232 (1.04), 8.236 (1.05), 8.254 , 8.257 (0.90), 8.602 (3.69),
9.076 (0.93), 9.097 (0.90).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 2.362 , 2.635 (0.74), 3.074 (16.00), 4.264 (0.74), 6.790 , 6.804 (1.04), 6.806
LC-MS (Method L6): Rt =
65 (1.16), 6.926 (0.98), 6.928 (1.04), 6.941 (0.55), 7.173 (0.80), 7.358 (0.86), 7.372 (0.80), 7.654 (1.04), 7.657 (1.16), 7.667 (1.66),
1.69 min; MS (ESIpos): m/z =
7.680 , 7.683 (0.98), 7.697 (0.92), 7.752 (1.90), 7.753 (1.96), 7.849 (1.04), 7.852 (1.16), 7.864 (0.98), 7.866 (0.98), 8.277
459 [M+H]+
(0.98), 8.280 (1.10), 8.294 (0.92), 8.297 (0.98), 8.479 , 8.489 (1.53), 8.630 (3.74), 9.093 (0.92), 9.109 .
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (3.16), 0.007 (2.43), 2.085 (0.91), 2.479 (16.00), 3.063 ), 3.290 (1.71), 4.259
LC-MS (Method L6): Rt =
66 , 5.753 (4.07), 6.787 (0.96), 6.789 , 6.805 , 6.923 (1.01), 6.925 (1.05), 6.938 , 6.940 (0.59), 7.170 (0.86),
1.08 min; MS (ESIpos): m/z =
7.229 (4.94), 7.355 (0.90), 7.369 , 7.626 (0.70), 7.640 (1.04), 7.643 (0.94), 7.657 , 7.718 (1.11), 7.721 (1.23), 7.732
453 [M+H]+
(0.83), 7.735 (0.84), 8.141 (0.84), 8.219 (0.97), 8.222 (1.05), 8.236 (0.90), 8.239 (0.91), 8.601 (3.53), 9.079 (0.94), 9.095 (0.92).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.73), 0.008 (1.62), 1.083 (7.08), 1.101 (16.00), 1.119 (7.35), 2.523 , 3.360
(2.01), 3.378 (5.98), 3.395 (5.74), 3.413 (1.81), 4.238 (1.03), 4.246 (0.84), 4.259 (1.48), 4.269 (1.39), 4.277 (0.92), 4.286 (0.88),
LC-MS (Method L1): Rt =
67 5.239 , 5.259 (0.94), 6.786 (1.61), 6.789 (1.77), 6.807 (1.84), 6.809 (1.93), 6.913 (0.87), 6.916 (0.88), 6.931 (1.76), 6.934
1.42 min; MS (ESIpos): m/z =
(1.80), 6.950 (1.09), 6.953 (1.08), 7.152 (0.90), 7.156 (0.98), 7.174 (1.49), 7.191 (0.74), 7.195 (0.72), 7.362 (1.54), 7.378 (1.43),
520 [M+H]+
7.628 (0.85), 7.634 (2.10), 7.638 (4.21), 7.644 , 7.649 (4.32), 7.657 (2.01), 7.660 (1.75), 7.678 (1.75), 7.797 (1.98), 7.800
(2.12), 7.815
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.845 (0.84), 2.040 , 2.050 (0.89), 2.057 (0.88), 2.068 (0.71), 4.052 (0.72), 4.064
(0.80), 4.069 (1.50), 4.075 (0.94), 4.087 (0.97), 4.092 , 4.167 (0.77), 4.172 (0.97), 4.180 (0.89), 4.187 (1.11), 5.072 (1.29),
LC-MS (Method L1): Rt = 5.088 (1.26), 5.753 (0.58), 6.752 (2.43), 6.754 (2.55), 6.768 (2.63), 6.771 (2.67), 6.844 (1.23), 6.846 (1.20), 6.859 (2.46), 6.861
68 1.36 min; MS s): m/z = (2.43), 6.874 (1.49), 6.876 (1.41), 7.069 (2.20), 7.082 (1.84), 7.134 (1.29), 7.138 (1.18), 7.151 (2.04), 7.165 (1.14), 7.168 (0.92),
583 [M+H]+ 7.593 (2.44), 7.595 , 7.610 (2.69), 7.612 (2.56), 7.680 (0.95), 7.709 , 7.711 , 7.713 (4.04), 7.716 (8.15), 7.718
(16.00), 7.721 (5.44), 7.831 (2.20), 7.845 (2.64), 7.848 (2.23), 7.863 (2.06), 8.037 (2.79), 8.039 (2.83), 8.051 (2.40), 8.054 (2.29),
8.418 (6.05), 8.870 (4.59), 8.961 (0.63), 9.079 (2.41), 9.095 (2.29), 9.192 (9.46).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (4.56), 0.008 , 1.234 , 1.880 (1.58), 1.890 (0.87), 1.901 (1.75), 1.912
(1.84), 1.923 (0.87), 1.933 (1.74), 2.350 (0.80), 2.361 (1.45), 2.369 (1.79), 2.381 (1.55), 2.392 (1.49), 2.401 (1.25), 2.775 (0.78),
LC-MS (Method L1): Rt = 2.797 (1.46), 2.816 (1.81), 2.837 (2.31), 2.858 (1.06), 2.937 (1.44), 2.945 (1.55), 2.959 (1.61), 2.966 (1.48), 2.976 (1.06), 2.985
69 0.86 min; MS (ESIpos): m/z = , 2.998 (0.95), 3.005 (0.79), 5.345 (0.97), 5.365 (2.65), 5.384 (2.58), 5.405 (0.85), 5.754 (15.35), 7.164 (0.99), 7.182 (3.03),
514 [M+H]+ 7.195 (4.52), 7.200 (5.02), 7.215 (3.94), 7.230 (2.07), 7.247 (4.63), 7.264 (2.46), 7.277 (3.90), 7.293 (2.68), 7.402 (2.41), 7.420
(3.40), 7.441 (2.65), 7.539 , 7.610 (2.91), 7.615 (5.39), 7.620 (4.00), 7.646 (16.00), 7.651 (11.73), 7.738 (4.35), 7.756 (3.85),
8.133 (12.50), 8.155 (3.28), 8.795 (9.42), 8.838 (3.65), 8.858 (3.47), 9.979 (4.48), 12.732 (2.72).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 2.912 (16.00), 3.056 (8.85), 3.304 (1.27), 5.751 (0.73), 6.786 (0.85), 6.788 (0.88), 6.802
LC-MS d L6): Rt =
70 (0.93), 6.805 (0.92), 6.832 , 6.848 , 6.883 (0.92), 6.887 (1.01), 6.888 (1.00), 6.921 (0.87), 6.923 (0.83), 7.219 (0.72),
1.42 min; MS (ESIneg): m/z =
7.235 (1.00), 7.251 (0.60), 7.591 (0.61), 7.605 (0.91), 7.608 (0.71), 7.622 (0.84), 7.675 , 7.678 (0.97), 7.689 (0.69), 8.132
465 [M-H]-
, 8.150 (0.79), 8.153 (0.78), 8.168 (0.74), 8.567 (2.33), 9.079 (0.74).
¹H-NMR (500 MHz, CHLOROFORM-d) δ [ppm]: 3.144 (16.00), 3.851 (8.34), 4.212 (0.71), 6.859 (1.08), 6.861 (1.16), 6.875 (1.18),
LC-MS (Method L6): Rt =
71 6.877 (1.26), 6.908 (0.59), 6.910 , 6.923 (1.17), 6.925 (1.11), 6.938 (0.69), 6.940 (0.64), 7.204 (0.94), 7.302 (0.98), 7.318
0.97 min; MS (ESIneg): m/z =
(0.92), 7.590 (0.88), 7.604 (1.17), 7.607 (1.08), 7.621 (1.12), 7.653 (1.78), 7.757 (1.31), 7.760 (1.38), 7.772 (1.15), 7.774 (1.07),
476 [M-H]-
7.886 , 8.127 (1.09), 8.130 (1.10), 8.144 (1.04), 8.147 (0.99), 9.040 (1.35).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.934 (0.65), 0.951 (1.40), 0.969 (0.72), 1.815 (0.91), 1.825 (1.04), 1.842 (1.24), 1.859
(0.77), 2.014 (1.18), 2.027 (1.17), 2.035 (1.12), 2.049 (0.88), 2.694 (1.05), 4.031 (0.92), 4.052 (1.96), 4.059 , 4.073 (1.35),
LC-MS d L1): Rt = 4.080 , 4.158 (1.43), 4.168 , 4.176 (1.62), 4.186 (0.92), 4.196 (0.91), 5.044 (0.78), 5.058 (1.79), 5.077 , 5.092
72 1.34 min; MS s): m/z = , 6.686 (3.38), 6.691 (5.17), 6.696 (3.37), 6.736 (3.20), 6.754 (3.60), 6.845 (1.55), 6.864 (3.34), 6.883 (2.11), 7.082 (3.20),
515 [M+H]+ 7.102 (2.64), 7.117 (1.82), 7.122 (1.57), 7.138 (2.83), 7.156 (1.43), 7.665 (2.79), 7.668 (2.76), 7.686 (3.87), 7.689 (3.76), 7.710
(16.00), 7.714 (7.25), 7.776 (2.70), 7.794 (3.62), 7.815 , 7.938 (5.43), 7.942 (5.37), 7.987 (3.52), 7.990 (3.35), 8.005 (3.05),
8.008 (2.74), 8.147 (5.19), 8.153 (5.21), 8.914 (3.01), 8.935 (2.93), 9.116 ).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.06), 0.008 (1.57), 2.133 (0.74), 2.366 (0.70), 2.524 (2.87), 2.710 , 3.079
(16.00), 4.252 (0.87), 4.260 (0.94), 5.753 (3.02), 5.955 (1.19), 6.777 (1.02), 6.794 (1.11), 6.881 , 6.900 (1.22), 6.902 (1.13),
LC-MS (Method L1): Rt =
73 6.918 (0.70), 7.029 (0.98), 7.031 (1.06), 7.047 (1.44), 7.135 (1.44), 7.156 (2.13), 7.174 (1.26), 7.248 (1.09), 7.254 , 7.262
0.71 min; MS (ESIpos): m/z =
(1.04), 7.308 (1.02), 7.322 (0.96), 7.342 (0.81), 7.404 (1.37), 7.424 (1.15), 7.629 (0.83), 7.647 (1.07), 7.650 (0.89), 7.668 (1.04),
463 [M+H]+
7.733 , 7.737 (1.35), 7.751 (0.94), 7.754 (0.87), 8.192 (1.00), 8.196 (1.04), 8.214 (0.98), 8.217 (0.87), 8.469 (3.80), 9.059
(0.93), 9.080 (0.89), 11.099 .
LC-MS (Method L6): Rt =
74 ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.169 (16.00), 3.645 , 3.658 (1.38), 6.782 (0.83), 6.799 (0.91), 6.803 (0.87), 6.899
1.42 min; MS (ESIpos): m/z =
(0.86), 7.602 (1.31), 7.607 (1.19), 7.622 (4.81), 7.627 (2.96), 8.133 (2.91), 8.546 (2.19).
508 [M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (0.95), 2.085 (1.49), 3.061 (10.00), 3.173 (16.00), 3.455 (2.24), 3.469
LC-MS (Method L6): Rt = (1.54), 3.554 (0.89), 3.567 (1.31), 3.585 (1.41), 6.788 (1.20), 6.791 (1.37), 6.809 (1.39), 6.812 , 6.926 (1.31), 6.929 (1.31),
75 2.54 min; MS (ESIpos): m/z = 6.944 (0.78), 6.947 (0.77), 7.174 (1.05), 7.357 (1.04), 7.372 (1.00), 7.637 (2.10), 7.641 ), 7.645 (3.82), 7.663 , 7.667
536 [M+H]+ (1.27), 7.685 (1.30), 7.805 (1.45), 7.809 (1.59), 7.823 (1.19), 7.827 (1.19), 8.299 (1.28), 8.303 (1.36), 8.320 (1.23), 8.324 (1.19),
8.712 (5.32), 9.065 (1.22), 9.086 (1.19).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.51), 0.008 (2.41), 2.063 (1.06), 2.073 (1.60), 2.143 (0.95), 2.157 (1.15), 2.327
(0.87), 2.523 (2.45), 2.670 (0.84), 3.334 , 3.356 (4.85), 3.567 (2.37), 3.581 (5.84), 3.593 (3.89), 3.684 (3.13), 3.697 (2.74),
LC-MS (Method L1): Rt =
76 4.269 (3.13), 4.278 (2.53), 4.286 (1.74), 5.247 (1.52), 5.266 (1.51), 6.783 (2.84), 6.786 (3.12), 6.804 (3.25), 6.807 (3.39), 6.884
0.92 min; MS s): m/z =
(1.49), 6.887 (1.55), 6.903 (3.11), 6.906 (3.03), 6.921 (1.86), 6.924 (1.77), 7.143 (1.48), 7.148 (1.63), 7.165 (2.50), 7.182 ,
522 [M+H]+
7.186 (1.20), 7.294 (2.53), 7.314 (2.37), 7.531 (1.18), 7.551 (1.97), 7.569 (1.32), 7.609 (3.49), 7.614 , 7.624 (16.00), 7.628
(9.17), 7.750 (2.78), 7.766 (2.37), 8.381 (1.85), 8.402 (1.76), 8.558 (5.29), 9.023 (1.39), 9.042 (1.36).
¹H-NMR (400 MHz, 6) δ [ppm]: 2.063 (0.91), 3.712 (0.91), 4.023 (3.89), 4.028 (3.96), 4.242 (1.32), 4.251 (1.33), 4.261
(1.86), 4.270 (2.06), 4.282 (1.19), 4.674 (1.12), 4.887 (1.03), 4.916 (1.04), 4.929 (2.17), 4.947 (2.17), 4.961 (1.00), 5.241 ,
LC-MS (Method L1): Rt =
77 5.261 , 5.754 (5.20), 6.794 , 6.814 (2.13), 6.905 (0.96), 6.907 (1.01), 6.923 (1.92), 6.926 (1.96), 6.942 (1.13), 6.945
0.88 min; MS (ESIpos): m/z =
(1.13), 7.156 (1.19), 7.160 (1.25), 7.177 (1.78), 7.195 (0.88), 7.199 (0.81), 7.327 (1.71), 7.346 , 7.626 (1.09), 7.630 (1.31),
533 [M+H]+
7.640 (16.00), 7.647 (1.70), 7.659 (2.46), 7.664 (2.09), 7.681 , 7.839 (1.82), 7.842 (2.20), 7.857 (1.59), 7.860 (1.81), 8.138
(2.43), 8.305 (1.86), 8.309 (2.07), 8.327 (1.68), 8.330 (1.74), 8.711 (2.71), 8.734 (6.72), 8.846 (0.69), 9.226 (1.85), 9.246 (1.78).
¹H-NMR (400 MHz, 6) δ [ppm]: 1.356 (0.92), 3.007 (16.00), 3.407 , 3.421 (1.08), 3.473 (1.23), 3.486 (0.97), 3.552
LC-MS (Method L1): Rt =
78 (1.13), 3.559 (1.40), 3.565 (1.84), 3.573 , 5.754 (2.61), 6.794 (0.83), 6.813 (0.96), 6.927 (0.88), 7.329 , 7.638 (0.93),
1.41 min; MS (ESIpos): m/z =
7.643 (1.08), 7.652 (3.47), 7.657 , 7.666 (0.89), 7.687 (0.67), 7.810 (0.96), 7.827 (0.77), 8.237 (0.79), 8.240 , 8.258
580 [M+H]+
(0.74), 8.764 (3.04), 8.881 (0.82), 8.901 (0.79).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.20), 0.008 , 1.091 (1.05), 1.157 (1.00), 1.175 (2.17), 1.193 (1.28), 1.234
(2.13), 1.391 (1.14), 1.908 (3.71), 1.916 , 1.924 (10.00), 1.932 (4.39), 1.941 (3.75), 1.956 (1.50), 1.988 (1.88), 2.462 (0.91),
LC-MS (Method L6): Rt = 2.472 (1.20), 2.689 (7.43), 2.825 (0.94), 2.845 , 2.865 (1.56), 2.965 (0.92), 2.977 (0.96), 3.288 (1.30), 3.650 (3.10), 3.666
79 1.67 min; MS (ESIpos): m/z = (7.98), 3.682 (2.94), 5.489 (1.79), 5.509 (1.80), 7.211 (2.58), 7.215 (2.00), 7.221 (3.24), 7.228 (2.98), 7.231 (3.71), 7.233 ,
502 [M+H]+ 7.245 (1.09), 7.259 (2.43), 7.271 (1.46), 7.356 (1.78), 7.365 (1.99), 7.377 (1.40), 7.477 (1.97), 7.495 (2.48), 7.498 (2.33), 7.516
(2.30), 7.604 (1.42), 7.610 (3.39), 7.614 (5.27), 7.620 (16.00), 7.624 (6.54), 7.709 (2.80), 7.713 (3.02), 7.727 (2.49), 7.731 (2.42),
8.263 (2.41), 8.266 (2.49), 8.284 (2.32), 8.288 (2.22), 8.452 (9.01), 8.878 (2.24), 8.899 (2.20).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.90), -0.008 (7.64), 0.008 (7.69), 0.146 (0.95), 1.175 (0.44), 1.236 (2.24), 1.879
(1.70), 1.916 (1.03), 1.936 (0.98), 1.950 (0.87), 1.968 , 1.988 (0.87), 2.327 (1.36), 2.366 (1.49), 2.523 (5.17), 2.670 (1.57),
LC-MS (Method L1): Rt =
80 2.710 (1.16), 2.815 (0.49), 2.835 (0.85), 2.855 (1.11), 2.874 (1.26), 2.893 (0.67), 2.959 (0.72), 2.972 (0.87), 2.981 (0.80), 2.993
0.91 min; MS (ESIpos): m/z =
(0.90), 3.021 (0.54), 3.798 (0.87), 3.816 (0.93), 4.640 , 4.654 (1.23), 4.662 (1.13), 5.511 (0.54), 5.530 (1.39), 5.549 (1.36),
546 [M+H]+
.567 (0.54), 7.231 (2.24), 7.240 (2.39), 7.248 (3.68), 7.253 , 7.271 (2.68), 7.285 (1.05), 7.446 (1.44), 7.453 (1.57), 7.467
(1.34), 7.629 (1.65), 7.640 (16.00), 7.667 (1.67), 7.801 (2.32), 7.816 (1.85), 8.282 (1.65), 8.301 (1.57), 8.695 (6.92), 12.590 (0.62).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.26), 0.008 (1.50), 3.074 (16.00), 4.253 (0.86), 4.262 (0.91), 5.754 (4.63), 6.778
LC-MS (Method L1): Rt =
81 (0.85), 6.781 (0.95), 6.799 , 6.801 (1.02), 6.913 (0.95), 6.917 , 6.932 (0.59), 7.164 (0.79), 7.343 (0.82), 7.648 (0.69),
0.92 min; MS (ESIpos): m/z =
7.665 (1.10), 7.669 , 7.687 (1.14), 7.721 (1.10), 7.725 (1.20), 7.739 (0.70), 7.743 (0.63), 8.265 (0.99), 8.269 (1.00), 8.286
478 [M+H]+
(0.94), 8.290 (0.86), 8.566 (3.67), 9.075 (0.84), 9.096 (0.82).
LC-MS (Method L6): Rt = ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.288 (1.60), 3.300 (2.14), 3.311 (16.00), 3.865 (1.20), 3.877 (2.00), 3.888 (1.13), 6.780
82 2.08 min; MS (ESIpos): m/z = (0.66), 6.783 (0.71), 6.800 , 6.803 (0.77), 6.922 (0.70), 6.925 , 7.385 (0.70), 7.720 (0.80), 7.741 (0.83), 7.764 (0.84),
520 [M+H]+ 7.768 (0.91), 8.304 (0.65), 8.308 , 8.325 (0.62), 8.635 (2.82), 9.161 (0.64).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (3.64), 1.988 (0.96), 2.038 (0.93), 2.045 (0.98), 2.057 (1.02), 2.073
(1.49), 2.080 (1.22), 2.189 , 2.203 (1.36), 2.215 (1.27), 2.224 (1.27), 3.259 (1.29), 3.277 (3.60), 3.290 (8.31), 3.334 (2.18),
3.610 (5.58), 3.867 (6.16), 3.880 ), 3.892 (6.04), 4.234 (2.20), 4.241 (1.69), 4.254 (2.29), 4.261 (2.71), 4.269 (2.31), 4.275
LC-MS d L6): Rt = (1.84), 4.285 (1.84), 5.232 (0.89), 5.247 (2.02), 5.267 (2.02), 5.281 (0.89), 6.685 (0.98), 6.706 (1.07), 6.779 (3.53), 6.782 ,
83 2.26 min; MS (ESIpos): m/z = 6.800 (4.02), 6.803 (4.29), 6.901 (1.93), 6.904 , 6.919 (3.93), 6.922 (3.96), 6.938 (2.44), 6.941 (2.38), 7.146 (1.98), 7.150
568 [M+H]+ (2.13), 7.167 (3.18), 7.185 (1.62), 7.189 (1.60), 7.363 (3.33), 7.380 (3.22), 7.384 (3.18), 7.389 (2.04), 7.409 (4.31), 7.426 (3.07),
7.429 (3.18), 7.466 (2.24), 7.471 (2.76), 7.482 (2.33), 7.486 (3.64), 7.490 (1.80), 7.502 (1.51), 7.506 (1.38), 7.602 (1.44), 7.620
(2.38), 7.640 (1.22), 7.704 , 7.722 (4.38), 7.725 (3.36), 7.742 (4.40), 7.779 (4.49), 7.783 , 7.797 (2.96), 7.800 (2.76),
8.308 (3.76), 8.312 (3.84), 8.329 (3.56), 8.333 (3.38), 8.612 ), 9.161 (3.69), 9.182 (3.62).
LC-MS (Method L5): Rt =
84 0.69 min; MS (ESIpos): m/z =
517 [M+H]+
LC-MS d L5): Rt =
85 1.38 min; MS (ESIpos): m/z =
564 [M+H]+
LC-MS (Method L5): Rt =
86 1.20 min; MS (ESIpos): m/z =
524 [M+H]+
LC-MS (Method L5): Rt =1.25
87 min; MS s): m/z = 519
[M+H]+
LC-MS (Method L5): Rt =0.71
88 1,3 min; MS (ESIpos): m/z = 519
[M+H]+
LC-MS (Method L5): Rt =0.95
89 2,2 min; MS (ESIpos): m/z = 506
[M+H]+
LC-MS (Method L5): Rt =1.33
90 4,9 min; MS (ESIpos): m/z = 534
[M+H]+
LC-MS (Method L5): Rt =1.12
91 2,9 min; MS (ESIpos): m/z = 546
[M+H]+
LC-MS (Method L5): Rt =1.12
92 2,9 min; MS (ESIpos): m/z = 546
[M+H]+
LC-MS (Method L5): Rt =1.33
93 min; MS (ESIpos): m/z = 564
[M+H]+
LC-MS (Method L5): Rt =0.72
94 min; MS (ESIpos): m/z = 545
[M+H]+
LC-MS (Method L5): Rt =0.96
95 min; MS (ESIpos): m/z = 532
[M+H]+
LC-MS (Method L5): Rt =0.74
96 1,4 min; MS (ESIpos): m/z = 545
[M+H]+
LC-MS (Method L5): Rt =1.01
97 min; MS (ESIpos): m/z = 544
[M+H]+
LC-MS (Method L5): Rt =0.90
98 min; MS (ESIpos): m/z = 533
[M+H]+
LC-MS (Method L5): Rt =0.97
99-1 2,2 min; MS s): m/z = 539
[M+H]+
LC-MS (Method L5): Rt =0.93
99-2 2,1 min; MS (ESIpos): m/z = 520
[M+H]+
LC-MS (Method L5): Rt =0.87
100 1,9 min; MS (ESIpos): m/z = 492
[M+H]+
LC-MS (Method L5): Rt =0.85
101 1,8 min; MS (ESIpos): m/z = 518
[M+H]+
LC-MS (Method L5): Rt =0.85
102 min; MS (ESIpos): m/z = 504
[M+H]+
LC-MS (Method L5): Rt =0.71
103 min; MS (ESIpos): m/z = 557
[M+H]+
LC-MS (Method L5): Rt =1.26
104 min; MS (ESIpos): m/z = 516
[M+H]+
LC-MS (Method L5): Rt =1.27
105 min; MS (ESIpos): m/z = 516
[M+H]+
LC-MS (Method L5): Rt =1.24
106 3,7 min; MS s): m/z = 516
[M+H]+
LC-MS (Method L5): Rt =1.31
107 min; MS (ESIpos): m/z = 546
[M+H]+
LC-MS (Method L5): Rt =1.03
108 min; MS (ESIpos): m/z = 504
[M+H]+
LC-MS (Method L5): Rt =1.42
109 min; MS (ESIpos): m/z = 564
[M+H]+
LC-MS d L5): Rt =1.38
110 min; MS (ESIpos): m/z = 544
[M+H]+
LC-MS (Method L5): Rt =1.00
111 min; MS (ESIpos): m/z = 550
[M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.14), 0.008 (2.96), 0.146 , 1.917 (0.92), 1.937 (0.96), 1.949 (1.08), 1.968
(0.98), 2.328 (0.72), 2.568 (1.52), 2.587 , 2.605 (1.54), 2.624 (0.91), 2.640 (0.62), 2.670 (0.64), 2.849 (0.85), 2.868 (1.12),
LC-MS (Method L1): Rt =
112 2,6 2.887 (1.37), 2.908 (0.64), 2.974 (0.91), 2.988 (0.95), 3.707 (1.26), 3.726 (2.13), 3.736 (2.13), 3.753 (1.19), 3.841 (2.10), 3.873
1.10 min; MS s): m/z =
(4.31), 3.905 (2.01), 5.508 (0.54), 5.528 (1.68), 5.549 , 7.224 (2.73), 7.233 (3.15), 7.241 (3.80), 7.271 (2.34), 7.414 (1.68),
538 [M+H]+
7.429 (1.43), 7.640 (16.00), 7.665 (1.81), 7.684 (2.39), 7.705 (2.19), 7.835 (2.72), 7.850 (2.23), 8.239 (2.35), 8.258 (2.17), 8.695
(9.00), 9.086 (2.09), 9.106 (2.05).
LC-MS (Method L5): Rt =1.04
113 min; MS (ESIpos): m/z = 545
[M+H]+
LC-MS (Method L5): Rt =1.40
114 min; MS s): m/z = 566
[M+H]+
LC-MS (Method L5): Rt =1.05
115 min; MS (ESIpos): m/z = 533
[M+H]+
LC-MS (Method L5): Rt =1.25
116 3,4 min; MS (ESIpos): m/z = 559
[M+H]+
LC-MS (Method L5): Rt =1.25
117 min; MS (ESIpos): m/z = 565
[M+H]+
LC-MS (Method L5): Rt =1.33
118 min; MS (ESIpos): m/z = 552
[M+H]+
LC-MS (Method L5Method
119 L5): Rt =0.92 min; MS
(ESIpos): m/z = 506 [M+H]+
LC-MS (Method L5): Rt =0.94
120 min; MS (ESIpos): m/z = 502
[M+H]+
LC-MS (Method L5): Rt =1.00
121 min; MS (ESIpos): m/z = 524
[M+H]+
LC-MS (Method L5): Rt =0.90
122 2 min; MS (ESIpos): m/z = 547
[M+H]+
LC-MS (Method L5): Rt =0.98
123 min; MS (ESIpos): m/z = 544
[M+H]+
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.007 (0.42), 1.234 (0.43), 1.937 (0.49), 1.954 (1.37), 1.962 (0.72), 1.971 (1.46), 1.979
(1.53), 1.988 (0.69), 1.996 (1.47), 2.013 (0.54), 2.446 (0.68), 2.453 (0.82), 2.462 (1.42), 2.469 (1.84), 2.478 (2.17), 2.518 (7.50),
2.809 (0.67), 2.826 , 2.842 (1.48), 2.858 , 2.874 (0.85), 2.960 , 2.967 (1.21), 2.978 (1.24), 2.984 (1.18), 2.992
LC-MS (Method L8): Rt = (0.89), 2.998 (0.84), 3.009 (0.81), 3.016 (0.70), 3.316 (1.98), 3.664 (0.52), 3.675 (1.21), 3.689 (2.49), 3.701 (2.76), 3.715 (2.35),
124 0.82 min; MS (ESIneg): m/z = 3.729 , 3.740 (0.44), 5.503 (0.84), 5.519 (2.36), 5.535 (2.35), 5.551 (0.79), 6.929 (2.26), 7.192 (0.72), 7.206 (4.09), 7.213
518 [M-H]- (4.86), 7.220 (5.20), 7.224 (3.60), 7.235 (1.11), 7.255 (3.09), 7.266 (1.77), 7.271 (1.27), 7.362 (2.40), 7.368 (2.53), 7.379 (2.23),
7.400 (2.23), 7.534 (2.37), 7.548 (3.14), 7.550 (2.96), 7.565 (2.60), 7.599 (3.07), 7.603 (6.46), 7.607 (4.90), 7.627 (16.00), 7.631
(11.94), 7.739 (3.66), 7.741 (3.78), 7.754 (3.17), 7.755 , 7.917 (1.31), 7.928 (2.35), 7.938 (1.20), 8.157 , 8.334 (3.01),
8.350 (2.81), 8.562 (10.41), 8.850 (3.16), 8.866 .
LC-MS (Method L5): Rt =0.95
125 2,1 min; MS s): m/z = 542
[M+H]+
LC-MS (Method L5): Rt =0.87
126 min; MS (ESIpos): m/z = 533
[M+H]+
LC-MS (Method L5): Rt =0.90
127 1,9 min; MS (ESIpos): m/z = 519
[M+H]+
LC-MS (Method L5): Rt =0.97
128 2,1 min; MS (ESIpos): m/z = 520
[M+H]+
LC-MS (Method L5): Rt =0.85
129 1,8 min; MS (ESIpos): m/z = 505
[M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.066 (16.00), 4.262 (0.81), 4.270 (0.92), 5.754 (1.15), 6.784 (0.98), 6.787 (1.02), 6.805
LC-MS (Method L1): Rt = (1.10), 6.807 (1.10), 6.923 (0.99), 6.926 (0.97), 7.169 (0.81), 7.353 (0.82), 7.373 (0.79), 7.455 (0.88), 7.460 (1.48), 7.464 (1.00),
130 0.85 min; MS (ESIpos): m/z = 7.469 , 7.487 (1.54), 7.506 (0.70), 7.532 (0.80), 7.536 (1.38), 7.540 (0.75), 7.554 (0.76), 7.623 (0.73), 7.643 (2.49), 7.648
458 [M+H]+ (1.12), 7.662 (1.03), 7.739 (1.15), 7.743 (1.22), 7.757 (0.88), 7.761 (0.82), 8.204 (1.00), 8.208 (1.02), 8.225 (0.96), 8.229 ,
8.611 (3.90), 9.078 , 9.098 (0.85).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.45), 0.008 (2.01), 2.031 (0.91), 2.038 , 2.086 (1.12), 2.199 (0.70), 3.673
(16.00), 3.742 (5.31), 4.174 (1.20), 4.181 (0.78), 4.195 (0.87), 4.203 (0.99), 4.287 (0.82), 4.296 (0.76), 4.304 (0.93), 5.125 (1.08),
LC-MS (Method L1): Rt = 5.142 (1.08), 6.796 (1.69), 6.816 (1.95), 6.878 (0.99), 6.881 (0.91), 6.897 (1.97), 6.916 , 6.957 (0.91), 6.972 (0.89), 7.152
131 1.40 min; MS (ESIpos): m/z = (1.31), 7.157 (1.12), 7.166 (1.84), 7.171 (2.18), 7.185 (2.45), 7.196 (1.01), 7.206 (1.77), 7.283 (0.80), 7.287 (0.91), 7.294 (1.69),
494 [M+H]+ 7.314 (1.54), 7.387 (2.01), 7.391 (1.99), 7.406 , 7.409 (1.59), 7.445 (2.22), 7.449 (2.24), 7.501 (6.85), 7.506 (6.87), 7.717
(0.85), 7.736 , 7.741 (2.47), 7.746 , 7.935 (2.81), 7.951 (2.83), 8.166 (0.63), 8.903 (1.69), 8.921 , 9.904 (1.94),
9.922 (2.56), 9.934 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.84), 0.008 (1.78), 3.075 ), 4.248 (0.91), 4.256 (1.05), 6.774 (1.08), 6.777
LC-MS (Method L6): Rt =
132 (1.18), 6.794 (1.23), 6.797 (1.29), 6.889 (0.56), 6.905 (1.13), 6.908 (1.14), 6.924 (0.71), 6.926 (0.68), 7.142 (0.63), 7.160 (0.95),
2.15 min; MS (ESIpos): m/z =
7.335 (0.74), 7.468 (0.66), 7.474 (0.64), 7.633 (0.61), 7.650 (1.67), 7.669 (2.82), 7.900 (2.22), 7.906 (2.18), 8.257 (1.14), 8.263
526 [M+H]+
, 8.276 (1.03), 8.282 (1.00), 8.537 (3.81).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.91), -0.008 (7.68), 0.008 (7.18), 0.146 (0.91), 2.027 (1.24), 2.035 (1.27), 2.046
(1.34), 2.062 , 2.070 (1.58), 2.078 , 2.085 (0.81), 2.184 (1.24), 2.196 (1.71), 2.209 (1.71), 2.218 (1.64), 2.230 (1.07),
2.366 (0.70), 2.710 , 3.247 , 3.289 , 3.334 (1.81), 3.866 (8.18), 3.876 (13.05), 3.888 , 3.906 (0.97), 4.204
LC-MS (Method L6): Rt =
133 (0.74), 4.212 (0.97), 4.224 (0.91), 4.232 (2.85), 4.240 (2.28), 4.252 (3.66), 4.264 (3.52), 4.271 (2.52), 4.280 (2.52), 4.299 (0.94),
2.40 min; MS (ESIpos): m/z =
.241 (2.11), 5.255 (2.08), 5.753 (4.53), 6.776 , 6.779 (5.00), 6.796 (5.20), 6.799 (5.50), 6.896 (2.21), 6.915 (4.70), 6.933
568 [M+H]+
(2.78), 7.142 (2.55), 7.147 (2.72), 7.164 (4.13), 7.181 (2.11), 7.186 (2.01), 7.357 (4.19), 7.374 (3.96), 7.444 (2.25), 7.450 (2.42),
7.476 (2.68), 7.482 (2.58), 7.686 (1.38), 7.703 (7.55), 7.711 (6.74), 7.720 (16.00), 7.728 (1.71), 7.909 (7.31), 7.915 (7.11), 8.282
(0.91), 8.291 (4.49), 8.300 (3.82), 8.307 (3.66), 8.316 (3.89), 8.325 (0.74), 8.606 , 8.610 (7.75), 9.160 , 9.181 (2.72).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 8.99 (d, 1H), 8.45 (s, 1H), 8.36 (d, 1H), 8.13 (s, 1H), 7.83 (br s, 1H), 7.73 (d, 1H), 7.60 -
134 1,9 0.84 min; MS (ESIpos): m/z = 7.63 (m, 3H), 7.54 (t, 1H), 7.32 (d, 1H), 7.16 (t, 1H), 6.91 (t, 1H), 6.79 (d, 1H), 5.21 - 5.27 (m, 1H), 4.22 - 4.30 (m, 2H), 3.07 (d, 3H),
578[M+H]+ 2.52 - 2.55 (m, 4H), 2.12 - 2.20 (m, 1H), 2.00 - 2.08 (m, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (2.98), 2.004 (1.02), 2.014 (0.94), 2.026 (1.43), 2.041 (1.28), 2.126
(1.31), 2.141 (1.56), 2.373 (2.15), 2.394 (2.92), 2.412 (2.16), 2.433 (1.25), 2.519 (4.80), 2.523 , 4.243 , 4.255 (4.75),
LC-MS (Method L1): Rt = 4.261 (3.01), 4.270 (2.58), 4.427 (5.50), 4.446 (8.06), 4.466 , 5.160 (0.92), 5.174 , 5.194 (1.64), 5.754 (2.42), 6.781
135 1,9 0.89 min; MS (ESIpos): m/z = (3.04), 6.785 (3.14), 6.802 (3.39), 6.805 (3.26), 6.887 (1.73), 6.890 (1.66), 6.906 (3.30), 6.909 (2.99), 6.924 (1.93), 6.927 (1.70),
504 [M+H]+ 7.142 (1.75), 7.146 (1.77), 7.163 (2.63), 7.180 (1.31), 7.185 (1.20), 7.291 (2.83), 7.311 (2.52), 7.434 (2.40), 7.452 (3.13), 7.455
(2.90), 7.473 (2.61), 7.592 (2.65), 7.597 (4.87), 7.602 (5.82), 7.611 (16.00), 7.616 (8.48), 7.698 (3.62), 7.701 (3.63), 7.716 (3.07),
7.719 (2.82), 8.058 (3.06), 8.061 (3.05), 8.080 (2.76), 8.083 (2.47), 8.430 (11.34), 8.946 (2.94), 8.966 (2.74).
LC-MS d L1): Rt =
136 2,1 ¹H-NMR (400 MHz, CHLOROFORM-d) δ [ppm]: -0.008 (1.56), 0.008 (1.98), 0.069 (0.62), 1.256 (1.23), 1.582 (16.00), 2.171 (1.20),
0.93 min; MS (ESIpos): m/z =
2.177 (0.59), 5.299 (1.83), 6.997 (0.57), 7.429 (0.69), 7.519 (1.23).
541 [M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.04), 0.008 (1.38), 1.199 (3.32), 1.216 (7.07), 1.234 (3.34), 2.086 (1.65), 3.048
LC-MS (Method L1): Rt = , 4.052 , 4.134 (0.95), 4.152 (2.94), 4.169 (2.79), 4.187 (0.86), 4.283 (1.07), 6.790 (1.19), 6.793 , 6.810 (1.31),
137 4,8 1.42 min; MS (ESIpos): m/z = 6.813 (1.32), 6.917 (1.20), 6.920 (1.17), 7.175 (0.96), 7.378 (0.94), 7.645 (16.00), 7.689 (0.97), 7.707 (1.22), 7.710 , 7.728
564 [M+H]+ (1.19), 7.840 (1.33), 7.843 (1.41), 7.858 (1.10), 7.861 (1.03), 8.354 (1.21), 8.358 (1.23), 8.375 (1.10), 8.379 (1.01), 8.756 (4.67),
9.196 (1.08), 9.217 (1.02).
¹H-NMR (400 MHz, 6) δ [ppm]: 2.087 (0.95), 2.095 (0.79), 2.206 (0.84), 2.218 , 2.228 (0.77), 3.056 (16.00), 3.516
(1.41), 3.529 (3.23), 3.541 (2.52), 3.601 (1.41), 3.614 (2.77), 3.628 (2.42), 3.641 (0.85), 4.245 (1.32), 4.253 (1.18), 4.265 ,
LC-MS (Method L1): Rt =
138 2,7 4.274 (2.23), 4.290 (1.20), 5.100 (1.14), 5.115 (2.39), 5.130 (1.09), 5.279 (1.29), 5.298 (1.29), 5.752 , 5.754 (1.27), 6.792
1.12 min; MS (ESIpos): m/z =
(2.55), 6.813 (2.83), 6.910 (1.24), 6.928 (2.57), 6.947 (1.49), 7.159 (1.29), 7.176 (2.06), 7.197 (0.97), 7.357 (2.18), 7.376 (1.99),
522 [M+H]+
7.625 (2.25), 7.628 , 7.631 (3.12), 7.634 (5.58), 7.638 (12.01), 7.640 , 7.643 (5.84), 7.646 (4.00), 7.665 (1.93), 7.801
(2.81), 7.819 (2.22), 8.275 (2.37), 8.296 (2.15), 8.673 (7.74), 9.303 (2.25), 9.323 (2.20).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.58 (s, 1H), 8.29 (dd, J = 9.4, 6.2 Hz, 1H), 7.77 - 7.68 (m, 2H), 7.61 (t, J =
139 3.33 min, m/z = 510/512 9.3 Hz, 1H), 7.47 - 7.41 (m, 1H), 7.37 - 7.31 (m, 1H), 7.20 - 7.13 (m, 1H), 6.95 - 6.88 (m, 1H), 6.82 - 6.77 (m, 1H), 5.27 - 5.19 (m,
(M+H)+ 1H), 4.30 - 4.19 (m, 2H), 3.07 (s, 6H), 2.27 - 2.12 (m, 1H), 2.07 - 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.07 (d, J = 8.2 Hz, 1H), 8.58 (s, 1H), 8.27 (dd, J = 9.4, 6.2 Hz, 1H), 7.64 - 7.48 (m, 3H), 7.34 (d, J =
140 LC-MS (Method L2): Rt =
6.9 Hz, 1H), 7.31 - 7.23 (m, 1H), 7.20 - 7.13 (m, 1H), 6.95 - 6.88 (m, 1H), 6.82 - 6.76 (m, 1H), 5.28 - 5.20 (m, 1H), 4.32 - 4.19 (m,
2.98 min, m/z = 478 (M+H)+
2H), 3.06 (s, 6H), 2.22 - 2.14 (m, 1H), 2.09 - 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.58 (s, 1H), 8.27 (dd, J = 9.4, 6.2 Hz, 1H), 7.60 (t, J = 9.3 Hz, 1H), 7.55 -
141 LC-MS (Method L2): Rt =
7.45 (m, 3H), 7.43 - 7.31 (m, 2H), 7.20 - 7.12 (m, 1H), 6.95 - 6.88 (m, 1H), 6.83 - 6.76 (m, 1H), 5.28 - 5.19 (m, 1H), 4.32 - 4.19 (m,
3.03 min, m/z = 476 (M+H)+
2H), 3.07 (s, 6H), 2.25 - 2.14 (m, 1H), 2.09 - 1.98 (m, 1H).
1H-NMR (400 MHz, 6) δ 9.17 (d, J = 8.2 Hz, 1H), 8.67 (s, 1H), 8.34 (dd, J = 9.4, 6.2 Hz, 1H), 7.66 (t, J = 9.3 Hz, 1H), 7.40 -
142 LC-MS (Method L2): Rt =
7.28 (m, 2H), 7.22 - 7.13 (m, 3H), 6.96 - 6.89 (m, 1H), 6.82 - 6.76 (m, 1H), 5.29 - 5.21 (m, 1H), 4.33 - 4.19 (m, 2H), 3.88 (q, J = 5.8,
3.68 min, m/z = 520 (M+H)+
4.5 Hz, 4H), 3.28 (q, J = 4.5 Hz, 4H), 2.27 - 2.16 (m, 1H), 2.10 - 2.00 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 8.1 Hz, 1H), 8.68 (s, 1H), 8.34 (dd, J = 9.4, 6.2 Hz, 1H), 7.66 (t, J = 9.3 Hz, 1H), 7.55 -
143 LC-MS (Method L2): Rt =
7.49 (m, 1H), 7.40 - 7.29 (m, 3H), 7.21 - 7.13 (m, 1H), 6.96 - 6.89 (m, 1H), 6.82 - 6.76 (m, 1H), 5.29 - 5.21 (m, 1H), 4.33 - 4.19 (m,
3.86 min, m/z = 536 (M+H)+
2H), 3.87 (t, J = 4.5 Hz, 4H), 3.28 (q, J = 4.6 Hz, 4H), 2.26 - 2.18 (m, 1H), 2.11 - 2.02 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.85 (s, 1H), 7.83 (dd, J = 9.8, 2.9 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.55 (d, J = 8.3 Hz, 1H),
LC-MS (Method L2): Rt =
144 7.50 (dd, J = 8.6, 2.9 Hz, 1H), 7.45 (dd, J = 8.3, 2.0 Hz, 1H), 7.29 (d, J = 7.7 Hz, 1H), 7.26 – 7.17 (m, 1H), 6.94 (td, J = 7.5, 1.1 Hz,
4.14 min; m/z = 552/554
1H), 6.87 (dd, J = 8.3, 1.0 Hz, 1H), 6.82 (d, J = 7.3 Hz, 1H), 5.38 (d, J = 7.3 Hz, 1H), 4.36 (dq, J = 9.2, 3.4, 2.9 Hz, 1H), 4.20 (ddd, J
(M+H)+
= 11.6, 9.6, 2.7 Hz, 1H), 3.97 – 3.84 (m, 4H), 3.44 – 3.33 (m, 4H), 2.47 – 2.35 (m, 1H), 2.29 – 2.19 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, Chloroform-d) δ 8.89 (s, 1H), 7.76 (dd, J = 9.9, 2.9 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H),
145 3.82 min; m/z = 510/512 7.49 – 7.43 (m, 2H), 7.29 (d, J = 7.7 Hz, 1H), 7.24 – 7.18 (m, 1H), 7.08 (d, J = 7.5 Hz, 1H), 6.93 (td, J = 7.5, 1.1 Hz, 1H), 6.88 – 6.84
(M+H)+ (m, 1H), 5.40 – 5.33 (m, 1H), 4.38 – 4.31 (m, 1H), 4.23 – 4.16 (m, 1H), 3.10 (s, 6H), 2.44 – 2.34 (m, 1H), 2.25 – 2.16 (m, 1H).
LC-MS d L2): Rt = 1H-NMR (400 MHz, Chloroform-d) δ 8.85 (d, J = 2.7 Hz, 1H), 7.81 (dd, J = 10.0, 2.8 Hz, 1H), 7.54 (dd, J = 7.9, 1.6 Hz, 1H), 7.40 (dd,
146 3.55 min; m/z = 510/512 J = 8.3, 2.8 Hz, 1H), 7.34 – 7.15 (m, 4H), 7.07 – 6.97 (m, 1H), 6.91 (td, J = 7.5, 1.1 Hz, 1H), 6.85 (dd, 1H), 5.40 – 5.29 (m, 1H), 4.37
(M+H)+ – 4.30 (m, 1H), 4.22 – 4.14 (m, 1H), 3.12 (s, 6H), 2.43 – 2.32 (m, 1H), 2.23 – 2.14 (m, 1H).
1H-NMR(399,9532 MHz, DMSO): δ= 9.121 (0.91); 9.1007 (0.93); 8.634 (3.89); 8.3134 (0.72); 8.2547 (0.98); 8.2517 (1.05); 8.2336
(1.09); 8.2306 (1.1); 7.805 (1.01); 7.7903 (1.21); 7.7874 (1.21); 7.6694 (1.03); 7.6485 (1.18); 7.6304 (12.69); 6.8945 ; 6.8875
(1.57); 6.7982 (0.58); 6.7911 (0.47); 6.7761 (1.29); 6.7688 ; 6.7441 (2.53); 6.7219 (1.02); 5.2287 (0.58); 5.2095 (0.58); 4.2178
147 2,76 (0.58); 4.2045 (1.04); 4.1982 (0.85); 4.1864 (0.55); 4.1782 (0.56); 3.6948 (11.21); 3.3162 (70.62); 3.2923 (0.36); 3.0725 (16); 2.6745
(0.55); 2.6703 (0.76); 2.6659 (0.57); 2.5055 (89.32); 2.5011 (123.65); 2.4967 (94.57); 2.3324 (0.52); 2.328 (0.71); 2.3236 (0.52);
2.1952 (0.33); 2.185 (0.35); 2.1736 (0.35); 2.0579 (0.35); 2.0505 (0.41); 1.3981 (6.55); 0.1458 (0.5); 0.008 (4.19); -0.0001 (108.21); -
0.0083 (4.43); -0.1497 (0.5)
1H-NMR(399,9532 MHz, DMSO): δ= 8.8981 (0.68); 8.8777 (0.7); 8.6125 (3.39); 8.3132 (0.55); 8.2499 (0.74); 8.2465 (0.82); 8.2286
; 8.2252 (0.85); 7.805 (0.71); 7.8016 (0.8); 7.7871 (0.96); 7.7838 ; 7.6657 ; 7.6476 (0.82); 7.6444 (0.97); 7.6324
(11.7); 7.3105 (0.9); 7.2897 (1); 6.8463 (0.92); 6.8409 ; 6.7994 (0.64); 6.7934 (0.54); 6.7787 (0.58); 6.7727 (0.53); 5.4719
148 2,84 (0.54); 5.4526 (0.54); 3.7345 (9.41); 3.3174 6); 3.0587 (12.87); 3.0247 (0.38); 2.8426 ; 2.8226 (0.35); 2.6747 (0.57);
2.6702 (0.79); 2.6658 (0.58); 2.5368 (0.56); 2.5237 (2.21); 2.5101 (44.34); 2.5056 (94.37); 2.5011 (132.67); 2.4965 ); 2.4921
(48.15); 2.3324 (0.55); 2.3281 (0.77); 2.3234 (0.56); 1.398 (16); 0.1459 (0.57); 0.008 (4.36); -0.0002 (135.3); -0.0084 (4.88); -0.1496
(0.56)
¹H-NMR (400 MHz, CHLOROFORM-d) δ [ppm]: 2.171 (1.43), 2.631 (16.00), 3.229 (12.71), 3.305 (1.03), 3.313 (1.03), 4.269 (0.86),
LC-MS (Method L1): Rt = 6.828 (1.34), 6.830 (1.40), 6.848 (1.53), 6.851 (1.54), 6.950 (1.41), 6.953 (1.37), 6.969 (0.85), 6.972 (0.79), 7.198 (1.15), 7.327
149 2,2 0.94 min; MS (ESIneg): m/z = (1.22), 7.346 (1.12), 7.390 (1.53), 7.395 (2.99), 7.400 (1.71), 7.512 (6.31), 7.517 (5.89), 7.551 (0.97), 7.569 (1.53), 7.572 (1.24),
589 [M-H]- 7.590 (1.44), 7.661 (1.63), 7.665 , 7.679 (1.23), 7.683 (1.12), 8.058 , 8.062 (1.45), 8.079 (1.31), 8.083 (1.23), 8.983
(5.10).
¹H-NMR (400 MHz, 6) δ [ppm]: 2.132 (1.28), 2.205 (1.37), 2.328 (0.59), 3.040 (16.00), 3.931 (0.61), 3.975 (4.59), 3.984
LC-MS (Method L1): Rt =
150 3,1 (4.71), 4.281 , 5.309 (1.69), 5.326 , 6.779 , 6.799 (3.08), 6.883 (1.42), 6.901 (2.80), 6.920 (1.72), 7.140 ,
1.11 min; MS (ESIpos): m/z =
7.159 (2.50), 7.175 (1.25), 7.348 (2.66), 7.365 (2.47), 7.643 (14.76), 7.660 (2.25), 7.678 (2.82), 7.699 (1.88), 7.820 (3.02), 7.835
536 [M+H]+
(2.42), 8.139 (1.05), 8.304 (2.56), 8.326 (2.33), 8.755 (6.56).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (0.73), 2.827 (5.86), 2.831 (9.97), 2.836 , 3.063 (16.00), 4.234
LC-MS (Method L6): Rt = (0.56), 4.253 (0.85), 4.262 (0.92), 6.778 (0.94), 6.781 (1.01), 6.799 (1.07), 6.801 (1.08), 6.894 (0.49), 6.897 (0.49), 6.912 (1.00),
151 1.55 min; MS (ESIpos): m/z = 6.915 , 6.931 (0.61), 6.934 (0.57), 7.026 (0.55), 7.043 (0.90), 7.055 (1.02), 7.060 (0.67), 7.082 (0.74), 7.142 (0.50), 7.146
503 [M+H]+ (0.54), 7.164 (0.80), 7.339 (0.78), 7.359 (0.78), 7.606 (0.49), 7.623 (1.27), 7.643 (1.95), 7.650 , 7.663 (0.52), 8.214 (0.96),
8.220 (0.91), 8.234 (0.91), 8.240 (0.83), 8.542 (4.00), 9.073 (0.89), 9.093 (0.86).
1H-NMR(399,9532 MHz, DMSO): δ= 9.0892 ; 9.0691 (0.96); 8.6414 (4.26); 8.2521 (0.97); 8.2488 (1.02); 8.2308 (1.12); 8.2275
(1.08); 7.8117 (0.96); 7.8084 (1.01); 7.7939 (1.28); 7.7906 ; 7.6681 ; 7.65 (1.06); 7.6469 (1.19); 7.633 (11.43); 7.4321
(0.64); 7.4139 (0.79); 7.411 (0.8); 7.3933 (0.66); 6.7953 (0.48); 6.7887 (0.52); 6.774 (0.91); 6.7673 (0.95); 6.7527 (0.46); 6.746
152 3 ; 6.6796 (0.98); 6.673 (0.85); 6.6532 (1.02); 6.6466 (0.82); 5.7538 ; 5.2288 (0.51); 5.2099 (0.52); 4.315 (0.48); 4.3057
(0.46); 4.2996 (0.54); 4.2881 (0.57); 4.2791 (0.52); 4.2653 (0.45); 4.2581 (0.58); 3.3173 (12.38); 3.0582 (16); 2.5238 (0.61); 2.5104
(12.16); 2.5059 (24.77); 2.5014 (33.92); 2.4969 (25.2); 2.4926 (12.16); 2.1993 (0.33); 2.1898 (0.34); 2.177 (0.37); 2.078 (0.34);
2.0714 (0.39); 0.008 (1.15); -0.0002 (30.44); -0.0084 (1.11)
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.241 (8.09), 1.253 (15.76), 1.265 , 2.024 (1.23), 2.030 (1.43), 2.037 (1.48), 2.046
(1.79), 2.053 (1.70), 2.146 (1.59), 2.157 (1.87), 2.166 , 3.508 (1.58), 3.519 (4.30), 3.530 (5.43), 3.540 (4.15), 3.552 ,
LC-MS (Method L1): Rt =
153 2,1 4.266 (5.31), 4.273 (4.37), 4.292 (0.68), 5.238 (1.23), 5.248 (2.59), 5.260 (2.52), 5.270 (1.13), 6.788 , 6.802 (4.77), 6.899
0.92 min; MS (ESIpos): m/z =
(2.30), 6.912 (4.55), 6.924 (2.56), 7.152 (2.32), 7.165 (3.89), 7.177 (1.93), 7.302 (4.05), 7.315 (3.75), 7.522 (2.63), 7.535 (4.17),
492 [M+H]+
7.548 (2.83), 7.606 (6.74), 7.620 (16.00), 7.662 , 7.731 (4.94), 7.743 (4.36), 7.808 (2.02), 7.816 (3.34), 8.412 (4.22), 8.426
(4.01), 8.509 (10.45), 9.013 (4.02), 9.027 (3.89).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.40), -0.008 (3.14), 0.008 (2.78), 0.833 (0.80), 0.851 (1.18), 1.028 (0.44), 1.103
(0.60), 1.118 (0.70), 1.235 (1.90), 1.874 (16.00), 1.914 (1.00), 2.063 (0.78), 2.108 , 2.163 (0.90), 2.366 (0.68), 2.518 ,
LC-MS (Method L1): Rt =
154 2.523 (3.14), 2.709 (0.54), 3.508 (0.82), 4.232 (0.58), 4.249 (1.20), 4.258 (1.14), 4.275 , 4.293 (0.98), 4.302 (1.16), 5.233
0.97 min; MS (ESIpos): m/z =
(0.52), 5.249 (1.04), 5.266 , 6.776 (2.22), 6.794 (2.46), 6.877 (1.16), 6.893 (2.38), 6.911 (1.44), 7.135 (1.28), 7.155 (2.02),
521 [M+H]+
7.174 (1.06), 7.340 (1.82), 7.359 (1.74), 7.574 (1.36), 7.592 (1.96), 7.617 (4.01), 7.622 (5.21), 7.628 (11.15), 7.633 (5.41), 7.726
, 7.789 (2.38), 7.805 (2.08), 8.516 (1.20), 8.538 (1.18), 8.604 (3.14), 9.016 , 9.036 (1.58), 9.575 (0.84), 10.034 (0.98).
1H-NMR (400 MHz, DMSO-d6) δ 9.17 (dd, J = 8.1, 4.5 Hz, 1H), 8.64 (d, J = 2.4 Hz, 1H), 8.37 (dd, J = 9.4, 6.3 Hz, 1H), 7.74 - 7.64
155 LC-MS (Method L2): Rt =
(m, 2H), 7.47 - 7.32 (m, 3H), 7.20 - 7.12 (m, 1H), 6.95 - 6.88 (m, 1H), 6.82 - 6.76 (m, 1H), 5.29 - 5.20 (m, 1H), 4.32 - 4.18 (m, 2H),
3.77 min, m/z = 536 (M+H)+
3.93 - 3.83 (m, 4H), 3.31 - 3.22 (m, 4H), 2.27 - 2.16 (m, 1H), 2.10 - 2.01 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 8.1 Hz, 1H), 8.66 (s, 1H), 8.33 (dd, J = 9.4, 6.2 Hz, 1H), 7.79 - 7.62 (m, 3H), 7.47 - 7.42
156 3.96 min, m/z = 552/554 (m, 1H), 7.40 - 7.34 (m, 1H), 7.21 - 7.13 (m, 1H), 6.96 - 6.89 (m, 1H), 6.83 - 6.76 (m, 1H), 5.29 - 5.21 (m, 1H), 4.33 - 4.19 (m, 2H),
(M+H)+ 3.91 - 3.83 (m, 4H), 3.30 - 3.23 (m, 4H), 2.25 - 2.19 (m, 1H), 2.10 - 2.02 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 8.1 Hz, 1H), 8.66 (s, 1H), 8.36 - 8.28 (m, 1H), 7.65 (t, J = 9.3 Hz, 1H), 7.54 (q, J = 8.7
157 LC-MS (Method L2): Rt =
Hz, 2H), 7.41 - 7.25 (m, 2H), 7.21 - 7.13 (m, 1H), 6.92 (t, J = 7.1 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.25 (q, J = 5.7 Hz, 1H), 4.33 -
3.61 min, m/z = 520 (M+H)+
4.19 (m, 2H), 3.93 - 3.82 (m, 4H), 3.31 - 3.21 (m, 4H), 2.21 (dt, J = 8.6, 4.4 Hz, 1H), 2.11 - 2.00 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.86 (s, 1H), 7.82 (dd, J = 9.8, 2.9 Hz, 1H), 7.52 – 7.44 (m, 2H), 7.36 – 7.19 (m, 4H), 6.93 (td, J
158 LC-MS (Method L2): Rt =
= 7.5, 1.1 Hz, 1H), 6.89 – 6.80 (m, 2H), 5.43 – 5.34 (m, 1H), 4.41 – 4.32 (m, 1H), 4.24 – 4.15 (m, 1H), 3.96 – 3.84 (m, 4H), 3.44 –
3.85 min; m/z = 520 (M+H)+
3.33 (m, 4H), 2.46 – 2.36 (m, 1H), 2.28 – 2.19 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.85 (s, 1H), 7.81 (dd, J = 9.8, 2.9 Hz, 1H), 7.62 – 7.59 (m, 1H), 7.52 – 7.38 (m, 4H), 7.28 (d, J =
159 LC-MS d L2): Rt =
7.7 Hz, 1H), 7.24 – 7.18 (m, 1H), 6.96 – 6.83 (m, 3H), 5.43 – 5.30 (m, 1H), 4.40 – 4.31 (m, 1H), 4.25 – 4.15 (m, 1H), 3.96 – 3.83 (m,
3.95 min; m/z = 518 (M+H)+
4H), 3.44 – 3.31 (m, 4H), 2.45 – 2.34 (m, 1H), 2.28 – 2.17 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 7.87 (dd, J = 9.8, 2.9 Hz, 1H), 7.53 – 7.46 (m, 2H), 7.34 – 7.26 (m, 2H), 7.24 – 7.17
160 LC-MS (Method L2): Rt =
(m, 2H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.89 – 6.80 (m, 2H), 5.40 – 5.33 (m, 1H), 4.39 – 4.31 (m, 1H), 4.23 – 4.12 (m, 1H), 3.96 – 3.84
3.91 min; m/z = 536 (M+H)+
(m, 4H), 3.44 – 3.33 (m, 4H), 2.44 – 2.34 (m, 1H), 2.26 – 2.18 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.82 (s, 1H), 7.89 (dd, J = 9.8, 2.9 Hz, 1H), 7.45 (dd, J = 8.3, 2.9 Hz, 1H), 7.37 – 7.18 (m, 4H),
161 LC-MS (Method L2): Rt =
7.14 (d, J = 7.5 Hz, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.86 (dd, J = 8.3, 1.0 Hz, 1H), 6.79 (s, 1H), 5.41 – 5.34 (m, 1H), 4.39 – 4.31
3.83 min; m/z = 536 (M+H)+
(m, 1H), 4.22 – 4.14 (m, 1H), 3.97 – 3.87 (m, 4H), 3.47 – 3.34 (m, 4H), 2.45 – 2.35 (m, 1H), 2.26 – 2.18 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.86 (s, 1H), 7.84 (dd, J = 9.7, 2.9 Hz, 1H), 7.51 (dd, J = 8.6, 2.9 Hz, 1H), 7.29 (d, J = 7.7 Hz,
162 LC-MS (Method L2): Rt =
1H), 7.24 – 7.12 (m, 3H), 6.97 – 6.78 (m, 4H), 5.42 – 5.34 (m, 1H), 4.40 – 4.32 (m, 1H), 4.24 – 4.15 (m, 1H), 3.96 – 3.85 (m, 4H),
3.89 min; m/z = 520 (M+H)+
3.44 – 3.33 (m, 4H), 2.46 – 2.36 (m, 1H), 2.29 – 2.19 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.85 (s, 1H), 7.84 (dd, J = 9.7, 2.8 Hz, 1H), 7.50 (dd, J = 8.5, 2.8 Hz, 1H), 7.39 (s, 1H), 7.32 –
163 LC-MS (Method L2): Rt =
7.13 (m, 4H), 6.94 (t, J = 7.1 Hz, 1H), 6.90 – 6.80 (m, 2H), 5.42 – 5.34 (m, 1H), 4.41 – 4.32 (m, 1H), 4.24 – 4.15 (m, 1H), 3.96 – 3.84
4.05 min; m/z = 536 (M+H)+
(m, 4H), 3.44 – 3.32 (m, 4H), 2.46 – 2.35 (m, 1H), 2.29 – 2.19 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 7.86 (dd, J = 9.8, 2.9 Hz, 1H), 7.51 (dd, J = 8.3, 2.7 Hz, 1H), 7.44 – 7.36 (m, 2H),
164 LC-MS (Method L2): Rt =
7.28 (d, J = 7.8 Hz, 1H), 7.23 – 7.18 (m, 1H), 7.14 (t, J = 8.9 Hz, 1H), 6.92 (td, J = 7.5, 1.1 Hz, 1H), 6.89 – 6.81 (m, 2H), 5.41 – 5.32
3.94 min; m/z = 536 (M+H)+
(m, 1H), 4.39 – 4.30 (m, 1H), 4.23 – 4.14 (m, 1H), 3.95 – 3.84 (m, 4H), 3.44 – 3.33 (m, 4H), 2.45 – 2.33 (m, 1H), 2.27 – 2.16 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 7.87 (dd, J = 9.9, 2.8 Hz, 1H), 7.44 (dd, J = 8.3, 2.8 Hz, 1H), 7.34 – 7.26 (m, 3H),
165 LC-MS (Method L2): Rt = 7.24 – 7.18 (m, 1H), 7.10 (td, J = 8.2, 2.5 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H), 6.80 (d, J = 5.9 Hz, 1H), 5.43 –
3.82 min; m/z = 536 (M+H)+ 5.30 (m, 1H), 4.39 – 4.31 (m, 1H), 4.22 – 4.14 (m, 1H), 3.96 – 3.86 (m, 4H), 3.46 – 3.34 (m, J = 3.8 Hz, 4H), 2.45 – 2.35 (m, 1H),
2.27 – 2.17 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, Chloroform-d) δ 8.80 (s, 1H), 7.87 (dd, J = 9.8, 2.9 Hz, 1H), 7.55 (dd, J = 8.0, 1.6 Hz, 1H), 7.43 (dd, J = 8.2, 2.8
166 3.95 min; m/z = 552/554 Hz, 1H), 7.33 – 7.17 (m, 4H), 6.94 – 6.77 (m, 3H), 5.41 – 5.30 (m, 1H), 4.37 – 4.31 (m, 1H), 4.21 – 4.14 (m, 1H), 3.95 – 3.85 (m, 4H),
(M+H)+ 3.45 – 3.33 (m, 4H), 2.44 – 2.34 (m, 1H), 2.25 – 2.16 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 8.2 Hz, 1H), 8.66 (s, 1H), 8.32 (dd, J = 9.4, 6.2 Hz, 1H), 7.65 (t, J = 9.3 Hz, 1H), 7.56 -
167 LC-MS (Method L2): Rt =
7.47 (m, 3H), 7.43 - 7.34 (m, 2H), 7.21 - 7.14 (m, 1H), 6.97 - 6.89 (m, 1H), 6.80 (d, J = 8.2, 0.9 Hz, 1H), 5.30 - 5.22 (m, 1H), 4.33 -
3.68 min, m/z = 518 (M+H)+
4.19 (m, 2H), 3.88 (t, J = 4.6 Hz, 4H), 3.32 - 3.22 (m, 4H), 2.28 - 2.17 (m, 1H), 2.11 - 1.98 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 8.33 - 8.25 (m, 1H), 7.60 (t, J = 9.3 Hz, 1H), 7.38 - 7.27 (m,
168 LC-MS (Method L2): Rt =
2H), 7.22 - 7.12 (m, 3H), 6.95 - 6.88 (m, 1H), 6.82 - 6.76 (m, 1H), 5.27 - 5.19 (m, 1H), 4.32 - 4.19 (m, 2H), 3.07 (s, 6H), 2.25 - 2.14
3.07 min, m/z = 478 (M+H)+
(m, 1H), 2.09 - 1.98 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.33 - 8.26 (m, 1H), 7.61 (t, J = 9.3 Hz, 1H), 7.54 - 7.49 (m,
169 LC-MS (Method L2): Rt =
1H), 7.39 - 7.28 (m, 3H), 7.20 - 7.13 (m, 1H), 6.95 - 6.88 (m, 1H), 6.82 - 6.76 (m, 1H), 5.27 - 5.19 (m, 1H), 4.32 - 4.19 (m, 2H), 3.07
3.26 min, m/z = 494 (M+H)+
(s, 6H), 2.25 - 2.14 (m, 1H), 2.09 - 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.17 (dd, J = 8.1, 3.6 Hz, 1H), 8.66 (d, J = 1.2 Hz, 1H), 8.37 (dd, J = 9.4, 6.3 Hz, 1H), 7.68 (t, J =
170 LC-MS (Method L2): Rt =
9.1 Hz, 1H), 7.63 - 7.49 (m, 2H), 7.46 - 7.34 (m, 2H), 7.17 (t, J = 7.7 Hz, 1H), 6.92 (t, J = 7.2 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 5.30 -
3.82 min, m/z = 536 (M+H)+
.21 (m, 1H), 4.33 - 4.19 (m, 2H), 3.88 (t, J = 4.3 Hz, 4H), 3.32 - 3.23 (m, 4H), 2.21 (d, J = 3.1 Hz, 1H), 2.06 (d, J = 6.4 Hz, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (dd, J = 8.1, 4.3 Hz, 1H), 8.56 (d, J = 1.2 Hz, 1H), 8.34 (dd, J = 9.4, 6.3 Hz, 1H), 7.74 - 7.59
171 LC-MS (Method L2): Rt =
(m, 2H), 7.46 - 7.31 (m, 3H), 7.16 (t, J = 7.1 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.28 - 5.18 (m, 1H), 4.32 - 4.18
3.23 min, m/z = 494 (M+H)+
(m, 2H), 3.08 (s, 6H), 2.19 (dd, J = 9.0, 4.8 Hz, 1H), 2.09 - 2.00 (m, 1H).
1H-NMR (400 MHz, 6) δ 9.07 (d, J = 7.4 Hz, 1H), 8.53 (d, J = 1.2 Hz, 1H), 8.31 (dd, J = 9.5, 6.3 Hz, 1H), 7.64 - 7.56 (m, 2H),
172 LC-MS (Method L2): Rt =
7.47 - 7.38 (m, 1H), 7.38 - 7.29 (m, 2H), 7.19 - 7.12 (m, 1H), 6.94 - 6.86 (m, 1H), 6.81 - 6.75 (m, 1H), 5.22 (q, J = 6.8, 6.3 Hz, 1H),
3.05 min, m/z = 494 (M+H)+
4.31 - 4.18 (m, 2H), 3.07 (s, 6H), 2.24 - 2.13 (m, 1H), 2.07 - 1.98 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.91 (s, 1H), 7.75 (dd, J = 9.9, 2.9 Hz, 1H), 7.52 – 7.44 (m, 2H), 7.36 – 7.18 (m, 4H), 7.11 (d, J =
173 LC-MS (Method L2): Rt =
7.4 Hz, 1H), 6.93 (td, J = 7.5, 1.1 Hz, 1H), 6.87 (dd, J = 8.3, 1.0 Hz, 1H), 5.40 – 5.33 (m, 1H), 4.39 – 4.31 (m, 1H), 4.23 – 4.15 (m,
3.40 min; m/z = 478 (M+H)+
1H), 3.10 (s, 6H), 2.44 – 2.35 (m, 1H), 2.25 – 2.17 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.93 (s, 1H), 7.75 (dd, J = 9.9, 2.9 Hz, 1H), 7.62 – 7.59 (m, 1H), 7.52 – 7.46 (m, 2H), 7.44 – 7.39
174 LC-MS (Method L2): Rt =
(m, 2H), 7.30 (d, J = 7.7 Hz, 1H), 7.24 – 7.18 (m, 1H), 7.12 (d, J = 7.5 Hz, 1H), 6.93 (td, J = 7.5, 1.2 Hz, 1H), 6.87 (dd, J = 8.3, 1.0
3.46 min; m/z = 476 (M+H)+
Hz, 1H), 5.41 – 5.34 (m, 1H), 4.39 – 4.31 (m, 1H), 4.23 – 4.16 (m, 1H), 3.10 (s, 6H), 2.44 – 2.35 (m, 1H), 2.25 – 2.17 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.88 (s, 1H), 7.81 (dd, J = 10.0, 2.9 Hz, 1H), 7.51 – 7.45 (m, 2H), 7.34 – 7.27 (m, 2H), 7.23 –
175 LC-MS (Method L2): Rt =
7.17 (m, 2H), 7.04 (d, J = 7.6 Hz, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.86 (dd, J = 8.2, 1.1 Hz, 1H), 5.40 – 5.33 (m, 1H), 4.38 – 4.31
3.59 min; m/z = 494 (M+H)+
(m, 1H), 4.22 – 4.15 (m, 1H), 3.11 (s, 6H), 2.43 – 2.34 (m, 1H), 2.24 – 2.16 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.86 (s, 1H), 7.82 (dd, J = 10.0, 2.9 Hz, 1H), 7.42 (dd, J = 8.3, 2.9 Hz, 1H), 7.37 – 7.30 (m, 1H),
176 LC-MS (Method L2): Rt =
7.29 – 7.12 (m, 4H), 7.02 (s, 1H), 6.91 (td, J = 7.5, 1.1 Hz, 1H), 6.85 (dd, J = 8.3, 1.0 Hz, 1H), 5.40 – 5.32 (m, 1H), 4.37 – 4.30 (m,
3.40 min; m/z = 494 (M+H)+
1H), 4.22 – 4.14 (m, 1H), 3.12 (s, 6H), 2.42 – 2.33 (m, 1H), 2.23 – 2.15 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.91 (s, 1H), 7.78 (dd, J = 9.9, 2.9 Hz, 1H), 7.48 (dd, J = 8.6, 2.9 Hz, 1H), 7.30 (d, J = 7.7 Hz,
177 LC-MS d L2): Rt =
1H), 7.24 – 7.13 (m, 3H), 7.04 (d, J = 7.4 Hz, 1H), 6.94 (td, J = 7.5, 1.2 Hz, 1H), 6.91 – 6.84 (m, 2H), 5.41 – 5.34 (m, 1H), 4.39 – 4.32
3.51 min; m/z = 478 (M+H)+
(m, 1H), 4.24 – 4.16 (m, 1H), 3.11 (s, 6H), 2.44 – 2.35 (m, 1H), 2.25 – 2.17 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.90 (s, 1H), 7.77 (dd, J = 9.9, 2.9 Hz, 1H), 7.47 (dd, J = 8.6, 2.9 Hz, 1H), 7.40 (s, 1H), 7.32 –
178 LC-MS (Method L2): Rt = 7.24 (m, 2H), 7.24 – 7.18 (m, 1H), 7.15 (dt, J = 8.4, 2.1 Hz, 1H), 7.05 (d, J = 7.5 Hz, 1H), 6.93 (td, J = 7.5, 1.1 Hz, 1H), 6.86 (dd, J =
3.73 min; m/z = 494 (M+H)+ 8.3, 0.9 Hz, 1H), 5.40 – 5.33 (m, 1H), 4.38 – 4.31 (m, 1H), 4.23 – 4.16 (m, 1H), 3.10 (s, 6H), 2.44 – 2.34 (m, 1H), 2.25 – 2.16 (m,
1H-NMR (400 MHz, Chloroform-d) δ 8.88 (s, 1H), 7.80 (dd, J = 10.0, 2.9 Hz, 1H), 7.48 (dd, J = 8.3, 2.8 Hz, 1H), 7.44 – 7.35 (m, 2H),
179 LC-MS (Method L2): Rt = 7.28 (d, J = 7.8 Hz, 1H), 7.23 – 7.17 (m, 1H), 7.13 (t, J = 8.9 Hz, 1H), 7.04 (d, J = 7.4 Hz, 1H), 6.92 (td, J = 7.5, 1.1 Hz, 1H), 6.86 (dd,
3.63 min; m/z = 494 (M+H)+ J = 8.3, 1.0 Hz, 1H), 5.39 – 5.33 (m, 1H), 4.38 – 4.30 (m, 1H), 4.22 – 4.14 (m, 1H), 3.11 (s, 6H), 2.43 – 2.34 (m, 1H), 2.24 – 2.16 (m,
1H-NMR (400 MHz, Chloroform-d) δ 8.87 (s, 1H), 7.81 (dd, J = 10.0, 2.9 Hz, 1H), 7.41 (dd, J = 8.3, 2.9 Hz, 1H), 7.34 – 7.26 (m, 3H),
180 LC-MS (Method L2): Rt =
7.23 – 7.18 (m, 1H), 7.12 – 7.00 (m, 2H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.86 (dd, J = 8.3, 1.1 Hz, 1H), 5.40 – 5.33 (m, 1H), 4.38 –
3.34 min; m/z = 494 (M+H)+
4.30 (m, 1H), 4.22 – 4.14 (m, 1H), 3.12 (s, 6H), 2.43 – 2.34 (m, 1H), 2.24 – 2.15 (m, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.14), 0.008 , 1.356 (0.66), 2.056 (0.64), 2.064 , 2.075 , 2.091
(1.03), 2.099 (0.87), 2.106 (0.63), 2.192 (0.43), 2.201 (0.68), 2.213 (0.94), 2.225 (0.91), 2.235 (0.85), 2.247 (0.57), 2.255 (0.46),
2.523 (1.40), 2.899 (3.69), 3.449 (0.46), 3.461 , 3.480 (2.72), 3.492 (5.13), 3.504 (4.92), 3.515 (2.44), 3.535 (0.65), 4.230
LC-MS (Method L1): Rt =
181 (0.50), 4.251 (1.50), 4.259 (1.25), 4.272 (2.17), 4.281 (2.06), 4.298 (1.28), 4.317 (0.47), 5.241 (0.65), 5.255 (1.41), 5.274 (1.39),
1.37 min; MS (ESIpos): m/z =
.288 (0.61), 6.792 (2.63), 6.810 (2.75), 6.812 (2.85), 6.918 (1.30), 6.921 (1.35), 6.937 (2.66), 6.939 (2.66), 6.955 (1.62), 6.958
550 [M+H]+
(1.57), 7.156 (1.35), 7.160 (1.44), 7.177 (2.18), 7.194 (1.07), 7.198 (1.05), 7.389 (2.31), 7.407 (2.12), 7.632 (5.83), 7.636 (16.00),
7.638 (8.92), 7.689 (1.90), 7.707 (2.69), 7.710 (2.47), 7.728 (2.42), 7.832 (3.00), 7.835 (3.26), 7.850 (2.42), 7.853 (2.35), 8.260
(2.52), 8.263 (2.63), 8.281 (2.36), 8.284 (2.26), 8.718 (9.84), 9.157 (2.51), 9.177 (2.41).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.74), 0.008 (0.62), 1.407 (16.00), 2.086 (0.51), 2.523 (0.47), 4.258 (0.40), 4.268
LC-MS (Method L1): Rt =
182 3,3 (1.03), 4.283 , 4.289 (0.91), 4.297 (0.51), 4.305 (0.58), 6.787 (0.59), 6.806 (0.68), 6.893 (0.65), 7.167 (0.52), 7.328 (0.53),
1.08 min; MS s): m/z =
7.347 (0.50), 7.578 , 7.599 (0.48), 7.611 , 7.615 (0.79), 7.626 (2.75), 7.631 (1.63), 7.769 (0.69), 7.787 (0.59), 8.210
578 [M+H]+
(0.42), 8.334 (0.53), 8.355 (0.50), 8.579 (1.74), 9.051 (0.51), 9.072 (0.50).
LC-MS (Method L1): Rt = ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.431 (16.00), 3.042 (4.04), 3.948 (2.03), 4.284 (0.56), 6.792 (0.61), 6.811 (0.68), 6.911
183 6 1.49 min; MS (ESIpos): m/z = (0.63), 7.173 (0.49), 7.354 (0.52), 7.373 (0.48), 7.644 (7.05), 7.683 (0.45), 7.701 (0.62), 7.722 (0.55), 7.837 (0.68), 7.840 (0.68),
592 [M+H]+ 7.855 (0.56), 7.858 , 8.350 (0.60), 8.353 (0.58), 8.371 (0.56), 8.374 (0.52), 8.763 , 9.234 (0.57), 9.254 (0.55).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.32), 0.912 (7.39), 0.931 (16.00), 0.949 (7.79), 1.634 (0.73), 1.652 (2.85), 1.670
(5.25), 1.688 (5.08), 1.706 (2.51), 1.725 (0.52), 2.008 (0.45), 2.024 (0.86), 2.033 (1.06), 2.042 (1.11), 2.058 (1.52), 2.068 (1.52),
2.086 (3.21), 2.126 (0.70), 2.138 (1.27), 2.155 (1.51), 2.167 (1.10), 2.178 (0.76), 2.328 , 2.523 (2.24), 2.670 (0.48), 3.451
LC-MS (Method L1): Rt =
184 3 (1.52), 3.468 (3.30), 3.476 (3.00), 3.482 (2.99), 3.489 (3.03), 3.506 (1.25), 4.235 (0.77), 4.253 (2.65), 4.268 (4.11), 4.278 (3.48),
0.95 min; MS (ESIpos): m/z =
4.286 (2.21), 4.306 (0.49), 5.236 (1.01), 5.251 (2.08), 5.269 (1.99), 5.284 (0.85), 5.754 (0.58), 6.782 , 6.803 (3.93), 6.880
506 [M+H]+
(1.99), 6.899 (3.97), 6.917 (2.28), 7.141 (1.96), 7.145 (1.96), 7.162 (3.10), 7.180 (1.49), 7.287 (3.39), 7.305 (3.06), 7.516 ,
7.535 (3.39), 7.555 (2.58), 7.600 , 7.605 , 7.621 (14.17), 7.626 (9.44), 7.732 (4.27), 7.750 , 7.951 (2.25), 8.412
(3.35), 8.433 (3.11), 8.535 (9.75), 8.986 (3.00), 9.006 (2.85).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.108 (4.30), 1.783 (2.07), 1.917 (2.11), 1.930 (1.65), 2.075 , 2.086 , 2.156
(1.41), 2.171 (1.60), 2.185 , 2.328 (0.70), 2.366 , 2.670 (0.85), 2.709 (0.44), 2.752 (4.01), 2.770 (0.64), 2.789 (0.58),
LC-MS (Method L1): Rt =
185 2 2.994 (3.16), 3.009 (6.19), 3.024 (3.45), 3.168 , 3.417 (1.38), 3.527 (1.42), 3.731 (1.06), 4.266 (4.94), 5.247 (2.07), 5.260
0.72 min; MS (ESIneg): m/z =
(1.94), 5.754 (8.83), 6.786 (3.64), 6.806 (4.14), 6.897 (1.83), 6.916 (3.84), 6.934 (2.23), 7.150 (1.96), 7.167 (3.21), 7.186 (1.56),
505 [M-H]-
7.323 (3.41), 7.341 (3.12), 7.540 (2.24), 7.559 (3.64), 7.579 (2.41), 7.611 , 7.617 (16.00), 7.746 (4.79), 7.763 (4.88), 8.346
(1.16), 8.400 (0.60), 8.421 , 8.442 (3.22), 8.513 , 8.538 (1.10), 9.052 (1.55), 9.069 (1.55).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), 0.008 (3.60), 0.146 (0.48), 1.140 (6.02), 1.235 (0.55), 1.889 (1.18), 2.031
(2.12), 2.051 (2.52), 2.063 (2.18), 2.073 (1.69), 2.116 (2.61), 2.156 (1.44), 2.170 (1.66), 2.186 (0.98), 2.206 (0.83), 2.327 (1.00),
2.366 (0.43), 2.669 (1.05), 2.710 (0.52), 3.475 (2.09), 3.503 (2.40), 3.737 (1.58), 3.759 (1.14), 3.813 (0.91), 3.835 (1.75), 3.865
LC-MS (Method L1): Rt =
186 (2.04), 3.877 (2.60), 3.892 (1.74), 3.903 (1.61), 4.254 , 4.266 , 4.280 (3.06), 4.366 (2.18), 4.538 (0.55), 5.032 (2.78),
0.80 min; MS (ESIpos): m/z =
.207 , 5.221 (1.83), 5.241 (1.89), 5.255 (0.85), 6.781 (3.54), 6.801 (4.00), 6.891 (1.71), 6.910 (3.70), 6.929 (2.12), 7.145
534 [M+H]+
(1.81), 7.162 (2.90), 7.183 (1.41), 7.305 (3.14), 7.324 (2.84), 7.464 (2.18), 7.482 (3.14), 7.503 (2.58), 7.606 (4.72), 7.610 (4.81),
7.621 (16.00), 7.625 (9.59), 7.706 (3.90), 7.724 (3.35), 8.133 (13.65), 8.279 (3.24), 8.299 (3.04), 8.434 (10.50), 9.044 (3.03), 9.065
(2.98), 12.729 (0.68).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.83), -0.008 (7.47), 0.008 (6.76), 0.146 (0.89), 1.235 , 1.260 (2.01), 1.335
(2.31), 1.901 (1.24), 2.005 (1.48), 2.017 (2.25), 2.028 (2.37), 2.040 (2.49), 2.049 (2.61), 2.085 (0.53), 2.149 (1.42), 2.167 (1.24),
2.185 (1.19), 2.200 (0.89), 2.327 (1.36), 2.366 (0.83), 2.523 (4.80), 2.670 (1.60), 2.710 (1.07), 3.501 (1.84), 3.527 (2.07), 3.732
LC-MS (Method L1): Rt =
187 (1.54), 3.780 (1.01), 3.800 (1.78), 3.821 (1.54), 3.852 (1.72), 3.862 (1.78), 3.879 (1.54), 3.889 (1.42), 4.258 (5.39), 4.270 (3.32),
0.80 min; MS (ESIpos): m/z =
4.374 (2.31), 5.029 (3.67), 5.037 (3.61), 5.197 , 5.212 (2.01), 5.231 (2.07), 5.246 (0.95), 5.753 , 6.782 (3.61), 6.803
534 [M+H]+
(4.09), 6.895 (1.84), 6.913 (3.97), 6.932 (2.31), 7.147 (1.96), 7.165 (3.20), 7.182 (1.60), 7.310 (3.38), 7.328 (3.08), 7.463 ,
7.483 (2.79), 7.503 (2.13), 7.609 (3.08), 7.621 (16.00), 7.625 (9.84), 7.709 (3.67), 7.725 (3.20), 8.132 (2.01), 8.276 (3.08), 8.297
(2.90), 8.428 (6.76), 9.044 (2.37), 9.065 (2.37), 12.724 (0.71).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.51), 0.008 (2.40), 1.778 (0.76), 1.789 (0.83), 1.806 (1.00), 1.999 (0.94), 2.012
(0.94), 2.020 (0.92), 2.034 (0.71), 2.327 (0.91), 2.670 (1.00), 4.034 (0.75), 4.055 (1.64), 4.076 , 4.161 (1.16), 4.171 (1.05),
LC-MS (Method L1): Rt =
188 4,5 4.179 (1.30), 4.198 (0.76), 5.017 (0.70), 5.031 (1.46), 5.050 (1.46), 5.065 (0.67), 5.754 (0.43), 6.746 (2.94), 6.766 (3.26), 6.848
1.18 min; MS (ESIneg): m/z =
(1.33), 6.868 , 6.885 (1.86), 7.049 , 7.066 (2.16), 7.127 (1.46), 7.148 (2.40), 7.165 (1.19), 7.419 (2.81), 7.438 (3.05),
514 [M-H]-
7.721 (4.19), 7.724 (6.58), 7.730 (16.00), 7.734 (7.25), 7.816 (2.30), 7.835 (3.08), 7.856 (2.38), 8.049 (3.13), 8.052 (3.29), 8.067
(2.75), 8.136 (6.83), 8.138 (6.75), 8.649 (6.74), 8.652 , 9.105 (2.64), 9.125 (2.56), 9.233 ).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.12 - 9.22 (m, 2H), 8.35 (s, 2H), 8.03 (dd, 1H), 7.88 - 7.96 (m, 1H), 7.79 - 7.88 (m, 1H),
189 5 1.27 min; MS (ESIpos): m/z = 7.67 - 7.76 (m, 2H), 7.25 (d, 1H), 7.11 - 7.20 (m, 1H), 6.88 - 6.97 (m, 1H), 6.76 (d, 1H), 5.01 - 5.13 (m, 1H), 4.07 - 4.28 (m, 2H), 2.02
534 [M+H]+ - 2.15 (m, 1H), 1.94 (dtd, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.34), 0.008 (11.80), 0.146 , 1.234 (0.47), 2.050 (1.17), 2.058 (1.31), 2.072
(1.34), 2.085 (1.95), 2.210 (1.70), 2.222 , 2.231 (1.56), 2.245 (1.09), 2.327 (1.39), 2.366 (0.75), 2.523 (4.79), 2.669 ,
2.710 , 3.060 (0.45), 3.162 , 3.174 (0.58), 3.249 (1.59), 3.269 (5.20), 3.280 (11.55), 3.291 (13.72), 3.864 (8.68), 3.875
LC-MS (Method L1): Rt =
190 (14.11), 3.886 (8.04), 4.223 (0.95), 4.244 (2.73), 4.252 (2.17), 4.265 (3.56), 4.293 , 4.312 (0.81), 5.245 (1.11), 5.259 ,
1.11 min; MS (ESIpos): m/z =
.277 , 5.292 (1.09), 5.754 , 6.788 (4.59), 6.809 (5.04), 6.917 , 6.933 , 6.952 (2.87), 7.157 (2.56), 7.175
518 [M+H]+
(4.03), 7.192 , 7.377 (4.26), 7.395 (4.01), 7.484 (3.14), 7.506 (6.04), 7.528 (4.70), 7.586 , 7.591 (2.98), 7.598 (2.95),
7.603 (3.09), 7.612 (2.11), 7.619 (1.89), 7.625 (1.92), 7.673 , 7.691 (4.84), 7.712 (4.31), 7.796 (8.77), 7.815 (7.35), 8.253
(4.51), 8.256 (4.54), 8.274 (4.20), 8.419 (0.42), 8.679 (16.00), 9.157 (4.45), 9.177 (4.29).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.284 (1.86), 3.296 (2.09), 3.310 (16.00), 3.864 (1.44), 3.875 (2.23), 3.886 (1.28), 4.236
LC-MS (Method L1): Rt =
191 (0.43), 4.260 (0.54), 5.248 (0.41), 6.782 (0.73), 6.802 (0.80), 6.924 (0.74), 6.941 (0.43), 7.168 (0.63), 7.364 , 7.383 (0.61),
1.14 min; MS (ESIpos): m/z =
7.593 (0.46), 7.617 (0.89), 7.641 (0.45), 7.675 (0.47), 7.688 (0.55), 7.695 (0.75), 7.706 (0.80), 7.714 (0.54), 7.726 (0.64), 7.774
536 [M+H]+
(0.85), 7.790 (0.54), 8.295 (0.68), 8.313 (0.62), 8.626 (2.30), 9.156 (0.68), 9.176 (0.65).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (0.67), 1.038 (0.70), 1.056 (1.42), 1.073 (0.73), 1.356 (16.00), 2.069
(0.41), 2.183 (2.23), 2.198 (0.40), 2.523 (0.65), 3.162 (5.24), 3.175 (5.43), 3.261 (1.01), 3.272 (2.30), 3.284 (2.43), 3.295 (1.34),
3.862 (1.80), 3.873 (3.10), 3.884 (1.73), 4.062 (0.46), 4.075 (1.30), 4.088 (1.26), 4.101 , 4.231 (0.62), 4.238 (0.48), 4.252
LC-MS (Method L1): Rt =
192 (0.64), 4.259 (0.79), 4.267 (0.64), 4.274 , 4.283 (0.53), 4.335 (0.42), 5.238 (0.57), 5.257 (0.58), 6.631 , 6.784 (1.09),
1.25 min; MS (ESIpos): m/z =
6.802 (1.21), 6.870 (1.34), 6.902 (0.56), 6.905 (0.54), 6.921 (1.16), 6.939 (0.71), 6.942 (0.64), 7.148 (0.56), 7.152 (0.59), 7.169
552 [M+H]+
(0.92), 7.187 , 7.190 (0.45), 7.362 (0.95), 7.381 , 7.502 (2.90), 7.506 (3.06), 7.636 (0.78), 7.659 (1.54), 7.682 (0.86),
7.688 (1.02), 7.693 (1.74), 7.698 (0.87), 8.319 (0.77), 8.334 (0.82), 8.342 (0.81), 8.358 (0.73), 8.680 (4.09), 9.152 (1.05), 9.172
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.61), -0.008 (8.00), 0.008 (5.20), 0.146 (0.61), 1.903 , 2.018 (3.13), 2.029
(3.53), 2.040 (3.33), 2.050 (3.82), 2.156 , 2.170 (2.36), 2.185 (1.71), 2.327 (2.03), 2.366 (1.50), 2.518 (10.92), 2.523 (9.71),
LC-MS (Method L6): Rt =
193 2.669 (2.07), 2.710 (1.58), 3.472 (1.54), 3.499 (2.56), 3.523 (1.34), 3.736 (2.19), 3.833 (1.71), 3.863 , 3.876 (2.52), 3.892
1.46 min; MS (ESIpos): m/z =
, 4.257 (5.69), 4.266 , 4.370 (3.09), 5.029 (4.51), 5.220 (2.48), 5.754 (1.38), 6.783 (4.95), 6.802 (5.28), 6.894 (2.88),
552 [M+H]+
6.913 (5.20), 6.931 (3.01), 7.146 (2.80), 7.164 (4.35), 7.184 (1.99), 7.307 (4.39), 7.326 (3.78), 7.461 , 7.480 (3.49), 7.500
(2.36), 7.721 (4.75), 7.739 (4.06), 7.789 (16.00), 7.805 (15.51), 8.275 (3.57), 8.297 (3.25), 8.439 (5.32), 9.042 (3.25), 9.063 (3.09).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.76), 1.243 , 1.862 (2.65), 1.904 (3.87), 2.034 (6.99), 2.142 , 2.157
LC-MS (Method L6): Rt = , 2.327 (2.86), 2.365 (1.05), 2.668 (3.16), 2.689 (9.05), 2.709 (1.60), 2.889 (0.97), 3.508 (3.16), 3.741 (3.75), 3.873 (5.09),
194 1.37 min; MS s): m/z = 4.249 (14.53), 4.384 (6.23), 5.049 (4.97), 5.203 , 5.754 (16.00), 6.770 (9.35), 6.791 ), 6.876 (5.64), 6.895 (11.49), 6.912
534 [M+H]+ (6.48), 7.135 (5.73), 7.153 (8.80), 7.172 (4.63), 7.286 ), 7.305 (12.25), 7.422 , 7.494 (4.88), 7.537 (6.19), 7.663 (5.05),
8.133 (2.95), 8.331 (10.27), 9.031 (3.83).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.44), -0.008 (12.33), 0.008 (10.95), 0.146 (1.32), 1.258 (0.72), 1.902 , 2.034
LC-MS d L1): Rt = , 2.148 (5.11), 2.164 , 2.180 (4.39), 2.197 (3.67), 2.327 , 2.366 (2.71), 2.523 (12.27), 2.670 (4.75), 2.689 (1.26),
195 0.75 min; MS (ESIpos): m/z = 2.709 (1.98), 2.812 (0.78), 3.509 (4.03), 3.745 (4.09), 3.874 (7.82), 4.257 (16.00), 4.376 (6.92), 5.037 (7.10), 5.221 (6.32), 5.754
536 [M+H]+ (14.80), 6.777 (11.31), 6.797 (12.27), 6.882 (7.64), 6.901 (15.28), 6.919 (8.84), 7.142 (6.86), 7.159 (10.83), 7.178 , 7.292
(12.75), 7.311 (11.49), 7.493 (5.29), 7.585 (5.23), 7.664 (9.26), 8.132 (2.05), 8.320 (6.26), 8.361 (10.23), 9.030 (4.45).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.87), 1.913 (2.01), 2.048 (3.88), 2.170 (2.51), 2.327 (1.94), 2.523 (5.82), 2.669
LC-MS (Method L1): Rt = (1.97), 3.516 (1.51), 3.868 (2.41), 4.265 (7.06), 4.377 (3.51), 5.044 (3.01), 5.223 (2.74), 5.754 (16.00), 6.784 (6.46), 6.803 (6.93),
196 0.74 min; MS (ESIpos): m/z = 6.892 (3.08), 6.910 (6.43), 6.928 (3.88), 7.147 (3.25), 7.164 (5.12), 7.183 (2.68), 7.301 (4.92), 7.320 (4.62), 7.492 (5.12), 7.567
518 [M+H]+ (3.68), 7.579 (3.75), 7.684 (3.48), 7.701 (3.18), 7.779 (5.82), 7.784 (5.72), 7.798 (5.82), 7.803 (5.62), 8.131 (2.91), 8.260 (2.74),
8.409 (3.45), 9.059 (1.97).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 , 2.055 (0.47), 2.182 (0.43), 2.194 (0.43), 2.523 (1.20), 3.072 (16.00), 4.234
LC-MS (Method L1): Rt = (0.76), 4.241 (0.67), 4.253 (1.11), 4.261 (1.14), 4.276 (0.61), 5.233 (0.66), 5.253 (0.62), 5.754 (0.79), 6.781 (1.22), 6.799 (1.31),
197 0.93 min; MS (ESIpos): m/z = 6.895 (0.67), 6.914 (1.23), 6.933 (0.72), 7.147 (0.66), 7.164 (0.99), 7.182 (0.48), 7.342 (1.07), 7.361 (0.96), 7.586 (0.87), 7.609
494 [M+H]+ (1.65), 7.634 (1.59), 7.652 , 7.668 (1.04), 7.673 (1.40), 7.687 (1.16), 7.707 (0.85), 7.733 (1.36), 7.747 (0.90), 8.252 (1.19),
8.256 (1.15), 8.273 (1.10), 8.558 (4.01), 9.072 (1.07), 9.092 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.98), 0.008 , 1.031 (16.00), 1.046 (15.86), 2.114 (0.42), 2.123 (0.49), 2.130
(0.48), 2.180 (0.43), 2.207 (0.73), 2.231 (0.54), 2.290 (0.86), 2.524 (0.71), 2.599 (7.81), 2.716 (2.57), 2.767 (1.36), 2.782 (4.28),
3.063 (13.77), 3.096 (5.64), 3.118 (5.22), 3.128 (2.34), 3.758 (0.72), 3.774 (0.93), 3.789 (0.67), 4.223 (0.45), 4.234 (0.63), 4.240
LC-MS (Method L1): Rt = (0.73), 4.263 (1.22), 4.268 (1.11), 4.291 (0.83), 4.347 (0.83), 4.356 (1.15), 4.374 (0.55), 4.384 (0.64), 6.029 , 6.045 ,
198 1.17 min; MS (ESIpos): m/z = 6.054 , 6.070 (0.47), 6.750 (0.57), 6.770 (0.61), 6.816 (1.14), 6.836 (1.59), 6.854 (0.46), 6.942 (0.62), 6.952 (0.92), 6.970
506 [M+H]+ (1.59), 6.989 (0.90), 7.088 (0.43), 7.162 (1.02), 7.181 (1.47), 7.200 (0.67), 7.303 (1.07), 7.322 (0.94), 7.359 (0.50), 7.378 (0.44),
7.584 (1.50), 7.588 (2.38), 7.600 (0.65), 7.604 (0.60), 7.623 (0.60), 7.641 (2.51), 7.645 (2.60), 7.653 (1.17), 7.674 (6.23), 7.678
(4.23), 7.684 (1.61), 7.760 (0.60), 7.763 , 7.778 (0.49), 7.781 (0.49), 7.810 , 7.828 (1.43), 8.233 (1.73), 8.252 (1.81),
8.270 , 8.621 (1.03), 8.626 (0.75), 8.649 (1.42), 8.685 (3.00).
¹H-NMR (400 MHz, 6) δ [ppm]: 1.524 (0.76), 1.830 (0.77), 1.842 (0.85), 2.669 (0.44), 3.368 (16.00), 3.946 (0.56), 3.970
LC-MS (Method L1): Rt = , 3.993 (1.00), 4.034 (1.18), 4.049 (1.17), 4.939 (1.39), 4.958 (1.38), 5.753 (0.43), 6.593 (3.28), 6.613 (3.44), 6.720 (2.29),
199 1.47 min; MS (ESIpos): m/z = 6.740 (2.71), 6.751 (1.49), 6.769 (2.88), 6.792 (2.81), 6.811 (1.48), 6.997 (1.58), 7.015 (1.39), 7.099 (1.40), 7.123 (3.83), 7.142
554 [M+H]+ (4.69), 7.163 , 7.676 (2.67), 7.680 (2.28), 7.686 (2.02), 7.707 (3.17), 7.716 (8.16), 7.721 (7.33), 7.909 (2.73), 7.925 (2.29),
7.963 (2.59), 7.984 (2.17), 8.892 (2.25), 8.912 (2.12), 8.993 (6.13).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.45), -0.008 (4.14), 0.008 (3.74), 0.146 (0.49), 1.157 (4.28), 1.175 (8.62), 1.192
, 1.237 (1.13), 1.398 (6.32), 1.988 (16.00), 2.019 (1.27), 2.040 (1.53), 2.054 (1.76), 2.073 , 2.191 (1.72), 2.204 (1.64),
2.213 (1.69), 2.227 (1.15), 2.327 (1.34), 2.366 (0.92), 2.522 , 2.669 (1.41), 2.710 (0.92), 3.247 (1.22), 3.265 (2.51), 3.295
LC-MS (Method L1): Rt = (9.16), 3.874 (12.08), 4.002 , 4.020 (3.83), 4.038 (3.76), 4.056 , 4.200 (0.85), 4.224 (2.40), 4.249 (3.43), 4.258 (2.82),
200 1.14 min; MS (ESIpos): m/z = 4.275 (2.47), 5.230 (2.35), 5.245 , 5.754 (7.59), 6.774 (5.36), 6.795 (5.92), 6.887 (2.61), 6.905 (5.47), 6.924 (3.27), 7.142
552 [M+H]+ (2.89), 7.159 (4.46), 7.177 (2.21), 7.181 (2.21), 7.344 (6.79), 7.360 (6.16), 7.363 (7.33), 7.370 (3.55), 7.374 (2.84), 7.389 (3.59),
7.393 (3.43), 7.452 (2.96), 7.466 (3.38), 7.472 (4.89), 7.485 (5.24), 7.491 (2.68), 7.505 (2.61), 7.646 (3.76), 7.669 (6.51), 7.691
(3.88), 7.734 (6.13), 7.737 , 7.754 (5.36), 7.757 (5.12), 8.341 (3.74), 8.356 (3.99), 8.364 (3.95), 8.380 (3.64), 8.604 (9.75),
8.612 ), 9.143 (2.98), 9.149 , 9.163 , 9.170 (2.96).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.72), 0.008 (2.48), 2.030 (0.56), 2.039 (0.58), 2.051 , 2.066 (0.88), 2.073
(0.77), 2.086 (3.11), 2.181 (0.62), 2.193 (0.79), 2.205 , 2.215 (0.72), 2.227 , 2.327 (0.60), 2.332 (0.43), 2.523 (1.88),
2.559 (1.25), 2.578 (1.51), 2.596 (1.97), 2.614 (1.49), 2.634 (0.95), 2.651 (0.54), 2.665 (0.50), 2.669 , 2.674 (0.47), 3.710
LC-MS (Method L1): Rt = (1.27), 3.720 (1.53), 3.728 (2.20), 3.737 (2.18), 3.744 (1.48), 3.755 , 3.845 , 3.877 (3.98), 3.909 (1.91), 4.223 (0.41),
201 1.08 min; MS (ESIpos): m/z = 4.244 , 4.252 (1.09), 4.264 (1.96), 4.272 (2.19), 4.287 (1.15), 4.306 (0.42), 5.237 (0.54), 5.251 (1.20), 5.271 (1.20), 5.285
554 [M+H]+ (0.52), 5.754 (4.52), 6.792 (2.31), 6.810 (2.55), 6.812 (2.55), 6.904 (1.13), 6.907 (1.12), 6.923 (2.38), 6.942 (1.43), 6.944 (1.35),
7.156 (1.18), 7.160 (1.25), 7.177 (1.91), 7.195 (0.96), 7.199 (0.91), 7.355 (1.97), 7.373 (1.85), 7.638 (16.00), 7.657 (0.42), 7.664
, 7.682 (2.37), 7.685 (2.13), 7.703 (2.16), 7.834 (2.60), 7.837 (2.71), 7.852 (2.23), 7.855 (2.07), 8.237 (2.33), 8.240 ,
8.258 (2.24), 8.261 , 8.688 (8.85), 9.217 (2.14), 9.237 (2.09).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.84), -0.008 (8.37), 0.008 (8.34), 0.146 (0.90), 0.994 (0.52), 1.236 (1.34), 1.336
(0.57), 1.782 (1.25), 1.916 (1.25), 2.327 (1.74), 2.366 (1.09), 2.670 (1.88), 2.710 (1.09), 2.765 (2.18), 2.781 (4.28), 2.797 (2.15),
LC-MS (Method L1): Rt =
202 3.963 (0.87), 3.984 (2.07), 4.006 (1.34), 4.111 (1.55), 4.873 (1.80), 4.888 (3.60), 4.905 (2.43), 4.921 (1.58), 4.936 (1.88), 4.953
1.04 min; MS (ESIpos): m/z =
(1.31), 6.688 (3.46), 6.709 , 6.716 (1.80), 6.735 (3.46), 6.754 (2.51), 6.856 (3.41), 6.875 (2.53), 7.058 (1.66), 7.079 (2.70),
533 [M+H]+
7.097 (1.53), 7.614 (11.50), 7.618 (16.00), 7.636 (4.99), 7.641 (5.42), 7.657 (1.20), 7.680 (1.61), 7.743 (1.77), 7.761 (4.12), 7.781
(3.76), 7.798 (4.58), 7.812 (2.21), 8.383 (2.67), 8.403 (2.70), 8.563 (2.67), 8.580 (2.43), 8.662 (0.57), 9.033 (11.99), 11.367 (0.60).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.46), 2.064 (0.79), 2.071 (0.81), 2.084 (0.92), 2.099 (1.21), 2.206 (0.83), 2.218
(1.14), 2.230 (1.08), 2.240 (1.07), 2.252 (0.73), 2.327 (0.63), 2.522 (1.85), 2.669 (0.67), 3.484 (3.25), 3.654 (5.30), 3.666 ,
LC-MS (Method L4): Rt =
203 4.223 (0.66), 4.244 (1.80), 4.251 , 4.265 (1.77), 4.272 (2.23), 4.282 (1.77), 4.297 (1.50), 4.316 (0.61), 5.240 (0.78), 5.254
3.85 min; MS (ESIpos): m/z =
(1.76), 5.273 (1.72), 5.287 , 5.754 (1.31), 6.794 (3.28), 6.814 (3.60), 6.920 (1.57), 6.937 (3.30), 6.955 (1.94), 7.160 (1.66),
582 [M+H]+
7.163 (1.71), 7.181 (2.72), 7.198 (1.33), 7.392 , 7.409 (2.68), 7.635 (8.69), 7.639 (16.00), 7.647 (5.36), 7.652 (4.23), 7.707
(2.28), 7.725 (3.22), 7.746 (2.80), 7.872 , 7.887 (2.92), 8.399 (3.12), 8.417 (2.89), 8.770 (11.57), 9.239 , 9.260 (2.96).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.38), -0.008 (13.30), 0.008 (13.66), 0.146 (1.50), 1.235 (1.56), 2.049 (1.20), 2.076
(1.68), 2.206 (1.50), 2.217 (1.62), 2.226 (1.44), 2.322 , 2.327 , 2.331 , 2.366 (2.52), 2.522 (13.90), 2.664 (3.00),
2.669 (3.84), 2.674 (2.88), 2.709 (2.46), 3.218 (3.96), 3.241 (9.11), 3.262 (8.45), 3.273 (10.25), 3.285 (11.63), 3.858 (7.85), 3.870
LC-MS (Method L1): Rt =
204 (13.30), 3.881 , 4.223 (0.72), 4.243 (2.64), 4.251 (2.10), 4.264 (3.90), 4.273 (3.96), 4.289 (2.16), 4.381 (4.85), 4.403 (9.65),
0.83 min; MS (ESIpos): m/z =
4.425 (4.67), 5.240 (1.02), 5.255 (2.40), 5.275 (2.34), 5.288 (0.96), 5.753 , 6.784 (4.43), 6.802 (4.91), 6.871 (3.66), 6.890
508 [M+H]+
(7.49), 6.909 (5.87), 6.923 , 6.942 (2.82), 7.109 (4.55), 7.127 (3.90), 7.151 (2.46), 7.168 (3.78), 7.186 (1.92), 7.237 (4.19),
7.256 (3.78), 7.363 (4.01), 7.382 (3.72), 7.618 (2.64), 7.636 , 7.657 (5.27), 7.674 (5.69), 7.678 (6.05), 7.692 (3.06), 7.696
(2.52), 8.202 (4.25), 8.206 (4.07), 8.223 (3.90), 8.227 (3.54), 8.583 (16.00), 9.155 (4.25), 9.176 .
205 LC-MS d L2):Rt = 3.94 1H-NMR (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 8.20 (d, J = 9.1 Hz, 1H), 7.67 – 7.63 (m, 1H), 7.56 (dd, J = 8.0, 1.5 Hz, 1H), 7.34
min; m/z = 568/570 (M+H)+ (td, J = 7.8, 2.5 Hz, 1H), 7.25 (d, J = 7.7 Hz, 1H), 7.23 – 7.12 (m, 2H), 6.94 – 6.80 (m, 3H), 5.39 – 5.31 (m, 1H), 4.38 – 4
LC-MS (Method L2): Rt =
206 1H-NMR (400 MHz, Chloroform-d) δ 8.85 (s, 1H), 8.17 (d, J = 9.1 Hz, 1H), 7.64 (d, J = 9.1 Hz, 1H), 7.43 (t, J = 1.9 Hz, 1H), 7.30 –
4.15 min; m/z = 568/570
7.17 (m, 4H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.86 (dd, J = 8.3, 1.0 Hz, 1H), 6.80 (d, J = 7.4 Hz, 1H), 5.40 – 5.33 (m, 1H)
(M+H)+
LC-MS (Method L2): Rt =
207 1H-NMR (400 MHz, Chloroform-d) δ 8.84 (d, J = 1.7 Hz, 1H), 8.14 (dd, J = 9.1, 1.4 Hz, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.55 (dd, J =
3.41 min; m/z = 526/528
8.1, 1.5 Hz, 1H), 7.34 (td, J = 7.8, 2.2 Hz, 1H), 7.26 (d, 1H), 7.23 – 7.14 (m, 2H), 6.94 – 6.83 (m, 3H), 5.38 – 5.31 (m, 1H
(M+H)+
LC-MS (Method L2): Rt =
208 1H-NMR (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 8.09 (d, J = 9.1 Hz, 1H), 7.59 (d, J = 9.1 Hz, 1H), 7.42 (s, 1H), 7.32 – 7.15 (m, 4H),
3.61 min; m/z = 526/528
6.97 – 6.82 (m, 3H), 5.33 (q, J = 5.2 Hz, 1H), 4.38 – 4.28 (m, 1H), 4.22 – 4.13 (m, 1H), 3.12 (s, 6H), 2.42 – 2.32 (m, 1H
(M+H)+
LC-MS (Method L2): Rt =
209 1H-NMR (400 MHz, form-d) δ 8.78 (d, J = 1.7 Hz, 1H), 7.57 – 7.50 (m, 2H), 7.32 – 7.17 (m, 5H), 6.94 – 6.77 (m, 3H), 5.40 –
3.85 min; m/z = 552/554
.33 (m, 1H), 4.38 – 4.30 (m, 1H), 4.22 – 4.14 (m, 1H), 3.91 – 3.80 (m, 4H), 3.44 – 3.31 (m, 4H), 2.44 – 2.33 (m, 1H), 2.25 –
(M+H)+
LC-MS (Method L2): Rt =
210 1H-NMR (400 MHz, Chloroform-d) δ 8.81 (s, 1H), 7.61 (dd, J = 8.1, 5.3 Hz, 1H), 7.47 – 7.36 (m, 3H), 7.32 – 7.18 (m, 3H), 6.93 (td, J
4.13 min; m/z = 552/554
= 7.5, 1.1 Hz, 1H), 6.86 (dd, J = 8.3, 1.0 Hz, 1H), 6.81 (d, J = 7.5 Hz, 1H), 5.41 – 5.33 (m, 1H), 4.40 – 4.32 (m, 1H), 4.
(M+H)+
LC-MS (Method L2): Rt =
211 1H-NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 8.0 Hz, 1H), 8.73 (s, 1H), 8.20 (d, J = 2.1 Hz, 1H), 7.92 (d, J = 2.1 Hz, 1H), 7.68 (s, 3H),
4.39 min, m/z = 568/570
7.39 (d, J = 7.6 Hz, 1H), 7.18 (t, J = 7.4 Hz, 1H), 6.93 (t, J = 7.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 5.25 (d, J = 7.1
(M+H)+
LC-MS (Method L2): Rt =
212 1H-NMR (400 MHz, DMSO-d6) δ 9.22 (dd, J = 8.0, 5.3 Hz, 1H), 8.62 (d, J = 3.1 Hz, 1H), 8.22 (d, J = 2.4 Hz, 1H), 7.77 (d, J = 2.3 Hz,
4.12 min, m/z = 568/570
1H), 7.73 (dd, J = 8.0, 1.6 Hz, 1H), 7.46 (td, J = 7.8, 4.5 Hz, 1H), 7.41 – 7.33 (m, 2H), 7.16 (t, J = 7.0 Hz, 1H), 6.91 (
(M+H)+
LC-MS (Method L2): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.13 (dd, J = 8.1, 5.1 Hz, 1H), 8.54 (d, J = 1.5 Hz, 1H), 8.22 (d, J = 2.4 Hz, 1H), 7.74 – 7.69 (m,
213 3.75 min, m/z = 526/528
2H), 7.45 (td, J = 7.8, 4.4 Hz, 1H), 7.41 – 7.31 (m, 2H), 7.20 – 7.12 (m, 1H), 6.90 (t, J = 7.5 Hz, 1H), 6.78 (dd, J = 8.2, 1.0
(M+H)+
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, 6) δ 9.21 (dd, J = 8.1, 5.5 Hz, 1H), 8.54 (d, J = 3.0 Hz, 1H), 7.67 (dd, J = 8.0, 1.6 Hz, 1H), 7.52 (d, J =
3.27 min, m/z = 548 (M+H)+ 7.3 Hz, 1H), 7.49 – 7.34 (m, 3H), 7.33 – 7.26 (m, 1H), 7.16 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.1
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.21 (d, J = 8.2 Hz, 1H), 8.62 (s, 1H), 7.68 (d, J = 7.4 Hz, 1H), 7.63 – 7.55 (m, 3H), 7.49 – 7.37 (m,
3.56 min, m/z = 548 (M+H)+ 2H), 7.21 – 7.14 (m, 1H), 6.97 – 6.90 (m, 1H), 6.83 – 6.77 (m, 1H), 5.31 – 5.23 (m, 1H), 4.33 – 4.20 (m, 2H), 3.87 – 3.78 (m
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.326 (0.43), 3.568 (16.00), 3.897 (2.36), 3.910 (6.78), 3.954 (0.55), 4.259 (0.56), 5.263
LC-MS (Method L1): Rt =
(0.41), 6.778 (0.76), 6.798 (0.79), 6.909 (0.76), 6.928 (0.43), 7.141 , 7.162 (0.66), 7.359 (0.68), 7.379 (0.61), 7.754 (0.48),
216 0.94 min; MS s): m/z =
7.771 (0.70), 7.792 (0.53), 7.952 , 7.970 (0.69), 8.151 (1.35), 8.356 (0.70), 8.378 (0.67), 8.396 (1.42), 8.590 , 8.803
565 [M+H]+
, 9.184 (0.66), 9.205 .
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 7.67 (d, J = 7.4 Hz, 1H), 7.62 - 7.56 (m, 3H), 7.45 - 7.35 (m,
3.04 min, m/z = 506 (M+H)+ 2H), 7.21 - 7.14 (m, 1H), 6.97 - 6.89 (m, 1H), 6.80 (dd, J = 8.2, 1.0 Hz, 1H), 5.30 - 5.21 (m, 1H), 4.33 - 4.20 (m, 2H), 2.
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) : δ 9.11 (dd, J = 7.9, 5.8 Hz, 1H), 8.49 (d, J = 1.8 Hz, 1H), 7.66 (dd, J = 8.0, 1.6 Hz, 1H), 7.50 (d, J =
3.03 min, m/z = 506 (M+H)+ 7.3 Hz, 1H), 7.45 - 7.38 (m, 2H), 7.35 (d, J = 6.8 Hz, 1H), 7.33 - 7.26 (m, 1H), 7.16 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.
LC-MS (Method L6): Rt = ¹H-NMR (600 MHz, DICHLOROMETHANE-d2) δ [ppm]: 2.505 (11.27), 3.076 (9.00), 3.332 (16.00), 4.248 , 4.262 (0.80), 5.254
219 1.28 min; MS (ESIpos): m/z = (0.50), 6.784 , 6.797 (1.22), 6.915 (0.81), 6.927 (0.45), 7.055 (0.40), 7.071 (0.64), 7.148 (0.45), 7.161 , 7.343 (0.79),
476 [M+H]+ 7.356 (0.75), 7.625 (0.76), 7.643 (1.22), 8.223 (0.76), 8.237 (0.72), 8.548 (1.64), 9.091 (0.69), 9.104 (0.67), 10.063 (0.80).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.32), 0.008 , 1.236 (0.84), 1.817 ), 1.834 (9.96), 2.029 (1.50), 2.037
(1.62), 2.048 (1.70), 2.064 (2.32), 2.071 (2.04), 2.198 , 2.210 (1.96), 2.219 (1.89), 2.231 (1.34), 2.327 (0.87), 2.366 (0.64),
LC-MS (Method L6): Rt = 2.669 (0.92), 2.710 (0.59), 3.607 (1.18), 3.634 (0.65), 3.880 ), 4.208 (0.97), 4.230 (2.88), 4.257 (4.12), 4.266 (3.48), 4.273
220 1.86 min; MS (ESIpos): m/z = (2.88), 4.282 (2.93), 4.294 (1.13), 4.300 (1.21), 5.224 , 5.239 (3.07), 5.258 (3.05), 5.273 (1.35), 6.779 (5.76), 6.799 (6.47),
498 [M+H]+ 6.894 (2.26), 6.913 (4.68), 6.932 (2.70), 6.998 (2.00), 7.017 (4.09), 7.036 (2.35), 7.146 (3.37), 7.165 , 7.182 (3.02), 7.199
(4.41), 7.222 (3.20), 7.274 (2.47), 7.352 (5.14), 7.371 (4.90), 7.465 (0.67), 7.486 (0.43), 7.610 (3.69), 7.627 (5.66), 7.676 (4.79),
7.696 (5.53), 7.714 (3.21), 8.095 (0.41), 8.114 , 8.262 (5.39), 8.283 (5.12), 8.578 (14.71), 9.146 (2.67).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.072 (1.74), 2.203 (1.62), 2.327 (1.90), 2.366 (1.16), 2.669 (2.05), 2.710 (1.47), 3.286
LC-MS (Method L6): Rt = (11.07), 3.877 (14.20), 4.237 (2.72), 4.262 (3.40), 5.249 (2.54), 5.268 (2.69), 6.781 (4.77), 6.802 (5.41), 6.903 (2.42), 6.921 (5.14),
221 2.11 min; MS (ESIpos): m/z = 6.940 (2.97), 7.149 (2.63), 7.168 (3.98), 7.185 (2.05), 7.320 (3.24), 7.343 , 7.365 (7.89), 7.381 (3.79), 7.480 (3.06), 7.487
518 [M+H]+ (4.62), 7.496 (3.43), 7.502 (4.47), 7.510 (2.88), 7.520 (3.15), 7.532 (2.66), 7.543 (2.57), 7.686 (2.75), 7.704 (4.93), 7.725 (4.83),
7.767 (5.66), 7.782 (3.55), 8.292 (4.37), 8.310 , 8.624 (16.00), 9.156 (4.28), 9.176 (4.41).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.64), 2.023 (0.54), 2.038 (1.00), 2.046 (1.02), 2.058 (1.08), 2.073 (1.49), 2.081
(1.28), 2.088 (0.94), 2.184 (0.70), 2.193 (1.09), 2.205 (1.44), 2.217 (1.35), 2.227 , 2.240 (0.90), 2.248 (0.69), 2.327 (0.51),
2.366 (0.43), 2.669 (0.49), 3.259 (1.78), 3.278 (5.13), 3.289 (11.26), 3.301 (15.43), 3.312 (16.00), 3.867 (7.04), 3.878 (11.75), 3.889
LC-MS (Method L6): Rt = (6.69), 4.209 (0.69), 4.216 (0.81), 4.237 (2.18), 4.245 (1.75), 4.264 (2.74), 4.271 (2.61), 4.287 (2.00), 4.306 , 5.236 ,
222 2.07 min; MS (ESIpos): m/z = 5.250 (2.07), 5.269 (2.07), 5.283 (0.94), 6.783 (3.72), 6.803 (4.15), 6.814 (0.48), 6.906 (1.85), 6.924 (3.92), 6.942 (2.32), 7.148
520 [M+H]+ (1.95), 7.152 (2.07), 7.169 (3.35), 7.190 (2.50), 7.200 (1.81), 7.208 (1.77), 7.222 (1.73), 7.369 (3.48), 7.387 (3.23), 7.562 (0.70),
7.570 (0.83), 7.578 (0.92), 7.585 (1.40), 7.598 (1.38), 7.606 (1.34), 7.611 (1.38), 7.619 (0.86), 7.626 (0.75), 7.634 (0.68), 7.707
, 7.725 (3.96), 7.746 (3.74), 7.799 (4.59), 7.814 (2.97), 8.285 , 8.314 (3.61), 8.317 (3.68), 8.335 (3.42), 8.338 (3.29),
8.650 (12.72), 8.724 , 9.169 (3.62), 9.189 (3.54).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.175 (0.49), 1.863 (1.82), 1.911 (2.02), 2.036 (3.68), 2.085 (1.72), 2.163 (2.23), 2.198
LC-MS (Method L1): Rt = (1.58), 2.327 (1.01), 2.669 (1.08), 2.709 (0.62), 3.163 , 3.174 (3.15), 3.529 (1.52), 3.655 (0.88), 3.763 (1.37), 3.882 (2.44),
223 0.70 min; MS (ESIpos): m/z = 4.089 (0.62), 4.170 (3.56), 4.256 (6.88), 4.379 (3.32), 5.049 (3.25), 5.211 , 5.753 (9.32), 6.777 (6.14), 6.796 (6.47), 6.881
518 [M+H]+ (3.02), 6.900 , 6.918 (4.00), 7.140 (3.30), 7.158 (5.04), 7.175 (2.77), 7.293 (5.66), 7.311 (5.73), 7.328 (2.80), 7.349 (2.01),
7.502 (5.11), 7.651 , 8.133 (16.00), 8.321 (3.22), 8.355 (6.29), 8.737 (1.30), 9.047 (1.75), 12.596 (0.49).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 , 0.146 (0.80), 2.056 (2.10), 2.203 (2.12), 2.327 , 2.366 (1.27), 2.670
LC-MS (Method L1): Rt = (2.02), 2.709 (1.14), 3.893 (16.00), 4.229 (3.13), 4.249 (4.61), 4.256 (4.76), 4.495 (1.40), 5.241 (2.87), 5.258 , 6.770 (4.84),
224 0.79 min; MS (ESIpos): m/z = 6.790 (5.39), 6.878 (2.36), 6.896 (5.10), 6.914 (3.06), 7.134 (2.59), 7.152 (4.45), 7.171 (2.20), 7.333 (4.66), 7.352 , 7.507
523 [M+H]+ , 7.525 (7.95), 7.550 (6.37), 7.569 (7.48), 7.588 (3.21), 7.691 (2.72), 7.709 (5.02), 7.730 (4.14), 7.788 (5.95), 7.804 ,
8.195 (5.05), 8.214 (4.89), 8.287 (4.58), 8.308 (4.38), 8.483 ), 9.143 (4.43), 9.164 (4.50), 9.188 (10.17).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.049 (0.55), 2.058 , 2.069 (0.65), 2.084 (0.92), 2.092 , 2.200 (0.60), 2.210
(0.84), 2.222 , 2.231 (0.80), 2.244 (0.52), 2.387 (16.00), 2.670 (0.42), 3.246 (0.74), 3.266 (2.20), 3.278 (5.05), 3.290 (5.63),
LC-MS (Method L6): Rt = 3.652 (0.65), 3.863 (4.10), 3.874 (7.04), 3.885 (4.04), 4.225 (0.44), 4.246 (1.32), 4.253 (1.09), 4.267 (1.92), 4.276 (1.85), 4.293
225 2.04 min; MS (ESIpos): m/z = (1.21), 4.312 (0.44), 5.246 (0.55), 5.260 (1.28), 5.279 (1.30), 5.293 (0.57), 5.754 (0.74), 6.788 (2.36), 6.809 (2.64), 6.915 (1.17),
498 [M+H]+ 6.933 (2.52), 6.952 (1.46), 7.048 (1.44), 7.072 (1.45), 7.156 (1.29), 7.175 (2.10), 7.191 (2.25), 7.222 (4.45), 7.376 , 7.395
(2.06), 7.659 (1.34), 7.678 (2.39), 7.698 (2.06), 7.758 (2.87), 7.776 (1.90), 8.243 (2.30), 8.264 (2.08), 8.668 (7.28), 9.157 (2.21),
9.178 (2.16).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.279 (0.79), 3.291 (1.79), 3.312 (16.00), 3.868 (1.47), 3.879 (2.45), 3.889 (1.39), 4.237
LC-MS (Method L6): Rt = (0.46), 4.258 (0.61), 4.286 (0.43), 5.249 (0.45), 5.268 (0.45), 5.754 (0.77), 6.781 (0.85), 6.801 , 6.904 (0.42), 6.922 (0.86),
226 2.10 min; MS (ESIpos): m/z = 6.941 (0.50), 7.149 (0.43), 7.167 (0.75), 7.304 (0.41), 7.324 (1.03), 7.344 (0.75), 7.366 (0.78), 7.385 (1.17), 7.400 (0.72), 7.644
518 [M+H]+ (0.68), 7.695 (0.42), 7.713 (0.86), 7.734 (0.84), 7.754 (1.05), 7.769 (0.52), 8.300 (0.71), 8.318 (0.70), 8.629 (2.54), 9.157 (0.74),
9.177 (0.72).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.030 (1.38), 2.038 (1.48), 2.053 (1.64), 2.064 (2.14), 2.072 (1.92), 2.187 (1.53), 2.199
(1.97), 2.210 (1.94), 2.220 (1.83), 2.233 (1.30), 2.669 (0.41), 3.254 , 3.287 (11.31), 3.876 (16.00), 4.213 (1.15), 4.234 ,
LC-MS (Method L6): Rt = 4.241 (2.68), 4.255 (4.56), 4.264 (4.46), 4.281 (2.83), 4.300 (1.09), 5.229 (1.31), 5.244 (2.94), 5.262 , 5.277 (1.27), 5.753
227 2.02 min; MS s): m/z = , 6.777 (4.98), 6.798 (5.63), 6.896 (2.63), 6.914 (5.47), 6.933 (3.20), 7.144 (2.90), 7.163 (4.73), 7.182 (2.38), 7.244 (2.61),
518 [M+H]+ 7.265 (2.55), 7.289 (2.22), 7.297 (1.96), 7.311 (3.96), 7.318 (3.43), 7.332 (2.42), 7.340 (2.20), 7.355 (5.09), 7.374 (4.69), 7.573
, 7.586 (3.35), 7.595 (3.06), 7.608 (2.68), 7.666 (2.45), 7.683 (11.68), 7.703 (5.74), 7.721 (2.06), 8.279 (4.22), 8.283 (4.22),
8.299 (3.93), 8.303 , 8.598 (13.90), 9.158 , 9.178 (4.64).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.050 (0.48), 2.057 (0.51), 2.071 (0.57), 2.085 (0.76), 2.092 (0.66), 2.199 (0.53), 2.210
(0.69), 2.221 (0.68), 2.231 (0.64), 2.244 (0.44), 3.245 (0.65), 3.265 (1.89), 3.276 (4.16), 3.288 (4.44), 3.822 (16.00), 3.844 (0.52),
LC-MS (Method L6): Rt =
3.864 , 3.874 (5.85), 3.884 (3.40), 4.246 (1.08), 4.253 (0.91), 4.267 (1.58), 4.276 (1.53), 4.293 , 5.244 , 5.258
228 2.11 min; MS (ESIpos): m/z =
(1.07), 5.277 (1.07), 5.291 (0.47), 5.754 (1.95), 6.788 (1.90), 6.809 (2.13), 6.916 (0.97), 6.935 (2.06), 6.954 , 7.062 (2.64),
530 [M+H]+
7.094 (2.80), 7.156 (1.06), 7.175 (1.70), 7.197 (3.47), 7.378 (1.82), 7.397 (1.68), 7.662 , 7.682 (1.95), 7.701 (1.50), 7.782
(2.37), 7.799 (1.71), 8.251 , 8.272 (1.79), 8.677 (5.49), 9.160 (1.84), 9.180 (1.81).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.69), -0.008 (5.65), 0.008 (5.56), 0.146 (0.66), 1.997 (0.61), 2.012 , 2.023
(1.58), 2.031 (1.41), 2.044 (2.52), 2.059 (2.38), 2.072 (0.97), 2.127 , 2.141 (2.46), 2.155 (2.88), 2.169 (1.49), 2.191 (1.36),
2.203 (0.61), 2.327 (1.22), 2.366 (1.05), 2.523 (3.99), 2.669 (1.30), 2.709 (1.13), 3.057 (15.92), 3.069 (16.00), 4.247 (5.37), 4.259
LC-MS (Method L1): Rt =
(8.78), 4.273 (5.09), 5.218 (1.36), 5.233 (3.02), 5.253 (3.02), 5.267 (1.38), 6.780 (5.48), 6.800 (6.06), 6.889 (2.85), 6.891 ,
229 0.76 min; MS (ESIpos): m/z =
6.908 (6.03), 6.926 , 7.139 (2.88), 7.143 (3.02), 7.160 (4.73), 7.178 (2.35), 7.182 (2.30), 7.304 (5.04), 7.322 (4.71), 7.414
443 [M+H]+
(1.99), 7.434 (5.79), 7.446 (4.98), 7.464 (7.53), 7.484 (3.74), 7.508 (4.98), 7.511 (9.38), 7.515 (6.42), 7.530 (7.11), 7.553 ,
7.632 (8.14), 7.636 (4.76), 7.667 (5.87), 7.684 (4.76), 7.756 (1.49), 8.133 (6.12), 8.233 (1.00), 8.312 , 8.333 (4.21), 8.424
(15.67), 8.963 (3.43), 8.983 (3.35), 12.706 (0.72).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.039 (0.49), 2.074 (0.74), 2.206 , 2.217 (0.65), 2.228 , 3.247 (0.58), 3.279
(4.26), 3.291 (4.54), 3.861 (3.48), 3.872 (5.83), 3.883 (3.38), 3.919 (16.00), 4.240 (1.05), 4.247 (0.85), 4.261 (1.44), 4.288 (0.95),
LC-MS (Method L6): Rt =
.239 (0.43), 5.254 (1.04), 5.273 (1.05), 5.287 (0.48), 5.754 , 6.783 (2.11), 6.803 , 6.907 (0.98), 6.926 (2.11), 6.945
230 1.93 min; MS (ESIpos): m/z =
(1.22), 7.152 , 7.172 (2.27), 7.192 (1.76), 7.202 , 7.220 (1.17), 7.288 (1.26), 7.305 (1.27), 7.318 (1.25), 7.334 (1.22),
532 [M+H]+
7.367 (1.77), 7.386 (1.63), 7.661 (0.93), 7.680 (2.04), 7.700 (1.95), 7.722 (2.44), 7.738 (1.14), 8.258 , 8.276 (1.55), 8.620
(6.28), 9.153 (1.82), 9.173 (1.77).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.072 (0.90), 2.204 (0.83), 2.327 (0.69), 2.366 (0.42), 2.408 (16.00), 2.670 (0.67), 3.282
LC-MS (Method L6): Rt = (5.02), 3.294 (5.70), 3.862 (3.95), 3.873 (6.80), 3.885 (3.85), 4.237 (1.27), 4.259 (1.58), 4.285 (1.15), 5.249 (1.24), 5.268 (1.26),
231 2.25 min; MS (ESIpos): m/z = 6.783 (2.54), 6.803 (2.69), 6.906 (1.22), 6.924 (2.41), 6.941 (1.48), 7.147 (1.32), 7.169 , 7.186 (1.00), 7.326 (2.64), 7.352
532 [M+H]+ (2.75), 7.365 (2.13), 7.381 (1.93), 7.448 (3.44), 7.465 (3.40), 7.674 (1.50), 7.692 (2.59), 7.713 (2.56), 7.743 (2.91), 7.757 (1.61),
8.273 , 8.277 (2.20), 8.294 (2.00), 8.612 (8.94), 9.154 (2.17), 9.175 (2.13).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.033 (0.68), 2.041 , 2.052 (0.79), 2.068 (1.07), 2.075 (0.94), 2.189 (0.70), 2.201
(0.97), 2.213 (0.96), 2.222 (0.91), 2.235 (0.63), 2.327 (0.60), 2.366 , 2.669 (0.68), 2.709 (0.48), 3.254 (0.88), 3.273 (2.55),
3.286 (5.77), 3.588 (15.32), 3.591 ), 3.864 (4.82), 3.875 , 3.886 (4.64), 4.213 (0.57), 4.234 (1.64), 4.241 (1.30), 4.261
LC-MS (Method L6): Rt =
(2.03), 4.269 (1.72), 4.276 (1.38), 4.285 (1.39), 4.304 (0.57), 5.232 (0.65), 5.246 (1.48), 5.265 (1.51), 5.279 (0.66), 6.782 (2.77),
232 1.90 min; MS (ESIpos): m/z =
6.802 , 6.901 (1.38), 6.919 (2.88), 6.936 (1.69), 7.032 (0.93), 7.037 (0.97), 7.048 (1.14), 7.053 (2.04), 7.059 (1.39), 7.069
532 [M+H]+
(1.33), 7.075 (1.25), 7.145 (1.39), 7.149 (1.51), 7.167 (2.40), 7.184 (2.10), 7.204 (1.50), 7.227 (1.53), 7.249 (0.88), 7.354 (2.50),
7.372 (2.32), 7.637 (0.62), 7.643 (1.31), 7.655 (4.76), 7.659 (6.97), 7.678 (3.56), 7.695 (1.24), 8.249 (2.35), 8.255 (2.38), 8.269
(2.16), 8.274 (2.15), 8.597 , 9.143 (2.61), 9.163 (2.55).
LC-MS (Method L2): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 8.1 Hz, 1H), 8.71 (s, 1H), 8.46 (d, J = 8.9 Hz, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.70 (t, J =
233 4.22 min, m/z = 602 (Cl2
1.9 Hz, 1H), 7.40 – 7.30 (m, 3H), 7.20 – 7.13 (m, 1H), 6.95 – 6.88 (m, 1H), 6.82 – 6.76 (m, 1H), 5.28 – 5.20 (m, 1H), 4.32
pattern) (M+H)+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.59), -0.008 (5.31), 0.008 , 0.146 (0.56), 2.049 (1.06), 2.057 (1.15), 2.069
(1.17), 2.084 , 2.091 (1.48), 2.198 (1.12), 2.211 (1.57), 2.223 (1.45), 2.233 (1.45), 2.246 (0.95), 2.327 (1.17), 2.366 (1.12),
2.523 (3.97), 2.669 (1.34), 2.710 (1.17), 3.249 (1.26), 3.268 (4.20), 3.280 , 3.291 (10.83), 3.651 (1.90), 3.865 (7.83), 3.876
LC-MS (Method L1): Rt =
(13.26), 3.887 (7.52), 4.225 (0.87), 4.245 (2.52), 4.253 (1.99), 4.267 (3.33), 4.293 (2.21), 4.312 (0.81), 5.245 (1.03), 5.259 (2.35),
234 1.10min; MS (ESIpos): m/z =
.279 (2.38), 5.293 (1.06), 6.789 (4.36), 6.809 (4.90), 6.917 , 6.933 , 6.951 (2.80), 7.154 (2.49), 7.157 (2.57), 7.175
502 [M+H]+
(4.00), 7.193 (1.99), 7.247 (1.76), 7.253 (1.29), 7.265 (1.59), 7.271 (3.41), 7.277 , 7.294 (1.87), 7.300 , 7.319 (4.84),
7.324 (5.48), 7.340 , 7.356 (1.23), 7.377 (4.17), 7.396 (3.86), 7.681 (3.13), 7.700 (4.62), 7.720 (4.20), 7.827 (4.95), 7.831
(5.20), 7.845 (4.06), 7.848 (3.92), 8.273 (4.31), 8.276 (4.39), 8.295 (4.11), 8.693 (16.00), 9.165 (4.20), 9.185 (4.11).
¹H-NMR (400 MHz, 6) δ [ppm]: 2.091 (2.67), 2.220 (2.73), 2.327 (2.60), 2.367 (5.33), 2.668 (4.62), 2.710 (5.79), 3.882
LC-MS (Method L1): Rt =
(16.00), 4.244 (3.32), 4.266 (4.62), 5.255 (3.12), 6.789 (4.36), 6.809 , 6.915 (2.34), 6.934 (4.75), 6.952 (2.73), 7.155 (2.80),
235 1.29min; MS (ESIpos): m/z =
7.174 (4.29), 7.195 (2.15), 7.381 (4.62), 7.399 (4.16), 7.706 (2.47), 7.724 , 7.743 (2.99), 7.886 (7.28), 7.903 (12.75), 7.985
568 [M+H]+
(7.15), 8.302 (4.75), 8.323 (4.36), 8.693 (9.95), 9.174 (4.29), 9.194 (4.10).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (2.92), 0.008 (2.76), 1.236 (1.50), 1.259 (1.23), 1.299 , 1.983 (0.59), 1.996
(1.10), 2.008 (1.36), 2.016 (1.23), 2.030 (2.09), 2.044 (1.95), 2.057 (0.80), 2.118 (0.75), 2.132 (2.09), 2.146 (2.34), 2.161 (1.32),
2.181 (1.28), 2.195 (0.53), 2.300 (1.82), 2.327 (0.64), 2.366 (0.61), 2.523 (2.31), 2.669 (0.73), 2.709 (0.69), 3.057 (12.33), 3.070
LC-MS (Method L6): Rt = (12.39), 3.341 , 3.370 , 3.382 (0.48), 3.874 , 4.237 (4.47), 4.249 (7.39), 4.264 (4.32), 4.482 (1.02), 4.497 (1.07),
236 1.38 min; MS (ESIpos): m/z = 4.858 (10.93), 5.146 (0.64), 5.206 (1.12), 5.221 (2.49), 5.240 (2.47), 5.255 (1.12), 5.359 (0.43), 6.772 (4.55), 6.793 (4.96), 6.878
462 [M+H]+ (2.39), 6.880 (2.39), 6.896 (4.95), 6.899 (4.90), 6.915 (2.97), 6.917 , 7.132 (2.42), 7.135 , 7.153 (4.02), 7.170 (2.01),
7.174 (1.96), 7.232 (0.48), 7.250 (0.41), 7.274 (1.85), 7.293 (8.65), 7.312 (7.85), 7.327 (1.21), 7.333 (1.21), 7.345 (3.29), 7.355
(13.29), 7.365 (4.96), 7.376 (1.77), 7.527 (1.53), 7.545 (2.97), 7.566 (2.27), 7.591 (1.64), 7.608 (2.84), 7.629 , 7.647 (2.65),
7.765 (1.79), 8.133 (0.54), 8.367 (16.00), 8.391 (3.06), 8.958 (2.52), 8.979 (2.52), 10.023 (0.51), 11.746 (5.38).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.77), 0.146 (0.83), 0.853 (0.66), 1.235 , 1.259 (3.13), 1.298 (2.19), 1.985
(1.63), 1.998 (1.98), 2.019 (2.99), 2.035 (2.68), 2.126 (2.85), 2.140 (3.27), 2.159 (2.19), 2.175 (1.95), 2.327 (1.98), 2.366 (1.29),
2.669 (2.37), 2.710 (1.57), 3.051 (15.79), 3.061 (16.00), 3.370 (1.57), 3.382 (1.70), 3.395 (1.15), 3.413 (0.73), 3.508 (0.97), 3.520
(1.18), 3.534 (0.94), 3.561 (1.11), 3.574 (1.22), 4.233 (6.02), 4.245 (10.37), 4.259 (6.33), 4.482 (2.37), 4.496 (2.33), 4.858 (9.39),
LC-MS d L6): Rt =
.131 (0.66), 5.146 (1.29), 5.160 (0.63), 5.198 (1.74), 5.213 (3.69), 5.233 (3.76), 5.247 (1.77), 5.359 (1.22), 6.768 (7.10), 6.788
237 1.57 min; MS (ESIpos): m/z =
(7.93), 6.874 (3.27), 6.893 (7.03), 6.911 (4.24), 7.132 (3.58), 7.150 , 7.171 (2.85), 7.219 , 7.286 (6.26), 7.307 (11.55),
512 [M+H]+
7.320 (3.51), 7.355 (11.93), 7.365 (3.90), 7.393 (4.45), 7.398 (4.56), 7.418 (4.73), 7.424 (4.42), 7.460 (0.94), 7.518 (4.42), 7.536
(7.55), 7.556 (7.23), 7.585 , 7.601 (5.11), 7.614 (3.20), 7.634 (2.19), 7.706 , 7.724 (1.50), 7.774 (2.57), 7.871 (11.10),
7.877 (10.96), 7.910 (2.57), 7.927 , 7.954 (0.59), 8.022 (0.70), 8.139 (1.18), 8.340 (15.06), 8.374 (5.91), 8.394 (5.57), 8.427
(0.73), 8.946 (4.28), 8.967 (4.28), 10.022 (3.72), 11.746 (4.21).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (0.56), 0.008 (0.52), 2.523 , 3.277 (0.80), 3.290 (1.68), 3.310 (16.00), 3.333
LC-MS (Method L1): Rt = (0.41), 3.867 (1.46), 3.877 (2.48), 3.889 (1.37), 4.232 (0.50), 4.253 (0.68), 4.264 , 4.271 (0.44), 4.280 (0.43), 5.241 (0.43),
238 1.05 min; MS (ESIpos): m/z = 5.260 (0.43), 6.777 (0.84), 6.798 , 6.912 (0.84), 6.930 (0.49), 7.141 (0.44), 7.145 (0.46), 7.162 (0.73), 7.354 (0.77), 7.371
518 [M+H]+ (0.72), 7.447 (0.89), 7.456 (1.29), 7.468 (0.84), 7.475 (0.99), 7.668 (0.48), 7.680 , 7.685 (1.24), 7.690 , 7.709 (1.11),
7.727 , 8.286 (0.80), 8.291 (0.82), 8.306 (0.74), 8.311 (0.72), 8.589 (2.41), 9.154 (0.41).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.278 (3.88), 3.284 (1.78), 3.297 (2.06), 3.310 (16.00), 3.875 (2.72), 4.236 (0.51), 4.258
LC-MS (Method L1): Rt = (0.65), 4.285 (0.46), 5.248 (0.49), 5.267 (0.50), 6.782 (0.98), 6.801 , 6.902 (0.49), 6.921 (0.99), 6.939 (0.59), 7.150 (0.51),
239 1.18 min; MS (ESIpos): m/z = 7.168 (0.80), 7.186 (0.41), 7.264 (0.62), 7.271 (0.72), 7.279 (0.66), 7.286 (0.65), 7.367 , 7.385 (0.82), 7.442 (0.63), 7.452
532 [M+H]+ (0.65), 7.673 , 7.691 (1.06), 7.711 (1.07), 7.732 (1.23), 7.746 (0.57), 8.279 (0.87), 8.299 (0.80), 8.624 (3.45), 9.154 (0.86),
9.175 (0.85).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.50), 0.008 (0.44), 2.345 (4.63), 3.275 (0.72), 3.287 (1.65), 3.299 (1.87), 3.310
LC-MS (Method L1): Rt = (16.00), 3.865 (1.37), 3.876 (2.36), 3.888 (1.31), 4.237 (0.45), 4.259 (0.60), 4.269 (0.56), 5.249 (0.43), 5.268 (0.43), 6.782 (0.83),
240 1.19 min; MS (ESIpos): m/z = 6.803 , 6.924 (0.83), 6.941 , 7.147 (0.41), 7.150 (0.43), 7.167 (0.71), 7.184 (0.80), 7.192 (0.61), 7.198 (0.56), 7.367
532 [M+H]+ (0.70), 7.385 (0.66), 7.447 (0.53), 7.451 (0.52), 7.463 (0.55), 7.682 (0.43), 7.700 (0.93), 7.720 (1.01), 7.731 (1.02), 7.735 (1.15),
7.748 (0.49), 8.284 (0.71), 8.288 (0.72), 8.305 (0.69), 8.309 (0.65), 8.626 (3.04), 9.154 (0.75), 9.175 (0.74).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.219 ), 1.414 (0.57), 1.908 (0.65), 1.924 (0.64), 1.941 (0.52), 1.959 (0.45), 2.501
LC-MS (Method L1): Rt =
(12.69), 2.889 (0.42), 3.164 (0.96), 3.174 (0.90), 5.530 (0.45), 5.549 (0.44), 7.233 (0.64), 7.241 (0.67), 7.250 (1.06), 7.271 (0.78),
241 1.38 min; MS (ESIpos): m/z =
7.448 (0.44), 7.456 (0.48), 7.469 (0.40), 7.639 (5.38), 7.652 (0.69), 7.672 (0.56), 7.809 (0.75), 7.826 (0.60), 8.314 (0.64), 8.335
602 [M+H]+
(0.58), 8.687 (2.17), 9.077 (0.63), 9.097 .
LC-MS (Method L6): Rt = ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.198 (16.00), 1.918 (0.63), 1.932 (0.85), 1.945 (0.51), 4.260 (0.44), 6.788 (0.61), 6.808
242 1.39 min; MS (ESIpos): m/z = (0.69), 6.939 , 7.186 (0.52), 7.394 (0.55), 7.412 (0.51), 7.638 , 7.655 , 7.676 (0.53), 7.815 (0.70), 7.832 (0.56),
618 [M+H]+ 8.315 (0.60), 8.334 (0.55), 8.684 (2.06), 9.236 (0.58), 9.257 (0.57).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.59), 0.008 (0.57), 1.194 (16.00), 1.209 (0.55), 2.041 (0.61), 2.056 (0.60), 2.067
LC-MS (Method L6): Rt =
(0.49), 2.086 (0.43), 4.279 (0.48), 4.293 (0.85), 4.305 (0.52), 6.785 (0.57), 6.804 (0.64), 6.881 , 7.163 (0.49), 7.292 ,
243 2.63 min; MS (ESIpos): m/z =
7.310 (0.49), 7.643 (3.60), 7.659 (0.61), 7.680 (0.50), 7.819 (0.64), 7.834 (0.53), 8.352 , 8.371 (0.52), 8.689 (2.03), 9.172
618 [M+H]+
(0.56), 9.192 (0.54).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.63), 0.008 (2.13), 1.862 (1.03), 1.885 (0.89), 1.898 (0.91), 2.002 (0.76), 2.023
(1.37), 2.034 (1.59), 2.054 (1.51), 2.156 (0.85), 2.170 (1.04), 2.185 (0.86), 2.201 (0.61), 2.311 (0.43), 2.327 , 2.376 (16.00),
2.392 (2.37), 2.669 , 3.033 (0.41), 3.192 (0.48), 3.205 (0.71), 3.213 , 3.228 , 3.305 (2.36), 3.461 (0.98), 3.489
LC-MS (Method L6): Rt = (1.75), 3.516 (0.92), 3.691 (0.53), 3.707 (1.16), 3.728 (0.79), 3.788 (0.70), 3.805 , 3.821 (0.86), 3.831 (1.06), 3.844 (1.78),
244 1.27 min; MS (ESIpos): m/z = 3.857 , 3.871 (1.20), 3.883 (0.74), 4.163 (3.03), 4.258 (2.73), 4.266 (3.03), 4.279 (1.47), 4.374 (1.56), 5.215 (0.85), 5.227
498 [M+H]+ , 5.247 , 5.260 (0.41), 6.780 (2.43), 6.799 (2.76), 6.891 (1.22), 6.910 (2.68), 6.928 (1.78), 7.014 (1.49), 7.038 (1.51),
7.144 (1.33), 7.162 , 7.179 (2.31), 7.205 (5.13), 7.253 (0.67), 7.305 (2.22), 7.324 (2.00), 7.450 (1.52), 7.469 (2.29), 7.489
(1.84), 7.638 (2.80), 7.653 (2.35), 8.144 (10.55), 8.227 (2.36), 8.248 (2.20), 8.418 (4.54), 8.423 (4.98), 8.786 (1.00), 9.041 (1.92),
9.061 (1.88).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.77), -0.008 (6.72), 0.008 (6.90), 0.146 (0.79), 1.055 (0.79), 1.862 (1.68), 1.885
(1.70), 1.895 (1.97), 2.006 (1.70), 2.027 (2.95), 2.040 , 2.060 (1.95), 2.072 (1.32), 2.085 (1.63), 2.145 (1.45), 2.159 (1.57),
2.175 (1.52), 2.327 (1.52), 2.365 (1.04), 2.669 (1.41), 2.709 (0.77), 2.976 (0.89), 3.005 (1.41), 3.073 (1.32), 3.083 (1.34), 3.113
(0.93), 3.164 (2.00), 3.177 (2.34), 3.187 (2.36), 3.200 (2.22), 3.304 (2.68), 3.466 (1.97), 3.496 (2.86), 3.524 (1.75), 3.695 (1.16),
LC-MS (Method L6): Rt =
3.719 (1.95), 3.737 (1.34), 3.788 (0.68), 3.810 (1.16), 3.828 (1.48), 3.848 (2.50), 3.864 (2.18), 3.874 (3.20), 3.889 (1.95), 3.900
245 1.24 min; MS (ESIpos): m/z =
(1.23), 3.937 (0.43), 4.163 (11.73), 4.255 (5.47), 4.374 (2.88), 5.226 (1.84), 5.266 , 6.772 (4.31), 6.791 (5.17), 6.809 (1.38),
532 [M+H]+
6.879 (2.04), 6.899 , 6.916 (3.56), 6.935 (0.70), 7.016 (1.41), 7.032 (2.79), 7.048 (1.86), 7.084 , 7.105 (0.68), 7.137
(2.31), 7.156 (4.45), 7.177 (3.63), 7.204 (2.20), 7.225 (1.41), 7.242 (0.68), 7.287 (3.50), 7.306 (3.22), 7.342 (0.93), 7.359 (0.98),
7.448 (2.31), 7.466 (3.93), 7.487 (3.79), 7.526 (5.13), 7.541 (3.06), 7.688 (1.57), 7.696 (1.68), 7.705 (3.70), 8.204 (16.00), 8.276
(4.47), 8.297 (3.47), 8.360 (10.80), 8.716 (4.06), 9.014 (1.95), 9.027 (2.34), 9.035 , 9.047 (1.97), 9.155 , 9.176 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.15), 0.008 (1.23), 1.862 (0.77), 1.876 (0.55), 1.888 (0.61), 1.900 (0.68), 1.908
(0.60), 1.997 (0.55), 2.020 , 2.030 (1.23), 2.039 (0.98), 2.049 (0.99), 2.061 (0.58), 2.150 (0.56), 2.165 (0.68), 2.180 (0.59),
2.195 , 2.523 (0.68), 3.169 (1.12), 3.207 (0.44), 3.230 , 3.305 (0.99), 3.471 , 3.498 (1.19), 3.525 (0.73), 3.655
LC-MS (Method L6): Rt = (0.44), 3.699 (0.41), 3.723 (0.82), 3.736 (0.56), 3.743 (0.59), 3.803 (0.57), 3.820 (0.55), 3.828 (0.57), 3.835 (0.56), 3.846 (1.52),
246 1.21 min; MS (ESIpos): m/z = 3.858 (1.38), 3.873 (0.89), 3.885 (1.01), 3.896 (0.64), 3.911 (16.00), 3.924 (2.42), 4.160 (2.23), 4.247 (1.69), 4.253 (2.01), 4.259
532 [M+H]+ (1.98), 4.374 (1.08), 5.210 (0.63), 5.219 (0.73), 5.231 , 5.240 (0.56), 6.776 , 6.794 (1.90), 6.796 (1.93), 6.886 (0.87),
6.904 (1.89), 6.923 (1.25), 7.140 (1.08), 7.148 (1.24), 7.158 (1.75), 7.166 (1.29), 7.175 (1.95), 7.194 (1.17), 7.263 (1.08), 7.280
(1.12), 7.294 (2.16), 7.311 (1.67), 7.451 (1.14), 7.469 (1.65), 7.490 (1.47), 7.599 (1.95), 7.615 , 8.140 (6.92), 8.264 (1.70),
8.276 (0.41), 8.286 (1.58), 8.370 (4.09), 8.372 , 8.738 (0.72), 9.025 (1.07), 9.032 , 9.046 (1.07), 9.053
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.77), 0.008 (1.62), 1.754 , 3.086 (16.00), 4.249 (0.89), 4.257 (0.88), 5.230
LC-MS (Method L6): Rt =
(0.54), 6.777 (1.07), 6.797 (1.20), 6.890 (0.49), 6.908 (1.04), 6.926 (0.63), 7.143 (0.51), 7.160 (0.85), 7.178 (0.42), 7.339 (0.86),
247 1.82 min; MS (ESIpos): m/z =
7.357 (0.83), 7.586 (0.46), 7.600 (0.44), 7.669 (0.76), 7.686 (1.09), 7.708 (1.03), 7.788 (1.10), 7.803 (0.82), 8.233 (0.62), 8.303
478 [M+H]+
, 8.321 (1.02), 8.550 (2.65), 9.066 (0.59), 9.088 (0.56).
1H-NMR(399,9532 MHz, DMSO): δ= 8.8586 (3.81); 8.8384 (3.7); 8.7959 (0.89); 8.6133 (16); 8.3145 (0.54); 8.2003 (5.17); 8.1796
(6.09); 8.1605 ; 8.1408 (0.42); 8.1194 (0.37); 7.7297 (2.81); 7.7117 (6.49); 7.6916 (5.56); 7.674 (8.15); 7.6572 (3.78); 7.5658
(3.63); 7.5485 (5.05); 7.5233 (0.53); 7.4659 (2.08); 7.4474 (5.9); 7.4352 (6.58); 7.4201 ; 7.401 (7.64); 7.3696 ; 7.1855
(0.44); 7.1677 (2.86); 7.1479 (5.7); 7.1292 (3.51); 6.9273 (3.58); 6.9086 (6.16); 6.8902 (3.03); 6.7978 ; 6.7802 (7.27); 6.76
248 3,41 (6.4); 5.3045 (0.38); 5.2303 (1.66); 5.215 (3.56); 5.1967 ; 5.1821 ; 4.2872 (1.16); 4.2678 (3.46); 4.2545 (6.45); 4.2294
(3.77); 4.209 (1.09); 4.0558 (0.79); 4.0381 (2.17); 4.0204 (2.21); 4.0027 (0.72); 3.7036 (0.64); 3.4987 (41.77); 3.4769 (2.9); 3.3203
(34.08); 3.2937 (39.4); 3.2522 (2.31); 2.6698 (1.63); 2.5008 (284.9); 2.3275 (1.72); 2.162 (2.06); 2.1511 (2.35); 2.1408 ; 2.0491
(2.34); 2.0417 (2.67); 2.0242 ; 2.0072 (1.6); 1.9885 (9.27); 1.2351 (0.38); 1.1928 (2.3); 1.175 (4.51); 1.1572 (2.22); -0.0001
(28.96); -0.0051 (8.21)
1H-NMR(399,9532 MHz, DMSO): δ= 8.8722 (2.6); 8.8534 (4.17); 8.8356 (2.45); 8.6283 (16); 8.3151 (0.4); 8.2158 (4.05); 8.1962
; 7.7428 (2.44); 7.7248 (7.39); 7.7193 (7); 7.7157 (6.57); 7.7049 (13.43); 7.6994 (14.58); 7.6871 (2.66); 7.4723 (2.01); 7.4623
(2.04); 7.453 ; 7.4429 (3.96); 7.4331 (2.87); 7.4227 (5.23); 7.3996 (4.11); 7.3619 (3.39); 7.3461 (5.37); 7.3279 ; 7.1671
(2.41); 7.1484 (5.12); 7.1288 (3.22); 6.9268 (2.74); 6.9082 (4.77); 6.8896 (2.27); 6.7797 (6.81); 6.7595 (6.15); 5.2265 (1.31); 5.2117
249 3,99 (3.11); 5.1938 (3.02); 5.1779 (1.3); 4.2866 (1.01); 4.2674 (3.19); 4.2527 (5.74); 4.245 (5.26); 4.2269 (3.27); 4.2067 ; 4.0557
(0.4); 4.0377 (1.21); 4.0198 ; 4.0022 (0.41); 3.4991 (33.03); 3.3194 (26.59); 3.2941 (42.87); 2.6699 (1.31); 2.6325 (1.42);
2.5047 (173.21); 2.5007 (220.51); 2.4968 (169.05); 2.3277 (1.28); 2.1552 (1.78); 2.1467 (1.98); 2.1354 (1.9); 2.0536 (1.58); 2.0461
; 2.0382 (2.41); 2.0293 (1.73); 2.0221 (1.72); 2.0124 (1.48); 2.0033 (1.41); 1.9882 (5.54); 1.3973 (0.39); 1.1925 (1.29); 1.1746
(2.48); 1.1569 (1.25); 2 )
1H-NMR(399,9532 MHz, DMSO): δ= 8.8638 (2.16); 8.8431 (2.2); 8.7403 (8.57); 8.3148 (0.35); 8.2096 (2.24); 8.2067 (2.37); 8.1883
(2.63); 8.1855 (2.59); 7.8776 (2.13); 7.8749 (2.29); 7.8598 (2.88); 7.8571 ; 7.7436 (2.21); 7.7227 (2.59); 7.7045 (1.68); 7.6508
(16); 7.4465 (2.08); 7.4284 (2.26); 7.181 (0.97); 7.1773 (1.02); 7.16 (2.16); 7.1425 (1.33); 7.1389 (1.31); 6.9459 (1.54); 6.9275
(2.62); 6.9086 (1.24); 6.7901 (2.91); 6.7708 (2.62); 5.246 (0.57); 5.2307 (1.34); 5.2111 (1.31); 5.1962 (0.59); 4.2989 (0.4); 4.2923
250 4,87
(0.34); 4.2803 (1.25); 4.2648 (2.35); 4.2564 (2.18); 4.2462 (1.28); 4.238 (1.35); 4.2183 (0.41); 3.4928 (21.15); 3.3195 (28.27); 3.2832
(18.37); 2.6707 (0.76); 2.5055 (99.44); 2.5013 (134.25); 2.4971 (103.62); 2.3283 (0.8); 2.1902 (0.48); 2.1778 (0.73); 2.169 ;
2.1575 (0.88); 2.1451 (0.68); 2.0765 (0.62); 2.0678 (0.83); 2.0606 (0.98); 2.0512 (0.71); 2.0439 (0.7); 2.034 (0.6); 2.0254 (0.58);
1.3977 (0.96); -0.0002 (18.38)
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.832 (0.78), 0.872 (0.63), 1.225 (1.56), 1.239 (2.99), 1.254 (2.68), 1.285 (0.49), 2.012
(5.28), 2.125 (0.61), 2.136 (1.21), 2.143 (1.50), 2.153 (1.46), 2.162 (2.19), 2.172 (2.02), 2.181 , 2.253 (0.83), 2.265 (1.86),
LC-MS (Method L4): Rt = 2.277 (2.20), 2.290 (1.59), 2.306 (1.15), 2.317 (0.53), 3.149 (1.15), 3.179 (10.27), 3.371 (1.35), 3.379 (2.47), 3.394 (3.63), 3.403
2.76 min; MS s): m/z = (5.57), 3.412 (3.40), 3.423 (3.54), 3.431 (5.99), 3.440 (3.84), 3.456 (2.58), 3.465 (1.35), 3.947 (9.47), 3.955 (15.45), 3.964 (8.40),
251 523 [M+H]+ 4.057 (0.45), 4.071 (1.28), 4.086 , 4.100 , 4.278 (4.64), 4.288 (6.97), 4.294 (4.07), 4.299 (4.02), 5.328 (1.19), 5.339
, 5.354 (2.69), 5.365 , 5.443 (0.90), 5.448 (1.32), 6.779 (4.78), 6.796 (5.27), 6.863 (2.26), 6.878 (4.67), 6.893 (2.69),
7.124 (2.45), 7.139 (3.94), 7.154 (2.07), 7.309 (4.10), 7.324 (3.86), 7.506 (4.42), 7.520 (5.68), 7.613 (3.66), 7.628 (5.26), 7.644
(3.03), 7.658 (2.51), 7.672 (4.37), 7.689 (3.02), 7.811 (6.72), 7.814 (7.13), 7.818 (4.61), 7.821 (6.00), 7.825 , 7.828 (6.36),
7.831 (5.94), 8.107 , 8.123 (5.32), 8.315 , 8.332 (4.30), 8.604 (16.00), 9.065 (6.90), 9.103 (2.34), 9.118 (2.15).
1H-NMR(399,9532 MHz, DMSO): δ= 9.0791 (1.76); 9.0587 (1.8); 8.5559 ; 8.1993 (1.5); 8.1925 (1.41); 8.1814 (1.62); 8.1744
(1.67); 7.6235 (0.75); 7.6058 (2.84); 7.5938 (3.05); 7.5875 (6.22); 7.5767 ; 7.5518 (1.11); 7.5301 (1.53); 7.4508 (0.54); 7.4455
(0.73); 7.4326 ; 7.4272 (2.02); 7.4216 (1.16); 7.4156 (2.28); 7.4084 (1.97); 7.4032 (1.72); 7.3998 (1.7); 7.385 (0.7); 7.3589
(1.41); 7.3368 (1.88); 7.3173 (1.39); 7.1739 (0.83); 7.1704 (0.86); 7.1527 (1.79); 7.1353 (1.12); 7.1318 (1.06); 6.9096 (1.27); 6.8915
252 2,23 (2.21); 6.8728 (1.02); 6.7927 (2.53); 6.7726 (2.28); 5.7542 (1.11); 5.2613 (0.49); 5.2466 (1.08); 5.2274 (1.08); 5.213 (0.48); 4.2679
(1.84); 4.2559 (3.15); 4.2415 (1.82); 3.3206 (48.83); 3.1342 (16); 3.0049 (0.62); 2.9974 (0.88); 2.9893 (1.13); 2.981 (0.87); 2.9732
(0.63); 2.9642 (0.34); 2.675 (0.38); 2.6705 (0.51); 2.6658 (0.38); 2.5232 (1.39); 2.5055 (63.06); 2.5011 (86.29); 2.4969 (64.79);
2.3323 (0.36); 2.3281 (0.5); 2.1894 (0.6); 2.1757 (0.69); 2.1696 (0.51); 2.156 (0.74); 2.1399 (0.74); 2.0304 (0.61); 2.0184 (0.69);
1.9969 (0.54); 1.9883 (0.86); 1.3979 (1.47); 0.6101 (1.75); 0.4165 (0.89); 0.0078 (0.39); -0.0001 (10.71); -0.0076 (0.41)
1H-NMR(399,9532 MHz, DMSO): δ= 9.0796 (1.17); 9.0621 (1.2); 8.5624 (8.02); 8.2214 (0.93); 8.2105 (1.57); 8.1983 (1.03); 7.6978
(2.04); 7.694 (2.19); 7.6778 (2.53); 7.674 (2.5); 7.6177 (5.4); 7.6041 (4.04); 7.4523 (0.69); 7.4433 (0.72); 7.4327 (1.48); 7.4239
(1.42); 7.4131 (0.92); 7.4041 (0.85); 7.3455 (1.88); 7.329 (3.1); 7.3099 (1.5); 7.174 ; 7.1702 (0.85); 7.1526 (1.69); 7.1353
(1.08); 7.1317 ; 6.9092 (1.19); 6.8909 ; 6.8721 (0.94); 6.793 (2.33); 6.791 (2.35); 6.7726 (2.13); 6.7706 ; 5.2566
(0.41); 5.242 ; 5.2229 (0.94); 5.2089 (0.4); 4.2665 (1.65); 4.2545 (2.8); 4.2402 (1.64); 3.3211 (41.34); 3.1368 (16); 3.0138
253 2,8
(0.45); 3.0047 (0.7); 2.9975 (0.96); 2.9893 (0.98); 2.9811 (0.72); 2.9735 (0.43); 2.6703 (0.39); 2.5235 (1.05); 2.51 (22.39); 2.5056
(47.11); 2.501 (65.73); 2.4966 (49.19); 2.4922 (23.62); 2.3279 (0.38); 2.1883 (0.57); 2.1742 (0.65); 2.1681 (0.49); 2.1546 (0.71);
2.1385 (0.72); 2.0349 (0.45); 2.0228 (0.65); 2.0115 (0.58); 2.0017 (0.49); 1.9882 (1.44); 1.9759 (0.32); 1.3975 (1.3); 1.175 (0.52);
0.6137 (1.77); 0.5976 (1.39); 0.4649 (0.32); 0.4414 (0.56); 0.4091 (1.27); 0.3695 (0.52); 0.0081 (0.44); -0.0002 (13.08); 4
(0.42)
(399,9532 MHz, DMSO): δ= 9.0974 (1.83); 9.0773 (1.86); 8.6752 (7.71); 8.3134 (0.64); 8.2118 (1.85); 8.2091 ; 8.1907
(2.14); 8.1877 (2.13); 7.7947 (1.87); 7.7919 (1.98); 7.777 (2.41); 7.7741 (2.31); 7.6416 (5.47); 7.6376 (12.68); 7.632 (5.99); 7.6281
(3.45); 7.6155 (1.99); 7.6126 (2.16); 7.5945 (1.52); 7.3629 (1.74); 7.3442 (1.88); 7.1889 (0.84); 7.1854 (0.87); 7.1674 (1.81); 7.1502
(1.1); 7.147 (1.07); 6.9334 (1.31); 6.9152 (2.18); 6.8988 ; 6.8964 (1.02); 6.8069 ; 6.7867 (2.52); 5.2728 (0.51); 5.2582
254 3,81 ; 5.2387 (1.12); 5.2248 (0.5); 4.281 (1.89); 4.2694 (3.1); 4.2546 (1.8); 3.3184 (46.33); 3.1217 (16); 3.0207 (0.68); 3.0129
; 3.0047 (1.28); 2.9963 (0.95); 2.9888 (0.68); 2.9802 (0.33); 2.6749 (0.85); 2.6706 (1.14); 2.6661 (0.85); 2.5101 (68.82); 2.5059
(137.4); 2.5014 (187.25); 2.4971 (140.59); 2.3327 (0.8); 2.3283 ; 2.3241 (0.79); 2.2024 (0.56); 2.1881 (0.67); 2.1696 (0.74);
2.1535 (0.7); 2.0686 (0.34); 2.0557 (0.71); 2.0447 ; 2.0308 (0.51); 2.0226 ; 2.0084 (0.53); 1.398 (3.21); 0.6121 (2.33);
0.5962 (2.26); 0.4148 (1.1); 0.4089 (1.1); 0.3834 (1.16); 0.0079 (1.22); -0.0002 (28.51); -0.0084 (1.03)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.40), -0.008 (3.66), 0.008 (2.37), 1.938 (0.67), 2.015 (1.79), 2.073 (1.20), 2.179
LC-MS (Method L1): Rt = , 2.328 (0.62), 2.366 (0.70), 2.385 (0.71), 2.669 (0.51), 3.356 (0.75), 3.498 (16.00), 3.893 (0.87), 3.915 (0.80), 4.216 (0.97),
255 1.21 min; MS (ESIpos): m/z = 4.238 (0.76), 4.267 (0.81), 4.625 (0.99), 4.640 (1.04), 4.659 (0.92), 5.267 (0.86), 6.791 (1.73), 6.810 (1.94), 6.925 (0.82), 6.941
576 [M+H]+ (1.72), 6.959 (1.12), 7.168 (0.89), 7.185 , 7.202 (0.70), 7.394 (1.48), 7.411 (1.37), 7.645 (11.29), 7.673 (1.76), 7.694 (1.53),
7.820 , 7.838 (1.61), 8.342 , 8.361 (1.56), 8.671 (6.40), 9.188 , 9.208 (1.60).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.12 (d, J = 8.1 Hz, 1H), 8.62 (s, 1H), 8.43 (d, J = 8.7 Hz, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.69 (t, J =
3.91 min, m/z = 560 (M+H)+ 1.9 Hz, 1H), 7.37 – 7.29 (m, 3H), 7.20 – 7.13 (m, 1H), 6.94 – 6.87 (m, 1H), 6.79 (dd, J = 8.2, 1.0 Hz, 1H), 5.26 – 5.19 (m
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.43), 0.146 (0.47), 1.754 (0.43), 1.862 (3.00), 1.901 (2.89), 1.909 (2.71), 2.031
(4.75), 2.040 (4.61), 2.049 (5.14), 2.157 (2.74), 2.171 (3.27), 2.186 (2.55), 2.203 (1.78), 2.327 (0.93), 2.366 (0.74), 2.670 (0.93),
2.709 (0.69), 3.038 (0.45), 3.165 (1.51), 3.210 (0.53), 3.232 (0.51), 3.476 (2.42), 3.502 (4.70), 3.528 (2.55), 3.654 (0.43), 3.708
(1.60), 3.732 (3.42), 3.752 (2.34), 3.780 (1.22), 3.802 , 3.820 (2.17), 3.829 (2.57), 3.851 (3.64), 3.861 (4.91), 3.875 (4.51),
LC-MS (Method L1): Rt =
3.888 , 3.900 (2.05), 4.169 , 4.258 (8.38), 4.267 (9.23), 4.280 (4.38), 4.372 (4.77), 5.035 (5.52), 5.201 (1.06), 5.214
257 0.71 min; MS (ESIpos): m/z =
(2.86), 5.227 (3.55), 5.235 (3.58), 5.247 (2.92), 5.261 (1.17), 6.782 (7.98), 6.801 (8.91), 6.893 (3.82), 6.912 (8.02), 6.930 (4.96),
502 [M+H]+
7.145 (4.32), 7.163 (6.95), 7.182 , 7.211 , 7.216 , 7.234 (5.55), 7.240 (4.20), 7.258 (3.02), 7.263 , 7.307
), 7.324 (15.84), 7.361 (1.03), 7.377 (1.64), 7.399 , 7.467 (4.96), 7.486 (7.17), 7.507 (5.81), 7.704 (8.95), 7.722 (7.93),
7.742 (0.47), 7.887 (0.48), 7.901 (0.42), 8.134 (12.65), 8.269 (7.33), 8.291 (7.25), 8.313 (0.63), 8.394 (1.77), 8.432 (13.03), 8.436
), 8.810 (1.36), 9.046 (5.84), 9.067 (5.58), 12.645 (0.58).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.99), 0.146 (1.21), 1.055 (1.10), 1.243 (0.89), 1.862 (1.56), 1.907 , 2.038
LC-MS (Method L6): Rt = (4.22), 2.085 (2.63), 2.159 (2.66), 2.327 (2.09), 2.366 (1.38), 2.669 (2.27), 2.710 (1.45), 3.509 (1.42), 3.743 (1.67), 3.873 (4.19),
258 1.25 min; MS (ESIneg): m/z = 4.251 (8.12), 4.394 (3.19), 5.059 (2.13), 5.200 (3.33), 5.754 ), 6.776 (5.14), 6.796 (5.68), 6.875 (3.87), 6.893 (7.49), 6.912
516 [M-H]- (4.43), 7.138 (3.69), 7.157 (5.46), 7.177 (3.37), 7.289 (6.17), 7.307 (5.53), 7.448 , 8.132 (3.30), 8.325 (3.87), 9.046 (1.53),
12.220 (0.64).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.71), -0.008 (15.12), 0.008 (13.06), 0.146 (1.65), 1.038 (1.12), 1.055 (2.24), 1.073
(1.12), 1.236 (0.71), 1.862 (3.06), 1.908 (2.82), 2.039 (5.47), 2.085 (3.00), 2.146 (3.35), 2.160 (3.59), 2.180 (2.88), 2.195 (2.53),
LC-MS (Method L6): Rt =
2.327 (2.82), 2.332 , 2.366 (2.29), 2.523 (8.71), 2.669 (2.59), 2.690 (0.53), 2.709 (2.24), 3.509 (2.00), 3.744 (2.29), 3.874
259 1.24 min; MS (ESIpos): m/z =
(5.88), 4.238 (8.06), 4.253 (10.94), 4.388 (4.47), 5.054 (3.29), 5.205 (4.24), 5.218 (4.18), 5.754 (16.00), 6.774 , 6.795 (7.59),
518 [M+H]+
6.878 (5.12), 6.896 (10.53), 6.915 (6.06), 7.139 , 7.157 (7.24), 7.177 (3.76), 7.235 (2.47), 7.290 (10.82), 7.309 (9.65), 7.501
(2.94), 7.561 (4.94), 8.132 (6.47), 8.337 (6.94), 9.043 (2.35), 12.703 (0.71).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.898 (1.49), 1.907 (1.43), 2.003 (1.23), 2.023 (2.16), 2.034 (2.52), 2.054 (2.37), 2.156
(1.33), 2.170 (1.58), 2.186 (1.26), 2.202 (0.87), 3.169 (4.19), 3.191 (0.45), 3.203 , 3.213 (0.51), 3.226 (0.59), 3.305 (1.15),
3.472 , 3.498 , 3.524 (1.46), 3.696 (0.91), 3.720 (1.91), 3.741 (1.28), 3.776 (0.63), 3.798 (1.12), 3.817 (1.15), 3.826
LC-MS (Method L1): Rt =
(1.36), 3.841 (1.73), 3.853 (2.81), 3.867 (2.34), 3.881 , 3.893 (1.16), 4.168 (2.20), 4.258 (4.22), 4.266 (4.57), 4.376 (2.54),
260 0.72 min; MS (ESIpos): m/z =
.217 (1.39), 5.228 (1.80), 5.248 (1.46), 5.753 (16.00), 6.780 (4.05), 6.800 , 6.892 (1.82), 6.910 , 6.929 (2.45), 7.143
500 [M+H]+
(2.06), 7.162 , 7.181 (1.72), 7.306 (3.35), 7.325 (3.06), 7.417 (1.77), 7.436 (4.71), 7.450 (3.62), 7.469 (5.99), 7.487 (4.73),
7.503 (3.14), 7.521 (4.74), 7.540 (2.68), 7.635 (6.07), 7.659 (4.38), 7.677 (3.91), 8.153 (14.28), 8.247 (3.60), 8.268 (3.45), 8.421
(6.72), 8.425 (7.54), 8.792 (0.74), 9.041 , 9.062 (2.77).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.36), 0.008 (1.23), 1.897 (0.69), 2.031 (1.04), 2.050 (1.12), 2.156 (0.59), 2.170
(0.71), 2.185 (0.60), 3.169 (0.99), 3.191 (0.41), 3.203 (0.54), 3.212 (0.50), 3.226 (0.59), 3.305 (1.07), 3.464 (0.73), 3.490 (1.25),
3.518 (0.67), 3.712 (0.82), 3.734 (0.57), 3.790 (0.55), 3.814 (16.00), 3.829 (3.10), 3.847 (1.23), 3.861 (1.14), 3.874 (1.02), 3.887
LC-MS (Method L1): Rt =
(0.52), 4.163 , 4.258 , 4.266 (2.12), 4.374 (1.12), 5.234 (0.76), 5.245 (0.63), 5.754 (0.64), 6.781 (1.81), 6.799 (2.04),
261 0.75 min; MS (ESIpos): m/z =
6.893 (0.86), 6.912 (1.84), 6.930 (1.24), 7.025 (1.53), 7.030 (2.93), 7.035 (1.95), 7.075 , 7.079 (2.80), 7.127 (0.40), 7.145
530 [M+H]+
(0.92), 7.162 (1.62), 7.183 (2.94), 7.186 (3.43), 7.231 (0.46), 7.307 (1.49), 7.326 (1.37), 7.451 (1.09), 7.469 (1.61), 7.490 (1.32),
7.659 (1.99), 7.675 (1.69), 8.151 (5.55), 8.239 (1.63), 8.260 (1.58), 8.422 , 8.427 (3.75), 8.793 (0.92), 9.041 (1.50), 9.062
(1.45).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.82), -0.008 (6.72), 0.008 , 0.146 (0.82), 0.889 (0.41), 1.236 (0.68), 1.862
(2.00), 1.904 (2.50), 2.036 (4.81), 2.057 (3.23), 2.073 (2.58), 2.148 (2.61), 2.162 (3.02), 2.178 (2.26), 2.196 (1.91), 2.327 (1.88),
LC-MS (Method L6): Rt = 2.366 , 2.523 (5.70), 2.669 (1.82), 2.709 , 3.524 (2.23), 3.755 (2.17), 3.818 (2.88), 3.885 (3.41), 4.175 (1.41), 4.243
262 1.28 min; MS (ESIpos): m/z = (6.72), 4.256 (8.63), 4.379 (4.34), 5.041 (4.81), 5.211 , 5.224 (3.41), 5.754 (2.38), 6.775 (7.63), 6.794 (8.22), 6.883 (3.88),
518 [M+H]+ 6.899 , 6.918 (4.81), 7.139 (4.20), 7.156 (6.55), 7.174 (3.29), 7.295 (8.04), 7.312 (8.40), 7.326 (3.90), 7.367 (3.20), 7.383
, 7.400 (2.00), 7.487 , 7.506 (3.58), 7.525 (2.50), 7.634 (5.31), 8.133 (16.00), 8.325 (4.08), 8.360 (8.78), 9.040 (2.67),
9.057 (2.67), 12.699 (1.38).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (1.52), 1.234 (0.49), 2.012 , 2.029 (0.92), 2.045 (0.89), 2.059
(1.10), 2.075 (1.44), 2.091 (1.89), 2.105 (1.51), 2.122 (0.75), 2.141 (0.59), 2.187 (0.65), 2.204 (0.65), 2.223 (0.59), 2.237 (0.50),
2.470 , 2.523 (1.48), 3.358 , 3.375 (0.74), 3.392 (0.84), 3.410 (0.50), 3.489 (16.00), 3.885 (0.41), 3.901 (0.97), 3.922
LC-MS (Method L6): Rt =
(0.95), 3.939 (0.41), 4.277 (1.55), 4.291 , 4.303 (1.60), 4.716 (1.07), 4.729 (1.23), 4.737 (1.20), 4.750 (1.01), 5.254 (0.41),
263 2.33 min; MS (ESIpos): m/z =
.268 (0.92), 5.288 (0.94), 5.301 (0.42), 5.754 , 6.784 (1.67), 6.804 (1.85), 6.888 (0.85), 6.891 , 6.906 (1.80), 6.925
576 [M+H]+
(1.08), 7.143 (0.86), 7.147 (0.92), 7.164 (1.44), 7.182 (0.72), 7.186 (0.72), 7.292 (1.53), 7.311 (1.42), 7.639 (1.85), 7.643 (3.39),
7.648 (8.87), 7.652 (4.00), 7.673 , 7.676 (1.64), 7.694 (1.64), 7.821 (2.01), 7.824 (2.06), 7.839 (1.67), 7.842 (1.59), 8.351
, 8.354 (1.71), 8.372 (1.62), 8.375 (1.52), 8.678 (6.32), 9.190 (1.68), 9.210 (1.63).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.146 (0.40), 1.139 (16.00), 1.158 (15.94), 1.234 (0.94), 1.963 (2.29), 1.974 (2.70), 2.061
LC-MS (Method L1): Rt = (3.26), 2.078 (3.19), 2.097 (1.79), 2.163 (1.02), 2.327 (0.81), 2.670 , 2.710 , 3.615 (2.37), 4.233 (1.49), 4.254 (2.33),
264 1.53 min; MS (ESIpos): m/z = 4.262 (2.43), 5.217 (1.48), 5.236 (1.45), 5.754 (5.93), 6.777 (2.79), 6.798 (3.23), 6.902 (1.43), 6.921 (2.91), 6.940 (1.74), 7.146
546 [M+H]+ (1.44), 7.166 (2.27), 7.184 (1.15), 7.347 (2.34), 7.365 (2.28), 7.641 (4.23), 7.646 (4.54), 7.657 (14.09), 7.661 , 7.678 (2.81),
7.698 (2.23), 7.819 (3.12), 7.837 (2.42), 8.297 (2.64), 8.318 (2.50), 8.803 (9.16), 8.970 (2.59), 8.991 (2.51).
LC-MS d L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.00 (d, 1H), 8.51 (s, 1H), 8.41 (d, 1H), 8.14 (s, 1H), 7.82 (t, 1H), 7.70 - 7.76 (m, 1H), 7.58 -
265 0.89 min; MS (ESIpos): m/z = 7.64 (m, 3H), 7.53 (dd, 1H), 7.30 (d, 1H), 7.13 - 7.20 (m, 1H), 6.86 - 6.96 (m, 1H), 6.79 (d, 1H), 5.19 - 5.30 (m, 1H), 4.21 - 4.33 (m,
492 [M+H]+ 2H), 3.48 - 3.59 (m, 2H), 1.96 - 2.22 (m, 2H), 1.25 (t, 3H).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 , 0.006 , 1.907 (2.42), 2.028 (0.58), 2.033 (0.60), 2.044 (0.71), 2.056
(0.83), 2.166 (0.52), 2.175 (0.71), 2.185 (0.75), 2.193 (0.77), 2.204 (0.50), 2.358 (0.89), 2.361 (1.22), 2.365 (0.93), 2.369 ,
2.392 (0.70), 2.407 (0.71), 2.514 (3.50), 2.518 (3.01), 2.522 (2.34), 2.631 (0.87), 2.635 (1.14), 2.639 (0.81), 3.866 (0.46), 3.878
LC-MS (Method L1): Rt = (1.06), 3.895 (0.91), 4.183 (0.43), 4.188 (0.44), 4.205 (1.12), 4.224 (0.89), 4.229 (0.73), 4.243 (0.75), 4.250 (1.08), 4.262 (0.91),
266 0.91 min; MS (ESIpos): m/z = 4.277 (0.46), 4.638 (0.83), 4.649 (1.02), 4.654 (1.33), 4.665 (1.06), 5.254 (0.54), 5.264 (1.14), 5.280 (1.10), 5.291 (0.50), 6.786
562 [M+H]+ (2.22), 6.788 (2.18), 6.802 (2.42), 6.804 (2.32), 6.919 (1.16), 6.921 (1.08), 6.933 (2.26), 6.935 (2.11), 6.948 (1.31), 6.950 (1.18),
7.169 (1.12), 7.172 (1.16), 7.186 (1.76), 7.200 (0.93), 7.203 , 7.388 (1.80), 7.403 (1.70), 7.629 (1.72), 7.634 (4.02), 7.637
(8.89), 7.639 (16.00), 7.642 (4.87), 7.652 (2.18), 7.654 (1.91), 7.669 (1.82), 7.806 (2.51), 7.809 (2.42), 7.821 (2.05), 7.823 (1.86),
8.303 (1.86), 8.320 (1.72), 8.680 (8.25), 12.586 (0.91).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.068 (1.35), 2.198 (1.21), 2.210 (1.21), 2.220 (1.14), 3.278 (5.85), 3.289 (6.25), 3.311
LC-MS (Method L6): Rt = (12.56), 3.604 (16.00), 4.215 (0.92), 4.237 , 4.265 , 5.246 (1.68), 5.263 (1.68), 5.753 (4.55), 6.780 (2.37), 6.800 (2.65),
267 1.85 min; MS (ESIpos): m/z = 6.899 (1.40), 6.917 (2.61), 6.935 (1.60), 7.114 , 7.136 (3.72), 7.164 (2.76), 7.181 (4.24), 7.186 (4.32), 7.355 (2.53), 7.374
530 [M+H]+ (2.43), 7.410 (2.28), 7.415 (2.25), 7.432 (2.02), 7.437 , 7.527 (0.74), 7.547 (0.73), 7.582 (0.60), 7.629 (6.11), 7.647 (3.02),
7.665 (1.10), 8.224 (2.04), 8.238 , 8.571 (5.47), 9.139 (2.37), 9.159 (2.29).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.66), 2.032 (1.12), 2.040 (1.20), 2.051 (1.31), 2.057 (1.32), 2.067 (1.86), 2.072
(1.94), 2.082 (1.19), 2.090 , 2.178 (0.94), 2.187 (1.30), 2.199 (1.63), 2.211 (1.54), 2.221 (1.49), 2.233 , 2.242 (0.78),
2.254 (0.49), 2.669 (0.48), 3.233 (0.95), 3.245 (1.65), 3.264 (4.14), 3.277 (8.27), 3.290 (9.38), 3.303 (8.05), 3.310 , 3.608
(4.08), 3.694 , 3.841 (0.90), 3.860 (7.34), 3.871 (12.70), 3.882 (7.04), 3.901 (0.86), 4.165 (0.48), 4.175 (0.48), 4.183 ,
LC-MS (Method L6): Rt = 4.208 , 4.216 (1.03), 4.236 (2.56), 4.244 (2.08), 4.257 (3.61), 4.267 (3.55), 4.274 (2.38), 4.283 , 4.296 (0.92), 4.302
268 1.68 min; MS (ESIpos): m/z = , 5.186 (0.41), 5.232 (1.10), 5.246 (2.38), 5.265 (2.35), 5.280 (1.03), 5.753 (0.98), 6.749 , 6.780 (4.50), 6.800 ,
514 [M+H]+ 6.834 (0.58), 6.854 (0.72), 6.871 (0.52), 6.897 (2.22), 6.916 (4.62), 6.934 (2.69), 6.999 (3.38), 7.007 (3.89), 7.021 (3.65), 7.029
(3.73), 7.042 , 7.075 (2.55), 7.087 (2.73), 7.098 (4.07), 7.110 (4.00), 7.143 (2.39), 7.147 (2.50), 7.164 , 7.176 (2.61),
7.184 (4.22), 7.197 (3.38), 7.205 (3.28), 7.219 (1.66), 7.228 (1.63), 7.245 (0.65), 7.265 (0.49), 7.355 (3.98), 7.373 (3.68), 7.519
(0.46), 7.540 (0.43), 7.584 (0.65), 7.599 (0.48), 7.609 (0.82), 7.615 (2.02), 7.629 (9.79), 7.648 (5.53), 7.666 (1.75), 8.217 (3.69),
8.223 (3.68), 8.236 (3.32), 8.242 (3.35), 8.280 (0.46), 8.532 (1.30), 8.572 (16.00), 9.118 (0.49), 9.140 (4.50), 9.160 (4.10).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 , -0.008 (8.18), 0.008 (7.45), 0.146 (0.90), 1.862 (1.33), 1.901 (1.64), 2.006
(1.70), 2.026 (2.93), 2.039 (3.18), 2.058 (1.87), 2.071 (1.25), 2.144 (1.40), 2.158 , 2.174 (1.40), 2.192 (1.09), 2.327 (1.27),
2.366 (0.88), 2.669 , 2.709 (0.82), 2.988 (0.49), 3.018 (0.82), 3.080 , 3.090 (0.82), 3.120 (0.64), 3.168 (3.38), 3.189
(1.64), 3.199 (1.70), 3.212 (1.83), 3.304 (6.01), 3.458 (2.03), 3.487 (2.61), 3.517 (1.76), 3.654 (0.60), 3.683 (1.07), 3.692 (1.19),
LC-MS (Method L1): Rt = 3.715 (2.54), 3.728 (1.58), 3.736 (1.37), 3.767 (0.66), 3.789 (1.35), 3.807 (1.58), 3.831 (1.83), 3.847 (3.20), 3.861 (2.56), 3.874
269 0.75 min; MS (ESIpos): m/z = (3.40), 3.888 , 4.152 (7.55), 4.252 (5.35), 4.377 (2.97), 5.035 (0.45), 5.209 (1.89), 5.225 (1.93), 5.264 (0.43), 6.772 (4.37),
530 [M+H]+ 6.790 (5.03), 6.809 (0.90), 6.878 (2.19), 6.897 (4.78), 6.916 (3.30), 6.935 (0.49), 7.094 (6.19), 7.116 (7.26), 7.135 (2.60), 7.153
, 7.161 (6.99), 7.168 (8.02), 7.214 (1.25), 7.221 (1.29), 7.289 (3.71), 7.307 , 7.341 (0.72), 7.361 (0.64), 7.384 (4.27),
7.390 (4.02), 7.406 (3.71), 7.412 (3.61), 7.421 (3.04), 7.440 (4.06), 7.450 (1.05), 7.460 (3.61), 7.501 (5.07), 7.504 , 7.518
, 7.659 (1.00), 7.677 (1.58), 8.177 (16.00), 8.233 (4.10), 8.254 (3.80), 8.331 (8.27), 8.335 (8.60), 8.688 , 9.014 (2.13),
9.024 (2.44), 9.035 , 9.045 (2.24), 9.145 (0.62), 9.165 (0.59).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.06), 0.008 (2.02), 1.862 (0.52), 1.902 (0.65), 1.991 (0.45), 2.008 (0.70), 2.029
(1.17), 2.041 (1.33), 2.052 (0.81), 2.062 (0.77), 2.074 (0.49), 2.085 (0.95), 2.145 (0.64), 2.159 (0.70), 2.175 , 2.194 (0.46),
3.468 , 3.498 (0.87), 3.528 (0.48), 3.592 (16.00), 3.702 (0.50), 3.722 (0.73), 3.738 (0.54), 3.795 (0.43), 3.813 (0.59), 3.833
LC-MS (Method L6): Rt = (0.70), 3.855 (1.29), 3.868 (0.86), 3.881 (0.82), 3.893 (0.49), 4.151 (0.44), 4.241 (1.65), 4.254 (2.29), 4.378 (1.10), 5.041 (0.99),
270 1.17 min; MS (ESIpos): m/z = 5.210 (0.85), 5.224 (0.81), 5.753 (5.11), 6.773 (1.87), 6.793 , 6.877 (0.94), 6.896 (1.98), 6.914 (1.21), 6.988 (0.94), 6.995
514 [M+H]+ (1.10), 7.010 (0.97), 7.018 (1.04), 7.061 (0.93), 7.072 (1.01), 7.084 (1.51), 7.095 (1.44), 7.136 (1.03), 7.156 (2.10), 7.165 (0.92),
7.177 (1.39), 7.186 , 7.200 (0.54), 7.208 (0.52), 7.289 (1.68), 7.307 (1.53), 7.430 (0.89), 7.448 (1.57), 7.469 (1.45), 7.511
, 7.528 (1.16), 8.134 (5.18), 8.235 (1.56), 8.256 (1.45), 8.331 (2.76), 8.335 (3.59), 9.027 (0.68), 9.036 , 9.047 (0.75),
9.057 (0.91).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.71), -0.008 (7.12), 0.008 (7.07), 0.146 (0.81), 1.157 , 1.175 , 1.192
(4.07), 1.234 (4.37), 1.258 (1.96), 1.298 (1.33), 1.759 (1.96), 1.913 (1.69), 1.988 (16.00), 2.051 (3.21), 2.153 (1.72), 2.168 (1.96),
2.328 (1.18), 2.366 (0.83), 2.669 (1.15), 3.482 (1.52), 3.509 (3.31), 3.537 (1.72), 3.601 (1.72), 3.749 (2.23), 3.858 (2.43), 3.871
LC-MS (Method L1): Rt =
(2.40), 3.884 , 3.898 (2.04), 4.003 (1.13), 4.021 (3.58), 4.038 (3.51), 4.056 (1.20), 4.179 (2.43), 4.265 (5.40), 4.372 (2.70),
271 0.78 min; MS (ESIpos): m/z =
.035 (4.93), 5.231 (2.18), 5.753 (0.91), 6.782 (5.20), 6.802 (5.72), 6.891 (2.33), 6.910 (5.06), 6.928 (3.21), 7.141 (2.50), 7.162
568 [M+H]+
(4.22), 7.184 (2.11), 7.304 (4.32), 7.322 (4.02), 7.480 , 7.499 (4.47), 7.519 (3.68), 7.757 , 7.774 (4.66), 7.854 (7.12),
7.898 (7.95), 7.970 (7.83), 8.137 (1.03), 8.299 (3.12), 8.322 (3.07), 8.420 (9.50), 8.427 (9.79), 8.804 (0.96), 9.056 (3.41), 9.075
(3.53).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.66), -0.008 (6.04), 0.008 (5.39), 0.146 (0.68), 1.902 (1.46), 1.911 (1.34), 2.001
, 2.011 (1.72), 2.032 (2.75), 2.042 (2.15), 2.148 (1.40), 2.161 (1.58), 2.177 (1.24), 2.195 , 2.270 (16.00), 2.327 (0.88),
2.332 (0.72), 2.366 (0.84), 2.522 (2.61), 2.669 (0.86), 2.709 (0.78), 3.209 (0.40), 3.232 (0.44), 3.479 (1.26), 3.507 (2.19), 3.537
LC-MS (Method L1): Rt = (1.20), 3.738 (1.70), 3.758 (1.16), 3.790 (0.56), 3.813 (1.00), 3.830 , 3.848 , 3.857 (1.48), 3.870 (2.75), 3.883 (2.11),
272 0.74 min; MS s): m/z = 3.896 (1.78), 3.909 (1.08), 4.169 (2.17), 4.244 (3.65), 4.256 (4.49), 4.374 (2.29), 5.034 (3.53), 5.212 (1.76), 5.225 (1.74), 5.233
532 [M+H]+ (1.40), 5.753 (11.87), 6.774 (3.91), 6.793 (4.33), 6.881 , 6.900 , 6.918 , 7.135 (2.07), 7.138 (2.15), 7.156 (3.47),
7.174 (1.84), 7.177 , 7.240 (1.90), 7.247 (2.25), 7.254 (2.13), 7.261 (2.07), 7.295 , 7.314 , 7.405 (2.07), 7.411
(2.15), 7.420 (2.31), 7.426 (2.01), 7.458 (2.45), 7.477 (3.53), 7.498 , 7.604 (4.17), 7.621 (3.31), 8.133 (5.33), 8.299 (3.03),
8.321 (2.85), 8.361 (7.30), 8.365 (8.02), 8.733 , 9.030 (2.93), 9.051 (2.79).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (2.37), 0.008 (2.35), 0.551 (0.53), 0.566 (0.84), 0.576 (1.24), 0.588 (1.45), 0.599
(1.08), 0.611 (1.48), 0.622 (1.39), 0.632 (0.86), 0.646 (0.65), 0.774 (0.62), 0.784 (0.88), 0.791 (1.19), 0.801 (1.30), 0.811 (1.67),
0.817 (1.59), 0.828 (1.34), 0.846 (0.86), 0.855 (0.59), 1.157 (4.26), 1.175 (8.61), 1.193 (4.39), 1.988 (16.00), 2.033 (0.49), 2.041
(0.65), 2.051 (0.77), 2.059 (0.84), 2.067 (1.09), 2.075 (1.07), 2.086 , 2.108 (0.49), 2.129 (0.92), 2.141 , 2.150 (0.81),
LC-MS (Method L6): Rt =
2.163 (0.50), 2.176 (0.40), 2.523 (1.27), 3.074 (1.32), 3.081 (1.31), 4.003 (1.26), 4.021 , 4.038 (3.76), 4.056 (1.22), 4.229
273 1.74 min; MS (ESIpos): m/z =
(0.56), 4.237 (0.42), 4.248 (1.37), 4.257 (1.41), 4.268 (1.85), 4.276 (1.87), 4.288 , 4.296 (1.55), 4.316 (0.56), 5.210 ,
504 [M+H]+
.225 , 5.244 (1.46), 5.259 (0.63), 6.783 (2.84), 6.804 (3.11), 6.881 (1.36), 6.884 (1.39), 6.900 (2.84), 6.902 (2.84), 6.918
(1.71), 6.921 (1.66), 7.139 (1.38), 7.143 (1.48), 7.160 (2.30), 7.178 (1.14), 7.182 (1.14), 7.290 (2.42), 7.309 , 7.495 (2.03),
7.513 (2.65), 7.515 (2.51), 7.534 (2.35), 7.593 (1.59), 7.598 (3.85), 7.602 (4.25), 7.614 (14.30), 7.618 (8.44), 7.726 (3.30), 7.742
(2.69), 7.744 (2.68), 8.497 (2.63), 8.581 (9.25), 8.625 (2.55), 8.644 (2.39), 8.925 (2.56), 8.945 (2.48).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.88), 0.146 (0.84), 2.052 (4.40), 2.066 (4.83), 2.214 (1.52), 2.327 (1.69), 2.367
LC-MS (Method L1): Rt = (1.09), 2.669 (1.57), 2.709 (0.86), 3.395 (1.87), 3.910 (1.80), 3.929 (1.91), 4.172 (0.60), 4.289 (4.76), 4.731 (1.76), 4.745 (2.27),
274 0.87 min; MS (ESIpos): m/z = 4.764 (1.74), 5.301 (1.84), 5.318 (1.95), 6.770 (3.24), 6.790 (3.65), 6.854 (1.59), 6.872 (3.37), 6.890 (2.08), 7.129 (1.78), 7.146
562 [M+H]+ (2.92), 7.165 (1.59), 7.303 (3.15), 7.322 (2.98), 7.643 (16.00), 7.674 (2.68), 7.808 (3.99), 7.825 (3.00), 8.323 (3.22), 8.343 (2.92),
8.686 (8.56), 9.294 (0.92), 12.581 (0.51).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.899 (0.93), 2.033 (1.88), 2.162 (1.12), 2.178 (0.96), 2.337 (16.00), 2.669 (0.47), 3.305
(4.05), 3.485 (0.97), 3.512 (1.74), 3.538 (0.94), 3.742 (1.19), 3.817 (0.74), 3.849 (0.94), 3.873 (2.10), 3.885 (1.33), 3.899 (1.41),
LC-MS (Method L6): Rt =
3.911 (0.81), 4.257 (3.03), 4.375 (1.62), 5.036 (0.83), 5.212 (1.24), 6.773 (2.99), 6.793 (3.25), 6.884 (1.29), 6.902 (2.92), 6.920
275 1.37 min; MS (ESIpos): m/z =
(1.71), 7.138 (1.51), 7.157 (4.16), 7.174 , 7.296 (2.55), 7.314 (2.22), 7.418 (2.01), 7.431 (2.00), 7.467 (1.65), 7.484 (2.51),
532 [M+H]+
7.506 (2.14), 7.606 (3.17), 7.623 (2.58), 8.136 (11.05), 8.306 , 8.327 (1.99), 8.361 (5.15), 8.365 (5.57), 9.029 , 9.051
(1.92).
LC-MS (Method L6): Rt =
1H-NMR (400MHz, DMSO-d6): δ [ppm]= 8.98 (d, 1H), 8.47 (s, 1H), 8.22 (br d, 1H), 8.03 (br s, 1H), 7.74 (d, 1H), 7.52 - 7.66 (m, 4H),
276 0.80 min; MS (ESIpos): m/z =
7.33 (d, 1H), 7.15 (t, 1H), 6.90 (t, 1H), 6.78 (d, 1H), 5.18 - 5.33 (m, 1H), 4.19 - 4.33 (m, 2H), 3.80 (br s, 2H), 1.99 - 2.23 (m, 2H).
522 [M+H]+
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.53 (s, 1H), 8.28 (m, 1H), 7.78 – 7.62 (m, 2H), 7.51 (m, 1H), 7.35 (d, J =
2.86 min; m/z = 460 (M+H)+. 7.1 Hz, 1H), 7.25 – 7.11 (m, 3H), 6.91 (m, 1H), 6.83 – 6.75 (m, 1H), 5.24 (q, J = 5.8 Hz, 1H), 4.25 (dt, J = 7.8, 4.8 Hz, 2H)
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 8.1 Hz, 1H), 8.64 (s, 1H), 8.40 (dd, J = 9.4, 6.3 Hz, 1H), 7.70 (t, J = 9.1 Hz, 1H), 7.65 –
3.64 min, m/z = 520 (M+H)+ 7.55 (m, 1H), 7.36 (d, J = 6.8 Hz, 1H), 7.30 – 7.21 (m, 2H), 7.20 – 7.13 (m, 1H), 6.95 – 6.87 (m, 1H), 6.79 (dd, J = 8.2,
LC-MS (Method L3): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.55 (s, 1H), 8.37 (dd, J = 9.4, 6.3 Hz, 1H), 7.68 – 7.54 (m, 2H), 7.34 (d, J
3.83 min, m/z = 478 (M+H)+ = 6.8 Hz, 1H), 7.30 – 7.20 (m, 2H), 7.20 – 7.12 (m, 1H), 6.94 – 6.87 (m, 1H), 6.79 (dd, J = 8.2, 1.1 Hz, 1H), 5.27 – 5.19 (
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.19 (d, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.34 (dd, 1H), 7.81 - 7.90 (m, 2H), 7.75 (dd, 1H),
280 0.89 min; MS (ESIpos): m/z = 7.47 - 7.56 (m, 2H), 7.36 (d, 1H), 7.12 - 7.21 (m, 1H), 6.87 - 6.97 (m, 1H), 6.79 (d, 1H), 5.20 - 5.32 (m, 1H), 4.18 - 4.33 (m, 2H), 3.89
507 [M+H]+ (t, 4H), 2.16 - 2.28 (m, 1H), 2.00 - 2.11 (m, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.22), 0.008 , 2.023 (0.43), 2.058 , 2.065 (0.63), 2.129 (0.65), 2.148
(0.95), 2.159 (1.39), 2.178 (1.50), 2.197 (0.65), 2.259 (0.60), 2.271 (0.78), 2.289 (0.71), 2.322 (0.52), 2.327 (0.59), 2.523 (1.62),
2.670 (0.57), 3.336 (1.52), 3.354 (0.97), 3.632 (0.46), 3.644 (0.81), 3.656 (0.92), 3.663 (0.86), 3.688 (16.00), 3.711 (1.43), 3.729
LC-MS (Method L6): Rt =
(0.81), 3.736 (1.08), 3.764 (1.60), 3.783 (1.39), 3.798 (1.66), 3.815 (1.41), 3.823 (0.84), 3.840 (0.60), 4.236 (1.01), 4.248 (1.31),
281 1.59 min; MS (ESIpos): m/z =
4.259 (1.81), 4.273 (1.00), 5.212 (0.93), 5.232 , 5.245 (0.41), 5.754 (0.44), 6.784 (1.82), 6.804 (1.98), 6.899 (0.92), 6.915
576 [M+H]+
(1.93), 6.934 , 7.149 (0.92), 7.153 (0.95), 7.170 (1.52), 7.187 (0.76), 7.334 (1.55), 7.352 (1.44), 7.548 (1.35), 7.566 ,
7.569 (1.62), 7.587 (1.49), 7.625 (12.56), 7.756 , 7.771 (1.68), 7.774 (1.70), 8.265 (1.73), 8.287 (1.54), 8.530 (5.88), 9.104
(1.73), 9.124 (1.66).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.90), 0.008 (1.01), 1.356 (0.76), 2.020 (0.41), 2.030 (0.40), 2.056 (0.64), 2.064
(0.53), 2.115 , 2.134 (0.66), 2.146 (0.97), 2.164 (1.20), 2.184 (0.89), 2.196 (0.51), 2.261 (0.56), 2.273 (0.71), 2.280 (0.50),
2.292 (0.68), 2.323 (0.44), 2.327 , 2.523 (1.03), 3.333 (1.42), 3.352 (0.88), 3.653 (0.41), 3.665 (0.84), 3.684 (16.00), 3.702
LC-MS (Method L6): Rt =
(0.75), 3.721 (1.33), 3.739 (0.72), 3.745 (0.78), 3.776 , 3.779 (2.21), 3.797 (2.25), 4.241 (0.94), 4.250 (1.38), 4.261 (1.78),
282 1.57 min; MS (ESIpos): m/z =
.218 , 5.238 (0.83), 5.754 (1.01), 6.784 (1.63), 6.804 (1.77), 6.895 (0.78), 6.897 (0.81), 6.915 (1.64), 6.932 (0.96), 6.934
576 [M+H]+
(0.96), 7.147 (0.79), 7.151 (0.87), 7.168 (1.32), 7.186 (0.66), 7.190 (0.67), 7.328 (1.35), 7.345 , 7.544 (1.16), 7.562 (1.51),
7.566 (1.48), 7.584 , 7.624 (12.39), 7.752 (1.74), 7.755 (1.89), 7.770 (1.51), 7.772 (1.51), 8.250 (1.50), 8.253 (1.57), 8.271
(1.41), 8.274 (1.38), 8.524 (5.96), 9.102 (1.54), 9.123 (1.50).
LC-MS (Method L6): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.05 (d, 1H), 8.44 (s, 1H), 8.29 (d, 1H), 7.71 (d, 1H), 7.57 - 7.64 (m, 3H), 7.44 - 7.52 (m,
283 0.81 min; MS (ESIpos): m/z = 1H), 7.32 (d, 1H), 7.11 - 7.20 (m, 1H), 6.87 - 6.95 (m, 1H), 6.79 (d, 1H), 5.18 - 5.28 (m, 1H), 5.03 (d, 1H), 4.36 (br s, 1H), 4.27 (br t,
534 [M+H]+ 2H), 3.79 - 3.93 (m, 2H), 3.68 - 3.79 (m, 1H), 3.49 (br d, 1H), 2.12 - 2.24 (m, 1H), 1.97 - 2.10 (m, 2H), 1.89 (br d, 1H).
LC-MS (Method L6): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.05 (d, 1H), 8.43 (s, 1H), 8.29 (d, 1H), 7.72 (d, 1H), 7.57 - 7.65 (m, 3H), 7.45 - 7.51 (m,
284 0.82 min; MS (ESIpos): m/z = 1H), 7.32 (d, 1H), 7.17 (t, 1H), 6.92 (t, 1H), 6.79 (d, 1H), 5.22 (br d, 1H), 5.03 (d, 1H), 4.37 (br s, 1H), 4.20 - 4.31 (m, 2H), 3.68 - 3.91
534 [M+H]+ (m, 3H), 3.51 (br d, 1H), 2.18 (br dd, 1H), 2.03 (br dd, 2H), 1.91 (br s, 1H).
1H-NMR(399,9532 MHz, DMSO): δ= 9.2548 (2.04); 9.2345 (2.1); 8.7855 (7.26); 8.3664 (2.02); 8.3479 (2.11); 8.3453 (2.18); 7.8787
; 7.8758 (1.94); 7.861 (2.47); 7.8581 (2.48); 7.7622 (1.94); 7.7414 (2.32); 7.7231 (1.43); 7.6547 (16); 7.377 (1.84); 7.3585
(1.98); 7.2033 (0.85); 7.1998 (0.91); 7.1823 (1.91); 7.1646 ; 7.1615 (1.18); 6.9343 (1.34); 6.9157 (2.31); 6.8969 (1.1); 6.8176
(2.6); 6.7972 (2.33); 5.7568 ; 5.3034 (0.53); 5.2897 (1.2); 5.2703 (1.21); 5.2561 (0.53); 4.2926 (1.27); 4.2792 (2.34); 4.2671
(1.8); 4.2581 (1.3); 4.2376 (0.33); 4.0706 (0.7); 4.0524 (2.63); 4.0345 (4.44); 4.0171 (4.89); 3.9996 (4.19); 3.9816 (2.38); 3.9627
285 4,62
(0.67); 3.6304 (3.62); 3.6065 ; 3.3187 (31.43); 3.1462 (13.89); 2.6701 (0.58); 2.6659 (0.46); 2.5055 (77.14); 2.5012 6);
2.4969 (75.96); 2.3321 (0.47); 2.3281 (0.61); 2.3241 (0.48); 2.2488 (0.44); 2.2418 (0.43); 2.2281 (0.71); 2.2163 (0.79); 2.2064 (0.75);
2.1941 (0.66); 2.1845 (0.36); 2.0978 (0.77); 2.0895 (0.89); 2.078 (0.63); 2.0643 (0.6); 2.0543 (0.57); 1.9886 (5.88); 1.3664 (0.32);
1.2071 (5.79); 1.1896 (12.06); 1.1762 (7.45); 1.1746 (7.59); 1.1724 (7.64); 1.1593 (11.84); 1.1417 (5.55); 0.0079 (0.56); -0.0002
(11.57)
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.226 (1.29), 0.233 (4.30), 0.237 (4.63), 0.239 (4.52), 0.243 (4.88), 0.249 , 0.340
(1.52), 0.346 , 0.350 (4.50), 0.357 (4.85), 0.360 (3.44), 0.368 (1.04), 1.356 , 2.038 (0.54), 2.043 (0.74), 2.048 (0.90),
2.055 (1.09), 2.058 (1.29), 2.064 (1.93), 2.069 (2.31), 2.075 (2.90), 2.080 (1.94), 2.085 (1.35), 2.091 (0.59), 2.138 (0.52), 2.147
, 2.153 (0.91), 2.160 (1.03), 2.166 (0.97), 2.175 (0.71), 2.183 (0.72), 2.430 (0.61), 2.875 (2.56), 2.886 (5.07), 2.896 (2.59),
LC-MS (Method L1): Rt = 3.568 (1.55), 3.578 , 3.587 , 3.597 (1.35), 4.235 (0.44), 4.240 (0.64), 4.246 (0.51), 4.253 (1.67), 4.259 (1.50), 4.267
286 0.71 min; MS (ESIpos): m/z = (2.05), 4.272 (2.07), 4.280 (1.42), 4.285 (1.84), 4.291 (0.49), 4.299 (0.60), 4.304 (0.43), 5.243 (0.77), 5.253 (1.54), 5.266 (1.49),
547 [M+H]+ 5.276 (0.69), 6.785 , 6.787 (3.06), 6.799 (3.15), 6.801 (3.19), 6.884 (1.60), 6.886 (1.58), 6.897 (3.02), 6.899 (2.96), 6.909
(1.78), 6.911 (1.69), 7.149 (1.45), 7.151 (1.48), 7.163 (2.43), 7.174 (1.26), 7.177 , 7.299 (2.47), 7.312 , 7.525 (2.41),
7.537 (2.93), 7.539 (2.68), 7.552 (2.48), 7.603 , 7.606 (5.93), 7.609 (4.64), 7.625 (16.00), 7.628 (11.38), 7.728 (0.51), 7.731
(0.49), 7.740 (3.43), 7.741 (3.45), 7.751 (2.98), 7.753 (2.90), 7.908 (1.67), 8.353 (2.70), 8.354 (2.72), 8.367 (2.61), 8.369 (2.48),
8.549 (9.74), 8.991 (2.87), 9.004 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.52), 0.146 , 1.883 , 1.896 , 1.912 (1.02), 1.927 (1.11), 1.943
(1.13), 1.961 (0.80), 1.971 (1.04), 1.990 (1.32), 2.009 (0.93), 2.061 (1.59), 2.074 (1.40), 2.084 (1.11), 2.098 (1.33), 2.109 (1.05),
LC-MS (Method L1): Rt = 2.191 , 2.202 (1.93), 2.226 (1.16), 2.240 (0.86), 2.327 (0.57), 2.366 (0.54), 2.669 (0.58), 2.710 (0.53), 3.225 (0.66), 3.239
287 0.98 min; MS (ESIpos): m/z = (1.63), 3.252 (3.85), 3.266 (3.91), 3.279 (2.86), 3.800 (0.70), 3.818 (1.59), 3.838 (1.38), 3.857 (0.53), 4.279 (3.25), 4.293 (5.39),
548 [M+H]+ 4.304 (3.56), 4.768 (1.59), 4.782 (3.24), 4.795 (1.56), 5.260 (0.71), 5.274 (1.51), 5.293 (1.51), 5.308 (0.71), 6.778 (2.68), 6.798
(3.02), 6.875 (1.45), 6.893 (3.03), 6.912 (1.75), 7.138 , 7.156 (2.35), 7.176 (1.18), 7.292 (2.47), 7.310 (2.24), 7.600 (1.83),
7.621 (2.91), 7.638 (16.00), 7.787 (3.16), 7.804 (2.53), 8.227 (2.56), 8.249 , 8.638 (8.70), 9.180 (2.48), 9.201 (2.46).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.149 (0.41), -0.008 (3.63), 0.008 , 0.146 (0.42), 0.853 (0.41), 1.235 (1.98), 1.571
, 1.770 (0.57), 1.783 (0.70), 1.800 (0.80), 1.813 (0.68), 1.832 (0.43), 1.896 (0.87), 1.916 (1.53), 1.934 (1.55), 1.951 (0.86),
1.997 (0.58), 2.004 (0.58), 2.018 (0.64), 2.032 (0.84), 2.105 (0.65), 2.117 (0.95), 2.135 (0.76), 2.149 (0.82), 2.172 (0.84), 2.185
LC-MS (Method L1): Rt = (0.78), 2.193 (0.74), 2.206 (0.55), 2.327 (0.80), 2.366 (0.49), 2.523 (2.44), 2.665 (0.62), 2.669 (0.80), 2.709 (0.47), 3.168 ,
288 0.99 min; MS s): m/z = 3.202 (3.42), 3.235 (0.84), 3.730 (0.53), 3.748 (1.27), 3.769 (1.21), 3.787 , 4.172 (0.78), 4.196 (1.49), 4.202 (1.69), 4.217
548 [M+H]+ (1.98), 4.233 (1.24), 4.246 (1.34), 4.252 (1.02), 4.262 (1.06), 4.273 (0.58), 4.281 (0.53), 4.775 (0.76), 5.232 (0.50), 5.246 ,
.266 (1.12), 5.280 , 6.792 (2.30), 6.813 (2.51), 6.929 (1.14), 6.946 (2.23), 6.964 (1.27), 7.169 (1.12), 7.173 (1.19), 7.190
(1.80), 7.208 (0.87), 7.409 (1.87), 7.427 , 7.603 (1.59), 7.622 (2.28), 7.625 (2.41), 7.637 (16.00), 7.651 (0.76), 7.789 (2.46),
7.804 (1.99), 8.208 (1.97), 8.227 (1.82), 8.554 (0.70), 8.654 (8.22), 9.267 (1.92), 9.288 (1.85).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.41), 0.853 , 0.936 (14.10), 0.967 (12.05), 0.979 (4.08), 1.010 (0.93), 1.091
(4.11), 1.112 (3.92), 1.128 (1.36), 1.141 (1.26), 1.209 (11.78), 1.226 (11.85), 1.257 (0.62), 1.863 (0.62), 2.038 (2.45), 2.070 (3.11),
2.086 (2.26), 2.124 (1.91), 2.137 (1.96), 2.328 (0.85), 2.366 (0.73), 2.524 (1.17), 2.670 (0.58), 2.711 (3.09), 3.066 (0.92), 3.075
LC-MS (Method L4): Rt = (0.86), 4.217 , 4.236 (2.48), 4.254 (2.47), 4.264 (2.19), 4.277 (2.14), 4.296 (2.20), 4.323 (1.05), 5.256 (1.20), 5.271 (2.47),
289 2.19 min; MS (ESIneg): m/z = 5.288 (2.36), 5.754 (6.01), 6.779 , 6.800 (4.70), 6.850 (1.07), 6.869 (3.08), 6.886 (3.51), 6.904 (1.82), 6.921 (0.41), 7.137
545 [M-H]- (2.50), 7.155 (4.01), 7.173 (2.04), 7.246 (2.37), 7.268 (3.62), 7.289 (1.98), 7.527 (2.12), 7.546 (3.59), 7.566 (2.59), 7.595 (5.35),
7.599 (4.71), 7.629 (16.00), 7.633 (13.65), 7.755 (4.31), 7.772 (3.86), 8.153 (1.08), 8.195 , 8.334 (0.71), 8.562 (0.74), 8.585
(0.69), 8.632 , 8.640 (2.11), 8.653 (2.92), 8.664 (5.42), 8.676 (5.87), 8.916 (1.70), 8.935 (3.21), 8.955 (1.84), 8.981 (0.70),
9.001 (0.72), 9.015 (0.69), 9.035 (0.60), 9.091 (0.68), 9.148 (0.75).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.02), -0.008 (8.92), 0.008 (8.60), 0.146 , 1.135 (7.45), 1.150 (7.45), 2.092
(0.86), 2.210 (0.77), 2.222 (0.70), 2.232 , 2.327 (1.38), 2.366 (0.75), 2.522 (3.76), 2.669 , 2.709 (0.68), 3.011 (0.88),
LC-MS (Method L6): Rt =
3.040 (1.40), 3.065 (1.22), 3.171 (0.86), 3.203 (2.49), 3.237 (1.13), 3.271 (0.95), 3.882 (0.86), 3.904 (1.86), 3.928 (2.90), 4.252
290 2.50 min; MS (ESIpos): m/z =
(1.18), 4.260 (1.02), 4.272 (1.81), 4.281 (1.77), 4.297 (0.97), 5.264 (1.11), 5.285 (1.13), 5.754 (6.81), 6.791 (2.20), 6.811 (2.42),
548 [M+H]+
6.898 , 6.916 (2.17), 6.932 , 7.158 (1.11), 7.175 (1.77), 7.193 (0.88), 7.373 , 7.390 , 7.639 (16.00), 7.682
(1.45), 7.700 (2.08), 7.720 (1.88), 7.832 (2.51), 7.847 (1.92), 8.269 (2.08), 8.287 (1.92), 8.703 (7.92), 9.162 (1.99), 9.182 (1.90).
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 (0.51), 1.849 (0.72), 1.904 (0.43), 1.909 (0.44), 2.009 , 2.029 (0.63), 2.039
(0.75), 2.044 (0.67), 2.050 (0.81), 2.054 (0.88), 2.060 (0.72), 2.086 (1.13), 2.161 (0.42), 2.169 (0.75), 2.177 (0.71), 2.184 (0.86),
2.191 (0.78), 2.205 (0.57), 2.517 (0.75), 2.520 (0.73), 2.523 (0.59), 3.517 (0.55), 3.523 (0.43), 3.529 , 3.553 (0.60), 3.563
(1.79), 3.570 (1.96), 3.578 (0.98), 3.712 (0.61), 3.733 (0.80), 3.751 (0.73), 3.758 (0.72), 3.773 (0.86), 3.777 (1.00), 3.791 ,
LC-MS (Method L1): Rt =
3.794 (1.30), 3.803 (1.20), 3.806 (1.23), 4.147 (0.64), 4.191 (0.42), 4.213 (0.68), 4.217 (0.52), 4.233 (0.62), 4.240 (1.21), 4.245
291 0.74 min; MS (ESIneg): m/z =
(0.85), 4.253 (2.20), 4.259 (2.32), 4.263 (2.48), 4.271 (1.51), 4.979 , 4.998 (0.65), 5.070 (0.63), 5.090 , 5.216 (0.57),
549 [M-H]-
.226 (1.21), 5.238 , 5.247 (0.54), 5.761 (0.76), 6.787 (2.54), 6.801 (2.68), 6.909 (1.25), 6.922 (2.41), 6.934 (1.36), 7.154
(1.22), 7.167 (1.95), 7.180 (1.02), 7.326 (1.05), 7.339 (1.97), 7.351 (1.01), 7.504 , 7.507 (1.14), 7.519 , 7.531 (1.20),
7.533 (1.22), 7.621 (16.00), 7.737 (2.63), 7.739 (2.75), 7.749 (2.42), 7.751 (2.42), 8.247 (1.17), 8.261 (2.15), 8.276 (1.14), 8.463
(4.46), 8.474 (4.71), 9.093 (1.35), 9.100 (1.40), 9.107 , 9.114 (1.26).
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 , 1.860 (0.51), 1.871 (0.77), 1.882 (0.62), 1.890 (0.44), 1.909 (0.41), 1.923
(0.56), 1.930 (0.52), 1.934 (0.54), 1.940 (0.70), 1.946 (0.52), 1.954 (0.72), 1.961 (0.49), 1.974 (0.44), 2.035 (0.45), 2.040 (0.47),
2.049 , 2.060 (0.97), 2.069 (0.59), 2.080 (0.42), 2.086 (1.00), 2.383 (0.46), 2.386 (0.48), 2.389 (0.45), 2.475 (0.54), 2.482
, 2.517 (1.22), 2.520 (1.25), 2.523 (0.98), 2.846 (0.43), 2.859 (0.55), 2.871 (0.67), 2.888 (0.55), 2.973 (0.59), 2.988 (0.60),
LC-MS (Method L1): Rt = 3.000 (0.43), 3.307 (0.67), 3.386 , 3.399 (0.44), 3.808 (0.49), 3.822 (0.49), 3.904 (0.48), 3.918 (0.47), 4.649 (0.59), 4.659
292 0.92 min; MS (ESIneg): m/z = , 4.663 (0.57), 4.672 , 4.757 (0.59), 4.766 (0.67), 4.771 (0.55), 4.779 (0.49), 5.535 (0.60), 5.547 (0.59), 5.578 (0.65),
546 [M-H]- 5.591 (0.64), 5.761 (4.08), 7.186 (0.77), 7.198 (0.64), 7.207 (0.58), 7.219 (1.00), 7.233 (0.76), 7.237 (0.74), 7.239 (0.73), 7.244
(1.42), 7.248 (0.86), 7.251 (0.95), 7.254 , 7.258 (1.17), 7.275 (0.96), 7.286 (0.49), 7.362 (0.89), 7.374 (0.74), 7.450 (0.61),
7.453 (0.66), 7.464 (0.59), 7.623 (0.42), 7.636 (0.92), 7.639 (2.00), 7.644 ), 7.646 ), 7.651 (1.35), 7.654 (1.10), 7.657
(1.10), 7.659 (0.98), 7.665 (0.95), 7.671 (0.88), 7.806 (1.15), 7.809 (1.53), 7.812 , 7.818 (1.12), 7.821 (1.26), 7.824 (0.95),
8.291 (0.84), 8.293 , 8.305 (0.81), 8.308 (0.78), 8.314 (0.95), 8.316 (0.95), 8.328 (0.80), 8.330 (0.76), 8.697 (6.20).
1H-NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 8.2 Hz, 1H), 8.61 (s, 1H), 8.22 (dd, J = 8.5, 1.4 Hz, 1H), 7.79 (dd, J = 7.1, 1.4 Hz, 1H),
LC-MS (Method L3): Rt =
7.64 (dd, J = 8.5, 7.1 Hz, 1H), 7.46 (d, J = 1.9 Hz, 1H), 7.36 (d, J = 6.8 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.21 – 7.14 (m, 1H), 6.97 –
293 4.24 min; m/z = 484/486
6.88 (m, 1H), 6.80 (dd, J = 8.2, 1.1 Hz, 1H), 5.30 – 5.20 (m, 1H), 4.34 – 4.18 (m, 2H), 3.06 (s, 6H), 2.79 (s, 6H), 2.27 – 2.14 (m, 1H),
(M+1)+
2.13 – 1.97 (m, 1H).
LC-MS (Method L3): Rt =
1H-NMR (400 MHz, 6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.19 (dd, J = 8.5, 1.5 Hz, 1H), 7.72 (dd, J = 7.1, 1.5 Hz, 1H),
294 3.20 min; m/z = 501/503
7.61 (dd, J = 8.4, 7.1 Hz, 1H), 7.36 (d, J = 6.7 Hz, 1H), 7.22 – 7.12 (m, 1H), 6.97 – 6.88 (m, 1H), 6.86 – 6.76 (m, 3H), 6.
(M+1)+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.900 (1.01), 1.909 (0.98), 2.019 (1.52), 2.030 (1.94), 2.148 (0.92), 2.162 (1.06), 2.178
(0.86), 2.194 (0.65), 2.399 (16.00), 3.169 (5.63), 3.232 (0.41), 3.305 (3.16), 3.314 , 3.479 (0.92), 3.506 , 3.533 (0.99),
LC-MS (Method L1): Rt = 3.711 (0.62), 3.734 (1.27), 3.755 (0.85), 3.789 (0.43), 3.811 (0.79), 3.829 (0.80), 3.845 (0.92), 3.856 (1.20), 3.866 (2.03), 3.879
295 0.74 min; MS (ESIpos): m/z = (1.33), 3.894 (1.36), 3.905 (0.71), 4.165 (0.98), 4.256 , 4.374 (1.70), 5.034 (0.67), 5.214 (1.23), 5.226 (1.24), 6.773 (2.58),
532 [M+H]+ 6.793 (2.90), 6.882 (1.30), 6.901 (2.73), 6.919 (1.67), 7.135 (1.40), 7.156 (2.32), 7.174 (1.20), 7.296 (4.04), 7.311 (2.43), 7.323
(2.78), 7.424 , 7.441 (2.63), 7.460 (1.52), 7.478 (2.53), 7.499 (1.95), 7.614 (2.84), 7.632 (2.37), 8.137 (4.85), 8.291 (2.22),
8.313 , 8.357 (5.32), 9.028 (1.63), 9.032 (1.65), 9.048 (1.65).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.98), 0.008 , 3.063 (16.00), 4.243 (0.55), 4.262 (0.79), 4.270 (0.88), 4.283
LC-MS (Method L6): Rt = (0.48), 5.248 (0.49), 5.268 , 6.785 (1.01), 6.805 (1.09), 6.905 (0.49), 6.923 (0.99), 6.939 (0.58), 7.150 (0.51), 7.167 (0.80),
296 1.34 min; MS (ESIpos): m/z = 7.348 (0.87), 7.366 (0.87), 7.378 (1.07), 7.396 (0.89), 7.428 (1.31), 7.447 (2.17), 7.465 (0.96), 7.574 (2.11), 7.591 (1.75), 7.595
424 [M+H]+ (1.21), 7.614 (0.67), 7.632 (1.09), 7.652 (1.07), 7.697 (1.20), 7.701 (1.29), 7.715 (0.80), 7.719 (0.73), 8.174 (1.00), 8.177 (1.02),
8.195 (0.93), 8.199 (0.88), 8.583 (3.79), 9.068 (0.83), 9.088 (0.78).
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 (0.54), 1.175 (0.51), 1.233 (0.88), 1.945 (0.48), 1.959 , 1.966 (0.68), 1.973
(1.44), 1.980 (1.50), 1.987 (0.67), 1.990 , 1.994 (1.45), 2.008 (0.53), 2.086 (2.18), 2.451 (0.53), 2.457 (0.63), 2.464 (1.16),
2.470 , 2.477 (1.47), 2.485 (1.96), 2.517 , 2.520 (0.88), 2.524 (0.72), 2.822 (0.63), 2.835 (1.18), 2.849 (1.35), 2.862
LC-MS d L1): Rt = (1.68), 2.875 (0.78), 2.969 (1.03), 2.975 (1.07), 2.984 (1.12), 2.989 , 2.995 (0.85), 3.001 (0.81), 3.010 (0.76), 3.016 (0.67),
297 0.84 min; MS (ESIpos): m/z = 3.588 (0.86), 3.598 , 3.602 (2.62), 3.608 (3.14), 3.617 (1.76), 3.632 (0.42), 3.652 (3.34), 3.661 (4.14), 3.669 (1.71), 4.909
492 [M+H]+ (0.68), 5.519 (0.77), 5.533 (2.21), 5.546 (2.18), 5.559 , 7.191 (0.82), 7.203 (2.41), 7.213 (3.76), 7.216 (3.96), 7.225 (2.72),
7.227 (2.72), 7.237 (1.21), 7.262 (3.11), 7.273 (1.90), 7.357 (2.79), 7.369 (2.30), 7.526 (2.39), 7.538 (2.98), 7.540 (2.73), 7.552
(2.48), 7.608 (2.68), 7.611 (5.84), 7.614 (4.57), 7.628 (15.29), 7.632 (11.06), 7.741 (3.49), 7.743 (3.42), 7.753 (3.14), 7.755 (2.91),
8.061 (1.26), 8.137 (16.00), 8.392 (2.82), 8.394 (2.80), 8.407 (2.71), 8.573 (9.90), 8.877 , 8.891 .
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 (0.41), 1.942 (0.52), 1.957 (1.44), 1.963 (0.74), 1.970 (1.55), 1.977 (1.60), 1.984
(0.73), 1.991 (1.56), 2.005 (0.56), 2.450 , 2.456 (0.67), 2.463 (1.22), 2.469 (1.51), 2.476 , 2.484 (1.77), 2.517 (0.76),
2.520 (0.73), 2.523 (0.57), 2.826 (0.69), 2.839 (1.33), 2.852 (1.51), 2.866 (1.87), 2.879 (0.87), 2.972 (1.15), 2.978 (1.19), 2.987
LC-MS (Method L1): Rt =
(1.24), 2.993 (1.19), 2.999 (0.94), 3.004 (0.89), 3.013 (0.85), 3.019 (0.75), 3.338 (3.68), 3.398 (0.51), 3.558 (0.53), 3.568 (2.60),
298 0.94 min; MS (ESIpos): m/z =
3.576 (6.35), 3.585 (4.12), 3.684 (1.95), 3.692 (4.19), 3.701 (3.62), 3.710 (1.33), 5.515 , 5.528 (2.43), 5.541 (2.41), 5.555
506 [M+H]+
(0.80), 7.195 (0.86), 7.207 (2.64), 7.216 (3.91), 7.219 (4.26), 7.228 (2.98), 7.230 (2.98), 7.240 (1.27), 7.265 (3.39), 7.276 ,
7.355 (2.95), 7.366 (2.41), 7.533 , 7.545 (2.81), 7.559 (2.13), 7.613 (4.94), 7.617 (4.00), 7.629 (16.00), 7.632 (10.79), 7.748
(3.54), 7.760 (3.14), 8.100 (1.02), 8.136 (6.62), 8.382 (2.78), 8.396 (2.64), 8.586 (8.69), 8.913 (2.35), 8.927 (2.27).
LC-MS (Method L6): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 11.89 (d, 1H), 8.62 (s, 1H), 8.16 (d, 1H), 7.70 (d, 1H), 7.58 - 7.66 (m, 3H), 7.50 - 7.58 (m,
299 1.72 min; MS (ESIpos): m/z = 1H), 7.10 - 7.30 (m, 4H), 5.51 - 5.65 (m, 1H), 4.70 (br d, 1H), 3.95 (br d, 1H), 3.17 (br s, 1H), 2.76 - 2.99 (m, 2H), 2.30 - 2.43 (m, 3H),
546 [M+H]+ 1.88 - 2.08 (m, 4H).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 2.060 (0.42), 2.066 (0.45), 2.075 (0.47), 2.088 (0.65), 2.094 , 2.183 (0.44), 2.193
(0.60), 2.203 (0.58), 2.210 (0.55), 2.443 (1.65), 2.460 (1.72), 3.126 , 3.139 , 3.155 (0.91), 3.168 (0.40), 3.453 (1.32),
LC-MS (Method L1): Rt = 3.468 (1.45), 3.473 (1.52), 3.487 (1.39), 3.880 (1.72), 3.887 (1.73), 3.902 (1.54), 3.909 , 4.231 (0.98), 4.237 (0.78), 4.247
300 2,6 1.14 min; MS (ESIpos): m/z = (1.45), 4.254 (1.38), 4.268 (0.84), 4.653 (1.89), 4.662 (1.90), 5.254 (0.43), 5.266 , 5.281 (0.89), 6.781 (1.78), 6.797 (1.91),
546 [M+H]+ 6.891 , 6.906 (1.77), 6.921 (0.96), 7.149 (0.84), 7.152 (0.86), 7.166 (1.42), 7.180 (0.70), 7.389 (1.48), 7.403 (1.38), 7.651
(16.00), 7.694 (1.17), 7.708 (1.63), 7.725 (1.38), 7.846 (1.88), 7.859 (1.51), 8.297 (1.59), 8.313 , 8.833 (5.84), 9.232 (1.60),
9.248 .
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.006 (0.68), 2.065 , 2.072 (0.53), 2.084 (0.50), 2.093 (0.68), 2.099 (0.58), 2.106
(0.41), 2.204 (0.47), 2.213 (0.62), 2.222 (0.62), 2.230 (0.60), 2.518 (0.74), 3.356 (1.31), 3.379 , 3.420 (1.28), 3.443 (1.40),
LC-MS (Method L1): Rt = 3.759 (0.97), 3.785 (1.89), 3.799 (2.05), 3.813 (2.09), 3.819 (1.80), 4.030 , 4.054 (2.69), 4.066 (2.67), 4.084 (2.39), 4.108
301 3,3 1.21 min; MS (ESIpos): m/z = (0.98), 4.252 (1.06), 4.258 (0.86), 4.268 (1.59), 4.275 (1.59), 4.288 (0.92), 5.257 (0.45), 5.269 (0.98), 5.284 (0.95), 5.295 (0.42),
576 [M+H]+ 6.789 (1.89), 6.805 (2.04), 6.916 (0.91), 6.931 , 6.946 (1.06), 7.155 (0.89), 7.158 (0.91), 7.172 (1.53), 7.186 (0.73), 7.396
(1.60), 7.410 (1.49), 7.641 (16.00), 7.674 (1.24), 7.688 , 7.705 (1.45), 7.813 (1.96), 7.815 (1.98), 7.827 (1.59), 8.614 (1.68),
8.631 (1.59), 8.696 (5.91), 9.169 (1.74), 9.186 (1.68).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.006 (1.48), 1.977 , 1.985 , 2.061 (0.94), 2.067 (1.00), 2.073 (1.28), 2.089
(1.37), 2.094 (1.18), 2.101 (0.84), 2.107 (0.62), 2.196 (0.68), 2.205 (1.01), 2.212 (1.42), 2.222 (1.44), 2.230 (1.70), 2.240 (1.49),
2.252 (3.88), 2.271 (3.21), 2.292 (0.43), 2.361 (0.59), 2.518 (1.55), 2.522 (1.14), 2.635 (0.56), 2.976 (2.42), 2.998 (2.58), 3.014
LC-MS (Method L1): Rt = (2.43), 3.037 (2.48), 3.530 (3.55), 3.548 (2.59), 3.554 (3.28), 4.225 (0.63), 4.230 (0.76), 4.247 (2.09), 4.253 , 4.264 (1.81),
302 1.32 min; MS (ESIpos): m/z = 4.271 (1.84), 4.281 (1.90), 4.287 (1.63), 4.294 (1.74), 4.303 (0.69), 4.309 (0.76), 4.316 , 4.414 , 5.247 (0.90), 5.259
560 [M+H]+ (1.92), 5.274 (1.85), 5.285 (0.82), 6.790 , 6.806 (3.88), 6.922 (1.77), 6.936 (3.59), 6.951 (2.00), 7.158 (1.76), 7.160 (1.81),
7.174 (2.97), 7.188 , 7.191 (1.38), 7.393 (3.10), 7.408 (2.87), 7.625 (10.72), 7.629 (16.00), 7.639 (5.39), 7.643 (5.55), 7.646
(2.39), 7.726 (0.54), 7.729 (0.50), 7.740 (2.23), 7.755 (3.44), 7.771 (2.93), 7.838 (3.90), 7.840 , 7.852 (2.90), 8.405 (3.15),
8.420 (2.90), 8.693 (11.68), 9.142 , 9.159 (3.24).
1H-NMR(399,9532 MHz, DMSO): δ= 9.1897 (3.07); 9.1697 ; 8.6999 (11.32); 8.267 (3.04); 8.2457 (3.34); 8.0999 ; 8.0853
(0.45); 7.842 (3.13); 7.8244 (4.12); 7.72 ; 7.6994 (3.57); 7.681 (2.24); 7.4668 (0.34); 7.4303 (0.34); 7.3979 (2.99); 7.3791
(3.33); 7.3415 (5.08); 7.3244 (4.63); 7.3196 (4.47); 7.3043 (1.56); 7.299 (1.58); 7.2806 (2.03); 7.2747 (2.74); 7.2519 (1.45); 7.1994
(1.49); 7.1795 (3.11); 7.1614 (1.93); 6.936 (2.19); 6.9174 (3.63); 6.8989 (1.79); 6.8126 (4.03); 6.7941 ; 6.5851 (0.63); 6.5692
(0.59); 5.2851 (0.87); 5.2712 (1.94); 5.2526 (2.07); 5.238 (0.95); 4.3128 (0.7); 4.296 (1.79); 4.2741 (2.81); 4.253 (1.76); 4.2464
303 3,94
(2.03); 4.2239 (0.71); 3.9767 ; 3.968 (2.61); 3.3189 7); 3.2442 (2.16); 3.2141 (4.55); 3.1853 (2.46); 2.959 (1.92); 2.9418
(6.23); 2.9307 (3.17); 2.9237 ; 2.9044 (1.79); 2.8953 (1.74); 2.6699 (3.71); 2.5052 (502.23); 2.5009 (661.81); 2.4966 (520.68);
2.3275 (3.85); 2.266 (0.88); 2.2232 (1.38); 2.2135 (1.48); 2.2008 (1.46); 2.1924 (1.27); 2.0867 ; 2.0741 (1.82); 1.2862 (0.38);
1.2687 (0.48); 1.1687 (2.99); 1.1489 (14.24); 1.1439 (16); 1.1337 ); 1.1285 (15.3); 0.9796 (0.37); 0.1461 (0.77); -0.0001
(185.99); -0.1498 (0.83)
1H-NMR(399,9532 MHz, DMSO): δ= 9.1774 (0.67); 9.1576 (0.76); 8.5944 (2.4); 8.2724 (1.07); 8.2562 (1.18); 7.9525 (2.49); 7.7608
(0.4); 7.7376 (0.43); 7.7214 (0.76); 7.705 (2.49); 7.689 (1.82); 7.6851 (2.8); 7.6687 (1.86); 7.6537 (0.93); 7.5047 (0.32); 7.4854
(0.91); 7.4653 (1.16); 7.4546 (0.67); 7.4446 (1.44); 7.4361 (1.53); 7.4247 (0.93); 7.4155 (0.83); 7.3794 (1.2); 7.3566 (1.16); 7.3429
(0.88); 7.3272 (1.2); 7.3088 (0.58); 7.1857 (0.62); 7.1676 (1.13); 7.1481 (0.72); 6.9174 (0.63); 6.8992 (0.95); 6.8804 (0.48); 6.8023
304 4,03
(1.65); 6.7815 (1.43); 5.2499 (0.69); 5.2313 (0.63); 4.2592 (0.98); 4.2328 (0.72); 3.9863 (0.92); 3.3191 (221.03); 3.2639 (0.83);
3.2244 (0.64); 3.1788 (0.44); 2.9416 (2.82); 2.9215 (1.53); 2.8905 (16); 2.7311 (14.48); 2.6702 (3.3); 2.5232 (7.65); 2.5054 (445.22);
2.5012 (567.66); 2.497 (406.38); 2.3321 (2.56); 2.3276 (3.26); 2.2056 (0.52); 2.1956 ; 2.1834 (0.61); 2.0737 (0.9); 1.1689 (1.1);
1.1501 (5.7); 1.135 (5.9); 0.1463 ; 0.0077 (6.72); -0.0003 (158.9); -0.1492 (0.77)
1H-NMR(399,9532 MHz, DMSO): δ= 9.0348 ; 9.027 (1.53); 9.0145 (1.71); 8.5999 (5.17); 8.5952 (4.9); 8.3156 (0.56); 8.2763
(2.51); 8.2726 (2.47); 8.2556 (2.81); 8.2518 (2.69); 7.761 (0.83); 7.7408 (1.05); 7.7366 (1.17); 7.7204 (1.9); 7.7118 (3.55); 7.7079
(3.89); 7.7027 ; 7.6918 (4.33); 7.6878 ; 7.6822 (4.39); 7.6687 ; 7.6652 (4.79); 7.651 (2.14); 7.505 (0.9); 7.4854
(1.99); 7.4656 (2.95); 7.4594 ; 7.4449 (3.55); 7.4401 (3.42); 7.4255 (3.77); 7.4152 (3.13); 7.3825 (1.69); 7.3796 (1.25); 7.3635
(1.11); 7.3418 (1.95); 7.3288 (2.47); 7.3136 (1.38); 7.2798 (1.9); 7.2633 (3.48); 7.2506 (1.55); 7.2324 (3.2); 7.2181 (3.48); 7.2031
(2.13); 7.1855 (0.81); 7.1649 (0.41); 7.1441 (0.33); 6.5786 (0.32); 5.5633 (0.47); 5.5512 (0.67); 5.5336 (1.2); 5.5215 (1.33); 5.5153
305 4,13 (1.19); 3.9808 (2.15); 3.6332 ; 3.3942 ; 3.3649 (0.63); 3.3197 (538.15); 3.2493 (2.06); 3.221 (1.81); 3.1926 (1); 3.1655
(0.46); 3.0162 (0.77); 2.9635 (3.49); 2.9414 (4.71); 2.9076 (2.72); 2.8901 (1.88); 2.8843 (2.04); 2.8632 (1.51); 2.8439 (1.23); 2.8236
(0.74); 2.761 (0.33); 2.7302 (1.28); 2.7155 (0.39); 2.6747 (4.3); 2.67 (5.87); 2.6656 (4.46); 2.6168 (0.41); 2.5905 (0.52); 2.5232
(16.08); 2.5054 (777.81); 2.501 (1009.77); 2.4966 (729.53); 2.4266 (0.57); 2.3322 (4.4); 2.3277 (5.87); 2.3234 (4.4); 2.2742 (0.35);
2.2675 ; 2.2222 (0.32); 2.1718 (0.36); 2.105 (1.65); 2.0945 (1.09); 2.0739 (3); 1.9705 (0.53); 1.9506 (1.22); 1.9296 (1.19);
1.919 (1.2); 1.8967 ; 1.8764 (0.43); 1.2914 (0.37); 1.2694 (0.4); 1.1687 (2.59); 1.1444 (16); 1.1291 (15.53); 1.0966 (0.51);
0.9654 (0.39); 0.1461 ; 0.0078 (11.48); -0.0002 (299.28); -0.0082 (14.69); -0.1498 (1.31)
1H-NMR(399,9532 MHz, DMSO): δ= 9.0457 ; 9.0244 (2.21); 8.7059 (8.46); 8.3157 ; 8.2677 (2.18); 8.2494 (2.31); 8.0868
(0.34); 7.8391 (2.16); 7.8242 (2.96); 7.7196 (2.12); 7.6988 (2.55); 7.6804 (1.63); 7.4555 (1.75); 7.4412 (2.02); 7.3429 ; 7.3267
(3.62); 7.3056 (1.37); 7.2952 (1.61); 7.2766 (4); 7.26 (2.09); 7.2539 (1.54); 7.2464 (3.22); 7.2405 (3.62); 7.2316 (3.27); 7.2236
; 7.2048 (0.59); 7.1689 (0.57); 7.1519 (0.6); 7.1375 (0.42); 6.5782 (0.53); 5.5813 (0.59); 5.5623 (1.71); 5.5425 (1.78); 5.5244
(0.59); 3.9738 (1.83); 3.3197 9); 3.2386 (1.55); 3.2294 (1.7); 3.2119 (1.9); 3.2003 (1.93); 3.0346 (0.53); 3.0265 (0.64); 3.0133
306 4,03
(0.66); 2.9954 (1.02); 2.9859 (1.13); 2.9726 (3.04); 2.9417 (5.18); 2.917 ; 2.897 (1.7); 2.8769 (1.23); 2.8572 (0.9); 2.8366
(0.65); 2.7309 (0.37); 2.6701 (3.8); 2.5751 (0.52); 2.5672 ; 2.5566 (1); 2.5452 (1.54); 2.5053 (506.49); 2.501 (657.35); 2.4967
(480.65); 2.355 (0.43); 2.3278 (3.92); 2.2456 (0.33); 2.2001 (0.4); 2.1674 (0.46); 2.0952 (0.44); 2.074 (1.44); 1.9927 (0.53); 1.9724
(1.13); 1.9617 (0.71); 1.9517 (1.18); 1.9397 (1.1); 1.9195 (1.05); 1.8986 (0.43); 1.2999 (0.38); 1.2692 (0.54); 1.1689 (3.6); 1.145
(16); 1.1296 (15.96); 1.1004 (0.93); 0.9694 (0.35); 0.1465 (0.88); 0.0077 (7.81); -0.0003 (197.85); -0.1495 (0.91)
LC-MS (Method L3): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.58 (s, 1H), 8.19 (dd, J = 8.5, 1.4 Hz, 1H), 7.74 (dd, J = 7.1, 1.4 Hz, 1H),
307 4.12 min; m/z = 501/503
7.63 (dd, J = 8.5, 7.1 Hz, 1H), 7.44 (d, J = 8.2 Hz, 1H), 7.40 – 7.31 (m, 2H), 7.24 – 7.13 (m, 2H), 6.97 – 6.88 (m, 1H), 6.
(M+1)+
LC-MS (Method L3): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.63 (s, 1H), 8.21 (dd, J = 8.5, 1.3 Hz, 1H), 7.78 (dd, J = 7.1, 1.3 Hz, 1H),
308 4.61 min; m/z = 535/537
7.63 (s, 3H), 7.37 (d, J = 7.6 Hz, 1H), 7.22 – 7.13 (m, 1H), 6.97 – 6.90 (m, 1H), 6.80 (dd, J = 8.2, 0.9 Hz, 1H), 5.30 – 5.
(M+1)+
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 7.9 Hz, 1H), 8.49 (s, 1H), 8.31 (d, J = 9.4 Hz, 1H), 7.67 – 7.60 (m, 2H), 7.44 – 7.31 (m,
3.08 min, m/z = 564 (M+H)+ 2H), 7.25 – 7.11 (m, 2H), 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.2 Hz, 1H), 5.23 (q, J = 6.0 Hz, 1H), 4.31 – 4.18 (m, 2H),
LC-MS (Method L2): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.20 (d, J = 8.1 Hz, 1H), 8.71 (s, 1H), 8.46 (d, J = 8.9 Hz, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.70 (t, J =
310 3.26 min, m/z = 564/566 (Cl2
1.9 Hz, 1H), 7.40 – 7.30 (m, 3H), 7.20 – 7.13 (m, 1H), 6.95 – 6.88 (m, 1H), 6.82 – 6.76 (m, 1H), 5.28 – 5.20 (m, 1H), 4.32
pattern) (M+H)+
LC-MS (Method L3): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.61 (s, 1H), 8.17 (dd, J = 8.5, 1.4 Hz, 1H), 7.72 (dd, J = 7.1, 1.4 Hz, 1H),
311 4.51 min; m/z = 501/503
7.67 – 7.58 (m, 2H), 7.51 (dd, J = 8.3, 2.1 Hz, 1H), 7.37 (d, J = 6.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.21 – 7.12 (m, 1H
(M+1)+
LC-MS (Method L3): Rt = 1H-NMR (400 MHz, 6) δ 9.09 (d, J = 8.2 Hz, 1H), 8.57 (s, 1H), 8.15 (dd, J = 8.3, 1.6 Hz, 1H), 7.67 – 7.56 (m, 2H), 7.36 (d, J
4.72 min; m/z = 453 (M+1)+ = 7.5 Hz, 1H), 7.21 – 7.10 (m, 2H), 6.96 – 6.89 (m, 1H), 6.83 – 6.77 (m, 1H), 6.75 – 6.68 (m, 2H), 6.58 – 6.52 (m, 1H), 5.6
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.32 (m, 1H), 7.81 – 7.68 (m, 2H), 7.58 – 7.47 (m, 1H), 7.37
3.43 min; m/z = 502 (M+H)+. (d, J = 7.1 Hz, 1H), 7.25 – 7.12 (m, 3H), 6.92 (m, 1H), 6.82 – 6.76 (m, 1H), 5.26 (q, J = 5.7 Hz, 1H), 4.26 (m, 2H), 3.88 (t,
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.23 (dd, J = 8.1, 4.6 Hz, 1H), 8.69 (d, J = 4.0 Hz, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.01 (d, J = 9.0 Hz,
4.05 min, m/z = 602 (M+H)+ 1H), 7.74 (dd, J = 8.1, 1.4 Hz, 1H), 7.56 – 7.41 (m, 1H), 7.40 – 7.23 (m, 2H), 7.17 (t, J = 7.7 Hz, 1H), 6.99 – 6.86 (m, 1
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.14 (dd, J = 8.1, 4.3 Hz, 1H), 8.60 (d, J = 2.5 Hz, 1H), 8.45 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 9.1 Hz,
3.80 min, m/z = 560 (M+H)+ 1H), 7.72 (dd, J = 8.1, 1.5 Hz, 1H), 7.48 – 7.40 (m, 1H), 7.37 – 7.27 (m, 2H), 7.15 (t, J = 7.7 Hz, 1H), 6.93 – 6.87 (m, 1
LC-MS d L3): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 8.1 Hz, 1H), 8.65 (s, 1H), 8.20 (d, J = 2.4 Hz, 1H), 7.87 (d, J = 2.4 Hz, 1H), 7.67 (s, 3H),
316 4.65 min, m/z = 526/528
7.36 (d, J = 6.7 Hz, 1H), 7.21 – 7.14 (m, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.80 (dd, J = 8.2, 1.1 Hz, 1H), 5.28 – 5.2
(M+H)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.21), -0.008 (16.00), 0.008 (10.22), 0.146 (1.17), 1.679 (1.28), 1.768 (1.70), 2.062
LC-MS (Method L6): Rt = , 2.328 (2.24), 2.367 (1.03), 2.524 (9.61), 2.671 (2.06), 2.711 (1.03), 3.648 (2.70), 3.664 (3.87), 3.681 (2.16), 3.818 (1.95),
317 1.40 min; MS (ESIpos): m/z = 3.833 (2.52), 3.851 , 4.252 (2.94), 4.451 (2.59), 5.176 (1.63), 5.755 (3.23), 6.818 (1.81), 6.837 (1.70), 6.894 (1.31), 7.193
534 [M+H]+ (1.60), 7.294 (1.38), 7.620 (3.48), 7.628 (4.43), 7.672 (1.77), 7.692 , 7.833 (2.98), 7.865 (1.63), 7.970 (6.14), 8.217 (1.67),
8.234 (1.67), 8.477 (2.98), 8.881 (10.47), 9.374 (0.85).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.83), -0.008 (6.59), 0.146 (0.79), 1.156 (0.87), 1.175 (1.80), 1.192 (0.87), 1.235
(0.41), 1.660 (1.14), 1.679 (1.24), 1.690 (1.49), 1.710 (1.37), 1.903 (1.53), 1.988 (3.52), 1.999 (1.41), 2.012 (2.20), 2.028 (2.14),
2.048 (1.84), 2.058 (1.57), 2.165 (1.18), 2.181 (1.02), 2.197 (0.75), 2.327 , 2.366 (0.85), 2.393 (1.28), 2.411 (1.60), 2.428
(1.39), 2.669 (1.26), 2.709 (0.81), 3.162 , 3.175 (2.69), 3.381 (0.77), 3.408 (1.45), 3.421 , 3.440 (1.20), 3.467 (1.26),
LC-MS (Method L1): Rt =
3.483 (3.03), 3.494 (2.47), 3.510 (2.92), 3.528 (1.91), 3.676 , 3.697 (2.53), 3.716 (2.92), 3.724 (2.72), 3.742 (3.19), 3.768
318 0.81 min; MS (ESIpos): m/z =
, 4.020 (0.71), 4.038 , 4.073 (0.66), 4.087 (0.68), 4.172 (0.56), 4.254 , 4.264 (2.90), 4.717 (2.13), 4.729 (4.29),
548 [M+H]+
4.742 , 5.193 (0.81), 5.207 (1.74), 5.226 (1.76), 5.240 (0.87), 5.754 (0.50), 6.777 (3.46), 6.797 (3.81), 6.896 (1.66), 6.913
(3.44), 6.931 (1.97), 7.144 (1.84), 7.161 (2.90), 7.180 (1.41), 7.319 (2.94), 7.338 (2.71), 7.477 (2.16), 7.496 (2.96), 7.517 (2.65),
7.606 (4.71), 7.610 (5.82), 7.619 (16.00), 7.623 (9.06), 7.711 (3.79), 7.727 (3.19), 7.873 (0.50), 8.267 (3.11), 8.288 (2.92), 8.442
(11.23), 9.024 (3.13), 9.044 (3.03).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.062 (2.28), 2.197 (2.14), 2.209 , 2.218 (2.01), 2.327 (0.67), 2.670 (0.64), 3.876
LC-MS (Method L6): Rt = ), 4.213 (1.25), 4.234 (3.18), 4.254 (4.91), 4.262 (4.94), 5.244 (2.95), 5.261 (2.87), 6.776 , 6.796 (4.81), 6.893 (2.44),
319 1.94 min; MS (ESIpos): m/z = 6.911 (4.65), 6.930 (2.84), 7.142 (2.94), 7.161 (4.44), 7.179 (2.33), 7.351 (7.88), 7.369 (5.89), 7.391 (2.42), 7.416 (5.69), 7.423
500 [M+H]+ (5.81), 7.435 (5.30), 7.454 (2.26), 7.537 (3.95), 7.553 (3.04), 7.629 (3.41), 7.645 (5.92), 7.671 , 7.691 (4.59), 7.709 (2.20),
8.265 (4.40), 8.285 (4.07), 8.575 (9.62), 9.149 (3.43), 9.168 (3.26).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.006 (0.66), 0.006 (0.45), 0.992 (6.88), 1.006 (14.64), 1.020 (7.28), 1.175 (0.69), 1.914
(0.43), 1.921 (0.59), 1.928 (1.00), 1.935 (0.80), 1.941 (0.98), 1.949 (0.81), 1.963 (0.80), 1.975 (1.05), 1.988 (2.98), 1.999 (2.31),
2.015 (2.16), 2.027 , 2.044 (1.11), 2.050 (0.91), 2.056 (0.64), 2.169 (0.46), 2.176 , 2.186 (0.98), 2.196 (1.00), 2.204
, 2.214 (0.73), 2.221 (0.48), 2.363 (0.83), 2.379 (0.99), 2.392 (0.95), 2.407 (0.54), 2.519 (0.54), 3.335 (0.80), 3.347 (1.08),
3.351 (1.20), 3.361 (1.13), 3.375 (0.71), 3.865 (0.61), 3.878 (1.35), 3.895 (1.41), 3.903 (1.08), 3.911 , 3.917 (0.96), 3.925
LC-MS (Method L1): Rt =
(2.97), 3.936 (3.39), 3.939 (3.31), 3.950 (2.96), 3.957 (0.88), 3.964 , 3.972 (0.69), 4.173 , 4.201 , 4.206 (0.61),
320 1.27 min; MS (ESIpos): m/z =
4.223 (1.57), 4.229 (1.11), 4.240 , 4.246 (1.02), 4.259 (1.03), 4.266 (1.36), 4.272 (1.21), 4.279 (1.31), 4.288 (0.64), 4.294
590 [M+H]+
(0.66), 4.301 (0.49), 4.604 (1.49), 4.615 (1.69), 4.621 (1.65), 4.631 (1.40), 5.243 , 5.254 (1.44), 5.270 , 5.281 (0.66),
.754 (0.82), 6.792 (2.76), 6.807 (2.92), 6.809 (2.90), 6.925 (1.36), 6.927 (1.41), 6.940 (2.72), 6.942 (2.70), 6.955 (1.55), 6.957
(1.49), 7.168 (1.42), 7.171 (1.43), 7.185 (2.32), 7.199 (1.13), 7.201 (1.08), 7.397 (2.28), 7.411 (2.13), 7.636 (4.40), 7.639 (7.81),
7.642 (16.00), 7.645 (6.46), 7.653 (2.33), 7.667 (2.83), 7.670 (2.89), 7.684 (2.31), 7.725 , 7.729 (0.54), 7.819 (2.92), 7.822
(3.03), 7.834 (2.48), 7.836 (2.40), 8.343 (2.59), 8.345 (2.59), 8.360 (2.42), 8.362 (2.31), 8.680 (9.87), 9.196 (2.58), 9.212 (2.50).
1H-NMR(399,953 MHz, CDCl3): δ= 9.1126 (4.72); 9.0958 (4.88); 9.0618 (1.78); 9.0408 (2.05); 8.1159 (0.51); 8.1073 (0.56); 8.0994
(0.58); 8.0917 (0.65); 8.0616 (0.48); 8.0511 (0.51); 8.0462 (0.52); 8.0366 (0.54); 7.9006 (1.45); 7.881 (1.8); 7.8347 (1.41); 7.8147
; 7.7661 (4.49); 7.761 (4.21); 7.7476 (6.54); 7.7434 (5.71); 7.7362 (3.9); 7.7155 (2.95); 7.6982 (1.01); 7.5821 (4.98); 7.5623
(5.73); 7.52 (0.37); 7.5044 (1.22); 7.4823 ; 7.3467 (2.17); 7.3277 (5.49); 7.3079 (3.8); 7.2837 (3.47); 7.2612 (26.99); 7.2424
(6.4); 7.2359 (6.6); 7.2239 (5.17); 7.2163 (7.07); 7.1926 (3.1); 7.1696 (0.93); 6.9454 (1.11); 6.9262 (1.9); 6.9079 (0.91); 6.8815
(1.42); 6.8676 ; 6.847 (7.37); 6.8332 (1.46); 6.8255 (2.03); 6.7513 (0.44); 6.7294 (0.44); 6.6499 (0.51); 6.6309 (0.48); 5.463
321 3,37 (0.52); 5.4511 (1.1); 5.4396 (1.55); 5.4277 (2.06); 5.4166 (1.59); 5.4055 (1.17); 5.3934 (0.57); 5.3772 (0.45); 5.3618 (0.93); 5.3447
; 5.3304 (0.42); 5.2987 (1.1); 4.345 (1.6); 4.327 (2.15); 4.3161 (2.64); 4.2918 (0.9); 4.284 (0.68); 4.2127 (0.88); 4.189 (2.02);
4.1633 (2.43); 4.1436 (2.4); 4.1261 (3.47); 4.1083 (3.64); 4.0904 (1.16); 3.2611 (13.51); 3.0936 (5.9); 3.0503 (16); 3.0032 (13.51);
2.9661 (13.47); 2.9245 (13.29); 2.3901 ; 2.38 (0.86); 2.3661 (1.02); 2.3536 (1.63); 2.3427 ; 2.3298 (1.66); 2.316 ;
2.3065 (1.38); 2.2921 (0.68); 2.28 (0.49); 2.2702 (0.36); 2.1215 (1.79); 2.1092 (1.54); 2.1028 (1.49); 2.0868 (2); 2.0744 (1.46);
2.0598 (0.73); 2.041 (13.3); 1.5769 (18.97); 1.3654 ; 1.3479 (0.92); 1.3301 (0.51); 1.2747 (3.51); 1.2568 (7.17); 1.239 (3.48); -
0.0003 (15.15)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.57), -0.008 (16.00), 0.008 ), 0.146 (1.64), 1.049 (0.50), 2.087 (0.63), 2.327
LC-MS (Method L6): Rt = (3.21), 2.366 (2.46), 2.523 (10.58), 2.669 (3.09), 2.710 (2.46), 3.611 , 3.879 (3.72), 4.269 (1.01), 5.259 (0.69), 6.787 (1.26),
322 2.26 min; MS (ESIpos): m/z = 6.807 (1.51), 6.915 (0.76), 6.932 (1.39), 6.950 (0.76), 7.153 (0.76), 7.174 (1.13), 7.374 (1.20), 7.391 (1.89), 7.410 (1.26), 7.583
550 [M+H]+ (1.70), 7.596 (2.08), 7.615 (1.70), 7.627 , 7.687 (0.94), 7.706 (1.26), 7.726 (1.32), 7.806 (1.45), 7.822 (1.32), 8.270 ,
8.291 (1.20), 8.660 (4.66), 9.158 (1.20), 9.180 (1.13).
LC-MS (Method L3): Rt =
1H-NMR (400 MHz, 6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.19 (dd, J = 8.5, 1.3 Hz, 1H), 7.73 (dd, J = 7.1, 1.3 Hz, 1H),
323 2.90 min; m/z = 543/545
7.62 (dd, J = 8.4, 7.2 Hz, 1H), 7.36 (d, J = 7.0 Hz, 1H), 7.22 – 7.12 (m, 1H), 7.09 – 6.97 (m, 3H), 6.97 – 6.87 (m, 1H), 6.
(M+1)+
LC-MS (Method L2): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.51 (s, 1H), 8.17 (dd, J = 8.2, 1.7 Hz, 1H), 7.67 – 7.50 (m, 2H), 7.34 (d, J
324 2.91 min; m/z = 501/503
= 7.1 Hz, 1H), 7.23 – 7.06 (m, 2H), 6.97 – 6.86 (m, 1H), 6.86 – 6.67 (m, 3H), 5.33 – 5.18 (m, 1H), 4.37 – 4.15 (m, 2H), 3.0
(M+1)+
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.63 (s, 1H), 8.20 (dd, J = 8.5, 1.3 Hz, 1H), 7.77 (dd, J = 7.1, 1.3 Hz, 1H),
LC-MS (Method L2): Rt =
7.63 (dd, J = 8.4, 7.2 Hz, 1H), 7.56 – 7.48 (m, 1H), 7.43 (dd, J = 13.3, 2.0 Hz, 1H), 7.37 (d, J = 6.9 Hz, 1H), 7.23 – 7.13 (m, 1H), 6.98
325 3.19 min; m/z = 519/521
– 6.89 (m, 1H), 6.80 (dd, J = 8.2, 0.9 Hz, 1H), 5.31 – 5.20 (m, 1H), 4.35 – 4.18 (m, 2H), 3.06 (s, 6H), 2.86 (d, J = 2.3 Hz, 6H), 2.28 –
(M+1)+
2.13 (m, 1H), 2.13 – 1.99 (m, 1H).
LC-MS (Method L2): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.01 (d, J = 7.1 Hz, 1H), 8.42 (d, J = 1.6 Hz, 1H), 8.27 (d, J = 9.4 Hz, 1H), 7.66 – 7.55 (m, 2H), 7.43
326 2.86 min, m/z = 522 (Cl2
– 7.30 (m, 2H), 7.23 – 7.12 (m, 2H), 6.89 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.21 (q, J = 5.9 Hz, 1H), 4.30 – 4
pattern) (M+H)+
LC-MS (Method L2): Rt =
1H-NMR (400 MHz, DMSO-d6) δ 9.01 (d, J = 8.2 Hz, 1H), 8.49 (s, 1H), 8.25 (d, J = 9.5 Hz, 1H), 7.62 – 7.54 (m, 2H), 7.34 (d, J = 7.0
327 2.96 min, m/z = 522 (Cl2
Hz, 1H), 7.30 (d, J = 1.9 Hz, 2H), 7.19 – 7.12 (m, 1H), 6.95 – 6.87 (m, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.27 – 5.18 (m, 1H),
pattern) (M+H)+
1H-NMR(399,9532 MHz, DMSO): δ= 9.1516 (1.99); 9.1309 (2.07); 8.6957 (7.38); 8.3158 (0.74); 8.1756 (2.08); 8.1554 (2.33); 7.8284
(2.07); 7.8125 (2.84); 7.6916 (1.99); 7.6725 (2.46); 7.6445 (16); 7.5625 (0.42); 7.5064 (0.53); 7.4855 (0.5); 7.4369 (0.53); 7.3832
(2.2); 7.3653 (2.36); 7.1937 (1.06); 7.1767 (2.08); 7.1581 (1.32); 6.948 (1.5); 6.9294 ; 6.9118 (1.23); 6.8712 (0.85); 6.8097
(2.74); 6.79 (2.61); 6.6398 (0.41); 6.5791 (0.42); 5.2663 (0.57); 5.253 (1.33); 5.2338 (1.23); 5.2205 (0.6); 4.3072 (0.46); 4.2867
328 3,3 (1.27); 4.2736 (2.25); 4.2461 (1.37); 4.2259 (0.44); 3.5335 (1.43); 3.5183 ; 3.503 (2.16); 3.374 (2.24); 3.3585 (3.93); 3.3413
(2.21); 3.32 (177.93); 3.1924 (2.23); 3.1748 (4.03); 3.1575 (2.36); 3.0637 (15.58); 2.6707 (3.2); 2.5016 (591.34); 2.3283 (3.36);
2.2181 (0.84); 2.2067 (0.96); 2.1977 (0.96); 2.1833 (1.83); 2.1627 (2.11); 2.1422 (4.09); 2.1222 (2.63); 2.0859 (5); 1.7864 (0.63);
1.7681 (1.98); 1.7497 (2.66); 1.7307 (1.77); 1.3554 (7.89); 1.2706 (0.49); 1.2335 (0.35); 1.1856 (0.35); 1.1692 ; 0.1462 (1.19);
0 (271.12); -0.1493 (1.3)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.68), 0.008 (0.56), 1.686 (0.43), 1.705 (0.40), 1.908 (16.00), 1.988 (0.70), 1.999
, 2.012 (0.70), 2.030 (0.70), 2.047 (0.66), 2.057 , 2.409 (0.49), 2.523 , 3.409 (0.50), 3.478 (0.83), 3.496 (0.94),
LC-MS d L1): Rt = 3.503 (0.93), 3.520 (0.72), 3.689 (0.90), 3.707 (1.31), 3.722 (1.18), 3.740 (0.74), 3.746 , 3.764 , 4.234 (0.64), 4.242
329 0.80 min; MS (ESIpos): m/z = (0.95), 4.254 (1.33), 4.730 , 5.206 (0.55), 5.225 (0.56), 6.778 (1.01), 6.799 (1.13), 6.895 (0.51), 6.912 (1.07), 6.931 (0.64),
548 [M+H]+ 7.142 , 7.145 , 7.163 (0.88), 7.180 (0.43), 7.184 (0.43), 7.322 (0.91), 7.341 (0.85), 7.478 (0.75), 7.496 (0.99), 7.499
(0.92), 7.517 (0.89), 7.601 (0.47), 7.606 (1.15), 7.610 (1.62), 7.618 (4.75), 7.622 (2.49), 7.709 (1.15), 7.712 (1.18), 7.727 (1.01),
7.729 (0.98), 8.139 (0.93), 8.258 (0.90), 8.261 (0.90), 8.280 (0.91), 8.440 (3.42), 9.025 (1.00), 9.046 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.17), 0.008 (0.88), 2.021 , 2.030 (0.47), 2.036 (0.52), 2.073 (1.14), 2.169
(0.52), 2.181 (0.50), 2.191 (0.48), 2.523 (0.76), 3.082 (16.00), 4.220 (0.74), 4.226 (0.64), 4.240 , 4.249 (1.20), 4.265 (0.72),
LC-MS (Method L6): Rt = 5.213 (0.69), 5.229 (0.68), 5.754 (1.51), 6.772 , 6.792 (1.55), 6.878 (0.73), 6.896 (1.52), 6.915 (0.91), 7.134 (0.75), 7.138
330 2.01 min; MS (ESIpos): m/z = , 7.155 (1.26), 7.173 (0.63), 7.176 (0.61), 7.322 (1.30), 7.337 (1.39), 7.352 (0.91), 7.356 (0.87), 7.363 (0.63), 7.366 (0.62),
510 [M+H]+ 7.382 (0.84), 7.386 (0.81), 7.446 (0.76), 7.459 (0.83), 7.466 (1.28), 7.479 (1.28), 7.485 (0.72), 7.499 (0.63), 7.592 (1.03), 7.615
, 7.638 (1.08), 7.726 (1.39), 7.730 (1.40), 7.746 (1.23), 7.750 (1.17), 8.310 (0.92), 8.325 (1.02), 8.333 (0.99), 8.349 ,
8.523 (2.23), 8.527 (2.23), 9.057 (0.86), 9.061 (0.87), 9.077 (0.86).
1H-NMR(399,9532 MHz, DMSO): δ= 9.1403 (1.94); 9.1288 (2); 9.1208 (2.32); 9.1103 (1.85); 8.6012 ); 8.4715 (0.58); 8.3155
(1.57); 8.2143 ; 8.1975 (2.56); 8.1729 ; 7.7323 (2.07); 7.7127 ; 7.6894 (10.46); 7.6737 (1.95); 7.4635 ; 7.4521
(1.74); 7.4433 (2.94); 7.4332 (2.77); 7.4235 ; 7.4143 (1.65); 7.3824 (1.86); 7.3618 (4.63); 7.3428 ; 7.3225 (1.63); 7.1895
(1.81); 7.171 (3.64); 7.1535 (2.27); 6.9433 (2.6); 6.9255 (4.32); 6.9084 (2.02); 6.8059 ; 6.7848 (4.45); 6.5782 (0.9); 5.2488
331 3,14 (1.97); 5.237 (2); 4.725 (1.91); 4.697 (7.04); 4.6722 (5.48); 4.6575 (5.6); 4.5955 (1.22); 4.5844 (1.61); 4.2921 (2.17); 4.2752 (3.94);
4.2675 (3.64); 4.2552 (2.23); 4.2471 (2.41); 4.2281 (0.89); 3.3183 (319.34); 3.2701 (0.87); 3.2496 (0.61); 3.1747 (0.71); 3.081 (16);
3.0759 (15.54); 2.9497 (1.08); 2.6703 (8.96); 2.5893 (0.63); 2.5051 (1239.6); 2.5012 24); 2.4971 (1204.24); 2.3276 (9.3);
2.2832 (0.88); 2.2475 ; 2.2286 (1.72); 2.2205 ; 2.1313 (0.96); 2.074 (5.92); 2.0168 (0.96); 1.2694 (0.87); 1.169 (4.47);
1.0034 (0.71); 0.9887 (0.75); 0.1463 (2.93); -0.0001 (642.47); -0.0792 (0.67); -0.1497 (3.13); -3.3083 (0.55)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.57), 0.146 (0.52), 2.063 (1.66), 2.099 (1.25), 2.118 (1.43), 2.130 (1.93), 2.149
(2.41), 2.167 (1.95), 2.220 (1.77), 2.233 (1.79), 2.251 (1.61), 2.263 (1.00), 2.327 (1.50), 2.366 (0.82), 2.669 , 2.710 (0.73),
LC-MS (Method L1): Rt =
3.195 (1.82), 3.214 (2.75), 3.232 (2.11), 3.670 (1.75), 3.682 , 3.727 (1.27), 3.745 (3.54), 3.768 (4.92), 3.788 (5.88), 3.807
332 0.84 min; MS (ESIpos): m/z =
(3.11), 3.831 , 4.241 (3.47), 4.252 (4.68), 5.212 (2.04), 5.232 (2.04), 6.779 (3.36), 6.799 (3.81), 6.894 (1.72), 6.912 (3.65),
562 [M+H]+
6.931 (2.13), 7.147 (1.88), 7.164 (3.13), 7.182 (1.54), 7.329 (3.36), 7.347 (3.06), 7.522 (2.18), 7.542 (3.36), 7.562 (2.63), 7.623
(16.00), 7.742 (3.99), 7.759 (3.43), 8.257 (3.50), 8.277 (3.29), 8.501 (9.67), 9.095 (3.34), 9.115 (3.29), 12.559 (0.52).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 2.092 (0.76), 3.286 (3.16), 4.171 (16.00), 4.267 (1.78), 5.273 (1.01), 6.793 (1.51), 6.817
LC-MS (Method L6): Rt =
(1.83), 6.912 (0.84), 6.931 (1.63), 6.949 (1.01), 7.160 (0.88), 7.182 (1.36), 7.359 , 7.378 (1.33), 7.703 (1.10), 7.723 (1.64),
333 2:56 min; MS s): m/z =
7.741 (1.31), 7.843 (4.97), 7.859 (4.94), 7.903 , 7.917 (1.37), 8.294 (1.60), 8.297 (1.77), 8.315 (1.52), 8.816 (5.70), 9.194
497 [M+H]+
(1.47), 9.213 (1.36).
1H-NMR (500 MHz, DMSO-d6) delta [ppm]: -0.007 (4.15), 0.007 (3.67), 1.235 (1.26), 1.395 (7.56), 1.409 (16.00), 1.423 (7.72), 1.950
(1.18), 1.966 (1.28), 1.975 (1.34), 1.991 (1.30), 2.522 (1.98), 2.853 (1.24), 2.869 (1.51), 2.885 (1.92), 2.901 (0.85), 2.981 ,
2.989 (1.09), 2.999 (1.11), 3.006 , 3.013 , 3.286 (5.84), 4.352 , 4.354 (1.53), 4.366 (4.56), 4.368 (4.83), 4.380
LC-MS (Method L7): Rt =
(4.46), 4.383 (4.79), 4.394 (1.38), 4.396 (1.51), 5.533 (0.78), 5.549 (2.29), 5.564 (2.27), 5.580 (0.78), 5.754 (0.91), 7.227 (2.02),
334 2.60 min; MS (ESIpos): m/z =
7.231 (3.49), 7.238 (4.46), 7.245 (4.52), 7.249 (3.34), 7.260 (1.11), 7.278 (2.99), 7.290 (1.65), 7.294 (1.20), 7.400 (2.19), 7.406
477 [M+H]+
(2.33), 7.417 (2.00), 7.654 (2.35), 7.658 (5.35), 7.661 (4.98), 7.674 (15.77), 7.678 (10.55), 7.714 (2.52), 7.729 (3.39), 7.731 (3.32),
7.745 (2.97), 7.889 (3.47), 7.891 (3.80), 7.903 (3.01), 7.906 (3.03), 8.304 (3.32), 8.307 , 8.321 (3.16), 8.324 (3.16), 8.842
(11.93), 8.998 (2.83), 9.015 (2.77).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.09), 0.008 (1.03), 1.300 (13.37), 1.315 (15.22), 1.320 (15.14), 1.335 (13.44),
2.077 (1.40), 2.086 (1.14), 2.175 (0.96), 2.188 (1.01), 2.198 (1.11), 2.211 (0.97), 3.287 (1.40), 4.251 (1.94), 4.260 (2.90), 4.271
, 4.279 , 4.285 (1.96), 4.831 (0.79), 4.847 (2.11), 4.862 (2.86), 4.877 (2.07), 4.892 (0.76), 5.271 (1.74), 5.291 (1.73),
LC-MS (Method L1): Rt =
.754 (1.60), 6.792 , 6.795 (3.21), 6.812 (3.38), 6.815 (3.52), 6.905 (1.65), 6.908 (1.68), 6.923 (3.35), 6.926 (3.31), 6.942
335 1.42 min; MS (ESIpos): m/z =
, 6.945 (1.96), 7.159 (1.66), 7.163 (1.75), 7.180 (2.64), 7.197 (1.36), 7.202 (1.34), 7.352 (2.66), 7.356 (2.66), 7.371 (2.57),
507 [M+H]+
7.375 (2.32), 7.648 (1.92), 7.653 (4.51), 7.658 (3.68), 7.680 (16.00), 7.685 (11.73), 7.701 (2.83), 7.719 (3.62), 7.722 (3.32), 7.740
(3.41), 7.880 (3.80), 7.884 , 7.898 (3.21), 7.902 (3.13), 8.304 (3.63), 8.308 (3.69), 8.325 (3.41), 8.329 (3.23), 8.844 (13.48),
9.131 (3.03), 9.152 (2.95).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.40), 0.008 (3.27), 1.234 (1.59), 1.255 (13.29), 1.270 (13.33), 1.324 (13.22),
1.339 (13.35), 1.958 (1.08), 1.976 (1.27), 1.988 (1.33), 2.008 (1.28), 2.517 (2.28), 2.849 (1.21), 2.869 (1.58), 2.889 (2.03), 2.908
LC-MS (Method L1): Rt = (0.90), 2.981 (1.12), 2.992 (1.19), 3.003 (1.21), 3.013 (1.12), 3.288 (2.34), 4.795 (0.80), 4.810 (2.09), 4.825 (2.87), 4.841 (2.06),
336 1.47 min; MS (ESIpos): m/z = 4.856 (0.77), 5.539 (2.27), 5.558 (2.27), 7.221 (2.05), 7.226 (3.83), 7.234 (4.60), 7.243 (5.51), 7.248 , 7.261 (1.41), 7.266
491 [M+H]+ (1.19), 7.275 , 7.289 , 7.297 (1.00), 7.402 (2.18), 7.409 (2.34), 7.423 (1.93), 7.651 (2.03), 7.656 (4.64), 7.661 (3.85),
7.682 (16.00), 7.687 ), 7.702 (2.80), 7.720 (3.59), 7.723 (3.36), 7.741 (3.39), 7.879 (3.80), 7.883 (4.13), 7.897 (3.21), 7.901
(3.15), 8.305 (3.55), 8.309 , 8.326 (3.40), 8.330 (3.18), 8.861 (12.80), 8.984 (2.98), 9.004 (2.89).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.13), 0.008 (3.33), 1.233 (0.81), 1.599 (1.35), 1.607 (1.77), 1.618 , 1.624
(2.67), 1.655 (1.41), 1.671 (1.41), 1.685 (1.17), 1.707 (0.97), 1.760 , 1.773 (2.47), 1.785 (3.62), 1.791 , 1.799 (3.24),
1.804 (3.14), 1.813 (3.40), 1.818 (3.25), 1.824 (2.52), 1.829 (2.47), 1.852 (1.86), 1.861 (1.79), 1.873 (1.75), 1.952 (1.31), 1.963
(0.89), 1.970 (1.48), 1.982 (1.57), 1.990 (0.88), 2.002 (1.52), 2.021 (0.70), 2.517 (2.37), 2.845 (1.39), 2.865 (1.83), 2.885 (2.35),
LC-MS (Method L1): Rt =
2.905 (1.05), 2.979 (1.28), 2.989 , 3.001 (1.41), 3.011 (1.32), 3.018 (0.95), 3.029 (0.85), 3.040 (0.83), 3.288 (1.16), 5.212
337 1.54 min; MS s): m/z =
, 5.218 (2.09), 5.224 (2.42), 5.229 (2.21), 5.236 (1.36), 5.518 (0.92), 5.537 , 5.556 , 5.575 (0.92), 5.754 (1.62),
517 [M+H]+
7.218 (2.33), 7.223 (4.35), 7.231 (4.99), 7.240 (6.10), 7.245 (4.34), 7.258 (1.57), 7.263 (1.32), 7.272 (3.57), 7.287 (1.82), 7.294
(1.20), 7.412 (2.53), 7.419 (2.76), 7.433 (2.33), 7.647 (1.83), 7.652 (4.58), 7.657 (3.89), 7.676 (16.00), 7.680 (11.73), 7.694 (2.99),
7.712 (3.95), 7.715 , 7.733 (3.62), 7.868 (4.03), 7.871 (4.39), 7.885 (3.41), 7.889 (3.40), 8.250 , 8.254 (4.05), 8.271
(3.65), 8.274 (3.52), 8.818 (13.85), 9.049 (3.54), 9.069 (3.47).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (1.69), 0.008 (1.48), 3.284 (16.00), 3.722 (1.56), 3.734 (2.60), 3.744 (1.75), 4.270
LC-MS (Method L6): Rt = (1.58), 4.419 (0.92), 4.428 (1.44), 4.431 (1.39), 4.437 (1.43), 4.439 (1.46), 4.448 (0.90), 6.794 , 6.797 (1.09), 6.814 (1.20),
338 2.62 min; MS (ESIpos): m/z = 6.817 , 6.921 (1.21), 6.924 (1.15), 6.940 (0.75), 7.181 (0.92), 7.352 (0.93), 7.372 (0.91), 7.658 , 7.662 (1.50), 7.676
523 [M+H]+ (5.94), 7.681 (3.69), 7.721 , 7.739 (1.31), 7.742 (1.17), 7.760 (1.24), 7.895 (1.40), 7.899 (1.44), 7.913 (1.18), 7.916 (1.10),
8.335 (1.30), 8.339 (1.31), 8.356 (1.25), 8.360 (1.14), 8.877 (4.74), 9.141 (1.07), 9.161 (1.04).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.97), -0.008 (8.24), 0.008 (7.67), 0.146 (1.01), 1.147 (0.93), 1.750 (1.59), 1.915
(1.63), 2.075 (1.10), 2.204 (0.97), 2.366 (1.45), 2.669 (0.79), 2.710 (1.37), 3.287 (6.79), 3.337 (2.25), 3.366 (1.90), 3.390 ,
LC-MS (Method L6): Rt = 3.865 (2.47), 3.895 , 4.253 (1.45), 4.282 (2.64), 4.748 , 4.758 (1.45), 5.272 (1.45), 5.292 (1.54), 6.795 (2.69), 6.798
339 2.54 min; MS (ESIpos): m/z = (2.87), 6.815 (2.91), 6.818 (3.13), 6.910 (1.41), 6.913 (1.37), 6.929 (2.78), 6.932 (2.82), 6.948 , 6.951 (1.72), 7.165 ,
549 [M+H]+ 7.169 (1.54), 7.189 (2.12), 7.208 (1.15), 7.387 (2.29), 7.407 (1.98), 7.652 (2.12), 7.657 (4.94), 7.661 (4.58), 7.678 (16.00), 7.683
(10.31), 7.725 (2.20), 7.742 (3.00), 7.746 (2.82), 7.764 (2.78), 7.894 (3.26), 7.898 (3.44), 7.912 , 7.916 , 8.366 (3.00),
8.370 (3.09), 8.387 (2.78), 8.391 (2.60), 8.852 (11.94), 9.170 (2.51), 9.191 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.233 (1.46), 2.060 (1.17), 2.072 (1.22), 2.096 (1.85), 2.106 (1.52), 2.180 (1.45), 2.200
(1.60), 2.216 (1.38), 2.232 (1.09), 2.710 , 3.289 (2.29), 3.770 (2.50), 3.782 (6.45), 3.794 (6.45), 3.807 (2.58), 4.251 (3.09),
4.260 (3.55), 4.268 (6.08), 4.280 (3.73), 4.310 (0.75), 4.322 (1.11), 4.337 , 4.348 , 4.359 (6.81), 4.370 (2.86), 4.385
LC-MS (Method L6): Rt =
(0.96), 5.066 , 5.079 , 5.093 (2.23), 5.263 (1.21), 5.277 (2.42), 5.296 , 5.311 (1.08), 5.753 (12.22), 6.792 (4.39),
340 2.35 min; MS (ESIpos): m/z =
6.812 (4.98), 6.902 (2.47), 6.920 (4.70), 6.939 (2.63), 7.160 (2.23), 7.179 , 7.198 (2.03), 7.349 (3.82), 7.366 (3.59), 7.603
509 [M+H]+
(0.66), 7.608 (0.74), 7.648 (2.33), 7.653 (5.18), 7.658 (5.13), 7.674 (16.00), 7.679 (12.12), 7.703 (2.84), 7.723 (4.62), 7.742 (3.57),
7.885 (3.87), 7.888 (4.97), 7.903 (3.20), 7.906 (3.94), 8.442 (3.94), 8.445 (4.43), 8.463 , 8.466 (4.03), 8.845 (14.44), 9.174
(4.04), 9.194 (3.96).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.356 (12.14), 1.405 (7.22), 1.423 (15.61), 1.441 (7.48), 2.073 (1.45), 2.082 (1.17), 2.091
(0.93), 2.183 (2.15), 2.192 (0.97), 2.203 (0.95), 3.568 (4.88), 4.247 (1.66), 4.256 (2.16), 4.268 (2.79), 4.274 (2.58), 4.283 (1.57),
4.359 (1.14), 4.366 (1.13), 4.377 (3.75), 4.383 (3.69), 4.394 (3.64), 4.401 (3.71), 4.412 (1.11), 4.418 (1.11), 5.274 (1.50), 5.294
LC-MS (Method L6): Rt =
(1.49), 6.793 (2.69), 6.796 (2.93), 6.814 (3.05), 6.817 (3.20), 6.871 (0.97), 6.908 (1.45), 6.911 (1.48), 6.927 (2.96), 6.930 (2.93),
341 2.64 min; MS (ESIpos): m/z =
6.946 (1.82), 6.949 (1.73), 7.160 (1.45), 7.165 (1.54), 7.182 (2.32), 7.199 (1.17), 7.203 , 7.352 (2.34), 7.372 (2.26), 7.376
493 [M+H]+
(2.03), 7.650 (1.93), 7.655 (4.49), 7.659 (4.77), 7.672 ), 7.677 (9.62), 7.709 (2.46), 7.727 (3.23), 7.730 (3.00), 7.748 (3.04),
7.888 (3.41), 7.891 (3.59), 7.905 (2.88), 7.909 (2.77), 8.301 (3.25), 8.305 (3.35), 8.322 (3.10), 8.326 (2.87), 8.833 (12.05), 9.137
(2.57), 9.158 (2.52).
LC-MS (Method L6): Rt =
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.951 (16.00), 1.175 (0.68), 1.783 , 1.802 (1.29), 1.820 , 1.988 (1.34), 4.409
342 3.11 min; MS (ESIpos): m/z =
(0.73), 4.414 (0.72), 7.655 (0.81), 7.659 (0.83), 7.670 (2.53), 7.675 (1.64), 7.720 (0.69), 7.878 (0.71), 8.816 (2.01).
533 [M+H]+
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.37), 0.008 (1.76), 1.147 (1.15), 1.926 (1.02), 1.944 (1.15), 1.957 (1.15), 1.976
(1.22), 2.366 (1.63), 2.710 (1.69), 2.838 (0.95), 2.858 (1.29), 2.878 (1.69), 2.956 (0.88), 2.966 (1.02), 2.979 (1.02), 2.987 (1.02),
LC-MS (Method L6): Rt = 3.289 (3.66), 5.382 (7.73), 5.386 (8.00), 5.415 , 5.565 (2.03), 5.584 (1.97), 7.132 (0.88), 7.150 , 7.169 , 7.204
343 2.84 min; MS (ESIpos): m/z = (1.97), 7.223 (4.00), 7.232 , 7.242 (1.97), 7.252 (1.29), 7.264 (3.53), 7.282 (1.69), 7.318 (2.24), 7.336 (4.81), 7.365 (1.76),
557 [M+H]+ 7.381 (2.98), 7.400 (2.92), 7.447 (1.15), 7.463 (1.76), 7.468 (1.97), 7.483 (2.10), 7.488 (1.29), 7.503 (1.08), 7.661 (1.56), 7.666
, 7.670 (4.95), 7.681 (16.00), 7.686 (9.15), 7.718 (2.51), 7.736 (3.19), 7.739 (3.12), 7.757 , 7.903 (3.39), 7.906 (3.80),
7.920 (2.92), 7.924 (2.98), 8.278 (3.12), 8.281 (3.46), 8.299 , 8.303 (2.98), 8.913 (11.73), 9.095 (2.71), 9.115 (2.71).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.235 (1.30), 1.935 (1.60), 1.954 , 1.965 (2.10), 1.986 (1.91), 2.005 (0.73), 2.672
(0.79), 2.711 (0.59), 2.843 (1.62), 2.863 (2.27), 2.884 (2.82), 2.904 (1.36), 2.969 (1.94), 2.982 (1.99), 5.450 (1.65), 5.478 (7.32),
LC-MS (Method L6): Rt =
.493 (7.42), 5.522 (1.77), 5.546 (1.27), 5.563 (3.23), 5.583 (3.15), 5.601 (1.18), 7.146 (1.70), 7.164 (4.06), 7.182 (3.27), 7.207
344 2.84 min; MS (ESIpos): m/z =
(2.49), 7.224 (4.59), 7.242 (2.89), 7.264 (6.36), 7.282 , 7.311 (1.84), 7.392 (5.56), 7.410 (6.38), 7.434 (2.03), 7.473 (1.31),
575 [M+H]+
7.495 (2.55), 7.518 (2.46), 7.540 (1.11), 7.665 (7.07), 7.680 (16.00), 7.706 (2.83), 7.724 (4.62), 7.744 (2.99), 7.898 (4.83), 7.916
, 8.213 , 8.234 (4.18), 8.918 , 9.128 (3.96), 9.147 (3.86).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.964 (0.76), 2.524 , 2.861 (0.81), 2.881 (1.06), 3.288 (1.25), 3.759 (16.00), 5.351
(4.36), 5.356 (4.34), 5.573 (1.21), 5.593 (1.19), 6.939 (1.06), 6.946 (1.14), 6.963 , 7.038 (1.56), 7.056 (4.26), 7.160 (1.59),
LC-MS (Method L6): Rt =
7.179 (1.19), 7.208 (0.94), 7.226 (1.85), 7.243 (1.17), 7.266 (2.21), 7.285 (1.11), 7.316 (1.26), 7.337 (1.99), 7.355 (1.09), 7.392
345 2.83 min; MS (ESIpos): m/z =
, 7.410 (1.52), 7.657 (1.23), 7.662 (2.51), 7.666 (2.55), 7.679 (7.30), 7.683 (4.89), 7.708 (1.19), 7.726 (1.75), 7.747 (1.41),
569 [M+H]+
7.892 (1.85), 7.895 (1.92), 7.910 (1.52), 7.913 (1.46), 8.273 (1.73), 8.277 (1.74), 8.294 (1.66), 8.298 (1.55), 8.899 (5.35), 9.092
(1.61), 9.113 (1.58).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.897 , 3.371 , 3.386 (1.01), 5.457 (1.45), 5.543 (1.27), 5.562 (1.29), 7.232
LC-MS (Method L6): Rt =
(1.04), 7.237 , 7.245 (2.18), 7.254 (2.72), 7.258 (2.05), 7.284 , 7.298 (0.86), 7.431 (1.08), 7.438 , 7.452 (1.00),
346 1.65 min; MS (ESIpos): m/z =
7.670 (16.00), 7.720 (1.27), 7.738 (1.69), 7.741 (1.59), 7.759 (1.49), 7.918 (1.80), 7.921 (1.89), 7.936 (1.57), 7.939 (1.51), 8.494
518 [M-HCl+H]+
(1.49), 8.515 (1.46), 8.867 (5.92), 9.235 (1.48), 9.255 (1.44).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.166 ), 2.055 (1.38), 2.069 (2.83), 2.084 (1.40), 2.873 (0.61), 2.889 , 3.108
LC-MS (METHOD L5): Rt = (11.26), 4.418 (0.63), 4.433 (1.14), 4.447 (0.94), 4.460 (1.14), 4.474 (0.60), 5.544 (0.93), 5.560 , 7.215 (1.08), 7.226 (1.40),
347 1.39 min; MS s): m/z = 7.230 (1.64), 7.243 (1.31), 7.257 (0.63), 7.273 (1.47), 7.287 (0.74), 7.417 (1.21), 7.432 (1.02), 7.647 (0.90), 7.651 (2.01), 7.654
549 [M+H]+ (1.86), 7.670 (4.81), 7.674 (4.24), 7.701 (0.83), 7.717 (1.39), 7.732 (0.97), 7.875 (1.18), 7.877 , 7.889 , 7.891 (1.21),
8.314 (1.14), 8.316 (1.40), 8.331 (1.09), 8.333 (1.27), 8.809 (3.64), 9.077 (1.18), 9.093 (1.15).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.235 (2.39), 1.331 , 1.554 (1.87), 1.570 (3.23), 1.583 (3.23), 1.587 (3.23), 1.810
(1.44), 1.948 (0.98), 1.967 (1.15), 1.978 (1.21), 1.998 (1.12), 2.327 (0.78), 2.366 (1.18), 2.391 (1.44), 2.410 (1.90), 2.429 (1.44),
2.523 (3.83), 2.670 (0.81), 2.710 (1.10), 2.849 (1.01), 2.868 (1.33), 2.889 (1.90), 2.976 (0.95), 2.987 , 2.999 (1.01), 3.008
LC-MS (Method L6): Rt =
(0.98), 3.563 (4.90), 4.171 (1.21), 4.188 (1.44), 4.194 (3.17), 4.212 , 4.218 (3.26), 4.236 (3.11), 4.241 (1.53), 4.260 ,
348 3.09 min; MS (ESIpos): m/z =
.535 (2.02), 5.554 (1.96), 7.214 (2.13), 7.226 (2.80), 7.230 (3.14), 7.243 (2.57), 7.247 (2.80), 7.261 (1.53), 7.265 (1.27), 7.275
531 [M+H]+
(3.06), 7.292 (1.38), 7.408 (2.42), 7.425 (1.96), 7.652 (1.99), 7.657 (4.73), 7.662 (5.19), 7.673 ), 7.678 (9.23), 7.714 (2.36),
7.732 (3.11), 7.735 (2.85), 7.753 (2.88), 7.882 (3.20), 7.885 , 7.900 (2.74), 7.903 (2.68), 8.304 (3.11), 8.308 (3.23), 8.325
(2.91), 8.329 (2.77), 8.812 (11.70), 9.046 (2.62), 9.066 (2.51).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.997 (1.88), 1.009 , 1.256 (13.03), 1.268 (13.05), 1.324 (13.05), 1.337 ), 1.963
, 1.978 (1.34), 1.987 (1.38), 2.004 (1.32), 2.514 (1.83), 2.523 (1.17), 2.852 (1.36), 2.868 (1.69), 2.884 (2.08), 2.900 (0.98),
2.986 (1.14), 2.995 (1.24), 3.004 (1.25), 3.012 (1.20), 3.018 (0.90), 3.027 (0.85), 4.801 (0.80), 4.813 (2.08), 4.825 (2.81), 4.837
LC-MS (METHOD L5): Rt =
(2.05), 4.850 (0.77), 5.526 (0.97), 5.541 (2.48), 5.557 (2.44), 5.571 (0.85), 7.222 (2.17), 7.227 (3.29), 7.233 (4.98), 7.241 (4.15),
349 1.37 min; MS (ESIpos): m/z =
7.245 (3.67), 7.256 (1.43), 7.260 (1.07), 7.274 (3.36), 7.287 (1.98), 7.291 (1.44), 7.404 (2.36), 7.408 (2.57), 7.420 (2.24), 7.649
490 [M+H]+
(3.36), 7.652 (6.92), 7.656 , 7.681 (16.00), 7.685 (13.01), 7.704 (2.74), 7.718 (3.50), 7.720 (3.56), 7.735 (3.17), 7.878 (3.68),
7.881 (4.09), 7.892 (3.13), 7.895 (3.25), 8.306 (3.47), 8.309 (3.76), 8.323 , 8.326 (3.32), 8.861 (12.86), 8.984 (3.14), 9.001
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.303 (2.43), 1.322 (5.61), 1.341 (2.50), 3.252 (2.09), 3.271 (2.06), 4.250 (1.06), 4.259
LC-MS (Method L1): Rt = (1.62), 4.268 (1.95), 4.275 (1.54), 4.284 , 5.305 (0.92), 5.325 (0.92), 6.783 (1.53), 6.785 , 6.803 (1.75), 6.806 (1.83),
350 5,06 1.35 min; MS (ESIpos): m/z = 6.911 (0.78), 6.914 (0.83), 6.930 (1.72), 6.932 (1.71), 6.948 , 6.951 (1.00), 7.149 (0.86), 7.153 (0.89), 7.170 (1.43), 7.350
477 [M+H]+ , 7.370 , 7.652 (16.00), 7.752 (1.09), 7.770 (1.68), 7.791 (1.47), 7.871 (1.93), 7.874 , 7.889 (1.44), 7.892 (1.42),
8.319 (1.50), 8.322 (1.58), 8.340 (1.43), 8.343 (1.39), 8.839 (5.77), 9.102 (1.60), 9.123 (1.55).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.10 (d, 1H), 8.81 (s, 1H), 8.30 (d, 1H), 8.28 (br d, 1H), 7.71 - 7.84 (m, 2H), 7.46 (t, 1H),
351 5,1 1.36 min; MS s): m/z = 7.30 - 7.40 (m, 3H), 7.12 - 7.22 (m, 1H), 6.93 (td, 1H), 6.79 (dd, 1H), 5.24 - 5.37 (m, 1H), 4.19 - 4.33 (m, 2H), 3.26 (q, 3H), 2.64 -
471 [M+H]+ 2.74 (m, 2H), 2.16 - 2.27 (m, 1H), 2.01 - 2.12 (m, 1H), 1.32 (t, 3H), 1.23 (t, 3H).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.08 (d, 1H), 8.82 (s, 1H), 8.25 (dd, 1H), 7.73 - 7.83 (m, 2H), 7.44 (s, 1H), 7.30 - 7.38 (m,
352 1.26 min; MS (ESIpos): m/z = 3H), 7.17 (t, 1H), 6.93 (t, 1H), 6.80 (d, 1H), 5.75 (s, 1H), 5.28 - 5.34 (m, 1H), 4.22 - 4.32 (m, 2H), 2.79 (s, 3H), 2.39 (s, 3H), 2.17 -
443 [M+H]+ 2.26 (m, 1H), 2.03 - 2.12 (m, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.60), 2.086 (0.58), 2.094 (0.47), 2.203 (0.46), 2.214 (0.45), 2.225 , 2.794
LC-MS d L1): Rt = (10.72), 4.248 (0.87), 4.271 (1.29), 4.276 (1.30), 4.286 (0.77), 5.299 (0.74), 5.318 (0.76), 5.754 , 6.787 (1.44), 6.808 (1.54),
353 1.28 min; MS (ESIpos): m/z = 6.911 (0.70), 6.928 (1.45), 6.946 (0.85), 7.150 (0.73), 7.154 (0.77), 7.171 (1.18), 7.189 (0.58), 7.353 (1.24), 7.372 (1.13), 7.656
463 [M+H]+ (16.00), 7.754 (1.00), 7.772 (1.46), 7.793 (1.32), 7.884 (1.64), 7.886 (1.70), 7.901 (1.28), 7.904 (1.19), 8.285 (1.42), 8.288 (1.42),
8.306 (1.32), 8.309 (1.24), 8.844 (4.54), 9.082 (1.27), 9.103 (1.21).
LC-MS d L6): Rt = ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.46), 0.008 (0.44), 1.175 (0.60), 1.187 (0.74), 1.193 (1.32), 1.205 (1.44), 1.211
354 2.46 min; MS (ESIneg): m/z = , 1.223 (0.71), 2.073 (0.67), 2.523 (0.41), 3.168 (16.00), 4.201 (0.40), 4.218 (0.81), 4.227 (0.56), 4.236 (0.80), 4.245 (0.62),
558 [M-H]- 6.804 (0.95), 6.826 (0.84), 7.683 (3.23), 7.897 (0.42), 8.001 (0.60), 8.018 (0.44), 9.111 (0.89), 9.124 (0.80).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.59), 0.008 (2.29), 2.135 (0.68), 2.224 (0.56), 2.327 (1.51), 2.366 (1.57), 2.522
LC-MS (Method L1): Rt =
355 (5.91), 2.669 (1.22), 2.710 (0.80), 4.264 (1.54), 4.275 , 4.710 (5.79), 5.292 (0.89), 5.311 (0.86), 6.798 (1.54), 6.816 (1.69),
1.25 min; MS s): m/z =
6.896 (0.83), 6.915 , 6.933 (0.95), 7.163 (0.83), 7.180 (1.34), 7.198 (0.65), 7.384 (1.40), 7.404 (1.25), 7.678 (16.00), 7.883
488 [M+H]+
(1.10), 7.901 (1.66), 7.923 (1.51), 7.989 (2.02), 8.004 , 8.417 (1.57), 8.435 (1.45), 9.029 (5.19), 9.375 (1.45), 9.395 (1.34).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 9.12 (d, 1H), 8.83 (s, 1H), 8.33 (d, 1H), 7.88 (d, 1H), 7.72 - 7.79 (m, 1H), 7.65 (s, 3H), 7.36
356 1.41 min; MS (ESIpos): m/z = (d, 1H), 7.14 - 7.22 (m, 1H), 6.93 (t, 1H), 6.80 (d, 1H), 5.25 - 5.37 (m, 1H), 4.20 - 4.34 (m, 2H), 3.17 - 3.26 (m, 2H), 2.20 (td, 1H), 1.99
491 [M+H]+ - 2.11 (m, 1H), 1.64 - 1.78 (m, 2H), 1.02 (t, 3H).
LC-MS (Method L1): Rt = 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 8.89 - 9.00 (m, 2H), 8.04 (d, 1H), 7.90 (d, 1H), 7.72 - 7.80 (m, 1H), 7.67 (s, 3H), 7.28 - 7.39
357 1.39 min; MS (ESIpos): m/z = (m, 1H), 7.16 (t, 1H), 6.92 (t, 1H), 6.78 (d, 1H), 5.54 (s, 1H), 5.19 - 5.29 (m, 1H), 5.03 (br s, 1H), 4.17 - 4.33 (m, 2H), 2.11 - 2.28 (m,
489 [M+H]+ 4H), 2.02 (br s, 1H).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.640 (1.22), 0.650 (1.42), 0.658 (1.28), 0.668 (0.69), 0.681 (0.74), 0.691 (1.29), 0.698
, 0.709 , 1.173 (1.12), 1.186 (2.68), 1.200 (2.43), 1.203 (2.55), 1.216 (0.95), 2.067 (0.40), 2.073 (0.54), 2.079 (0.80),
2.085 (0.85), 2.095 (0.95), 2.107 (1.22), 2.112 (1.05), 2.118 (0.74), 2.124 (0.52), 2.201 (0.53), 2.208 (0.81), 2.218 (1.13), 2.228
LC-MS (Method L1): Rt = (1.10), 2.235 (1.08), 2.246 (0.78), 2.253 (0.54), 2.409 (0.51), 2.420 , 2.426 (1.14), 2.437 (1.81), 2.449 (1.05), 2.455 (1.00),
358 4,9 1.34 min; MS (ESIpos): m/z = 2.466 (0.59), 4.230 (0.57), 4.235 (0.67), 4.252 (1.84), 4.258 (1.37), 4.269 (1.59), 4.275 (1.46), 4.280 (1.41), 4.287 (1.66), 4.293
489 [M+H]+ (1.43), 4.300 (1.50), 4.310 (0.60), 4.315 (0.65), 4.322 (0.46), 5.280 (0.80), 5.291 , 5.307 (1.69), 5.318 (0.75), 6.783 (3.28),
6.799 (3.54), 6.905 (1.59), 6.920 (3.31), 6.934 (1.85), 7.148 (1.91), 7.165 (2.68), 7.179 , 7.367 (2.83), 7.382 (2.86), 7.648
(16.00), 7.770 (1.92), 7.784 (3.02), 7.801 (2.71), 7.869 (3.37), 7.871 (3.35), 7.884 (2.52), 8.601 (2.89), 8.618 (2.72), 8.787 (0.65),
8.816 (9.10), 9.011 (2.78), 9.027 (2.65).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 , 0.006 (1.15), 1.527 (11.61), 1.542 (11.90), 1.554 ), 1.568 (11.39), 2.024
(0.41), 2.037 (0.85), 2.044 (0.90), 2.052 (0.94), 2.057 (0.92), 2.065 (1.24), 2.071 (1.06), 2.078 (0.75), 2.084 (0.55), 2.177 (0.52),
2.184 (0.80), 2.194 (1.16), 2.204 (1.11), 2.211 (1.11), 2.221 (0.74), 2.518 (0.93), 2.522 (0.72), 3.841 (0.48), 3.855 (1.08), 3.869
LC-MS (Method L1): Rt = , 3.883 , 3.898 (0.42), 4.218 (0.51), 4.224 (0.67), 4.240 , 4.247 (1.53), 4.257 (2.08), 4.262 (2.36), 4.268 (1.99),
359 1.38 min; MS (ESIpos): m/z = 4.274 (1.55), 4.281 (1.68), 4.290 (0.52), 4.297 (0.62), 4.303 (0.43), 5.264 (0.80), 5.276 (1.75), 5.292 (1.70), 5.303 (0.77), 6.784
491 [M+H]+ (3.41), 6.798 (3.68), 6.916 (1.72), 6.918 (1.66), 6.930 (3.46), 6.945 (2.02), 7.151 (1.65), 7.154 (1.69), 7.168 (2.77), 7.182 (1.36),
7.185 (1.32), 7.353 (2.85), 7.368 , 7.616 (12.83), 7.620 (16.00), 7.643 (4.67), 7.647 (6.31), 7.651 (2.84), 7.720 (2.36), 7.735
(3.26), 7.738 (2.76), 7.752 (2.91), 7.840 (3.95), 7.842 , 7.854 (3.15), 7.856 (2.93), 8.446 (3.04), 8.461 (2.92), 8.757 (12.10),
9.108 (3.03), 9.125 (2.93).
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 (1.55), 2.061 (0.52), 2.067 (0.77), 2.071 (0.86), 2.079 (0.95), 2.083 (0.89), 2.090
, 2.094 (0.95), 2.101 (0.63), 2.197 (0.52), 2.202 (0.70), 2.211 (1.08), 2.219 (1.07), 2.225 (1.08), 2.234 (0.81), 2.386 (0.48),
2.517 (1.21), 2.520 (1.17), 2.523 (0.96), 2.614 (0.48), 4.190 (1.43), 4.199 , 4.204 (1.08), 4.215 (5.45), 4.223 (1.99), 4.229
LC-MS (Method L1): Rt =
360 (4.83), 4.253 (1.43), 4.266 (1.08), 4.271 (1.32), 4.277 (1.21), 4.283 (1.51), 4.290 (0.72), 4.296 (0.76), 4.301 (0.61), 5.278 (0.77),
1.12 min; MS (ESIpos): m/z =
.288 (1.58), 5.301 (1.57), 5.310 (0.71), 6.785 (3.04), 6.798 (3.20), 6.888 (1.54), 6.890 (1.54), 6.901 , 6.913 (1.75), 6.915
506 [M+H]+
(1.67), 7.152 (1.45), 7.154 (1.49), 7.166 (2.44), 7.177 , 7.180 (1.20), 7.355 (2.91), 7.366 (4.77), 7.659 (8.30), 7.661 (16.00),
7.667 (5.88), 7.670 (4.36), 7.673 (1.81), 7.773 (2.24), 7.785 (2.96), 7.787 (2.70), 7.799 , 7.898 (3.37), 7.899 (3.46), 7.909
, 7.911 (2.71), 8.004 (2.52), 8.349 (2.84), 8.350 , 8.363 (2.68), 8.365 (2.58), 8.951 ), 9.490 , 9.504 (2.84).
LC-MS (Method L1): Rt = ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.70), 0.008 (0.49), 1.398 (16.00), 1.988 (0.45), 2.519 (0.43), 6.790 (0.48), 6.849
361 1.44 min; MS (ESIpos): m/z = (0.44), 6.851 (0.45), 6.870 (0.51), 6.872 (0.48), 6.966 (0.40), 7.673 (0.41), 7.696 (4.12), 7.933 (0.43), 7.951 (0.60), 7.953 (0.54),
474 [M+H]+ 7.972 (0.53), 8.054 (0.67), 8.057 (0.62), 8.071 (0.49), 8.075 (0.41), 9.279 (0.96), 9.311 (0.50).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (3.35), 0.008 (3.09), 1.942 (0.95), 1.962 (1.01), 1.973 (1.12), 1.994 (1.07), 2.877
(0.97), 2.897 (1.34), 3.072 , 3.089 (5.60), 3.105 , 3.287 (1.80), 3.448 (1.02), 3.452 (1.05), 3.463 , 3.469 (2.04),
LC-MS (Method L1): Rt = 3.479 (2.06), 3.483 (2.02), 3.500 (0.82), 4.961 (1.79), 4.975 (4.01), 4.989 (1.75), 5.573 (1.56), 5.593 (1.55), 5.754 (4.61), 7.226
362 1.25 min; MS s): m/z = (2.94), 7.234 (3.06), 7.240 (3.44), 7.248 (5.14), 7.258 (1.67), 7.266 , 7.276 (1.40), 7.279 (1.19), 7.511 (1.39), 7.523 ,
509 [M+H]+ 7.533 (1.20), 7.657 (3.86), 7.659 (5.48), 7.663 (16.00), 7.667 (6.58), 7.670 (3.35), 7.673 (2.04), 7.676 (1.25), 7.683 (0.83), 7.839
(1.73), 7.857 (2.68), 7.860 (1.98), 7.879 (2.73), 7.927 (2.89), 7.931 (3.10), 7.945 , 7.949 (1.80), 8.630 (2.51), 8.634 (2.52),
8.651 (2.41), 8.655 (2.15), 8.879 (10.16), 9.027 (2.07), 9.048 (2.05).
1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (2.58), 0.008 (2.57), 1.356 (1.00), 2.085 (16.00), 4.144 (1.13), 5.754 , 6.743
(1.76), 6.747 (2.04), 6.764 (1.98), 6.767 (2.24), 6.788 (1.04), 6.791 , 6.807 (2.03), 6.810 (1.93), 6.826 (1.26), 6.829 ,
6.992 (1.32), 6.995 (2.52), 6.997 (1.59), 7.013 , 7.015 (2.62), 7.017 (1.66), 7.111 , 7.116 , 7.132 (1.62), 7.138
LC-MS (Method L1): Rt =
363 (1.65), 7.141 , 7.150 (2.04), 7.153 (2.12), 7.157 (1.66), 7.159 (1.41), 7.169 (1.40), 7.171 (1.37), 7.265 (1.54), 7.285 (1.54),
1.37 min; MS (ESIpos): m/z =
7.584 (1.21), 7.589 (1.25), 7.604 (1.61), 7.609 (1.64), 7.623 (1.04), 7.628 (1.04), 7.681 , 7.684 (1.64), 7.686 (2.60), 7.690
558 [M+H]+
(5.09), 7.695 ), 7.698 (4.45), 7.700 (3.56), 7.734 (1.72), 7.751 , 7.755 (2.02), 7.773 (2.10), 7.916 (2.37), 7.919 (2.53),
7.934 (2.01), 7.938 (1.93), 8.298 (1.27), 8.300 (1.54), 8.303 (1.59), 8.305 (1.45), 8.310 (1.37), 8.312 (1.59), 8.315 (1.49), 8.317
(1.32), 8.336 (2.29), 8.339 (2.36), 8.357 (2.07), 8.361 (1.99), 9.071 (8.31), 9.124 (1.92), 9.144 (1.88).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (2.66), 0.008 (2.57), 2.119 (1.04), 2.128 (0.86), 2.366 , 2.710 (0.82), 3.060
(2.72), 3.077 , 3.093 (3.50), 3.287 (2.70), 3.438 (1.04), 3.454 (2.48), 3.468 (3.16), 3.481 (2.10), 3.497 , 4.254 (1.46),
4.263 (1.26), 4.273 (2.24), 4.282 (2.43), 4.297 (1.35), 4.946 (2.06), 4.960 (4.56), 4.974 (1.99), 5.291 (1.28), 5.310 (1.31), 6.781
LC-MS (Method L1): Rt =
364 (2.41), 6.784 (2.61), 6.802 (2.74), 6.805 (2.88), 6.910 (1.33), 6.913 (1.46), 6.928 (2.63), 6.932 (2.57), 6.947 (1.59), 6.950 (1.53),
1.28 min; MS s): m/z =
7.151 (1.31), 7.156 (1.35), 7.173 (2.21), 7.190 (1.24), 7.194 (1.13), 7.448 (2.17), 7.465 , 7.627 (1.00), 7.632 (1.04), 7.658
525 [M+H]+
(5.73), 7.662 (16.00), 7.666 (6.68), 7.669 (3.41), 7.675 , 7.838 (1.93), 7.856 (2.97), 7.859 (2.35), 7.877 (2.92), 7.929 (3.21),
7.932 (3.50), 7.946 (2.21), 7.950 , 8.624 (2.97), 8.627 (2.97), 8.645 (2.70), 8.649 (2.50), 8.881 (10.45), 9.155 (2.48), 9.175
(2.37).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.77), -0.008 (16.00), 0.008 (14.17), 0.146 (1.65), 1.236 (0.71), 2.104 , 2.217
(1.18), 2.327 (3.48), 2.366 (2.13), 2.523 (12.52), 2.669 (3.84), 2.709 (2.18), 4.249 (2.01), 4.269 (2.72), 4.297 (1.83), 5.284 (1.83),
LC-MS (Method L1): Rt =
365 5.303 (1.89), 5.754 (4.66), 6.784 (3.66), 6.804 (4.13), 6.917 (1.89), 6.932 (3.60), 6.951 (2.36), 7.155 (1.89), 7.173 (2.89), 7.193
1.32 min; MS (ESIpos): m/z =
(1.54), 7.357 (3.25), 7.362 (7.38), 7.366 (5.20), 7.394 (13.99), 7.398 (11.04), 7.430 (3.01), 7.447 (2.95), 7.814 (2.48), 7.832 (4.07),
507 [M+H]+
7.853 (4.07), 7.892 (4.43), 7.896 (4.84), 7.910 (2.89), 8.550 (3.96), 8.554 (3.84), 8.571 (3.72), 8.575 (3.48), 8.841 (14.23), 9.114
(3.31), 9.135 (3.25).
(399,9532 MHz, DMSO): δ= 9.129 (0.47); 9.1148 (0.47); 9.1094 (0.47); 8.7855 (1.25); 8.7775 (1.27); 8.6377 (0.78); 8.6169
(0.83); 7.8685 (0.52); 7.8505 (0.85); 7.8295 (0.79); 7.7781 (1.03); 7.7634 (0.65); 7.7608 (0.66); 7.7301 (0.69); 7.7265 (0.81); 7.7101
(0.84); 7.7068 ; 7.4773 (0.34); 7.4638 (0.65); 7.4576 (0.71); 7.4446 (0.66); 7.4301 (0.75); 7.4129 ; 7.3928 (0.56); 7.3822
366 4,79 (0.55); 7.3662 ; 7.1798 (0.35); 7.1614 (0.7); 7.1419 (0.43); 6.9335 (0.47); 6.915 (0.8); 6.8966 (0.39); 6.7926 (0.94); 6.7722
(0.84); 5.2907 (0.43); 5.2723 (0.45); 4.2863 (0.4); 4.2718 (0.77); 4.263 (0.76); 4.2526 (0.49); 4.2448 (0.48); 3.3189 (19.02); 3.0568
(0.38); 3.0385 ; 3.0201 (1.27); 3.0017 (0.5); 2.5053 (32.31); 2.501 (45.79); 2.4969 (38.72); 1.3977 (16); 1.1703 (1.73); 1.1519
(3.55); 1.1335 (1.74); 0.0074 (1.2); -0.0002 (26.74)
1H-NMR(399,9532 MHz, DMSO): δ= 9.1306 (2.01); 9.1101 (2.05); 8.8861 (7.98); 8.6364 (2); 8.6333 (2.17); 8.6154 (2.23); 8.6122
(2.26); 7.9429 (1.75); 7.9397 (1.94); 7.925 (2.69); 7.9218 (2.64); 7.8638 ; 7.8429 ; 7.8248 (1.46); 7.6937 (0.7); 7.6622
(16); 7.458 ; 7.4401 ; 7.1926 (0.85); 7.1892 (0.9); 7.1715 (1.84); 7.1543 (1.13); 7.1505 ; 6.948 (1.34); 6.9295
(2.26); 6.9106 (1.06); 6.8025 (2.51); 6.7834 (2.23); 6.5799 (0.36); 5.7548 (2.41); 5.3226 (0.52); 5.3079 (1.15); 5.2891 (1.14); 5.2746
367 5,48 (0.5); 4.3171 (0.37); 4.2984 ; 4.2828 (2.04); 4.2742 (1.92); 4.2638 (1.11); 4.2555 (1.22); 4.2357 (0.36); 3.3221 (28.56); 3.0452
; 3.0269 (4.39); 3.0085 (4.61); 2.9901 (1.55); 2.9503 (2.63); 2.5062 (35.71); 2.5018 (49.01); 2.4975 (37.88); 2.2455 (0.37);
2.2396 (0.4); 2.2253 (0.63); 2.2154 (0.69); 2.2039 (0.74); 2.1923 (0.58); 2.183 ; 2.1277 (0.35); 2.1193 (0.52); 2.1122 (0.71);
2.1045 (0.86); 2.0944 (0.61); 2.0876 (0.59); 2.078 (0.53); 2.0688 (0.48); 1.397 (6.52); 1.2337 (0.54); 1.1701 (1.44); 1.1529 ;
1.1345 ); 1.1161 (5.17); 0.0078 (2.03); -0.0002 (46.62)
1H-NMR(399,9532 MHz, DMSO): δ= 9.4079 (0.91); 9.3936 (0.81); 9.3876 ; 9.348 (0.54); 9.3284 (1.17); 9.3084 (0.7); 9.2139
(0.51); 9.2004 (1.18); 9.1877 (1.26); 9.1743 (0.63); 9.1376 (0.37); 9.124 (0.46); 9.1127 (0.45); 9.0815 (0.48); 9.069 (0.72); 9.0563
(0.54); 8.9299 (4.95); 8.9181 (2.18); 8.3146 (0.48); 7.8564 (6.67); 7.8446 (5.81); 7.8246 (0.32); 7.7421 (2.74); 7.7383 (2.93); 7.7222
(3.38); 7.7184 (3.39); 7.4976 (0.59); 7.4918 (1.24); 7.4783 (1.38); 7.4723 (2.72); 7.4633 (1.1); 7.4588 (1.07); 7.4523 (1.75); 7.4438
(0.68); 7.429 (1.04); 7.4219 (1.82); 7.4179 (1.54); 7.4031 (1.84); 7.399 (1.97); 7.3891 (1.42); 7.3854 (1.42); 7.38 (0.92); 7.3699
(1.26); 7.3497 (0.86); 7.3415 (0.86); 7.1887 (1.08); 7.1706 (2.27); 7.1526 (1.33); 6.9372 ; 6.9184 (2.37); 6.8998 (1.11); 6.8025
(2.56); 6.782 (2.28); 5.7548 (16); 5.244 (0.78); 5.2248 (1.32); 4.3011 (0.47); 4.2715 (1.25); 4.2597 (1.64); 4.2386 ; 4.2313
368 3,76 (1.34); 4.2105 (1.16); 4.19 (0.42); 4.0556 (0.74); 4.0378 (2.3); 4.02 (2.33); 4.0022 (0.78); 3.6324 (0.57); 3.6282 (0.47); 3.6193 (0.65);
3.6135 (1.07); 3.6005 (1.04); 3.595 (0.97); 3.5876 (0.71); 3.5816 ; 3.569 ; 3.5629 (0.59); 3.4779 (0.67); 3.3947 (0.75);
3.3771 (0.89); 3.3607 (0.77); 3.3457 (1.02); 3.3189 (76.03); 3.3011 (0.56); 3.2956 (0.52); 3.2762 (0.74); 2.6748 (0.91); 2.6703 (1.21);
2.6656 (0.94); 2.5235 (3.02); 2.5099 (69.23); 2.5056 (147.9); 2.501 (208.96); 2.4966 (158.74); 2.4924 (78.18); 2.3323 (0.85); 2.328
(1.2); 2.3235 (0.9); 2.2195 (0.41); 2.2066 (0.59); 2.1969 (0.68); 2.1869 (0.78); 2.1765 (0.84); 2.1662 (0.77); 2.1545 (0.61); 2.0945
(0.63); 2.085 (0.73); 2.0685 (0.72); 2.0511 (0.6); 1.9884 (9.96); 1.3946 (1.94); 1.3881 (1.89); 1.376 (4.14); 1.3695 (3.96); 1.3626
(3.1); 1.3577 (2.54); 1.3506 (2.19); 1.344 (5.38); 1.3253 (2.43); 1.1927 (2.64); 1.1749 (5.28); 1.1571 (2.56); 0.008 (1.98); -0.0001
); -0.0084 (2.3)
1H-NMR(399,9532 MHz, DMSO): δ= 9.2003 (2.67); 9.1806 (3.23); 9.167 ; 9.0322 (8.51); 9.019 (6.5); 8.9438 (4.48); 8.9221
(4.91); 8.3143 (2.06); 7.9838 (3.69); 7.9659 (6.23); 7.9442 (6.22); 7.9065 (7.21); 7.889 ; 7.7531 (5.21); 7.7495 (5.57); 7.7332
(6.28); 7.7295 (6.44); 7.508 (2.22); 7.4958 (2.14); 7.4886 (4.93); 7.4766 (4.41); 7.4689 (3.41); 7.4566 (5.08); 7.432 (6.44); 7.4078
(3.86); 7.3882 (1.78); 7.1782 ; 7.1588 (3.64); 7.1396 (2.31); 6.9267 (1.91); 6.9158 (2); 6.908 (3.3); 6.8978 (2.95); 6.8915
(1.75); 6.8809 (1.36); 6.789 (5.67); 6.7684 (5.12); 5.7544 (10.27); 5.214 (1.39); 5.2001 (2.98); 5.1805 (2.91); 5.1675 (1.28); 4.305
(1.02); 4.2955 (1.49); 4.2776 (2.26); 4.2627 (2.39); 4.2546 ; 4.2028 (1.82); 4.1938 (1.6); 4.1816 (2.42); 4.1738 (2.22); 4.1539
369 3,94 (1.1); 4.0375 (0.53); 4.0197 (0.62); 3.9026 (0.65); 3.7185 (0.69); 3.7005 (2.39); 3.6828 (6.64); 3.6642 (7.29); 3.6477 (3.14); 3.631
(1.2); 3.6135 (0.55); 3.5953 ; 3.3784 (0.72); 3.3184 (262.18); 2.675 (3.55); 2.6703 (4.96); 2.666 (3.64); 2.5236 (12.22); 2.5055
(584.02); 2.5011 (819.49); 2.4967 (626.86); 2.3325 (3.45); 2.3279 (4.64); 2.3235 (3.47); 2.1791 (1.23); 2.1677 (1.59); 2.1578 (1.93);
2.1464 (2.45); 2.133 (2.65); 2.1234 (2.57); 2.0956 (1.25); 2.0828 (0.81); 1.9882 (2.46); 1.3887 (0.5); 1.3197 (7.73); 1.3046 );
1.301 (16); 1.2858 (7.08); 1.2826 (7.64); 1.2589 (1.64); 1.2352 (4.77); 1.193 (1.14); 1.1751 (1.98); 1.1573 (1.17); 1.1406 (0.7);
1.1176 ; 1.0977 ; 0.8541 (0.85); 0.8372 (0.72); 0.768 (0.51); 0.7585 (0.6); 0.7287 (0.37); 0.1458 (0.91); 0.0079 (6.73); -
0.0002 (210.64); -0.0083 (8.7); -0.1499 (0.88)
(399,9532 MHz, DMSO): δ= 9.3994 (1.2); 9.3782 (2.63); 9.3572 (1.64); 9.1706 (1.25); 9.1482 (2.41); 9.1234 (1.62); 9.0407
; 9.0256 (5.14); 8.0137 (2.95); 7.9958 (3.69); 7.8636 ; 7.8447 (3.05); 7.824 (1.78); 7.6865 (2.25); 7.6816 (5.53); 7.6774
(5.78); 7.6659 (16); 7.6613 (10.26); 7.4424 (1.15); 7.4242 (1.23); 7.3796 (1.54); 7.3615 (1.65); 7.1997 (1.27); 7.1795 (2.54); 7.1609
(1.67); 6.9491 (1.99); 6.9307 (3.38); 6.9119 (1.61); 6.8111 (3.75); 6.7907 (3.34); 5.7549 (6.05); 5.2713 (0.45); 5.2578 (1.23); 5.239
; 5.2251 (1.09); 5.2116 (0.34); 4.3107 (0.44); 4.3029 (0.54); 4.2848 (1.37); 4.2718 (2.3); 4.2635 (1.9); 4.2523 (1.39); 4.2444
370 4,44 ; 4.2328 (0.73); 4.2244 (1.04); 4.217 (0.53); 4.2041 (0.33); 3.6141 (0.78); 3.6102 (0.99); 3.5958 (1.19); 3.5918 (1.15); 3.5813
(1.08); 3.5775 ; 3.5627 ; 3.5591 (1.28); 3.5409 (0.4); 3.3918 (1.1); 3.3729 (1.38); 3.3592 (1.03); 3.353 (1.23); 3.3401
(1.19); 3.3338 (1.2); 3.3202 (28.4); 3.3014 (0.76); 2.675 (0.44); 2.6707 (0.61); 2.6662 (0.47); 2.5235 (1.63); 2.5058 (73.82); 2.5014
(103.74); 2.497 (80.59); 2.493 (41.24); 2.3326 (0.43); 2.3281 (0.59); 2.3239 (0.48); 2.2328 (0.49); 2.2203 (0.71); 2.2113 (0.74);
2.1984 (1.03); 2.1872 ; 2.1772 (0.91); 2.165 (0.61); 2.155 (0.35); 2.1416 (0.36); 2.1271 (0.7); 2.1187 ; 2.1035 (0.67);
2.0935 (0.67); 2.0842 (0.76); 2.0783 (0.75); 2.0684 (0.55); 2.0605 (0.45); 2.0507 (0.37); 2.0437 (0.32); 1.3819 ; 1.3633 (8.24);
1.3575 (3.82); 1.3445 (4.22); 1.3387 (6.43); 1.3199 (2.77); 1.2332 (0.72); 1.1754 (0.4); -0.0002 (0.66)
1H-NMR(399,9532 MHz, DMSO): δ= 9.1895 ; 9.1694 (3.1); 9.1296 (0.37); 9.1153 (10.56); 8.9396 (3.14); 8.9368 (3.35); 8.9178
(3.51); 8.915 ; 8.3143 (0.49); 8.0499 (2.68); 8.0473 (2.89); 8.0321 ; 8.0293 (4.1); 7.9727 (3.41); 7.9543 (2.73); 7.951
(3.52); 7.9328 (2.34); 7.7006 (3.22); 7.6959 (6.75); 7.6912 (4.54); 7.655 (16); 7.6503 (13.06); 7.4831 (2.66); 7.4649 ; 7.1902
(1.31); 7.1863 (1.38); 7.1687 (2.79); 7.1515 ; 7.1478 ; 6.9385 (2.04); 6.9201 (3.47); 6.9036 ; 6.9012 (1.66); 6.7982
(3.87); 6.779 (3.55); 5.7544 (1.92); 5.2344 (0.76); 5.2216 (1.73); 5.2018 (1.72); 5.1876 (0.75); 4.3164 (0.62); 4.3031 (0.84); 4.2899
371 4,54 (1.38); 4.2793 (1.29); 4.2738 (1.51); 4.2653 ; 4.2225 (0.99); 4.2147 (1.33); 4.2016 (1.16); 4.1939 (1.75); 4.1864 (0.87); 4.1743
(0.72); 4.1658 (0.65); 3.7057 (0.34); 3.6883 (1.22); 3.6828 (1.08); 3.6702 (3.31); 3.6645 (3.08); 3.6516 (3.37); 3.6461 (3.16); 3.6329
(1.16); 3.6285 (1.24); 3.3193 (68.59); 2.675 (0.88); 2.6705 (1.18); 2.6659 (0.87); 2.5236 (3.14); 2.5101 (69.48); 2.5058 (144.19);
2.5013 (199.43); 2.4969 (149.23); 2.4928 (72.67); 2.3326 (0.83); 2.3282 ; 2.3238 (0.81); 2.2169 (0.37); 2.204 (0.5); 2.1912
(0.95); 2.1785 (1.25); 2.1702 (1.47); 2.1564 (1.69); 2.1486 (1.83); 2.14 (1.59); 2.126 (0.94); 2.1147 (0.54); 2.1053 (0.46); 1.3515
(0.39); 1.3055 (7.28); 1.2869 (15.83); 1.2685 (7.21); 1.2352 (4.31); 1.17 (0.64); 1.1521 (0.57); 0.8536 (0.58); 0.835 (0.32); -0.0002
(1.18)
1H-NMR(399,9532 MHz, DMSO): δ= 12.3602 (1.81); 9.1502 (2.55); 9.1301 (2.52); 8.892 ; 8.8835 (0.49); 8.6271 (2.4); 8.624
(2.53); 8.6058 (2.71); 8.6028 (2.68); 7.9529 (2.14); 7.9502 (2.26); 7.9352 (3.25); 7.9323 (3.12); 7.9076 (0.43); 7.8737 (2.65); 7.8528
(2.81); 7.8346 (1.74); 7.6694 (8.23); 7.6663 (16); 7.4556 (2.26); 7.4372 (2.36); 7.1902 (1.1); 7.1719 ; 7.1546 (1.4); 7.151 (1.4);
6.9475 (1.65); 6.9287 ; 6.91 (1.31); 6.8025 (3.17); 6.7815 (2.81); 5.3004 (0.68); 5.2866 (1.49); 5.2669 ; 5.2527 (0.64);
372 4,08 4.3167 (0.34); 4.3082 (0.53); 4.2896 (1.41); 4.2737 (2.43); 4.2645 (2.36); 4.2534 (1.28); 4.245 (1.54); 4.2252 (0.51); 4.2177 (0.4);
4.0377 ; 4.0198 (0.37); 3.3181 (128.86); 3.1629 (2.73); 3.145 (6.07); 3.1272 (3.01); 2.89 (0.57); 2.7306 (0.51); 2.6743 (2.28);
2.6697 (3.09); 2.6658 (2.38); 2.615 (0.4); 2.597 (0.4); 2.5228 (8.93); 2.5052 (404.28); 2.5009 (529.51); 2.4965 (389.18); 2.477 (6.31);
2.332 (2.29); 2.3276 (3.04); 2.323 (2.27); 2.2559 (0.33); 2.2437 (0.53); 2.2366 ; 2.2221 (0.88); 2.2127 (1.01); 2.2005 ;
2.1892 (0.78); 2.1288 (0.69); 2.1204 (0.93); 2.1136 (1.11); 2.1049 (0.78); 2.0969 (0.76); 2.0877 (0.7); 2.0787 (0.66); 1.9883 (1.45);
1.2344 ; 1.1925 (0.48); 1.1741 (0.82); 1.1569 (0.42); 1.1054 (0.4); 0.0077 (1.78); -0.0003 (53.99); -0.008 (2.53)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 4.172 (16.00), 4.245 (0.90), 4.254 (1.07), 4.269 (1.49), 4.273 (1.51), 4.283 (0.86), 5.274
LC-MS (Method L1): Rt = , 5.293 (0.83), 5.754 (12.35), 6.793 (1.40), 6.796 (1.53), 6.814 (1.59), 6.816 (1.66), 6.909 (0.74), 6.912 (0.74), 6.928 (1.55),
373 1.39 min; MS (ESIpos): m/z = 6.930 (1.54), 6.946 (0.93), 6.949 (0.91), 7.159 (0.76), 7.163 (0.82), 7.180 (1.29), 7.363 (1.33), 7.380 (1.25), 7.650 (0.88), 7.655
479 [M+H]+ (2.07), 7.659 (2.33), 7.670 (7.40), 7.675 (4.39), 7.702 (1.20), 7.720 , 7.723 (1.57), 7.741 (1.47), 7.886 (1.69), 7.890 (1.80),
7.904 (1.44), 7.908 (1.42), 8.296 (1.61), 8.299 (1.63), 8.317 (1.54), 8.320 (1.45), 8.811 , 9.192 (1.36), 9.212 (1.34).
384: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9731(0.6);8.9623(0.6);8.9531(0.6);8.9419(0.5);8.4859(0.4);8.3740(0.7);8.3670(0.7);8.3565(0.8);8.3495(0.8);8.3209(2.7);7.7618
(0.4);7.7477(0.4);7.7333(0.5);7.7203(0.4);7.6684(1.2);7.6517(1.2);7.6483(1.4);7.5524(0.5);7.5423(3.3);7.5361(1.8);7.5245(1.4);7.50
384 1.66 70(0.4);7.4333(0.4);7.4228(0.5);7.4138(0.9);7.4033(0.8);7.3941(0.6);7.3837(0.5);7.3046(1.3);7.2862(1.8);7.2711(0.5);7.1678(0.5);7.
1476(1.1);7.1280(0.6);6.9086(0.8);6.8899(1.2);6.8713(0.6);6.7857(1.6);6.7654(1.3);5.2479(0.3);5.2338(0.7);5.2140(0.7);4.2573(1.1);
4.2441(1.8);4.2314(1.1);3.3217(36.1);3.0620(2.2);3.0560(2.8);3.0504(2.7);3.0439(2.5);3.0278(0.6);2.5049(33.4);2.5007(44.2);2.496
(34.0);2.1736(0.3);2.1521(0.4);2.1380(0.6);2.1241(0.5);2.0312(0.5);2.0163(0.6);2.0038(0.3);1.9947(0.4);1.9884(0.4);1.3971(16.0);-
0.0002(19.8)
385: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9954(0.7);8.9747(0.7);8.4127(0.8);8.3889(3.2);7.8025(0.5);7.7890(0.5);7.6892(0.8);7.6729(1.1);7.5759(0.9);7.5701(0.4);7.5551
385 1.55 (1.2);7.5367(0.7);7.3163(0.7);7.2977(0.8);7.1731(0.7);7.1561(1.1);7.1385(0.6);6.9188(0.5);6.9014(0.9);6.8835(0.4);6.7948(1.0);6.77
45(1.0);5.2426(0.5);5.2229(0.5);4.2655(0.8);4.2517(1.4);4.2391(0.8);3.3230(12.3);3.0662(2.8);3.0538(2.8);2.5055(17.4);2.5013(22.6
);2.4970(17.0);2.1478(0.4);2.1343(0.4);2.0450(0.3);2.0307(0.4);1.9884(0.9);1.3974(16.0);1.1746(0.4);0.0078(0.5);-0.0002(12.0)
395: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9826(3.1);8.9620(3.2);8.4484(2.1);8.4334(2.3);8.4245(2.4);8.4103(12.6);8.3268(0.6);7.9292(1.8);7.9165(1.8);7.6580(3.8);7.653
2(7.4);7.6484(4.2);7.5327(2.4);7.5095(4.5);7.4864(2.4);7.4628(11.2);7.4594(10.8);7.3192(0.3);7.3065(2.9);7.2879(3.1);7.1773(1.4);7
1.4);7.1563(2.9);7.1388(1.9);7.1353(1.8);6.9190(2.0);6.9164(2.2);6.9001(3.6);6.8979(3.8);6.8819(1.8);6.8792(1.8);6.7961(4.0)
395 1.93 ;6.7940(4.1);6.7757(3.7);6.7735(3.6);5.7559(16.0);5.2477(0.8);5.2330(1.9);5.2134(1.9);5.1997(0.9);4.2618(3.1);4.2486(5.4);4.2356(
3.4);4.0379(0.4);4.0202(0.4);3.3218(86.0);3.0661(11.7);3.0536(11.8);2.6749(0.6);2.6705(0.8);2.6660(0.6);2.5238(2.8);2.5103(50.5);
2.5060(102.1);2.5015(134.9);2.4970(97.8);2.4927(47.7);2.3328(0.6);2.3282(0.8);2.3237(0.6);2.1916(0.4);2.1780(0.9);2.1627(1.0);2.
1574(0.9);2.1424(1.6);2.1289(1.5);2.1149(0.6);2.0549(0.5);2.0425(1.3);2.0280(1.5);2.0205(0.8);2.0150(0.9);2.0069(1.1);1.9887(2.2);
1.3973(10.5);1.3516(0.5);1.2587(0.4);1.2492(0.3);1.2333(0.9);1.1926(0.5);1.1748(1.0);1.1570(0.5);0.0080(1.2);-0.0001(34.0);-
(1.3)
427: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.8749(4.5);8.8543(4.6);8.6918(16.0);8.2529(4.8);8.2338(5.1);8.2316(5.1);7.8425(4.2);7.8272(6.1);7.7693(4.8);7.7486(5.2);7.730
;7.6505(0.9);7.6422(1.0);7.6350(1.2);7.6273(1.9);7.6235(2.0);7.6142(1.9);7.6064(1.9);7.6016(1.9);7.5948(1.2);7.5866(1.0);7.5
788(0.8);7.4334(4.3);7.4147(4.7);7.2421(2.4);7.2322(2.4);7.2202(2.3);7.1731(2.1);7.1554(4.4);7.1378(2.7);6.9373(3.2);6.9188(5.5);6
427 3.81 .9002(2.6);6.7863(6.0);6.7657(5.5);5.2365(1.2);5.2204(2.8);5.2018(2.8);5.1875(1.3);4.2935(0.8);4.2753(2.7);4.2587(4.8);4.2499(4.6)
;4.2384(2.6);4.2310(2.9);4.2102(0.9);4.0554(0.4);4.0378(0.9);4.0205(0.9);3.4979(41.4);3.4611(0.3);3.3196(127.6);3.2906(37.1);3.25
);3.2518(0.4);2.6711(1.5);2.6075(0.4);2.5052(201.2);2.5014(249.4);2.3279(1.4);2.1701(1.6);2.1600(1.7);2.1500(1.9);2.1376(1.
4);2.1280(0.8);2.0556(1.8);2.0483(2.1);2.0386(1.5);2.0298(1.5);2.0223(1.3);2.0126(1.2);1.9885(3.7);1.3978(3.7);1.2364(0.7);1.1922(
0.9);1.1746(1.9);1.1566(1.0);-0.0002(4.5)
445: 1H-NMR(400.0 MHz, d6-DMSO):
445 2.13 δ= 8.4154(0.6);8.4123(0.6);7.6823(0.4);7.6786(0.4);7.6571(0.4);7.6475(0.4);7.6400(0.9);6.7637(0.4);5.7524(16.0);4.0645(0.6);3.872
4(0.6);3.3200(2.8);2.5052(4.9);2.5008(6.3);2.4963(4.5);2.3205(0.4);1.9880(0.7);1.1752(0.4);-0.0002(4.8)
452: 1H-NMR(400.0 MHz, d6-DMSO):
δ= (3.6);8.7000(4.0);8.6897(16.0);8.2701(3.6);8.2667(4.0);8.2490(4.3);8.2456(4.2);7.8441(3.0);7.8409(3.3);7.8265(5.0);7.823
3(4.6);7.7697(4.4);7.7515(3.6);7.7486(4.4);7.7308(2.8);7.6522(0.7);7.6444(0.8);7.6369(0.9);7.6300(1.4);7.6246(1.4);7.6163(1.4);7.6
081(1.3);7.6034(1.4);7.5958(0.9);7.5887(0.8);7.5810(0.6);7.4927(0.3);7.4814(2.2);7.4729(2.9);7.4605(2.8);7.2674(1.3);7.2549(3.5);7
452 3.94 .2449(6.3);7.2328(9.0);7.2219(8.0);7.2162(3.8);7.2103(4.7);7.1981(0.5);5.7572(10.3);5.5284(1.0);5.5088(2.9);5.4887(2.9);5.4687(1.
923(37.5);3.3247(16.2);3.3105(0.7);3.2922(32.1);2.9922(0.7);2.9841(0.8);2.9705(0.9);2.9620(1.0);2.9529(1.6);2.9448(1.6);2.9
309(1.6);2.9228(1.4);2.8834(1.1);2.8630(2.4);2.8426(1.8);2.8234(1.2);2.8026(0.7);2.5231(1.6);2.5094(15.9);2.5051(32.4);2.5007(41.
);2.4962(30.3);2.4728(1.7);2.4643(1.4);2.4530(0.8);2.4449(0.6);1.9656(0.7);1.9440(1.9);1.9342(0.8);1.9232(1.9);1.9127(1.8);1.901
4(0.8);1.8918(1.7);1.8700(0.6)
481: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.8434(0.4);9.1777(1.2);9.1644(1.4);9.1583(1.5);9.1461(1.1);8.9656(0.6);8.5679(0.4);8.5578(0.4);8.3141(0.4);8.2906(0.3);8.2685
(0.4);8.2490(2.2);8.2440(2.2);8.2295(2.4);8.2244(2.4);8.0111(0.7);7.9895(0.6);7.9522(1.0);7.6897(2.8);7.6861(2.8);7.6697(3.4);7.66
61(3.2);7.6383(1.3);7.6206(3.6);7.6005(6.3);7.5945(4.4);7.5819(1.4);7.5774(0.8);7.5191(0.4);7.5077(0.4);7.4986(0.4);7.4872(0.4);7.
4510(1.0);7.4428(0.9);7.4319(1.9);7.4236(1.7);7.4122(1.2);7.4041(1.0);7.3352(2.6);7.3166(3.0);7.3077(2.3);7.2883(0.9);7.1880(1.2);
481 3,33 7.1703(2.4);7.1527(1.5);6.9365(1.3);6.9169(2.1);6.8982(1.0);6.8079(3.2);6.7875(2.9);5.7540(7.8);5.2734(1.3);4.3307(0.6);4.3220(0.
9);4.3038(1.1);4.2928(1.5);4.2828(0.9);4.2350(1.1);4.2103(1.5);4.1831(0.6);4.1709(0.8);4.0380(0.6);4.0202(0.6);3.8597(5.5);3.8494(
7.9);3.8384(5.6);3.5677(1.0);3.3182(55.2);3.2947(0.7);3.2627(6.5);2.8904(6.9);2.7313(6.1);2.6743(0.9);2.6700(1.2);2.6657(0.9);2.62
38(0.6);2.5054(151.3);2.5010(194.0);2.4966(144.4);2.4305(16.0);2.3321(0.9);2.3276(1.2);2.3234(0.8);2.2815(0.4);2.2703(0.6);2.258
4(0.6);2.2457(1.0);2.2346(1.0);2.2223(0.8);2.2102(0.7);2.0907(1.1);2.0764(0.8);2.0611(0.8);1.9881(2.2);1.9643(2.5);1.9078(0.7);1.2
982(0.8);1.2586(1.2);1.2354(1.8);1.1925(0.7);1.1749(1.3);1.1570(0.7);1.0448(0.8);1.0296(0.9);0.8533(0.5);0.8367(0.4);-0.0002(20.1)
482: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.2312(1.6);9.2113(1.7);8.8635(0.8);8.8560(0.7);8.6870(4.9);8.6846(4.8);8.4211(0.4);8.4187(0.4);8.4001(0.5);8.3976(0.5);8.3288
(2.1);8.3253(2.2);8.3085(2.4);8.3046(2.3);7.9518(2.0);7.9399(0.4);7.9219(0.6);7.9013(0.5);7.8692(0.6);7.8658(0.7);7.8512(0.4);7.84
81(0.4);7.7575(1.4);7.7398(3.3);7.7265(0.8);7.7194(3.5);7.7134(3.1);7.7092(5.0);7.7044(3.8);7.6931(3.6);7.6900(4.4);7.4756(0.6);7.
.9);7.4573(1.2);7.4481(1.9);7.4380(1.7);7.4285(1.2);7.4184(1.1);7.4106(0.4);7.4063(0.5);7.3859(0.6);7.3624(3.5);7.3434(4.0);
482 4,36 7.3282(1.0);7.1883(1.2);7.1679(2.6);7.1496(1.6);6.9420(0.4);6.9215(1.7);6.9027(2.5);6.8841(1.1);6.8042(3.6);6.7838(3.2);6.4934(0.
6);6.3542(1.2);6.2153(0.6);5.2813(0.6);5.2666(1.4);5.2495(1.3);5.2341(0.6);4.3072(0.4);4.2994(0.6);4.2811(1.5);4.2661(2.6);4.2573(
2.4);4.2461(1.4);4.2383(1.6);4.2184(0.5);3.6443(1.0);3.6356(1.1);3.6076(2.1);3.5982(2.1);3.5702(1.1);3.5611(1.1);3.3361(8.5);3.120
4(16.0);2.8898(12.3);2.7309(11.2);2.6697(0.4);2.5464(0.5);2.5320(0.4);2.5051(52.8);2.5008(69.0);2.4966(53.0);2.3273(0.4);2.2272(
.2132(1.0);2.2032(1.0);2.1911(1.0);2.1802(0.8);2.1700(0.5);2.0712(0.8);2.0635(1.0);2.0557(1.1);2.0404(0.8);2.0291(0.7);2.020
2(0.7);2.0057(0.3);-0.0003(6.8)
483: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1530(3.3);9.1331(3.3);8.3144(0.4);8.2384(3.3);8.2175(3.5);7.8013(3.3);7.7859(4.0);7.7833(4.0);7.6663(12.9);7.6617(16.0);7.64
(3.0);7.6257(7.6);7.6217(9.8);7.6044(2.4);7.3530(3.1);7.3342(3.3);7.1978(1.5);7.1799(3.2);7.1626(1.9);7.1591(1.9);6.9502(2.2);6.
483 4,51 9325(3.8);6.9143(1.8);6.8162(4.2);6.7962(3.8);5.7539(0.9);5.3110(0.9);5.2992(1.9);5.2910(1.6);5.2806(1.9);5.2681(0.9);4.3430(0.8);
4.3318(1.2);4.3146(1.5);4.3034(1.9);4.2377(1.5);4.2126(2.1);4.1903(1.0);4.1861(0.8);3.8582(7.3);3.8486(9.8);3.8372(7.6);3.3198(91
.4);3.2545(9.6);2.8907(1.6);2.7317(1.5);2.6703(1.1);2.5307(28.2);2.5057(131.0);2.5014(169.2);2.4972(132.2);2.4303(0.4);2.3280(1.
0);2.3238(0.9);2.2931(0.5);2.2833(0.7);2.2694(0.8);2.2569(1.3);2.2474(1.3);2.2359(1.1);2.2245(1.0);2.1036(1.5);2.0895(1.1);2.0744(
1.0);2.0689(1.0);1.3522(0.3);1.2983(0.4);1.2583(0.6);1.2331(1.0);1.0454(0.5);1.0302(0.5);-0.0002(21.6)
484: 1H-NMR(400.0 MHz, d6-DMSO):
δ= (4.3);9.0323(4.2);8.5051(0.4);8.4393(4.2);8.4350(4.5);8.4201(4.4);8.4155(4.6);8.3939(8.8);8.3868(9.2);8.3142(1.4);7.6897
(0.4);7.6761(6.0);7.6726(6.4);7.6560(7.9);7.6525(8.2);7.6359(2.7);7.6087(1.6);7.5964(2.8);7.5831(4.2);7.5660(16.0);7.5467(7.3);7.5
7);7.4346(2.4);7.4274(2.4);7.4149(4.7);7.4079(4.6);7.3953(2.9);7.3881(2.7);7.3083(6.5);7.3013(7.6);7.2893(5.4);7.1723(2.8);7
484 1,75 .1545(5.6);7.1369(3.3);6.9047(4.1);6.8873(6.8);6.8693(3.2);6.7945(7.5);6.7740(6.8);5.2588(1.6);5.2429(3.5);5.2246(3.4);5.2103(1.5)
;4.7025(4.2);4.6839(6.9);4.6682(6.4);4.6465(2.6);4.6386(2.2);4.3431(1.0);4.3325(1.0);4.2970(6.9);4.2829(10.8);4.2688(9.9);4.2575(
8.7);4.2461(5.4);4.2278(0.8);4.0556(1.0);4.0378(3.1);4.0200(3.2);4.0022(1.1);3.7921(5.4);3.7775(8.0);3.7605(5.6);3.4061(0.4);3.320
9(633.3);3.2515(0.4);2.6703(5.2);2.5056(663.0);2.5013(852.3);2.4971(645.4);2.3840(0.4);2.3324(3.9);2.3280(5.2);2.3082(0.4);2.191
;2.1797(1.6);2.1597(1.9);2.1448(2.9);2.1293(2.4);2.1159(1.1);2.0312(2.3);2.0180(2.4);1.9883(14.6);1.2981(0.3);1.2593(0.4);1.
2345(1.1);1.1926(3.6);1.1748(7.1);1.1570(3.5);1.0448(6.4);1.0295(6.3);0.8540(0.3);0.0078(1.1);-0.0002(31.7)
485: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0447(1.3);9.0241(1.4);8.6831(5.0);8.3580(0.9);8.3422(1.0);8.3344(1.0);8.3188(1.0);7.6986(1.6);7.6939(3.0);7.6892(1.8);7.6815
(1.1);7.6582(1.9);7.6350(1.0);7.5067(4.9);7.5025(4.7);7.4296(0.9);7.4176(1.1);7.4087(1.0);7.2865(0.5);7.2766(0.9);7.2645(1.5);7.25
485 4,61 29(0.7);7.2405(2.7);7.2354(1.7);7.2291(1.7);7.2245(1.3);7.2186(1.6);5.5624(0.4);5.5433(1.1);5.5237(1.1);5.5041(0.4);3.8775(2.7);3.
8671(4.2);3.8565(2.8);3.5679(2.1);3.3194(17.3);3.2870(3.4);3.2784(3.4);3.0030(0.3);2.9938(0.4);2.9851(0.5);2.9765(0.6);2.9634(0.6
);2.9552(0.5);2.9048(0.4);2.8845(0.9);2.8646(0.7);2.8450(0.5);2.6708(0.5);2.6662(0.4);2.5661(0.3);2.5564(0.6);2.5453(0.8);2.5356(1
.0);2.5237(2.6);2.5059(67.0);2.5015(85.5);2.4972(64.1);2.3327(0.4);2.3285(0.5);2.3238(0.4);1.9882(1.2);1.9554(0.6);1.9449(0.3);1.9
351(0.6);1.9237(0.6);1.9042(0.6);1.3978(16.0);1.1752(0.6);-0.0002(3.5)
486: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.3542(5.2);9.3302(5.6);9.1745(3.3);9.1546(3.4);8.5530(16.0);8.4199(3.0);8.4043(3.3);8.3963(3.5);8.3808(3.2);8.1903(5.9);8.170
2(6.4);7.7341(3.5);7.7112(6.5);7.6943(2.1);7.6878(5.3);7.6762(3.0);7.6661(2.0);7.6563(1.7);7.5069(2.7);7.4864(3.7);7.4659(2.1);7.3
456(4.0);7.3267(4.4);7.1685(2.0);7.1506(4.3);7.1329(2.6);7.1302(2.5);6.9072(3.0);6.8889(5.2);6.8703(2.4);6.7892(5.9);6.7690(5.4);5
.2557(1.2);5.2415(2.6);5.2224(2.7);5.2081(1.2);4.2961(0.7);4.2873(1.0);4.2804(0.9);4.2686(2.4);4.2592(2.3);4.2526(2.8);4.2429(3.4)
486 2.63 ;4.2350(2.7);4.2211(2.2);4.2140(2.8);4.1933(1.0);4.1864(0.8);4.0381(0.5);4.0204(0.5);3.8901(13.8);3.8786(8.0);3.8613(1.1);3.3619(
1.0);3.3512(1.8);3.3217(51.2);3.3073(9.9);3.2947(4.6);3.2752(1.7);3.2647(1.0);2.6702(0.9);2.6662(0.7);2.5404(3.4);2.5054(114.7);2.
5012(147.6);2.4969(111.5);2.3277(0.9);2.2413(0.6);2.2284(0.9);2.2203(1.2);2.2072(1.7);2.1979(1.7);2.1856(1.8);2.1736(1.3);2.1643
(0.8);2.0621(1.2);2.0540(1.7);2.0471(1.9);2.0314(1.4);2.0198(1.3);2.0125(1.2);2.0049(0.8);1.9975(0.6);1.9883(2.2);1.2586(0.4);1.23
50(0.4);1.1927(0.6);1.1749(1.1);1.1589(5.2);1.0697(4.9);1.0455(0.4);1.0301(0.4);0.1459(0.7);0.0073(6.8);-0.0002(147.2);-
0.1497(0.8)
490: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1477(4.1);9.1276(4.1);8.5827(12.2);8.3171(2.9);8.3016(3.0);8.2939(3.1);8.2782(2.8);7.9206(2.2);7.6395(3.1);7.6171(5.3);7.594
(2.9);7.3628(2.2);7.3551(2.2);7.3452(2.4);7.3386(2.3);7.2276(2.8);7.2178(2.4);7.2081(3.6);7.1982(3.5);7.1819(2.0);7.1787(2.0);7.1
607(4.1);7.1434(6.7);7.1244(2.7);7.0096(0.5);6.9931(0.7);6.9503(3.6);6.9211(5.0);6.9062(4.3);6.8877(2.0);6.7966(5.4);6.7764(4.8);5
490 2.96 .2635(1.1);5.2495(2.4);5.2301(2.4);5.2154(1.1);4.2964(0.9);4.2773(2.1);4.2608(2.5);4.2515(2.8);4.2266(2.2);4.1995(0.8);4.0557(1.2)
;4.0379(3.4);4.0201(3.4);4.0023(1.1);3.8713(11.2);3.3206(387.1);3.2966(7.4);3.2905(7.5);3.2825(7.0);3.2732(5.1);3.2568(2.4);3.239
(1.2);2.6747(1.8);2.6703(2.4);2.6661(1.8);2.5057(315.1);2.5013(404.4);2.4970(301.6);2.4284(0.4);2.3278(5.0);2.2944(14.1);2.2808
(14.3);2.2321(3.2);2.2139(1.4);2.2024(1.5);2.1933(1.5);2.1807(1.2);2.0542(1.7);2.0257(1.2);2.0200(1.1);2.0040(0.6);1.9883(14.3);1.
8912(14.0);1.8683(13.8);1.3979(16.0);1.2586(0.3);1.2359(0.8);1.1927(3.8);1.1749(7.5);1.1571(3.7);1.0448(0.8);1.0296(0.8);-
0.0002(5.2)
515: 1H-NMR(400.0 MHz, O):
δ= 9.1233(0.6);9.1025(0.6);8.5606(1.9);8.2915(0.5);8.2868(0.5);8.2717(0.5);8.2669(0.5);8.1363(10.5);7.7032(0.6);7.6996(0.6);7.683
515 3.00 2(0.8);7.6797(0.7);7.6686(0.8);7.6482(1.2);7.6420(0.9);7.4385(0.4);7.4299(0.4);7.3534(0.6);7.3361(0.7);7.1628(0.5);7.1460(0.3);7.1
3);6.9168(0.4);6.8993(0.6);6.7981(0.7);6.7787(0.6);4.2597(0.6);4.2485(0.5);4.2391(0.3);3.8361(0.4);3.8217(0.4);3.8088(0.5);3
.3351(2.2);3.3298(2.2);3.3070(2.3);3.1311(0.5);3.1135(0.7);3.0824(4.2);2.6708(0.4);2.5061(48.0);2.5017(62.2);2.4973(46.5);2.3283(
0.4);2.0857(16.0);2.0411(0.4);2.0329(0.4);1.7082(0.4);-0.0002(7.0)
516: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.8758(2.0);8.8723(2.0);8.8550(2.1);8.7191(6.4);8.7148(6.2);8.3524(1.2);8.3445(1.3);8.3368(1.4);8.3289(2.5);8.3210(1.5);8.3134
(1.4);8.3055(1.3);7.7689(2.3);7.7459(4.2);7.7227(2.4);7.7125(0.7);7.7045(0.7);7.6975(1.2);7.6926(1.2);7.6839(1.1);7.6712(1.2);7.66
40(0.7);7.6561(0.6);7.6484(0.5);7.4239(1.8);7.4047(1.9);7.3115(0.8);7.2995(1.1);7.2892(1.4);7.2665(0.7);7.1748(1.3);7.1716(1.4);7.
516 3,90 1539(2.8);7.1364(1.7);7.1330(1.7);6.9314(2.0);6.9130(3.4);6.8946(1.6);6.7840(3.8);6.7652(3.4);5.2246(0.7);5.2093(1.6);5.1923(1.6);
.1773(0.6);4.2981(0.4);4.2901(0.6);4.2828(0.5);4.2711(1.6);4.2620(1.6);4.2542(2.4);4.2456(2.6);4.2255(1.6);4.2200(1.2);4.2049(0.
4);4.1983(0.5);4.0560(0.4);4.0382(1.3);4.0204(1.3);4.0027(0.5);3.5003(16.0);3.4938(15.3);3.4796(0.6);3.3204(13.4);3.2904(24.9);3.
2554(0.4);2.6753(0.4);2.6707(0.6);2.6667(0.4);2.5061(71.2);2.5017(92.2);2.4972(69.1);2.3327(0.4);2.3285(0.5);2.3241(0.4);2.1784(
0.7);2.1686(0.8);2.1561(1.0);2.1492(1.0);2.1437(1.0);2.1362(0.8);2.0592(0.7);2.0512(0.9);2.0433(1.2);2.0354(1.1);2.0257(0.9);2.017
8(0.8);2.0087(0.8);2.0018(0.7);1.9887(6.0);1.3975(4.4);1.1929(1.5);1.1751(3.0);1.1573(1.4);0.0079(0.5);-0.0002(12.2);-0.0082(0.5)
518: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0894(1.9);9.0689(1.9);8.5253(6.9);8.4176(1.8);8.3983(2.0);7.9524(2.4);7.7616(2.1);7.7592(2.1);7.7438(2.6);7.7414(2.4);7.7153
(0.8);7.7027(1.6);7.6900(0.8);7.6238(6.7);7.6194(12.3);7.6103(4.6);7.6061(3.5);7.6009(1.5);7.5766(1.8);7.5583(2.0);7.5555(2.0);7.5
374(1.5);7.3313(1.8);7.3134(1.9);7.1897(0.9);7.1870(0.8);7.1692(1.8);7.1516(1.2);7.1480(1.1);6.9265(1.3);6.9239(1.3);6.9076(2.2);6
518 2.19 .8894(1.1);6.8867(1.0);6.8100(2.5);6.7896(2.3);5.2760(0.5);5.2619(1.1);5.2426(1.1);5.2280(0.5);4.6943(1.5);4.6787(2.2);4.6755(2.2)
;4.6691(1.7);4.6600(1.9);4.6536(2.3);4.6505(2.1);4.6349(1.6);4.3095(0.3);4.2989(1.9);4.2902(3.4);4.2843(4.8);4.2753(5.3);4.2612(3.
2);3.8016(1.6);3.7850(2.6);3.7698(1.8);3.3394(0.5);3.3204(30.7);3.3072(1.3);3.2882(0.7);3.2737(0.4);2.8904(16.0);2.7318(13.8);2.6
747(0.4);2.6701(0.5);2.6659(0.4);2.5058(64.7);2.5014(82.8);2.4969(60.3);2.4927(29.6);2.3281(0.5);2.1972(0.4);2.1851(0.4);2.1757(
0.6);2.1616(0.9);2.1460(0.7);2.1320(0.3);2.0740(2.6);2.0620(0.8);2.0505(0.8);2.0356(0.6);2.0263(0.6);2.0164(0.5);0.0079(1.5);-
0.0002(38.6);-0.0085(1.5)
522: 1H-NMR(601.6 MHz, d6-DMSO):
δ= 9.0428(0.8);9.0296(0.8);8.1535(0.8);8.1513(0.8);8.1394(0.9);8.1372(0.9);7.7631(0.8);7.7608(0.8);7.7512(1.0);7.7490(0.9);7.6672
522 2.88 7.6640(3.9);7.6101(0.9);7.6069(1.5);7.6038(0.7);7.5892(0.8);7.5772(0.8);7.5752(0.8);7.5632(0.7);7.3301(0.6);7.3172(0.7);7.18
57(0.4);7.1831(0.4);7.1716(0.7);7.1600(0.4);7.1574(0.4);6.9397(0.5);6.9380(0.5);6.9257(0.8);6.9149(0.4);6.9132(0.4);6.8047(0.9);6.
.9);5.7502(1.4);5.2771(0.4);5.2642(0.4);4.2903(0.4);4.2268(0.3);4.2106(0.5);3.3053(4.6);3.0336(16.0);2.5150(7.7);2.5060(4.4
);2.5030(9.2);2.5000(12.7);2.4970(9.2);2.4940(4.3);1.3973(0.8);-0.0002(9.1)
523: 1H-NMR(601.6 MHz, d6-DMSO):
δ= 9.0676(0.4);9.0547(0.6);9.0421(0.3);8.1664(0.9);8.1630(0.9);8.1534(1.1);8.1499(1.0);7.6767(1.1);7.6741(1.1);7.6632(1.3);7.6607
(1.2);7.5844(0.6);7.5726(1.4);7.5593(2.3);7.5550(1.3);7.5467(0.4);7.4260(0.6);7.4174(0.4);7.3207(0.5);7.3128(0.9);7.3014(1.2);7.17
523 2.11 40(0.4);7.1635(0.8);7.1501(0.4);6.9255(0.4);6.9132(0.5);6.7968(1.0);6.7823(0.9);5.3055(0.4);5.2630(0.4);5.2568(0.4);4.2883(0.4);4.
2826(0.4);4.2086(0.4);4.1667(0.4);3.3028(42.7);3.0387(16.0);3.0127(0.7);2.6147(0.4);2.6116(0.5);2.6084(0.4);2.6054(0.5);2.5208(0.
9);2.5178(1.1);2.5147(1.2);2.5059(28.6);2.5029(63.1);2.4999(88.1);2.4968(63.1);2.4938(29.0);2.4136(4.2);2.3869(0.4);2.3840(0.5);2
.3811(0.4);2.2183(0.4);2.2113(0.4);1.3983(11.6);0.0052(1.4);-0.0002(61.6);-0.0058(2.3)
524: 1H-NMR(601.6 MHz, d6-DMSO):
δ= 9.0713(0.8);9.0578(0.8);8.1990(0.9);8.1846(0.9);7.7017(0.8);7.6914(1.0);7.6896(1.0);7.6095(0.9);7.5972(1.0);7.5837(0.8);7.5631
(0.4);7.3217(0.8);7.3096(0.8);7.1789(0.8);7.1680(1.0);7.1566(0.6);6.9311(0.6);6.9192(1.0);6.9080(0.6);6.8015(1.0);6.7876(0.9);5.27
524 2.34 04(0.6);5.2579(0.5);4.3124(0.4);4.3049(0.4);4.2890(0.4);4.2232(0.5);4.2075(0.5);4.1930(0.3);4.1891(0.4);3.3025(59.1);3.2911(0.4);3
.0396(16.0);3.0127(0.9);2.6120(0.9);2.6084(0.7);2.6057(0.8);2.5210(1.5);2.5180(1.8);2.5145(1.8);2.5058(51.6);2.5030(107.0);2.500
0(145.0);2.4970(104.8);2.4942(49.6);2.4679(7.8);2.3842(1.0);2.2364(0.4);2.2282(0.3);2.2188(0.4);2.0703(0.4);1.3984(0.7);1.2362(0.
8);0.0966(0.4);0.0052(2.0);-0.0002(82.2);-0.0057(3.6);-0.1001(0.5)
525: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1140(1.1);9.1057(1.1);9.0945(1.2);9.0855(1.0);8.5540(6.4);8.3143(0.7);8.2423(1.9);8.2373(1.8);8.2225(2.0);8.2176(2.0);7.7020
(2.3);7.6983(2.3);7.6822(3.5);7.6783(2.8);7.6659(3.1);7.6457(5.0);7.6395(3.2);7.6264(1.0);7.4582(0.8);7.4470(0.9);7.4388(1.7);7.42
79(1.6);7.4191(1.1);7.4078(0.9);7.3495(2.8);7.3293(3.4);7.3094(0.8);7.1767(1.0);7.1592(2.0);7.1411(1.3);6.9254(1.4);6.9072(2.4);6.
525 2.62 8882(1.1);6.7955(2.8);6.7753(2.5);5.2371(1.1);5.2227(1.1);4.2896(0.5);4.2708(1.3);4.2555(2.3);4.2473(2.1);4.2358(1.2);4.2282(1.4);
4.2078(0.4);4.2005(0.3);3.5676(0.3);3.3679(1.4);3.3498(4.3);3.3208(300.6);3.0155(14.3);2.6749(1.8);2.6704(2.3);2.6663(1.7);2.523
;2.5058(309.0);2.5014(394.8);2.4970(286.9);2.3325(1.8);2.3280(2.3);2.3240(1.7);2.2142(0.5);2.2047(0.5);2.1922(0.8);2.1823(
0.8);2.1699(0.8);2.1586(0.6);2.1484(0.4);2.0360(0.8);2.0218(0.7);2.0092(0.6);2.0012(0.6);1.9885(0.8);1.3979(16.0);1.2461(3.0);1.22
88(6.1);1.2111(3.0);1.1924(0.3);1.1750(0.4);-0.0002(1.8)
526: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1145(1.7);9.0942(1.7);8.5403(7.4);8.1746(1.7);8.1548(1.8);7.6988(2.3);7.6951(2.4);7.6788(2.9);7.6748(3.6);7.6559(2.9);7.6357
(3.6);7.6280(3.1);7.6136(1.0);7.4537(0.9);7.4429(0.9);7.4343(1.8);7.4235(1.7);7.4147(1.2);7.4039(1.0);7.3536(3.2);7.3346(3.1);7.30
83(0.9);7.3051(0.8);7.1757(1.0);7.1569(2.0);7.1382(1.2);6.9241(1.2);6.9056(2.1);6.8868(1.0);6.7922(2.8);6.7720(2.5);5.7549(1.2);5.
526 3.29 2457(0.5);5.2315(1.2);5.2132(1.2);5.1980(0.5);4.2829(0.5);4.2761(0.4);4.2640(1.2);4.2546(1.2);4.2470(1.8);4.2373(1.9);4.2238(1.1);
4.2164(1.3);4.1962(0.4);4.1885(0.4);3.9291(0.3);3.9131(0.8);3.8976(1.1);3.8822(0.8);3.8664(0.4);3.5675(0.5);3.3231(30.0);2.9033(1
6.0);2.5054(39.1);2.5010(51.0);2.4966(38.0);2.2017(0.4);2.1928(0.5);2.1801(0.8);2.1703(0.8);2.1590(0.8);2.1480(0.6);2.1392(0.4);2.
0400(0.6);2.0328(0.8);2.0253(0.9);2.0145(0.7);2.0089(0.7);1.9987(0.6);1.9884(0.8);1.3068(3.5);1.2921(5.6);1.2777(3.4);1.2512(3.4);
1.2373(5.5);1.2230(3.7)
527: 1H-NMR(400.0 MHz, O):
δ= 9.1286(1.0);9.1083(1.1);8.6686(4.7);8.4516(3.2);8.2373(1.1);8.2341(1.1);8.2161(1.3);8.2128(1.2);7.8200(1.1);7.8167(1.2);7.8022
(1.5);7.7989(1.4);7.7348(2.1);7.7297(2.4);7.6837(1.2);7.6655(1.2);7.6626(1.3);7.6443(2.1);7.6384(11.9);7.6320(2.0);7.3779(1.0);7.3
527 3.63 605(1.1);7.1943(0.5);7.1905(0.5);7.1728(1.0);7.1559(0.7);7.1521(0.6);6.9502(0.7);6.9476(0.8);6.9293(1.3);6.9130(0.6);6.9103(0.6);6
.8094(1.4);6.8075(1.4);6.7889(1.4);5.2566(0.7);5.2372(0.7);4.2852(0.6);4.2699(1.2);4.2609(1.1);4.2491(0.6);4.2412(0.7);3.3594(0.7)
;3.3415(2.2);3.3200(56.0);3.0101(9.2);2.6752(0.5);2.6706(0.7);2.6662(0.5);2.5237(2.3);2.5103(47.2);2.5060(93.7);2.5015(122.2);2.4
970(89.4);2.4929(45.2);2.3326(0.6);2.3283(0.7);2.3238(0.6);2.2063(0.4);2.1961(0.4);2.1845(0.5);2.1724(0.3);2.0710(0.4);2.0632(0.5
);2.0484(0.4);2.0365(0.3);1.3978(16.0);1.2311(2.6);1.2134(5.1);1.1956(2.2);-0.0002(0.5)
534: 1H-NMR(400.0 MHz, O):
δ= 10.4184(1.5);9.1346(1.4);9.1144(1.4);8.6595(5.5);8.1798(1.4);8.1587(1.5);7.8117(1.4);7.7965(1.8);7.7941(1.7);7.7032(0.5);7.681
(1.4);7.6605(1.7);7.6458(10.6);7.3875(1.3);7.3689(1.4);7.1966(0.6);7.1784(1.4);7.1608(0.9);6.9817(0.5);6.9771(0.9);6.9724(0.5);6.
534 4,51 9544(1.0);6.9360(1.6);6.9173(0.8);6.8121(1.9);6.8008(2.0);6.7960(2.5);5.2728(0.4);5.2584(0.8);5.2391(0.9);5.2247(0.4);4.2869(0.8);
4.2708(1.1);4.2589(1.1);4.2454(0.7);4.2376(0.9);3.8866(0.7);3.8705(1.0);3.8538(0.7);3.3288(47.9);2.9128(10.7);2.6782(0.6);2.5136(
82.9);2.5093(107.6);2.5050(80.2);2.3403(0.5);2.3361(0.6);2.3319(0.5);2.2178(0.4);2.2040(0.5);2.1942(0.6);2.1821(0.6);2.1704(0.5);
2.0675(0.5);2.0600(0.6);2.0439(0.5);2.0335(0.4);2.0261(0.4);1.4053(16.0);1.2887(5.0);1.2725(5.0);1.2420(5.3);1.2258(5.0)
535: 1H-NMR(400.0 MHz, d6-DMSO):
δ= (0.8);8.8516(0.8);8.7041(2.9);8.2580(1.2);8.2352(1.4);7.8664(1.4);7.8435(1.3);7.6619(3.4);7.4145(0.7);7.3959(0.8);7.1707
535 4.46 7.1537(0.7);7.1329(0.4);6.9285(0.5);6.9101(0.9);6.8908(0.4);6.7836(1.0);6.7635(0.9);5.2026(0.5);5.1839(0.5);4.2665(0.4);4.25
83(0.4);4.2499(0.6);4.2428(0.6);4.2229(0.4);4.2156(0.5);3.4842(7.0);3.3198(29.6);3.2787(6.2);2.6708(0.3);2.5055(44.2);2.5014(56.4
);2.4974(43.0);2.3286(0.3);2.0317(0.4);1.9886(0.5);1.3980(16.0);-0.0003(15.4)
540: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1842(4.4);9.1640(4.4);8.6741(16.0);8.4617(0.4);8.3556(3.0);8.3401(3.2);8.3321(3.3);8.3164(3.3);7.6826(3.4);7.6594(6.4);7.636
2(3.2);7.4662(4.8);7.4486(5.5);7.4447(5.5);7.4269(4.5);7.3795(4.1);7.3605(4.4);7.1914(2.0);7.1887(2.0);7.1711(4.2);7.1530(2.6);7.1
500(2.5);6.9408(3.0);6.9222(5.1);6.9035(2.4);6.8037(5.7);6.7840(5.1);5.2738(1.2);5.2596(2.6);5.2405(2.6);5.2262(1.1);4.3027(1.0);4
540 3.72 .2958(0.9);4.2846(2.4);4.2751(2.3);4.2681(2.8);4.2591(3.5);4.2517(2.7);4.2384(2.1);4.2312(2.7);4.2103(1.0);4.2029(0.8);4.0555(0.7)
;4.0377(1.9);4.0199(1.9);4.0021(0.7);3.9008(1.0);3.8822(8.3);3.8717(14.3);3.8610(8.7);3.3197(180.6);3.2906(5.5);3.2801(11.1);3.26
87(10.7);3.2580(4.7);3.2387(1.4);2.6745(1.6);2.6702(2.1);2.5055(277.9);2.5013(357.7);2.4970(267.8);2.3321(1.6);2.3279(2.2);2.255
3(0.6);2.2451(0.9);2.2347(1.2);2.2216(1.7);2.2121(1.8);2.1999(1.8);2.1877(1.3);2.1789(0.8);2.0746(1.6);2.0676(1.9);2.0556(1.4);2.0
399(1.3);2.0329(1.2);1.9883(8.1);1.3978(1.0);1.2592(0.3);1.2341(0.8);1.1926(2.1);1.1748(4.1);1.1569(2.1);-0.0002(42.6)
541: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9748(0.6);8.9542(0.6);8.4871(0.4);8.4708(2.2);8.4638(0.5);8.4484(0.4);8.3359(2.1);7.9088(0.3);7.8960(0.4);7.7294(0.7);7.7258
(0.8);7.7093(0.9);7.7057(0.9);7.5431(0.5);7.5208(0.8);7.4979(0.5);7.4693(0.5);7.4610(0.4);7.4497(1.0);7.4300(0.6);7.3462(0.3);7.34
541 1.78 );7.3365(0.4);7.3272(1.1);7.3228(0.7);7.3076(0.8);7.3033(1.1);7.2820(0.7);7.1749(0.3);7.1716(0.3);7.1539(0.7);7.1363(0.4);7.
1330(0.4);6.9111(0.5);6.8923(0.8);6.8739(0.4);6.7934(0.9);6.7732(0.8);5.2315(0.4);5.2128(0.4);4.2613(0.7);4.2476(1.2);4.2347(0.7);
3.3288(21.4);3.0736(2.0);3.0669(1.4);3.0611(2.2);2.5180(17.5);2.5140(34.2);2.5095(44.3);2.5051(32.0);2.1427(0.3);2.0180(0.3);1.9
968(0.9);1.4060(16.0);1.2437(0.4);1.1831(0.4)
542: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9915(1.7);8.9705(1.8);8.5165(1.4);8.5013(1.5);8.4929(1.5);8.4778(1.3);8.3922(7.2);7.9585(0.8);7.9451(1.0);7.9379(1.0);7.9251
(0.8);7.6623(0.4);7.6538(0.5);7.6394(0.9);7.6341(0.9);7.6261(0.9);7.6139(0.9);7.5986(0.5);7.5902(0.4);7.5685(1.5);7.5457(2.8);7.52
28(1.5);7.3069(1.8);7.2877(2.0);7.2267(0.6);7.2113(0.8);7.2049(1.0);7.1995(1.0);7.1755(1.5);7.1717(1.5);7.1544(2.2);7.1367(1.4);7.
542 1.66 1332(1.2);6.9136(1.5);6.8949(2.6);6.8763(1.2);6.7934(3.0);6.7729(2.8);5.7556(16.0);5.2463(0.6);5.2312(1.4);5.2118(1.4);5.1972(0.6
);4.2576(2.0);4.2458(3.6);4.2342(2.0);4.0382(0.6);4.0204(0.6);3.3231(35.1);3.0726(4.9);3.0657(6.0);3.0603(5.8);3.0534(4.9);2.6753(
0.3);2.6706(0.4);2.5103(28.6);2.5062(55.4);2.5017(70.8);2.4972(50.6);2.3286(0.4);2.1779(0.8);2.1644(0.8);2.1576(0.7);2.1428(1.0);
2.1289(1.0);2.1160(0.4);2.0254(0.8);2.0189(0.8);2.0043(0.7);1.9887(3.0);1.3974(0.6);1.3525(0.5);1.2988(0.3);1.2590(0.5);1.2344(1.
2);1.1928(0.7);1.1750(1.4);1.1572(0.7);0.0079(1.9);-0.0002(47.9);-0.0085(1.8)
543: 1H-NMR(400.0 MHz, O):
δ= 9.1849(4.4);9.1647(4.3);8.7031(1.0);8.6905(16.0);8.6712(0.7);8.3740(3.5);8.3584(3.8);8.3503(3.9);8.3348(3.6);8.3149(0.5);7.683
6(3.9);7.6607(7.1);7.6380(3.7);7.6243(0.4);7.3846(4.1);7.3651(4.7);7.2348(0.5);7.2223(4.0);7.1898(5.8);7.1718(5.0);7.1540(3.1);7.1
505(2.8);6.9435(3.5);6.9267(5.9);6.9083(2.7);6.8046(6.4);6.7845(5.9);6.7131(0.4);5.7551(0.4);5.2587(2.7);5.2416(2.7);5.2278(1.2);4
543 4.25 .3052(1.2);4.2978(1.1);4.2860(2.8);4.2761(2.8);4.2697(3.2);4.2611(3.9);4.2528(2.9);4.2390(2.5);4.2324(3.0);4.2105(1.1);4.2039(0.9)
;4.0559(0.6);4.0377(1.8);4.0200(1.8);4.0019(0.6);3.8664(15.1);3.3202(106.3);3.2860(10.0);3.2751(9.5);2.6740(1.4);2.6705(1.8);2.66
60(1.4);2.5055(243.9);2.5012(311.2);2.4968(223.6);2.3279(1.8);2.3233(1.3);2.2376(1.3);2.2238(1.9);2.2145(2.0);2.2028(2.0);2.1943
(1.4);2.1895(1.5);2.0685(1.8);2.0522(1.6);1.9883(7.3);1.3976(5.4);1.3510(0.4);1.2985(0.4);1.2588(0.4);1.2354(1.3);1.1925(1.9);1.17
47(3.9);1.1568(1.8);0.1464(0.7);0.0222(0.4);0.0079(6.3);-0.0002(153.6);-0.0085(5.8);-0.1493(0.7)
544: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1606(3.0);9.1401(3.1);8.6477(12.1);8.2912(2.2);8.2755(2.4);8.2676(2.5);8.2521(2.3);7.6215(2.5);7.5986(4.5);7.5757(2.5);7.379
1(2.8);7.3620(3.0);7.1920(1.4);7.1885(1.4);7.1709(2.9);7.1534(1.8);7.1497(1.7);6.9443(2.1);6.9421(2.1);6.9256(3.6);6.9236(3.5);6.9
073(1.7);6.9047(1.7);6.8055(4.1);6.7851(3.8);6.6355(2.1);5.7553(12.7);5.2771(0.8);5.2633(1.8);5.2443(1.8);5.2300(0.8);4.3146(0.5);
544 2.80 4.3063(0.7);4.2990(0.6);4.2870(1.6);4.2781(1.6);4.2711(2.0);4.2624(2.4);4.2554(1.9);4.2420(1.5);4.2344(1.9);4.2136(0.7);4.2060(0.
);3.8626(9.5);3.8532(5.6);3.8342(0.7);3.8221(0.4);3.3200(38.5);3.2903(3.2);3.2796(6.3);3.2671(6.0);3.2350(1.0);2.6787(0.3);2.670
2(0.8);2.5231(2.6);2.5097(54.0);2.5055(106.3);2.5010(136.5);2.4965(96.8);2.4922(46.2);2.4203(16.0);2.3242(1.1);2.2576(0.5);2.243
6(0.7);2.2357(0.9);2.2233(1.1);2.2137(1.2);2.2007(1.2);2.1894(0.9);2.1807(0.6);2.0829(7.5);2.0400(1.0);2.0318(0.8);2.0158(0.4);1.9
882(0.8);1.5432(0.7);1.3973(1.0);1.3513(0.4);1.2587(0.5);1.2336(0.9);1.1746(0.4);0.1459(0.4);0.0079(3.7);-0.0002(97.6);-
0.0085(3.4);-0.1493(0.4)
545: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0012(2.2);8.9809(2.3);8.5133(1.7);8.4986(1.6);8.4897(1.6);8.4749(1.4);8.4325(7.9);8.2292(0.6);8.0071(1.3);7.9948(1.2);7.6863
(14.1);7.5760(1.7);7.5526(3.2);7.5293(1.7);7.3076(2.2);7.2888(2.2);7.1799(1.0);7.1765(1.2);7.1589(2.2);7.1414(1.4);7.1380(1.3);6.9
7);6.9184(1.6);6.9022(2.7);6.8999(2.7);6.8839(1.3);6.8811(1.3);6.8673(3.0);6.8082(0.3);6.7983(3.0);6.7961(3.0);6.7779(2.8);6
545 1.90 .7756(2.6);5.7552(16.0);5.2468(0.7);5.2319(1.5);5.2124(1.4);5.1971(0.6);4.2623(2.5);4.2494(4.1);4.2359(2.4);4.0381(0.9);4.0202(1.
0);3.3223(44.4);3.0701(8.6);3.0576(8.5);3.0357(0.8);2.6753(0.4);2.6709(0.6);2.6665(0.4);2.5106(38.2);2.5063(75.6);2.5018(97.9);2.
4973(70.3);2.4929(33.9);2.3332(0.4);2.3285(0.6);2.3240(0.4);2.1939(0.3);2.1795(0.8);2.1646(0.8);2.1595(0.7);2.1436(1.1);2.1303(1.
0);2.1160(0.4);2.0570(0.5);2.0446(1.0);2.0307(1.2);2.0172(0.7);2.0089(0.8);1.9887(4.5);1.2590(0.4);1.2335(0.7);1.1928(1.2);1.1750(
2.3);1.1573(1.2);-0.0002(3.4)
546: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1871(4.2);9.1669(4.3);8.6805(16.0);8.3627(2.8);8.3473(3.0);8.3393(3.2);8.3236(2.9);7.6904(3.2);7.6672(6.0);7.6441(3.1);7.539
4(2.8);7.4347(8.4);7.4122(8.4);7.3793(3.9);7.3591(9.8);7.1913(2.0);7.1880(2.1);7.1785(3.6);7.1709(4.1);7.1531(2.5);7.1496(2.3);6.9
405(2.8);6.9219(4.7);6.9054(2.3);6.9030(2.3);6.8038(5.3);6.7850(4.9);5.7551(10.2);5.2756(1.1);5.2613(2.4);5.2412(2.4);5.2271(1.1);
546 3.68 4.3122(0.6);4.3044(1.0);4.2852(2.2);4.2768(2.1);4.2686(2.6);4.2604(3.2);4.2535(2.5);4.2393(2.0);4.2322(2.6);4.2123(1.0);3.8842(7.
735(13.0);3.8634(7.8);3.3201(103.8);3.2938(4.9);3.2835(10.0);3.2721(9.7);3.2610(4.3);3.2399(1.3);2.6748(1.0);2.6701(1.4);2.
6655(1.0);2.5055(190.0);2.5011(244.6);2.4967(177.2);2.4494(0.6);2.3276(1.4);2.3242(1.1);2.2561(0.6);2.2356(1.1);2.2230(1.5);2.21
42(1.6);2.2015(1.6);2.1897(1.2);2.1810(0.7);2.0889(0.9);2.0734(1.5);2.0661(1.7);2.0509(1.3);2.0397(1.2);2.0325(1.2);1.9882(0.6);1.
.4);1.2589(0.5);1.2354(1.3);0.1459(0.4);0.0078(3.5);-0.0002(86.5);-0.0082(3.6);-0.1499(0.4)
547: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9803(2.7);8.9596(2.7);8.4533(1.8);8.4383(2.0);8.4292(2.0);8.4129(11.0);7.9213(1.6);7.9079(1.6);7.5407(2.0);7.5240(2.5);7.517
(4.0);7.4943(2.0);7.3844(5.7);7.3618(5.8);7.3439(4.5);7.3054(2.7);7.2871(2.9);7.1782(1.3);7.1748(1.4);7.1612(3.1);7.1396(1.7);7.1
547 1.81 361(1.6);6.9171(2.0);6.8987(3.4);6.8820(1.6);6.8798(1.6);6.7965(3.8);6.7760(3.5);5.7553(11.4);5.2518(0.8);5.2370(1.7);5.2169(1.7);
.2030(0.8);4.2627(2.9);4.2496(5.0);4.2364(2.9);4.0557(1.2);4.0379(3.6);4.0201(3.7);4.0023(1.2);3.3210(22.0);3.0647(10.6);3.0522(
.4);2.6745(0.4);2.6702(0.5);2.6655(0.4);2.5056(68.9);2.5012(88.8);2.4968(63.5);2.3277(0.6);2.1932(0.4);2.1801(0.9);2.1656(0.9);
2.1595(0.8);2.1448(1.4);2.1311(1.3);2.1176(0.5);2.0530(0.5);2.0414(1.2);2.0266(1.4);2.0130(0.8);2.0054(1.0);1.9884(16.0);1.3975(2
.5);1.1926(4.0);1.1748(8.0);1.1570(3.9);0.0078(1.4);-0.0002(35.4);-0.0085(1.2)
548: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1827(2.9);9.1746(2.9);9.1624(3.2);9.1541(2.8);8.6506(10.0);8.6441(9.3);8.3965(3.4);8.3810(3.7);8.3731(3.8);8.3574(3.6);8.315
7(0.3);7.7100(3.6);7.6872(6.5);7.6643(3.3);7.5745(1.2);7.5534(2.7);7.5321(2.9);7.5111(1.3);7.3747(4.9);7.3560(6.6);7.3355(3.1);7.3
548 3.33 257(2.3);7.3156(1.9);7.3046(1.1);7.2896(1.7);7.2743(2.2);7.2492(2.1);7.2300(1.0);7.1862(2.3);7.1655(4.9);7.1478(3.0);6.9332(3.2);6
.9148(5.4);6.8959(2.6);6.8004(6.6);6.7799(6.0);5.7555(3.2);5.2752(0.8);5.2508(2.6);5.2420(2.6);4.3002(1.2);4.2936(1.0);4.2819(2.8)
3(2.7);4.2654(3.1);4.2555(3.7);4.2280(2.8);4.2046(1.0);3.8768(16.0);3.3206(24.3);3.2960(10.6);3.2914(10.6);3.2511(1.4);2.67
02(1.3);2.5058(182.0);2.5015(222.3);2.4972(161.2);2.3286(1.3);2.2435(1.1);2.2317(1.3);2.2215(1.8);2.2084(1.8);2.1980(1.8);2.0647
(2.1);2.0577(1.9);2.0466(1.7);2.0297(1.5);1.9886(0.8);1.3976(0.6);1.2331(0.4);1.1748(0.4);0.1462(0.3);-0.0002(64.9)
549: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1861(3.0);9.1775(3.0);9.1663(3.2);9.1573(2.8);8.6558(10.4);8.6485(9.7);8.4036(3.6);8.3879(4.0);8.3801(4.1);8.3645(3.7);7.715
8(3.7);7.6930(6.8);7.6701(3.6);7.4984(0.6);7.4765(1.7);7.4585(2.0);7.4508(1.9);7.4253(0.8);7.3779(5.5);7.3587(6.9);7.3388(2.2);7.3
549 3.59 334(2.2);7.3157(1.4);7.2930(0.5);7.1848(2.4);7.1676(5.0);7.1497(3.0);6.9361(3.1);6.9174(5.4);6.8989(2.5);6.8016(6.9);6.7814(6.3);5
.7559(2.5);5.2740(0.8);5.2602(2.1);5.2512(2.6);5.2405(2.6);5.2313(2.0);4.3086(0.8);4.3013(1.2);4.2948(1.0);4.2818(2.8);4.2730(2.7)
;4.2658(3.2);4.2565(3.6);4.2288(2.8);4.2034(1.0);3.8760(16.0);3.3215(55.4);3.2905(11.0);3.2507(1.4);2.6706(0.9);2.5058(119.4);2.5
015(151.2);2.4972(110.3);2.3287(0.9);2.3246(0.7);2.2345(1.2);2.2183(1.8);2.2090(1.8);2.2017(1.8);2.0818(1.2);2.0746(1.7);2.0663(
2.0);2.0592(1.9);2.0404(1.5);2.0321(1.5);2.0254(1.2);1.2343(0.6);-0.0002(41.6)
550: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.2014(2.6);9.1811(2.6);8.7076(8.9);8.4095(1.7);8.3941(1.9);8.3860(1.9);8.3705(1.8);7.7354(16.0);7.7206(2.0);7.6972(3.6);7.674
0(1.8);7.3844(2.5);7.3654(2.7);7.1898(1.2);7.1721(2.6);7.1543(1.6);6.9445(1.7);6.9254(3.0);6.9075(1.5);6.8061(3.4);6.7859(3.1);5.7
550 3.94 556(5.5);5.2691(0.7);5.2558(1.6);5.2362(1.6);5.2219(0.7);4.3031(0.6);4.2966(0.6);4.2847(1.4);4.2684(1.7);4.2592(2.1);4.2512(1.6);4
.2303(1.6);4.2087(0.6);4.2024(0.5);3.8768(8.7);3.3202(36.4);3.2865(6.7);3.2752(6.4);3.2441(0.8);2.6703(0.7);2.5053(96.3);2.5013(1
18.5);2.4974(89.0);2.3275(0.6);2.2343(0.7);2.2204(1.0);2.2115(1.1);2.1996(1.1);2.1886(0.8);2.0703(1.2);2.0576(0.9);2.0431(0.8);2.0
347(0.7);1.3974(0.4);1.2345(0.4);-0.0002(27.3)
553: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1942(4.5);9.1740(4.6);8.6557(16.0);8.3213(6.5);8.2983(7.3);8.2397(0.6);7.8522(0.4);7.8288(0.5);7.8164(7.8);7.7936(7.3);7.632
);7.5168(0.4);7.3705(4.3);7.3519(4.8);7.1870(2.2);7.1668(4.5);7.1485(2.8);6.9330(3.1);6.9143(5.5);6.8959(2.6);6.8001(6.2);6.
553 4.18 7796(5.6);5.2596(1.3);5.2452(2.9);5.2264(2.8);5.2114(1.2);4.2957(1.1);4.2877(1.0);4.2761(2.5);4.2673(2.4);4.2605(2.8);4.2489(3.1);
4.2407(2.7);4.2265(2.3);4.2194(2.9);4.1983(1.1);4.0552(0.9);4.0376(2.5);4.0198(2.5);4.0023(0.8);3.8740(14.9);3.3214(154.1);3.293
(5.8);3.2822(11.0);3.2705(10.5);3.2585(4.9);3.2385(1.7);3.2278(1.0);2.6701(1.4);2.5048(207.4);2.5012(254.2);2.3283(1.5);2.2354(
.2257(1.3);2.2134(1.8);2.2038(1.8);2.1918(1.9);2.1798(1.4);2.0681(1.3);2.0602(1.8);2.0537(2.0);2.0381(1.6);2.0268(1.4);2.019
4(1.3);1.9883(10.2);1.3975(3.1);1.1926(2.6);1.1748(5.2);1.1569(2.6);-0.0002(37.7)
556: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1775(4.0);9.1574(4.0);8.6286(16.0);8.2793(6.4);8.2565(7.2);7.7842(7.7);7.7614(7.2);7.3674(3.9);7.3493(4.2);7.3373(1.2);7.331
4(1.8);7.3260(1.1);7.3134(2.1);7.3077(3.5);7.3022(2.0);7.2894(1.2);7.2839(1.8);7.2783(1.0);7.1848(1.9);7.1813(1.9);7.1639(4.0);7.1
462(2.5);7.1426(2.4);7.0495(3.6);7.0319(3.7);6.9289(2.8);6.9112(4.9);6.8933(2.3);6.7977(5.5);6.7777(5.0);5.2649(1.1);5.2506(2.5);5
556 3.76 .2315(2.4);5.2174(1.1);4.3044(0.7);4.2959(0.9);4.2888(0.8);4.2769(2.2);4.2680(2.1);4.2605(2.5);4.2509(3.0);4.2426(2.4);4.2290(2.0)
;4.2219(2.6);4.2011(0.9);4.1935(0.7);4.0555(0.5);4.0377(1.3);4.0200(1.3);4.0024(0.4);3.9436(0.5);3.9000(1.0);3.8818(7.6);3.8708(1
3.2);3.8600(7.7);3.8413(0.9);3.3245(50.8);3.2916(4.7);3.2805(9.6);3.2687(9.2);3.2568(4.1);3.2378(1.4);3.2256(0.8);2.6700(0.7);2.50
55(102.0);2.5013(130.9);2.4971(94.4);2.3278(0.7);2.3235(0.6);2.2484(0.5);2.2360(0.8);2.2276(1.1);2.2147(1.6);2.2056(1.6);2.1931(
1.6);2.1805(1.1);2.1718(0.7);2.0755(0.8);2.0686(1.1);2.0602(1.5);2.0533(1.7);2.0417(1.3);2.0374(1.3);2.0257(1.2);2.0184(1.1);2.011
2(0.7);2.0030(0.5);1.9883(5.2);1.3974(2.9);1.1927(1.3);1.1749(2.7);1.1570(1.3);0.0076(2.5);-0.0002(60.6);-0.0083(2.4)
557: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1770(4.0);9.1568(4.0);8.6318(16.0);8.2815(6.3);8.2586(7.2);7.7872(7.7);7.7643(7.2);7.5227(2.3);7.5178(3.8);7.5126(2.4);7.500
6(2.4);7.4956(3.8);7.4903(2.2);7.3684(3.9);7.3501(4.2);7.2192(3.2);7.1851(3.5);7.1820(3.5);7.1648(4.7);7.1470(2.6);6.9298(2.8);6.9
121(4.8);6.8925(2.2);6.7984(5.5);6.7782(5.0);5.2636(1.1);5.2493(2.5);5.2297(2.4);5.2151(1.1);4.3038(0.7);4.2952(0.9);4.2888(0.8);4
557 4.23 .2770(2.2);4.2672(2.1);4.2608(2.5);4.2508(3.0);4.2422(2.3);4.2287(1.9);4.2214(2.5);4.2007(0.9);4.1935(0.7);4.0556(0.6);4.0380(1.7)
;4.0202(1.7);4.0025(0.6);3.8712(12.8);3.8615(7.6);3.8422(1.0);3.3270(205.6);3.2914(4.9);3.2806(9.1);3.2689(8.6);3.2572(4.0);3.237
1(1.4);3.2266(0.9);2.6709(1.1);2.5062(163.1);2.5020(209.0);2.4978(151.9);2.3325(0.9);2.3283(1.2);2.2365(0.8);2.2271(1.2);2.2144(
1.6);2.2047(1.6);2.1929(1.6);2.1816(1.1);2.0760(0.8);2.0596(1.5);2.0530(1.7);2.0413(1.3);2.0256(1.2);2.0181(1.1);1.9885(7.1);1.397
6(3.1);1.1928(1.8);1.1750(3.6);1.1571(1.8);-0.0001(4.8)
558: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1706(2.1);9.1527(2.1);8.6027(16.0);8.3154(0.4);8.2902(6.2);8.2673(7.0);7.8025(8.8);7.7881(4.9);7.7796(7.8);7.7481(1.9);7.728
6(3.3);7.7088(1.6);7.6194(3.7);7.3615(3.8);7.3434(4.1);7.1811(1.8);7.1774(1.8);7.1595(3.9);7.1424(2.4);6.9232(2.7);6.9052(4.6);6.8
558 4.13 1);6.7953(5.5);6.7750(4.9);5.7551(2.1);5.2581(1.1);5.2446(2.4);5.2255(2.4);5.2107(1.0);4.2995(0.7);4.2915(0.9);4.2856(0.9);4
.2727(2.2);4.2642(2.1);4.2566(2.4);4.2466(2.5);4.2376(2.0);4.2163(2.1);4.1951(0.8);4.0377(0.4);4.0201(0.4);3.8775(11.0);3.3239(26
.2894(6.2);2.6705(1.7);2.5236(4.5);2.5060(239.6);2.5017(306.1);2.4975(218.6);2.3284(1.8);2.2452(0.5);2.2233(1.1);2.2104(1.
6);2.2010(1.6);2.1894(1.6);2.1774(1.2);2.0573(1.4);2.0498(1.6);2.0372(1.3);2.0225(1.1);1.9886(1.7);1.3974(1.0);1.1924(0.4);1.1748(
0.9);1.1577(0.4);0.1461(0.6);0.0077(5.0);-0.0002(134.8);-0.0084(5.2);-0.1496(0.6)
564: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1810(3.4);9.1696(3.5);9.1614(3.8);9.1496(3.2);8.6214(12.6);8.6138(11.8);8.3155(9.4);8.2926(10.6);7.8206(10.0);7.7978(9.3);7.
7086(2.5);7.6910(5.4);7.6854(4.8);7.6715(3.4);7.6673(2.9);7.3843(1.6);7.3653(9.7);7.3517(10.5);7.3473(13.2);7.3334(5.8);7.3249(2.
564 201(3.2);7.3053(2.8);7.2898(1.2);7.1810(2.8);7.1612(6.0);7.1427(3.7);6.9258(3.4);6.9073(5.7);6.8889(2.7);6.7951(8.5);6.7751(
7.6);5.2617(1.1);5.2413(3.1);5.2284(3.2);4.3001(1.0);4.2943(1.4);4.2870(1.2);4.2748(3.3);4.2656(3.1);4.2585(3.6);4.2497(3.8);4.240
8(3.2);4.2317(2.4);4.2203(3.4);4.2129(2.7);4.1923(1.3);3.8727(16.0);3.3218(136.5);3.3010(10.8);3.2915(10.8);3.2796(9.0);3.2589(3.
1);3.2398(1.7);2.6700(2.2);2.5051(310.4);2.5010(398.1);2.4968(287.4);2.4242(0.4);2.3275(2.3);2.2091(2.0);2.2014(2.2);2.1944(2.1);
2.1809(1.7);2.0525(2.2);2.0436(2.2);2.0258(1.9);2.0176(1.6);1.2348(0.8);-0.0003(13.2)
565: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1794(1.1);9.1588(1.1);8.7822(0.5);8.6253(3.8);8.6202(3.9);8.3083(2.6);8.2853(2.9);7.8100(3.2);7.7871(3.1);7.5936(0.8);7.5864
(0.9);7.5823(0.9);7.5752(0.9);7.5711(1.0);7.5643(1.2);7.5604(1.0);7.5534(0.9);7.4579(0.8);7.4511(0.8);7.4423(0.8);7.4357(0.8);7.42
71(1.0);7.4220(1.0);7.4150(1.0);7.4053(2.2);7.4002(1.1);7.3875(1.7);7.3829(0.9);7.3655(2.0);7.3489(1.5);7.1836(0.8);7.1634(1.6);7.
565 4.03 1453(1.0);6.9293(1.1);6.9265(1.2);6.9101(1.8);6.8921(0.9);6.8893(0.9);6.7963(2.2);6.7760(1.8);5.2433(0.8);5.2305(0.7);4.2945(0.4);
4.2750(0.9);4.2602(0.9);4.2468(0.9);4.2383(0.9);4.2248(0.8);4.2184(1.0);4.1975(0.4);3.8814(3.0);3.8723(5.0);3.8602(3.1);3.8410(0.
);3.3215(139.8);3.2898(3.6);3.2785(3.4);2.6746(1.3);2.6702(1.7);2.6655(1.2);2.5235(4.2);2.5187(6.8);2.5100(110.3);2.5057(227.6);
2.5012(299.7);2.4966(210.2);2.4922(97.2);2.3368(0.6);2.3323(1.2);2.3278(1.7);2.3233(1.2);2.2084(0.6);2.1892(0.6);2.0604(0.5);2.0
532(0.7);2.0449(0.6);2.0371(0.5);2.0276(0.4);2.0192(0.5);1.5301(3.1);1.4948(3.2);1.4885(1.2);1.4529(0.9);1.3976(16.0);1.2344(0.4);
-0.0002(8.6)
566: 1H-NMR(400.0 MHz, O):
δ= 8.9879(3.8);8.9680(3.8);8.4481(5.6);8.4300(12.0);8.4220(8.5);7.9521(0.3);7.9237(2.0);7.8814(15.0);7.8752(16.0);7.8612(2.1);7.6
249(5.2);7.6083(8.1);7.5614(6.4);7.5405(6.8);7.5226(4.2);7.4339(4.4);7.4279(4.8);7.4173(4.7);7.4114(4.0);7.3027(4.2);7.2830(4.5);7
.1708(2.8);7.1673(2.8);7.1501(5.7);7.1322(3.5);7.1285(3.3);6.9055(4.0);6.9032(4.2);6.8847(7.0);6.8684(3.2);6.8659(3.2);6.7898(7.8)
566 1.71 ;6.7694(7.1);5.7569(11.9);5.2623(1.4);5.2467(3.2);5.2284(3.1);5.2128(1.3);4.9059(4.0);4.8931(8.8);4.8804(4.0);4.2857(0.9);4.2659(
3.8);4.2579(5.8);4.2484(6.9);4.2336(4.0);4.2151(1.0);4.0556(0.4);4.0378(1.2);4.0198(1.1);4.0021(0.4);3.6850(2.4);3.6707(7.8);3.657
3(10.0);3.6444(4.9);3.5952(5.7);3.5840(6.8);3.5721(4.3);3.3213(90.6);2.6744(1.3);2.6702(1.8);2.6657(1.3);2.5234(4.8);2.5098(122.4
);2.5055(249.9);2.5011(329.4);2.4966(234.1);2.4923(111.1);2.3323(1.3);2.3278(1.9);2.3234(1.4);2.1873(0.7);2.1740(1.2);2.1642(1.4
);2.1534(1.8);2.1403(2.5);2.1243(2.1);2.1117(1.0);2.0664(1.0);2.0521(2.3);2.0411(2.4);2.0253(1.7);2.0167(1.6);2.0074(1.3);1.9886(5
.2);1.2582(0.4);1.2344(1.0);1.1922(1.2);1.1743(2.6);1.1567(1.2);0.1459(0.7);0.0079(5.6);-0.0002(166.0);-0.0084(5.9);-0.1494(0.7)
567: 1H-NMR(400.0 MHz, O):
δ= 9.0073(3.6);8.9868(3.7);8.4799(13.7);8.4638(3.9);8.4434(4.0);7.9315(1.6);7.9195(3.1);7.9073(1.7);7.7132(4.1);7.6963(5.2);7.596
(0.8);7.5887(1.0);7.5790(4.5);7.5685(2.0);7.5606(5.4);7.5581(5.4);7.5477(1.9);7.5399(3.8);7.5256(0.8);7.3116(3.6);7.2930(4.0);7.1
762(3.3);7.1726(3.6);7.1555(5.2);7.1378(2.3);7.1341(2.2);6.9102(2.7);6.8919(4.6);6.8733(2.2);6.7949(5.1);6.7747(4.7);5.7571(3.2);5
567 1.42 .2731(1.0);5.2573(2.3);5.2384(2.3);5.2240(1.0);4.9044(2.7);4.8916(6.1);4.8787(2.9);4.3020(0.4);4.2928(0.6);4.2733(2.5);4.2651(3.9)
;4.2551(4.4);4.2492(4.0);4.2396(2.5);4.2218(0.6);3.6817(1.5);3.6675(5.2);3.6542(6.9);3.6416(3.4);3.6086(3.1);3.5963(6.2);3.5830(4.
7);3.5689(1.4);3.3218(25.0);2.6745(0.7);2.6703(1.0);2.6662(0.8);2.5233(2.6);2.5055(133.6);2.5012(174.2);2.4970(126.3);2.3276(1.0
);2.1948(0.4);2.1840(0.8);2.1720(0.9);2.1606(1.2);2.1486(1.7);2.1341(1.4);2.1194(0.7);2.0856(16.0);2.0641(1.7);2.0532(1.6);2.0376(
1.2);2.0288(1.1);2.0193(0.9);2.0128(0.7);2.0046(0.4);1.9887(0.9);1.2351(0.7);1.1745(0.4);-0.0001(3.6)
568: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0342(1.9);9.0140(2.0);8.5727(6.2);8.4892(2.2);8.4672(2.2);8.4420(0.6);8.2975(0.4);8.2615(1.1);8.0721(0.9);8.0606(1.6);8.0483
(1.0);7.9562(0.5);7.8662(2.1);7.8497(2.5);7.8153(16.0);7.7977(0.8);7.5936(1.8);7.5727(2.1);7.5543(1.6);7.3204(1.8);7.3024(2.2);7.1
9);7.1645(2.0);7.1470(1.4);7.1436(1.4);6.9222(1.3);6.9040(2.4);6.8850(1.3);6.8045(2.6);6.7848(2.5);5.7572(7.2);5.7396(0.3);5
568 1.53 .2804(0.6);5.2654(1.3);5.2464(1.4);5.2318(0.7);4.9134(1.6);4.9007(3.2);4.8881(1.6);4.3032(0.4);4.2833(1.4);4.2743(2.1);4.2633(2.5)
;4.2580(2.6);4.2482(1.7);4.2305(0.6);4.0379(0.8);4.0201(0.9);4.0023(0.3);3.6661(2.9);3.6533(3.7);3.6407(2.2);3.6145(2.2);3.6024(3.
4);3.5894(2.6);3.3241(7.3);3.3074(0.5);2.5060(41.9);2.5018(53.4);2.4975(40.1);2.1877(0.4);2.1793(0.5);2.1681(0.8);2.1557(1.0);2.1
410(0.9);2.1258(0.6);2.0946(0.5);2.0799(0.9);2.0699(1.0);2.0542(0.8);2.0447(0.7);2.0357(0.6);2.0293(0.5);1.9890(3.5);1.2988(0.4);1
.2585(0.5);1.2312(0.7);1.1925(1.0);1.1747(1.8);1.1569(1.0);-0.0002(1.2)
576: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 20.0029(0.9);9.1889(6.0);9.1694(6.2);8.6464(14.7);8.6381(15.0);8.3318(10.9);8.3089(11.9);7.8301(11.0);7.8072(10.0);7.6892(1.
6);7.6682(2.6);7.6486(2.6);7.4026(1.1);7.3714(3.5);7.3527(4.2);7.1816(5.1);7.1646(7.5);7.1472(4.8);6.9296(4.4);6.9103(7.1);6.8923(
576 3.90 3.8);6.7973(8.0);6.7765(7.6);5.2293(3.2);4.2951(1.7);4.2767(3.3);4.2608(3.3);4.2507(3.5);4.2420(3.3);4.2203(3.7);4.1924(1.5);3.916
1(1.0);3.9087(1.1);3.8728(16.0);3.7425(1.0);3.3196(381.7);3.2976(12.2);3.2873(11.7);3.2380(1.9);2.6744(7.0);2.6702(9.7);2.6655(7.
0);2.6612(3.6);2.5233(22.0);2.5099(648.2);2.5055(1360.8);2.5010(1822.1);2.4965(1299.0);2.4920(613.8);2.4282(2.0);2.3323(7.9);2.
3277(10.7);2.3234(7.8);2.2851(1.0);2.2044(2.7);2.0556(2.4);2.0356(2.2);1.2408(1.1);-0.0002(68.2)
577: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9783(4.8);8.9578(4.8);8.5458(3.4);8.5302(3.7);8.5222(3.6);8.5068(3.4);8.4827(1.4);8.4655(0.4);8.4574(0.4);8.4398(0.4);8.4133
8.4054(16.0);8.0443(0.8);8.0308(0.5);8.0114(0.4);7.9945(1.9);7.9831(3.6);7.9722(1.9);7.7219(5.6);7.7183(5.8);7.7019(6.8);7.6
982(6.6);7.5396(0.4);7.5281(3.8);7.5054(6.4);7.4834(4.5);7.4711(5.3);7.4516(9.8);7.4431(1.6);7.4319(5.6);7.4231(0.9);7.3921(0.3);7
.3727(0.6);7.3473(6.3);7.3436(6.5);7.3281(5.6);7.3245(4.7);7.3118(0.8);7.2873(4.7);7.2693(5.2);7.1660(2.4);7.1634(2.4);7.1455(5.1)
;7.1282(3.2);7.1246(3.0);6.8960(3.8);6.8769(6.2);6.8606(2.8);6.7853(6.9);6.7650(6.3);6.6074(0.5);6.5916(0.4);5.7570(8.6);5.2502(1.
577 1.66 6);5.2353(3.1);5.2157(3.0);5.2010(1.4);4.9112(3.8);4.8980(8.6);4.8853(3.9);4.2747(0.8);4.2402(7.3);4.2276(4.6);4.2100(0.7);4.1986(
0.4);4.0553(0.7);4.0376(2.0);4.0197(1.9);4.0019(0.8);3.6838(2.3);3.6695(7.4);3.6560(9.4);3.6437(4.5);3.5967(4.6);3.5846(8.3);3.571
;3.5569(2.0);3.5289(0.4);3.4240(0.3);3.3211(225.0);2.6744(2.4);2.6700(3.2);2.6655(2.3);2.6025(0.4);2.5795(0.3);2.5234(7.9);2
.5096(213.1);2.5055(434.5);2.5010(573.6);2.4966(408.4);2.4923(193.6);2.4434(0.9);2.4385(0.9);2.3322(2.3);2.3277(3.3);2.3232(2.3
);2.1689(1.4);2.1475(1.8);2.1338(2.6);2.1207(2.2);2.1056(1.0);2.0549(1.1);2.0409(2.3);2.0263(2.3);2.0117(1.7);2.0043(1.6);1.9886(9
.4);1.9081(0.3);1.3974(0.7);1.3508(0.3);1.2979(2.2);1.2583(3.0);1.2351(2.6);1.1922(2.3);1.1743(4.8);1.1565(2.2);0.8663(0.4);0.8537
(0.6);0.8378(0.4);-0.0002(22.2)
578: 1H-NMR(400.0 MHz, d6-DMSO):
δ= (2.2);8.9780(2.3);8.5049(8.6);8.4947(2.0);8.4861(1.8);8.4710(1.5);8.1238(1.0);8.1117(1.8);8.1003(1.0);7.6592(3.0);7.6544
(5.7);7.6497(3.2);7.5218(1.8);7.4987(3.4);7.4750(10.7);7.4705(9.2);7.2997(2.3);7.2817(2.5);7.1770(1.1);7.1734(1.1);7.1561(2.4);7.1
383(1.5);7.1350(1.4);6.9084(1.7);6.8916(3.0);6.8733(1.4);6.8711(1.4);6.7964(3.3);6.7761(3.0);5.7570(13.6);5.2638(0.6);5.2483(1.5);
578 1.84 5.2298(1.5);5.2142(0.7);4.9160(1.7);4.9034(4.0);4.8907(1.9);4.2892(0.4);4.2697(1.7);4.2614(2.4);4.2520(3.0);4.2376(1.8);4.2191(0.
4);4.0557(0.6);4.0379(1.9);4.0201(1.9);4.0023(0.6);3.6763(1.0);3.6615(3.2);3.6485(4.3);3.6362(2.3);3.6094(2.1);3.5974(3.8);3.5842(
2.9);3.5725(0.9);3.3230(35.7);2.6747(0.4);2.6706(0.5);2.6663(0.4);2.5238(1.2);2.5059(68.9);2.5015(90.7);2.4971(65.0);2.3284(0.5);
2.3240(0.4);2.1790(0.5);2.1660(0.6);2.1552(0.8);2.1422(1.1);2.1265(0.9);2.1138(0.4);2.0744(0.4);2.0596(1.1);2.0484(1.0);2.0333(0.
7);2.0239(0.7);2.0148(0.6);2.0076(0.4);1.9971(0.3);1.9888(8.2);1.3971(16.0);1.2586(0.4);1.1925(2.1);1.1747(4.2);1.1568(2.0);-
0.0002(3.7)
579: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0615(0.4);9.0402(0.5);9.0006(7.4);8.9800(7.6);8.6025(1.7);8.5834(5.4);8.5682(5.9);8.5596(5.8);8.5445(5.4);8.5056(1.2);8.4832
(15.4);8.4772(16.0);8.4524(0.5);8.4436(0.4);8.4293(0.3);8.1268(3.0);8.1146(2.0);8.0994(2.0);8.0864(3.4);7.6673(1.6);7.6596(2.1);7.
6507(2.3);7.6445(3.2);7.6391(3.2);7.6309(3.2);7.6236(3.1);7.6180(3.2);7.6113(2.0);7.6033(1.7);7.5953(1.4);7.5580(5.5);7.5351(10.2
);7.5124(5.4);7.4985(1.0);7.4754(1.7);7.3275(0.5);7.3007(7.9);7.2816(8.6);7.2356(2.1);7.2214(3.4);7.2145(3.9);7.1940(2.2);7.1750(4
.5);7.1713(4.3);7.1539(8.4);7.1364(5.3);7.1328(4.8);6.9344(0.4);6.9060(6.0);6.8874(10.0);6.8689(5.0);6.8113(0.6);6.7940(12.0);6.79
579 1.61 18(11.6);6.7736(10.7);6.7713(9.7);5.7574(15.4);5.2606(2.2);5.2456(4.9);5.2266(4.8);5.2116(2.0);4.9170(4.8);4.9062(9.9);4.9041(10.
1);4.8926(5.4);4.8800(0.5);4.2823(1.2);4.2589(7.8);4.2481(10.8);4.2360(6.9);4.2174(1.2);4.2072(0.5);4.0559(0.9);4.0380(2.7);4.020
3(2.8);4.0024(0.9);3.6805(3.2);3.6666(11.4);3.6537(15.0);3.6414(8.3);3.6174(4.2);3.6062(8.8);3.5961(10.2);3.5835(7.1);3.5594(1.0);
3.5452(0.4);3.3229(55.3);2.6798(0.6);2.6752(1.2);2.6707(1.6);2.6660(1.2);2.5240(4.0);2.5191(6.4);2.5106(102.4);2.5061(214.3);2.5
016(285.4);2.4971(201.0);2.4926(93.2);2.3326(1.1);2.3283(1.6);2.3239(1.2);2.1891(1.0);2.1779(2.0);2.1654(2.1);2.1559(2.6);2.1423
(4.1);2.1277(3.3);2.1137(1.4);2.0676(1.7);2.0536(3.7);2.0411(3.4);2.0261(2.4);2.0174(2.4);2.0082(1.9);1.9890(12.6);1.3971(1.9);1.2
992(2.0);1.2588(2.8);1.2348(1.5);1.1924(3.3);1.1747(6.6);1.1569(3.2);0.8537(0.4);0.0081(0.4);-0.0002(12.9);-0.0081(0.4)
589: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.3204(1.1);9.3135(1.1);9.3003(1.2);9.2927(1.0);8.5653(7.4);8.3124(1.6);8.3036(1.4);8.2966(1.7);8.2873(1.7);8.2791(0.4);7.7025
(2.2);7.6989(2.4);7.6825(2.7);7.6788(2.7);7.6719(0.8);7.6538(3.4);7.6470(3.3);7.6381(6.8);7.4567(0.8);7.4467(0.8);7.4374(1.7);7.42
75(1.6);7.4178(1.1);7.4076(1.0);7.3523(2.7);7.3323(3.6);7.3134(0.9);7.1863(0.9);7.1659(2.0);7.1482(1.2);6.9252(1.3);6.9067(2.2);6.
589 2.43 8881(1.0);6.8028(2.7);6.7823(2.4);5.7568(16.0);5.2942(0.5);5.2792(1.2);5.2607(1.2);5.2464(0.6);5.1484(0.9);5.1392(1.6);5.1338(1.5
);5.1246(0.8);4.2956(0.4);4.2771(1.2);4.2614(2.0);4.2522(2.0);4.2406(1.0);4.2328(1.2);4.2129(0.4);4.2075(0.3);4.0374(0.7);4.0196(0
6661(0.4);3.6505(1.0);3.6383(1.8);3.6256(1.9);3.5831(0.4);3.5455(2.6);3.3210(21.3);3.3034(0.4);3.0572(15.5);2.6701(0.6);2.66
54(0.5);2.5051(83.3);2.5007(109.1);2.4964(79.4);2.3273(0.6);2.3233(0.5);2.2266(0.5);2.2137(0.8);2.2033(0.8);2.1911(0.8);2.1798(0.
6);2.0667(0.8);2.0593(0.9);2.0497(0.7);2.0377(0.6);2.0327(0.6);2.0238(0.5);1.9884(2.9);1.2347(0.5);1.1919(0.8);1.1742(1.5);1.1564(
0.7);-0.0002(9.7)
590: 1H-NMR(400.0 MHz, O):
δ= 9.3230(1.9);9.3026(1.9);8.7282(0.8);8.6746(0.3);8.5838(8.2);8.3304(1.7);8.3262(1.8);8.3102(1.8);8.3060(2.0);7.9109(4.6);7.9048
7.6985(1.1);7.6845(3.0);7.6738(3.3);7.6536(2.8);7.6410(0.9);7.6360(1.4);7.4926(1.6);7.4863(1.7);7.4607(1.5);7.4549(1.4);7.35
29(1.9);7.3352(2.0);7.1897(1.2);7.1866(1.2);7.1682(2.1);7.1514(1.3);7.1473(1.2);6.9385(0.3);6.9281(1.4);6.9100(2.3);6.8922(1.1);6.
590 3.44 8203(0.4);6.8035(2.9);6.7849(2.4);5.7568(4.1);5.2936(0.6);5.2778(1.2);5.2600(1.2);5.2445(0.6);5.1331(1.4);4.3052(0.4);4.2974(0.6);
4.2901(0.6);4.2777(1.3);4.2616(2.0);4.2525(2.0);4.2406(1.1);4.2325(1.2);4.2122(0.4);3.6684(0.4);3.6540(0.9);3.6401(1.6);3.6268(1.
8);3.5844(0.4);3.5555(2.0);3.5444(2.6);3.5068(0.4);3.4949(0.4);3.3197(31.2);3.0560(16.0);3.0377(1.8);2.6746(0.8);2.6700(1.1);2.66
54(0.8);2.5231(2.9);2.5096(69.2);2.5054(141.9);2.5009(188.1);2.4965(135.6);2.4922(65.6);2.3321(0.8);2.3276(1.1);2.3232(0.8);2.24
78(0.4);2.2268(0.6);2.2135(0.9);2.2041(0.9);2.1919(0.9);2.1835(0.6);2.0762(0.6);2.0685(0.8);2.0611(1.0);2.0519(0.7);2.0343(0.7);2.
0262(0.6);1.9885(0.4);1.2580(0.4);1.2349(1.4);0.0079(0.4);-0.0002(12.9)
591: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.3476(1.8);9.3272(1.8);8.7005(7.3);8.5245(0.4);8.3686(2.0);8.3493(2.2);8.2720(1.2);7.9656(0.5);7.9319(2.0);7.9142(2.4);7.8341
(16.0);7.7034(1.8);7.6847(2.0);7.6642(1.4);7.3800(1.9);7.3618(2.0);7.2027(0.9);7.1993(0.9);7.1815(2.0);7.1641(1.2);7.1611(1.2);6.9
518(1.3);6.9330(2.3);6.9146(1.2);6.8173(2.8);6.7968(2.5);5.7572(12.0);5.3147(0.5);5.3002(1.2);5.2813(1.3);5.2664(0.6);5.1438(1.1);
591 3.25 5.1288(2.4);5.1136(1.1);4.3120(0.4);4.3050(0.4);4.2928(1.2);4.2757(1.9);4.2668(1.9);4.2535(1.1);4.2460(1.3);4.2258(0.4);4.2188(0.
4);4.0382(0.9);4.0204(0.9);3.6465(1.0);3.6331(2.4);3.6200(2.6);3.6066(1.4);3.5492(2.4);3.5372(2.9);3.3260(25.5);3.3049(0.4);3.062
4(14.0);2.5058(36.3);2.5017(45.5);2.4977(33.2);2.2521(0.4);2.2430(0.5);2.2305(0.8);2.2209(0.8);2.2089(0.9);2.1975(0.7);2.1887(0.4
);2.1046(0.6);2.0965(0.8);2.0895(0.9);2.0738(0.7);2.0620(0.6);2.0537(0.6);1.9891(3.8);1.2320(0.3);1.1926(1.0);1.1748(1.9);1.1572(1
.0);-0.0001(4.5)
595: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1408(0.9);9.1232(1.7);9.1128(1.2);9.1059(1.3);8.5911(7.4);8.3494(1.9);8.3335(2.1);8.3258(2.1);8.3102(1.9);8.1409(0.4);7.7554
7.7518(3.1);7.7353(3.7);7.7317(3.6);7.6777(2.3);7.6551(3.9);7.6324(2.2);7.5002(1.4);7.4897(1.3);7.4808(2.9);7.4702(2.7);7.46
(1.8);7.4505(1.6);7.4116(1.0);7.4079(1.1);7.3993(1.1);7.3919(1.8);7.3883(1.6);7.3754(1.7);7.3681(1.2);7.3560(2.0);7.3479(1.6);7.
3377(1.5);7.3327(1.4);7.1785(1.3);7.1608(2.8);7.1431(1.7);6.9110(1.4);6.8927(2.5);6.8746(1.2);6.7951(3.5);6.7747(3.2);5.7569(16.0
09(1.4);5.2174(1.3);4.2882(0.5);4.2691(1.6);4.2537(2.7);4.2444(2.3);4.2322(1.3);4.2033(0.4);4.0557(0.6);4.0378(1.6);4.0201(1
595 3.61 .6);4.0023(0.6);3.7509(0.6);3.7434(0.5);3.7279(1.0);3.7217(1.2);3.7117(0.7);3.7041(1.5);3.6822(1.2);3.6640(0.7);3.6542(0.7);3.6478
(1.1);3.6339(1.7);3.6281(1.2);3.6209(1.1);3.6138(1.3);3.6008(1.6);3.5817(2.2);3.5630(1.8);3.5434(0.5);3.3865(0.6);3.3682(1.5);3.35
52(1.7);3.3473(2.1);3.3228(43.4);3.2960(0.8);3.2790(0.6);3.2636(1.0);3.2544(1.1);3.2470(1.0);3.2390(1.1);3.2120(1.6);3.1913(1.2);3
.1782(1.4);3.1674(0.5);3.1565(0.9);3.1462(0.7);3.1236(0.4);3.0852(14.4);3.0806(13.3);2.6985(1.0);2.6799(1.2);2.6746(1.3);2.6704(1
.5);2.5233(2.1);2.5057(103.8);2.5013(135.2);2.4969(96.5);2.3325(0.6);2.3281(0.8);2.2037(0.7);2.1932(0.9);2.1822(1.1);2.1701(1.0);
2.1617(0.8);2.1490(0.5);2.0299(1.2);2.0158(1.4);1.9887(8.2);1.9661(1.1);1.9539(0.6);1.4852(0.6);1.4798(0.6);1.4688(1.0);1.4532(1.
1);1.4363(0.9);1.4216(0.6);1.2352(0.5);1.1923(1.8);1.1745(3.6);1.1567(1.8);0.0075(0.3);-0.0002(9.6)
596: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0701(3.4);9.0498(3.5);8.5625(0.6);8.5278(0.5);8.4640(2.2);8.4489(2.6);8.4390(11.6);8.4253(2.3);8.1352(0.7);7.8085(0.8);7.795
;7.7758(1.8);7.7613(0.9);7.7046(6.4);7.6992(7.6);7.6691(0.7);7.6622(1.0);7.6543(0.9);7.6470(1.4);7.6418(1.4);7.6338(1.4);7.6
213(1.4);7.6135(0.9);7.5969(2.8);7.5738(4.2);7.5512(2.2);7.5380(0.3);7.4597(6.8);7.4558(6.8);7.4405(0.4);7.2706(2.3);7.2503(2.8);7
596 2.30 .2145(1.7);7.1920(0.9);7.1737(1.8);7.1528(3.5);7.1353(2.1);6.8948(1.7);6.8760(2.8);6.8579(1.3);6.7898(4.9);6.7697(4.4);6.2235(4.2)
;6.2186(7.2);6.2137(4.2);6.1947(0.4);5.7572(15.7);5.2260(1.1);5.2118(2.2);5.1921(2.1);5.1777(0.9);4.4811(3.3);4.4655(7.5);4.4500(
3.9);4.4309(0.4);4.2266(4.2);4.2215(4.5);4.0560(1.1);4.0380(3.4);4.0202(3.4);4.0023(1.2);3.8362(3.8);3.8227(3.4);3.3218(25.8);2.89
00(0.6);2.7311(0.6);2.6707(1.0);2.5236(2.6);2.5057(130.4);2.5014(170.3);2.4971(122.6);2.3282(1.0);2.1418(0.9);2.1256(1.2);2.1084
(1.4);2.0941(1.3);2.0746(0.7);2.0126(1.0);1.9999(1.6);1.9888(16.0);1.9666(1.0);1.9535(0.7);1.2347(0.6);1.1924(3.8);1.1746(7.5);1.1
568(3.7);0.0080(0.4);-0.0001(12.0)
597: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0160(2.4);8.9955(2.4);8.5800(1.6);8.5647(1.7);8.5564(1.7);8.5410(1.7);8.5257(8.0);8.2056(1.8);7.6979(16.0);7.5619(1.8);7.538
(3.4);7.5151(1.7);7.2990(2.3);7.2808(2.6);7.1797(1.1);7.1764(1.2);7.1586(2.4);7.1412(1.5);6.9103(1.7);6.8921(2.9);6.8735(1.4);6.7
597 1.84 985(3.3);6.7784(3.0);5.2605(0.7);5.2452(1.5);5.2258(1.5);5.2103(0.6);4.9247(1.7);4.9122(3.9);4.8996(1.8);4.2873(0.3);4.2603(2.4);4
.2512(3.2);4.2197(0.4);3.6760(0.9);3.6623(3.1);3.6494(4.2);3.6376(2.3);3.6131(2.2);3.6014(3.8);3.5884(2.8);3.3245(128.5);2.6710(0
.9);2.5058(125.4);2.5015(161.2);2.4973(117.7);2.3284(0.9);2.1769(0.5);2.1553(0.8);2.1416(1.1);2.1263(1.0);2.1128(0.5);2.0598(1.1)
;2.0478(1.1);2.0324(0.8);2.0239(0.7);2.0143(0.6);-0.0001(5.0)
599: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0562(3.0);9.0349(3.1);8.5743(0.4);8.4690(1.5);8.4526(1.9);8.4440(1.9);8.4303(1.6);8.3837(8.0);8.1530(1.3);7.9531(0.3);7.8091
(1.4);7.7969(1.3);7.7809(1.2);7.7236(3.8);7.7207(3.8);7.7033(4.5);7.6086(1.1);7.5735(2.2);7.5518(3.6);7.5294(2.0);7.4708(1.4);7.46
599 1.26 08(1.8);7.4511(2.7);7.4413(3.2);7.4317(1.7);7.4217(1.9);7.3433(2.1);7.3279(3.6);7.3127(2.0);7.2532(3.2);7.2358(3.5);7.2145(0.4);7.
1976(0.5);7.1703(2.3);7.1507(4.4);7.1322(2.8);6.9427(0.3);6.8980(2.9);6.8795(4.7);6.8617(2.6);6.8121(0.5);6.7871(4.7);6.7668(4.2);
.7564(16.0);5.2306(1.0);5.2157(2.1);5.1972(2.0);5.1830(0.9);4.3402(3.3);4.2258(4.6);3.7613(3.1);3.5706(0.3);3.5591(0.4);3.5486(0
.4);3.4758(0.7);3.3304(5.7);3.1731(0.6);2.8900(1.4);2.7307(1.4);2.6707(1.6);2.5587(0.4);2.5016(305.4);2.4478(0.8);2.4148(0.4);2.40
82(0.4);2.3283(1.8);2.1700(0.5);2.1196(1.4);1.9881(2.0);1.9618(1.2);1.1742(0.4);-0.0003(14.4)
606: 1H-NMR(400.0 MHz, O):
δ= 9(0.4);11.6374(0.5);9.3368(2.0);9.3164(1.9);8.6542(0.4);8.6320(8.0);8.3582(2.0);8.3369(2.2);8.1752(0.6);8.1559(0.5);7.79
46(2.0);7.7787(2.7);7.7011(2.2);7.6792(2.2);7.6623(1.5);7.6399(0.6);7.6304(0.7);7.6154(0.9);7.6105(0.9);7.5953(0.9);7.5661(0.6);7.
3732(2.0);7.3556(2.2);7.2327(1.2);7.2036(1.6);7.1824(2.2);7.1642(1.3);6.9450(1.6);6.9252(2.4);6.9067(1.2);6.8179(2.7);6.7965(2.4);
606 2.63 5.3127(0.7);5.2980(1.3);5.2805(1.4);5.2646(0.6);5.1508(1.2);5.1352(2.6);5.1201(1.3);4.3135(0.6);4.3101(0.6);4.2925(1.2);4.2749(1.
657(1.9);4.2452(1.4);4.2228(0.6);3.6428(2.3);3.6278(2.6);3.6139(1.6);3.5956(0.5);3.5628(2.5);3.5489(3.0);3.3286(367.5);3.06
0);2.6830(4.0);2.6784(5.4);2.6738(4.0);2.6571(0.4);2.5916(0.5);2.5585(1.2);2.5138(734.5);2.5095(960.4);2.5050(690.4);2.432
7(0.8);2.3888(0.5);2.3406(4.0);2.3362(5.6);2.3320(4.1);2.2638(0.5);2.2521(0.8);2.2294(0.9);2.2202(0.8);2.2097(0.9);2.1954(0.9);2.1
014(0.6);2.0870(1.1);2.0807(1.0);2.0641(0.9);2.0539(0.8);1.7536(0.4);0.0082(2.7);-2.4241(0.4);-2.6703(0.5)
625: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0900(1.0);9.0696(1.1);8.5142(4.0);8.3294(1.0);8.3092(1.0);7.7732(0.5);7.7612(2.0);7.7455(1.8);7.6202(3.0);7.6160(7.0);7.6102
(2.8);7.6064(1.8);7.5945(2.0);7.5821(1.0);7.5610(1.1);7.5428(0.8);7.2876(1.0);7.2700(1.0);7.1885(0.5);7.1848(0.5);7.1681(1.0);7.15
625 1.24 01(0.6);7.1463(0.6);7.1283(2.2);6.9241(0.7);6.9055(1.3);6.8866(0.7);6.8599(2.3);6.8053(1.4);6.7852(1.3);5.7568(16.0);5.2445(0.6);5
.2257(0.6);4.3461(0.9);4.3314(2.0);4.3165(1.0);4.2612(1.0);4.2481(1.7);4.2348(1.1);3.7783(1.0);3.7693(0.9);3.7633(0.9);3.3256(11.
9);3.1318(1.5);2.5236(0.7);2.5101(19.3);2.5058(40.5);2.5013(54.2);2.4968(38.5);2.4925(18.1);2.1600(0.3);2.1388(0.5);2.1255(0.5);2
.0744(0.4);2.0394(0.4);2.0254(0.5);2.0027(0.3);0.0079(0.7);-0.0002(21.3);-0.0084(0.7)
629: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9739(1.9);8.9538(1.9);8.5544(0.4);8.3842(2.7);8.3611(3.0);8.3534(6.7);7.8907(1.2);7.8785(1.2);7.6553(3.6);7.6515(2.8);7.6466
(4.6);7.6418(2.6);7.6325(3.3);7.3204(1.6);7.2981(2.8);7.2783(1.9);7.1724(0.9);7.1505(1.7);7.1331(1.2);7.1292(1.1);6.9069(1.3);6.88
629 2.09 85(2.2);6.8727(1.1);6.7876(2.5);6.7691(2.1);5.2365(0.6);5.2227(1.1);5.2020(1.0);5.1865(0.5);4.2514(1.9);4.2395(3.2);4.2256(1.8);3.
3205(162.9);3.0650(1.7);3.0510(6.7);3.0385(6.8);2.6746(1.3);2.6702(1.7);2.6658(1.3);2.5456(0.4);2.5233(4.5);2.5098(111.1);2.5055
(228.2);2.5011(302.5);2.4966(215.4);2.4923(102.0);2.3324(1.2);2.3278(1.7);2.3236(1.2);2.1786(0.4);2.1705(0.6);2.1564(0.7);2.1345
(0.8);2.1206(0.8);2.1072(0.3);2.0227(0.7);2.0119(0.9);1.9896(0.6);1.9757(0.6);1.3975(16.0);1.2981(0.4);1.2580(0.6);1.2351(3.6);0.8
536(0.5);0.0078(1.2);-0.0002(36.1);-0.0084(1.4)
630: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0221(2.2);9.0014(2.2);8.6578(9.6);8.2917(3.5);8.2688(4.0);7.7935(4.4);7.7706(4.1);7.6936(2.7);7.6889(5.3);7.6841(2.9);7.3740
(3.2);7.3575(3.9);7.2960(0.5);7.2779(1.4);7.2596(5.4);7.2490(2.8);7.2439(2.0);7.2315(1.8);7.2267(1.4);7.2158(0.7);7.2100(0.7);6.79
630 5.59 34(0.4);6.7889(0.4);5.7565(13.4);5.6226(0.6);5.6026(1.6);5.5824(1.6);5.5623(0.6);3.9159(0.5);3.8839(6.4);3.8527(0.5);3.3624(0.7);3
.3515(1.3);3.3314(2.0);3.3200(16.7);3.2889(1.5);3.2793(2.4);3.2661(1.7);3.2475(1.3);3.2366(0.7);2.6747(0.4);2.6701(0.6);2.6658(0.
4);2.5236(1.4);2.5100(39.3);2.5057(82.0);2.5012(109.3);2.4967(78.5);2.4924(37.7);2.4266(1.5);2.4077(1.6);2.3956(1.7);2.3767(1.5);
2.3323(0.5);2.3280(0.6);2.3233(0.5);1.9885(0.7);1.8670(1.4);1.8451(1.4);1.8359(1.4);1.8144(1.2);1.3617(16.0);1.2982(0.6);1.2583(0
.8);1.2329(1.9);1.2207(14.1);1.1928(0.4);1.1747(0.5);0.8528(0.3);0.0081(0.4);-0.0002(13.8);-0.0083(0.5)
635: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 16.1140(0.5);10.4114(5.2);9.2742(4.1);9.2545(4.1);8.6672(16.0);8.4984(0.8);8.3161(0.7);8.2805(5.8);8.2574(6.8);7.9468(0.5);7.8
498(0.5);7.8211(0.5);7.8071(1.9);7.7922(13.1);7.7695(10.8);7.7494(1.6);7.7007(4.7);7.6894(5.4);7.6846(12.3);7.6801(10.0);7.6549(
0.5);7.6293(0.5);7.5660(2.6);7.5463(3.9);7.5265(1.9);7.4103(0.6);7.3731(7.7);7.3420(0.5);7.2955(0.6);7.2790(0.5);7.2579(0.6);7.174
8(0.6);7.1587(0.5);6.9763(2.6);6.9717(4.9);6.9672(2.8);6.7934(10.6);6.7888(10.5);5.7571(3.0);5.7200(1.4);5.7123(1.4);5.7007(2.3);5
635 4.08 .6927(2.3);5.6827(1.4);5.6722(1.3);4.2620(0.6);3.9041(0.7);3.8714(10.6);3.8595(8.3);3.3202(437.6);3.2547(10.3);3.2474(9.8);3.227
4(3.3);3.2003(3.5);3.1809(2.7);3.0551(0.6);3.0434(0.7);3.0415(0.8);3.0359(1.0);3.0236(1.1);2.6887(0.9);2.6736(7.4);2.6705(7.5);2.6
653(7.5);2.6262(2.8);2.6181(3.1);2.5684(1.0);2.5234(15.1);2.5055(828.6);2.5011(1116.3);2.4966(810.8);2.4925(396.0);2.3321(4.3);
2.3276(6.2);2.3235(4.8);1.6275(0.5);1.5493(0.6);1.3738(0.7);1.3611(0.6);1.3526(0.7);1.3364(0.7);1.3137(0.6);1.2976(3.0);1.2584(4.
);1.2492(1.9);1.2336(4.7);1.1866(0.7);1.1670(0.7);1.1470(0.5);0.8837(0.6);0.8665(1.0);0.8532(1.2);0.8343(0.9);0.7968(0.5);0.0080(
3.9);-0.0001(140.0);-0.0082(6.0);-0.1495(0.7)
636: 1H-NMR(400.0 MHz, d6-DMSO):
δ= (1.4);8.9919(1.4);8.9766(1.4);8.9719(1.4);8.5599(0.3);8.5003(0.6);8.4458(2.8);8.4226(3.0);8.3554(7.4);8.3047(0.3);8.0757
(1.1);8.0706(0.5);8.0539(1.2);7.9316(0.8);7.9195(1.1);7.9128(1.1);7.9002(0.8);7.6950(3.1);7.6724(3.0);7.6539(0.6);7.6428(0.5);7.62
85(0.9);7.6152(0.9);7.6017(0.9);7.5872(0.4);7.5792(0.4);7.4949(0.8);7.4737(0.7);7.3020(1.7);7.2826(1.7);7.1716(1.2);7.1510(2.4);7.
636 1.89 1329(1.9);7.1156(0.9);7.0876(0.6);6.9221(0.3);6.9074(1.5);6.8887(2.4);6.8702(1.2);6.7886(3.0);6.7683(2.6);5.7565(1.4);5.2367(0.7);
.2226(1.4);5.2034(1.3);5.1877(0.6);4.2500(2.2);4.2386(3.3);4.2272(2.0);3.3214(36.9);3.0794(2.4);3.0597(4.7);3.0529(5.6);3.0474(5
.6);3.0406(4.9);3.0261(0.9);2.6705(0.8);2.6665(0.6);2.5422(0.5);2.5379(0.5);2.5324(0.4);2.5238(1.9);2.5102(57.4);2.5061(114.6);2.5
9.9);2.4973(108.3);2.3331(0.6);2.3287(0.8);2.3240(0.7);2.1869(0.4);2.1731(0.8);2.1589(0.9);2.1531(0.7);2.1394(0.9);2.1240(
0.9);2.1119(0.4);2.0419(0.4);2.0252(0.8);2.0171(0.9);2.0075(0.9);1.9889(0.9);1.9713(0.5);1.3979(16.0);1.2984(0.6);1.2590(0.9);1.23
53(1.0);1.1749(0.4);0.8534(0.4);0.1464(0.6);0.0362(0.5);0.0081(6.1);0.0000(147.3);-0.0077(6.7);-0.0332(0.4);-0.1494(0.7)
637 (Atopisomer 1): 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9812(3.0);8.9606(3.1);8.5585(2.1);8.5432(2.2);8.5347(2.2);8.5195(2.0);8.4472(1.0);8.3740(10.8);7.8585(1.3);7.8460(2.4);7.833
;7.7210(3.3);7.7173(3.5);7.7009(4.0);7.6972(4.0);7.5268(2.4);7.5043(4.0);7.4818(2.7);7.4707(3.7);7.4513(6.4);7.4315(3.6);7.3
428(4.1);7.3391(4.3);7.3237(3.3);7.3200(3.0);7.2841(2.8);7.2656(3.1);7.1683(1.4);7.1645(1.4);7.1474(2.9);7.1298(1.8);7.1259(1.7);6
.9122(0.3);6.9043(2.1);6.9019(2.2);6.8834(3.6);6.8671(1.7);6.8646(1.7);6.7869(4.0);6.7664(3.6);6.5264(1.2);5.7564(10.6);5.2486(1.
637 2.00 0);5.2332(1.9);5.2138(1.8);5.1993(0.8);4.2563(3.3);4.2421(5.3);4.2296(3.1);4.0381(0.5);4.0202(0.5);3.5676(1.2);3.5530(1.0);3.5354(
3.3);3.5218(3.7);3.5179(3.7);3.5043(3.3);3.4865(1.0);3.3244(162.6);2.6748(0.7);2.6705(1.0);2.6659(0.7);2.5238(2.2);2.5189(3.5);2.5
103(62.0);2.5059(130.8);2.5015(175.3);2.4970(125.4);2.4927(59.8);2.3326(0.7);2.3281(1.0);2.3240(0.7);2.1843(0.4);2.1710(0.9);2.1
540(0.9);2.1492(1.0);2.1351(1.7);2.1215(1.5);2.1070(0.5);2.0365(0.6);2.0236(1.4);2.0079(1.5);1.9886(3.0);1.9756(0.8);1.9606(0.4);1
.3973(1.0);1.2982(0.6);1.2779(7.4);1.2600(16.0);1.2422(7.8);1.2362(2.8);1.1924(0.7);1.1745(1.4);1.1568(0.7);1.1179(0.4);0.1460(0.
7);0.0079(5.2);-0.0002(164.7);-0.0085(6.1);-0.1496(0.8)
637 (Atopisomer 2): 1H-NMR(400.0 MHz, d6-DMSO):
δ= 8.9813(3.2);8.9607(3.1);8.5586(2.0);8.5432(2.5);8.5346(2.2);8.5195(2.0);8.4528(0.5);8.4472(1.0);8.3793(4.0);8.3740(10.1);7.891
0(0.4);7.8462(2.8);7.8341(1.5);7.7210(3.6);7.7173(3.4);7.7009(4.4);7.6971(3.8);7.5269(2.3);7.5044(4.0);7.4817(2.8);7.4763(1.8);7.4
707(3.8);7.4564(2.4);7.4512(6.1);7.4370(1.4);7.4315(3.4);7.3722(0.4);7.3429(4.6);7.3392(4.1);7.3238(3.5);7.3201(2.9);7.2866(3.1);7
.2675(3.4);7.1684(1.7);7.1647(1.5);7.1491(3.3);7.1299(2.1);7.1260(1.7);6.9045(2.3);6.9017(2.3);6.8858(3.8);6.8672(1.8);6.8647(1.6)
637 2.00 ;6.7871(4.2);6.7666(3.8);6.5259(1.0);5.7618(3.4);5.7564(9.6);5.2477(1.1);5.2335(2.3);5.2150(2.0);5.1991(0.8);4.2561(4.1);4.2423(5.
9);4.2302(3.3);4.0378(0.5);4.0201(0.5);3.5734(0.5);3.5677(1.2);3.5530(1.3);3.5355(3.7);3.5222(4.6);3.5181(4.1);3.5044(3.6);3.4867(
1.0);3.3292(56.4);3.3241(147.2);2.6749(1.0);2.6704(1.0);2.5100(97.7);2.5060(162.3);2.5014(184.8);2.4969(125.4);2.3326(0.9);2.32
82(1.0);2.1711(1.0);2.1543(1.2);2.1482(1.2);2.1349(1.8);2.1213(1.6);2.1069(0.6);2.0234(1.7);2.0079(1.8);1.9942(1.9);1.9885(3.2);1.
.0);1.3973(1.0);1.2984(0.7);1.2778(7.7);1.2650(7.0);1.2599(16.0);1.2421(8.2);1.1924(0.8);1.1803(0.7);1.1746(1.4);1.1624(0.5
66(0.8);1.1175(0.4);0.8531(0.3);0.1461(0.7);0.0054(57.5);-0.0002(161.4);-0.0084(7.7);-0.1496(0.7)
638: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0008(3.2);8.9802(3.2);8.5200(2.1);8.5049(2.3);8.4962(2.3);8.4812(2.3);8.4700(11.1);7.9621(1.4);7.9491(2.6);7.9360(1.4);7.656
9(3.9);7.6521(7.7);7.6473(4.4);7.5206(2.6);7.4975(4.7);7.4688(12.2);7.4645(11.6);7.2968(3.0);7.2782(3.2);7.1784(1.5);7.1750(1.5);7
.1575(3.0);7.1400(1.9);7.1363(1.8);6.9153(2.2);6.8968(3.8);6.8803(1.8);6.8780(1.8);6.7978(4.2);6.7776(3.9);5.7568(14.4);5.2612(0.
638 2.23 8);5.2462(1.9);5.2271(1.9);5.2124(0.8);4.2879(0.4);4.2684(2.9);4.2535(5.0);4.2416(3.2);4.2248(0.4);4.0559(0.5);4.0381(1.4);4.0204(
1.4);4.0025(0.5);3.5657(1.0);3.5479(3.4);3.5341(3.8);3.5305(3.9);3.5167(3.4);3.4992(1.0);3.3244(45.5);2.6751(0.3);2.6708(0.4);2.66
);2.5240(1.0);2.5062(58.1);2.5018(77.3);2.4974(55.4);2.4933(26.6);2.3284(0.4);2.3242(0.3);2.1917(0.4);2.1800(0.8);2.1675(0.
8);2.1582(1.0);2.1439(1.7);2.1299(1.4);2.1160(0.6);2.0571(0.6);2.0444(1.4);2.0300(1.4);2.0168(0.9);2.0079(1.0);1.9976(0.8);1.9889(
6.3);1.3966(2.5);1.2716(7.6);1.2537(16.0);1.2359(7.6);1.1928(1.6);1.1750(3.2);1.1572(1.6);1.1006(0.4);0.1459(0.4);0.0078(2.9);-
0.0002(85.1);-0.0085(3.2);-0.1498(0.4)
639: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0037(3.5);8.9833(3.6);8.5928(2.3);8.5776(2.5);8.5692(2.5);8.5540(2.3);8.4447(8.2);7.9683(0.9);7.9555(1.6);7.9411(1.6);7.9269
(1.7);7.9141(0.9);7.6638(0.8);7.6556(0.8);7.6367(1.6);7.6280(1.5);7.6154(1.5);7.6000(0.8);7.5928(0.6);7.5575(2.4);7.5348(4.5);7.51
23(2.4);7.2980(3.6);7.2784(4.0);7.2281(1.0);7.2073(1.8);7.1856(1.1);7.1760(2.3);7.1556(3.8);7.1373(2.3);6.9128(2.6);6.8941(4.4);6.
639 2.03 8755(2.1);6.7945(5.2);6.7742(4.7);5.7562(7.5);5.2574(1.0);5.2421(2.3);5.2232(2.3);5.2089(1.0);4.2637(3.6);4.2504(6.3);4.2383(3.7);
4.0560(0.4);4.0382(1.2);4.0202(1.2);4.0029(0.4);3.5615(0.9);3.5447(2.8);3.5317(4.0);3.5142(2.9);3.3254(108.5);2.6706(0.7);2.5017(
124.2);2.3283(0.7);2.1918(0.5);2.1788(1.1);2.1587(1.2);2.1432(2.0);2.1298(1.7);2.1157(0.7);2.0354(1.5);2.0224(1.6);2.0015(1.1);1.9
887(6.0);1.3972(0.8);1.2987(0.3);1.2755(7.7);1.2577(16.0);1.2399(8.0);1.1925(1.4);1.1748(2.8);1.1570(1.4);1.1112(0.4);0.1461(0.5);
-0.0003(106.4);-0.1497(0.5)
640: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0190(2.7);8.9986(2.8);8.5860(1.9);8.5708(1.8);8.5624(1.9);8.5471(1.6);8.4880(8.4);8.4794(1.3);8.4515(0.7);8.4433(0.4);8.2878
(0.5);8.2279(2.1);8.0387(1.2);8.0254(2.1);8.0125(1.1);7.7914(0.8);7.6916(16.0);7.5748(0.5);7.5631(1.8);7.5519(0.4);7.5398(3.4);7.5
166(1.7);7.2969(2.4);7.2786(2.7);7.1814(1.1);7.1778(1.2);7.1606(2.5);7.1428(1.6);6.9190(1.7);6.9002(3.0);6.8820(1.5);6.7996(3.4);6
640 2.48 .7792(3.1);5.7563(6.7);5.2566(0.7);5.2422(1.7);5.2228(1.7);5.2079(0.8);4.2673(2.5);4.2530(4.4);4.2411(2.9);4.0382(0.5);4.0200(0.5)
;3.5675(1.1);3.5501(2.9);3.5331(3.2);3.5189(2.7);3.5015(0.8);3.3250(141.3);2.6708(0.8);2.5059(106.3);2.5018(136.0);2.4976(97.9);
2.3285(0.7);2.1793(0.7);2.1585(0.9);2.1438(1.4);2.1299(1.2);2.1166(0.5);2.0576(0.5);2.0442(1.2);2.0302(1.3);2.0171(0.8);2.0082(0.
9);1.9888(2.3);1.3974(1.0);1.2982(0.3);1.2718(5.9);1.2620(2.4);1.2539(12.0);1.2362(6.0);1.1928(0.6);1.1750(1.1);1.1571(0.6);0.146
1(0.6);0.0073(4.4);-0.0001(110.9);-0.0082(4.5);-0.1496(0.6)
641: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0727(0.5);9.0637(0.6);9.0525(0.6);8.4190(0.8);8.4096(1.8);8.4004(2.2);7.7346(0.4);7.6795(1.2);7.6757(1.2);7.6593(1.2);7.6558
(1.2);7.5940(0.5);7.5815(2.6);7.5618(1.4);7.5440(0.4);7.4389(0.5);7.4315(0.5);7.4194(0.9);7.4111(0.8);7.4002(0.5);7.3915(0.5);7.31
641 1.92 74(0.7);7.3021(1.5);7.2863(1.2);7.1704(0.5);7.1530(1.0);7.1323(0.6);6.9077(0.7);6.8882(1.2);6.8702(0.6);6.7922(1.4);6.7715(1.2);5.
2376(0.6);5.2210(0.6);4.2559(2.4);4.2484(2.3);3.7210(1.1);3.7090(0.9);3.3195(59.6);2.6702(1.5);2.5231(3.5);2.5054(198.0);2.5011(
259.6);2.4968(186.2);2.3320(1.1);2.3277(1.5);2.1827(0.3);2.1601(0.4);2.1464(0.6);2.1325(0.5);2.0385(0.4);2.0240(0.5);1.9970(11.1)
;1.9022(1.6);1.3977(16.0);0.1461(1.0);0.0077(7.6);-0.0002(219.7);-0.0081(8.5);-0.1498(1.1)
644: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1762(2.1);9.1562(2.2);8.6798(7.4);7.9799(1.3);7.9643(1.5);7.9565(1.5);7.9407(1.4);7.6877(2.4);7.6832(4.5);7.6479(3.0);7.5660
(1.5);7.5426(2.8);7.5196(1.4);7.4951(8.0);7.4914(7.9);7.3265(2.0);7.3076(2.2);7.1882(1.1);7.1662(4.4);7.1530(1.6);6.9288(1.5);6.91
644 2.03 04(2.5);6.8919(1.2);6.8417(3.1);6.8047(2.9);6.7842(2.6);5.2372(0.6);5.2226(1.3);5.2037(1.3);5.1892(0.6);4.3111(2.0);4.2962(4.0);4.
2811(2.3);4.2538(1.2);4.2359(1.7);4.2269(1.8);4.2119(1.1);4.2052(1.3);4.1841(0.4);4.0378(0.5);4.0200(0.6);3.5379(2.0);3.5229(3.8);
3.5078(1.9);3.3232(6.1);3.0749(16.0);2.8662(2.9);2.6705(0.7);2.5480(0.8);2.5053(97.3);2.5014(124.4);2.3284(0.7);2.2069(0.4);2.19
81(0.6);2.1838(0.8);2.1745(0.8);2.1629(0.8);2.1517(0.6);2.0745(3.5);2.0303(0.9);2.0162(0.7);2.0025(0.6);1.9887(2.6);1.2341(0.9);1.
.6);1.1746(1.2);1.1568(0.6);-0.0001(61.3)
647: (400.0 MHz, d6-DMSO):
δ= 9.2469(1.6);9.2267(1.7);8.7138(6.9);8.4548(3.2);8.3695(1.3);8.3539(1.4);8.3458(1.4);8.3303(1.3);7.7363(2.2);7.7312(2.4);7.6970
(2.2);7.6921(4.6);7.6877(3.4);7.6656(2.6);7.6424(1.4);7.6381(0.9);7.6330(1.2);7.6280(0.6);7.5214(6.3);7.5172(6.1);7.3823(1.5);7.36
49(1.6);7.1937(0.8);7.1902(0.8);7.1726(1.6);7.1552(1.0);7.1517(1.0);6.9391(1.1);6.9366(1.2);6.9180(2.0);6.9019(1.0);6.8993(1.0);6.
647 3.90 8088(2.2);6.8068(2.2);6.7884(2.0);6.7863(2.0);5.7561(12.1);5.2495(0.4);5.2362(1.0);5.2167(1.0);5.2022(0.5);4.2875(0.3);4.2695(0.9
);4.2546(1.8);4.2458(1.6);4.2339(0.9);4.2262(1.0);4.2061(0.3);4.0558(0.6);4.0380(1.7);4.0202(1.7);4.0024(0.6);3.7243(0.9);3.7057(2
.6);3.6886(2.0);3.6540(0.4);3.6195(1.1);3.6034(2.2);3.5864(1.6);3.5681(0.8);3.5517(0.4);3.3229(30.8);3.0469(13.3);3.0228(0.8);2.97
28(16.0);2.9526(0.6);2.6705(0.4);2.5240(0.9);2.5104(24.8);2.5061(52.1);2.5016(69.8);2.4971(49.8);2.4928(23.6);2.3283(0.4);2.2263
(0.3);2.2177(0.4);2.2054(0.6);2.1949(0.6);2.1835(0.7);2.1718(0.5);2.0912(0.5);2.0835(0.6);2.0764(0.8);2.0614(0.5);2.0499(0.5);2.04
18(0.5);1.9888(7.6);1.1927(2.0);1.1749(4.0);1.1571(1.9);0.0079(0.6);-0.0002(19.9);-0.0085(0.7)
648: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0572(2.9);9.0367(2.9);8.4493(10.6);8.1700(2.0);8.1550(2.1);8.1463(2.1);8.1314(2.0);7.7358(0.7);7.7309(0.8);7.6651(3.6);7.660
4(7.0);7.6556(4.0);7.6378(0.4);7.6329(0.5);7.4698(11.0);7.4663(10.8);7.4519(2.4);7.4287(4.1);7.4056(2.1);7.3170(2.8);7.2990(3.1);7
.1870(1.4);7.1840(1.4);7.1665(2.9);7.1487(1.8);7.1452(1.7);6.9224(2.0);6.9044(3.5);6.8874(1.7);6.8060(4.0);6.7857(3.6);5.7560(16.
648 2.06 709(0.8);5.5640(1.0);5.5582(0.9);5.4176(1.0);5.2110(0.8);5.1968(1.8);5.1775(1.8);5.1628(0.8);4.7415(0.4);4.7258(0.5);4.7120(
0.9);4.6976(0.9);4.6840(0.9);4.6565(3.0);4.6425(1.9);4.6234(1.6);4.6147(1.7);4.5979(2.4);4.5899(2.1);4.5582(1.4);4.5287(0.6);4.266
1(3.1);4.2539(5.1);4.2399(3.1);4.0559(0.6);4.0380(1.8);4.0202(1.8);4.0026(0.6);3.3241(88.4);3.0496(0.4);2.6708(0.7);2.5060(93.6);2
.5017(121.8);2.4974(88.1);2.3287(0.7);2.2024(0.4);2.1879(1.0);2.1736(1.1);2.1537(1.3);2.1387(1.3);2.1252(0.5);2.0539(0.6);2.0402(
1.2);2.0284(1.4);2.0149(0.9);2.0067(1.0);1.9888(8.4);1.3973(2.6);1.1928(2.1);1.1750(4.1);1.1572(2.0);0.0080(1.0);-0.0001(30.3)
649: (400.0 MHz, d6-DMSO):
δ= 9.3085(1.9);9.2880(2.0);8.6476(8.2);8.3888(1.4);8.3732(1.6);8.3651(1.6);8.3496(1.5);8.1547(0.5);7.6899(2.7);7.6851(5.2);7.6803
(2.9);7.6387(1.6);7.6155(3.1);7.5923(1.6);7.5128(7.7);7.5088(7.6);7.3587(2.0);7.3408(2.1);7.1945(0.9);7.1910(1.0);7.1736(2.0);7.15
59(1.2);7.1525(1.2);6.9340(1.5);6.9157(2.4);6.8992(1.2);6.8968(1.2);6.8099(2.7);6.7897(2.5);5.2926(0.5);5.2790(1.2);5.2593(1.2);5.
649 3.76 2449(0.6);5.1397(1.0);5.1247(2.2);5.1092(1.0);4.3009(0.4);4.2935(0.4);4.2812(1.1);4.2719(1.1);4.2537(1.6);4.2400(1.0);4.2326(1.2);
4.2124(0.4);4.2051(0.3);4.0377(0.8);4.0200(0.8);3.6455(0.8);3.6328(2.3);3.6195(2.5);3.6063(1.2);3.5285(2.3);3.5160(3.1);3.5041(1.
4);3.3211(12.7);3.0487(16.0);2.6747(0.4);2.6700(0.6);2.6660(0.4);2.5234(1.3);2.5097(37.4);2.5056(78.3);2.5011(104.9);2.4967(76.0
);2.3324(0.4);2.3278(0.6);2.3234(0.5);2.2371(0.4);2.2287(0.5);2.2165(0.8);2.2074(0.8);2.1953(0.8);2.1839(0.6);2.1748(0.4);2.0742(9
.8);2.0583(0.7);2.0518(0.7);2.0411(0.6);2.0328(0.6);1.9885(3.7);1.1924(1.0);1.1746(1.9);1.1568(0.9);0.0079(0.6);-0.0003(20.1);-
0.0085(0.8)
650: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1837(1.2);9.1634(1.3);8.6809(4.8);8.2435(0.9);8.2277(1.0);8.2197(1.0);8.2043(1.0);7.6933(1.4);7.6887(2.8);7.6837(2.0);7.6575
(1.9);7.6343(0.9);7.5177(4.8);7.5133(4.7);7.3620(1.2);7.3438(1.3);7.1910(0.6);7.1874(0.6);7.1697(1.2);7.1524(0.8);7.1492(0.7);6.93
650 4.51 44(0.9);6.9161(1.5);6.8981(0.7);6.8052(1.7);6.7851(1.5);5.7556(7.6);5.2537(0.3);5.2391(0.8);5.2201(0.8);5.2061(0.3);4.2758(0.7);4.
2596(1.2);4.2506(1.2);4.2386(0.7);4.2304(0.8);3.5520(1.3);3.5365(16.0);3.5178(1.3);3.3250(45.2);3.0097(10.2);2.7359(1.0);2.7216(
1.8);2.7177(1.9);2.7048(0.9);2.7002(0.9);2.5236(0.6);2.5059(34.1);2.5017(45.7);2.4974(33.7);2.2010(0.5);2.1907(0.5);2.1792(0.5);2.
1683(0.4);2.0735(0.3);2.0661(0.4);2.0583(0.5);2.0435(0.4);2.0318(0.4);2.0234(0.4);0.0074(0.6);-0.0002(16.6);-0.0080(0.7)
661: (400.0 MHz, d6-DMSO):
δ= 9.2660(1.8);9.2458(1.8);8.7364(6.3);8.4266(1.2);8.4110(1.3);8.4029(1.3);8.3875(1.3);7.7469(11.3);7.7294(1.3);7.7061(2.5);7.682
9(1.3);7.3840(1.6);7.3651(1.8);7.1922(0.8);7.1746(1.7);7.1566(1.0);7.1535(1.0);6.9384(1.2);6.9200(2.1);6.9014(1.0);6.8085(2.4);6.7
661 3.48 883(2.1);5.2480(0.5);5.2343(1.0);5.2148(1.1);5.2011(0.5);4.2879(0.3);4.2693(0.9);4.2543(1.8);4.2453(1.7);4.2331(0.9);4.2256(1.1);4
.2045(0.3);3.7270(1.0);3.7089(2.8);3.6921(2.1);3.6562(0.3);3.6219(1.1);3.6061(2.4);3.5891(1.7);3.5707(0.8);3.3195(31.5);3.0513(13
.4);2.9714(16.0);2.6701(0.4);2.5050(45.4);2.5008(60.1);2.4965(44.9);2.3276(0.4);2.2270(0.4);2.2193(0.4);2.2055(0.6);2.1953(0.7);2.
1842(0.7);2.1722(0.5);2.0920(0.5);2.0848(0.7);2.0775(0.8);2.0634(0.6);2.0509(0.5);2.0426(0.5);0.0077(2.0);-0.0002(58.4);-
0.0083(3.0)
666: 1H-NMR(400.0 MHz, O):
δ= 9.1888(0.4);9.1756(2.0);9.1551(2.1);8.8415(0.9);8.6572(7.6);8.3810(1.4);8.3654(1.5);8.3574(1.6);8.3419(1.4);8.1800(1.9);7.7145
(0.7);7.7106(0.7);7.7059(0.4);7.6898(2.4);7.6854(4.3);7.6809(2.5);7.6365(1.6);7.6133(3.0);7.5902(1.5);7.5413(1.0);7.5373(0.9);7.51
38(7.7);7.5099(7.4);7.4093(1.7);7.3948(1.9);7.3893(1.9);7.2887(1.0);7.2836(1.3);7.2686(2.6);7.2587(1.1);7.2540(1.1);7.2404(2.9);7.
666 4.19 2351(3.5);7.2262(3.2);7.2177(2.7);7.1992(0.5);5.7554(11.4);5.5865(0.6);5.5671(1.7);5.5474(1.8);5.5277(0.6);5.1663(0.3);4.4586(0.6
);4.4451(0.3);3.6266(3.1);3.6152(2.4);3.5424(2.7);3.5304(3.5);3.3506(1.4);3.2177(0.4);3.0483(16.0);3.0232(0.8);3.0095(0.7);2.9999(
0.8);2.9917(1.0);2.9833(1.0);2.9700(1.0);2.9614(0.9);2.9068(0.8);2.8863(1.6);2.8662(1.3);2.8468(0.9);2.8263(0.5);2.6707(0.3);2.569
4(0.4);2.5600(0.5);2.5497(0.8);2.5390(1.1);2.5290(1.2);2.5059(41.4);2.5017(53.0);2.4974(39.4);2.3925(2.1);2.3288(0.3);1.9889(1.1);
1.9703(1.1);1.9596(0.6);1.9500(1.1);1.9391(1.1);1.9293(0.5);1.9188(0.9);1.8974(0.3);1.2324(0.6);1.1749(0.4);-0.0001(16.4)
667: (400.0 MHz, d6-DMSO):
δ= 9.1838(0.9);9.1637(0.9);8.6672(3.8);8.2561(0.9);8.2533(1.0);8.2348(1.1);8.2318(1.0);7.8167(1.1);7.8136(1.0);7.7994(2.0);7.7952
(1.8);7.7744(1.0);7.7549(0.4);7.7051(1.0);7.6860(1.3);7.6714(1.0);7.6531(1.0);7.6502(1.1);7.6352(10.7);7.5676(0.6);7.5485(1.0);7.5
667 2.20 297(0.4);5.7451(0.3);5.7340(0.6);5.7256(0.6);5.7149(0.3);3.5677(1.1);3.3192(50.0);3.2454(0.6);3.2261(0.7);3.1987(0.8);3.1793(0.7);
3.0654(16.0);2.6876(0.8);2.6787(1.0);2.6704(0.7);2.6658(0.5);2.6408(0.7);2.6321(0.7);2.5234(1.7);2.5056(81.8);2.5013(106.7);2.49
68(76.8);2.3320(0.5);2.3280(0.6);2.3241(0.4);1.9883(1.2);1.3976(5.9);1.1925(0.3);1.1747(0.7);1.1568(0.3);0.1461(0.4);0.0078(3.7);-
0.0002(99.3);-0.0084(4.0);-0.1496(0.5)
668: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.1048(0.6);9.0845(0.6);8.5684(2.2);8.2951(0.9);8.2722(1.1);7.7677(1.1);7.7447(1.0);7.6197(2.0);7.3464(0.6);7.3272(0.6);7.1808
668 3.94 (0.3);7.1623(0.6);7.1415(0.4);6.9222(0.4);6.9036(0.8);6.8863(0.3);6.7970(0.8);6.7766(0.7);5.2280(0.4);5.2096(0.4);4.2664(0.4);4.23
98(0.5);4.2239(0.3);4.2180(0.4);3.3213(197.3);3.0723(9.7);3.0549(1.1);2.6700(1.0);2.5051(126.7);2.5011(167.6);2.4969(130.1);2.32
78(1.0);1.3975(16.0);0.1457(0.6);-0.0003(133.9);-0.1501(0.7)
669: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0888(1.0);9.0685(1.0);8.5482(3.5);8.2431(1.6);8.2203(1.8);7.7361(1.8);7.7132(1.7);7.3437(1.0);7.3234(1.3);7.2978(0.9);7.2924
669 2.67 7.2742(0.4);7.1768(0.5);7.1593(1.0);7.1385(0.6);7.0392(1.0);7.0204(1.0);6.9196(0.7);6.9008(1.2);6.8822(0.6);6.7944(1.4);6.77
41(1.2);5.2331(0.7);5.2138(0.6);4.2661(0.6);4.2491(0.9);4.2400(1.0);4.2265(0.6);4.2192(0.7);3.3208(107.7);3.0636(16.0);2.6703(0.9
52(108.3);2.5012(145.2);2.4972(117.6);2.3278(0.9);2.1920(0.4);2.1823(0.4);2.1690(0.4);2.0407(0.4);2.0341(0.5);2.0229(0.4);2
.0072(0.3);1.3976(2.0);0.1458(0.5);-0.0002(112.9);-0.1499(0.5)
670: (400.0 MHz, d6-DMSO):
δ= 9.0781(0.7);9.0580(0.8);8.5100(2.0);8.1805(1.6);8.1576(1.9);7.6967(2.0);7.6738(1.8);7.3393(0.8);7.3205(0.9);7.2257(1.6);7.1779
(0.4);7.1741(0.4);7.1563(0.8);7.1392(0.5);7.1353(0.5);7.0548(0.5);7.0243(0.5);6.9152(0.7);6.8967(1.1);6.8779(0.6);6.8661(0.5);6.84
670 2.84 07(0.5);6.7933(1.2);6.7749(1.1);5.7551(0.4);5.2322(0.5);5.2138(0.5);4.2667(0.5);4.2575(0.5);4.2498(0.6);4.2380(0.7);4.2252(0.4);4.
2173(0.6);3.5677(5.0);3.3190(47.9);3.0537(16.0);2.6747(0.4);2.6701(0.6);2.6656(0.4);2.5235(1.3);2.5099(32.8);2.5056(69.2);2.5011
(93.6);2.4966(68.7);2.4922(34.2);2.3633(0.6);2.3451(2.6);2.3280(0.8);2.3235(0.6);2.1902(0.4);2.1802(0.3);2.1680(0.3);2.0341(0.4);1
.3975(0.9);1.3203(1.7);1.2826(8.0);0.8894(0.7);0.1460(0.4);0.0079(3.1);-0.0002(94.5);-0.0084(4.2);-0.1497(0.4)
671: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0854(0.5);9.0650(0.5);8.6944(0.6);8.5236(3.9);8.2521(1.7);8.2292(1.8);7.7986(0.6);7.7790(1.0);7.7534(1.9);7.7395(0.5);7.7304
(2.0);7.7225(1.0);7.7009(0.6);7.6084(0.8);7.3380(0.8);7.3199(0.9);7.1766(0.5);7.1728(0.4);7.1553(0.9);7.1381(0.5);7.1340(0.5);6.91
671 3.00 50(0.6);6.8944(1.0);6.8759(0.5);6.7934(1.3);6.7728(1.1);5.7556(0.5);5.2278(0.6);5.2078(0.6);4.2631(0.6);4.2545(0.6);4.2459(0.7);4.
2376(0.8);4.2136(0.5);3.3202(122.1);3.0699(16.0);3.0549(2.9);2.6746(0.7);2.6700(0.9);2.6656(0.7);2.5233(2.3);2.5098(55.6);2.5055
(115.1);2.5011(154.0);2.4966(112.5);2.4923(56.1);2.3322(0.6);2.3278(0.9);2.3234(0.7);2.1869(0.4);2.1780(0.4);2.1659(0.4);2.0309(
0.4);0.8892(0.7);0.1457(0.7);0.0077(4.8);-0.0002(143.2);-0.0084(6.6);-0.1498(0.7)
672: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0722(0.4);9.0608(0.9);9.0405(0.9);8.5074(3.8);8.1786(1.6);8.1557(1.9);7.6922(1.9);7.6693(1.8);7.3389(0.8);7.3198(0.9);7.1783
(0.4);7.1747(0.4);7.1572(0.8);7.1400(0.5);7.1359(0.5);7.0250(1.5);6.9161(0.6);6.8975(1.1);6.8814(0.5);6.8787(0.5);6.8394(1.0);6.80
672 2.20 85(1.0);6.7953(1.3);6.7748(1.1);6.3561(0.3);5.2342(0.5);5.2146(0.5);4.2667(0.5);4.2568(0.5);4.2498(0.7);4.2396(0.8);4.2261(0.5);4.
2188(0.6);3.3229(33.8);3.0542(16.0);2.5234(0.5);2.5097(11.7);2.5056(24.2);2.5011(32.4);2.4966(23.8);2.4923(11.9);2.3130(4.7);2.3
061(4.8);2.1910(0.3);2.1813(0.4);2.1686(0.4);2.1573(1.8);2.0410(0.3);2.0334(0.4);1.2344(0.4);0.0079(1.1);-0.0002(31.5);-
0.0084(1.4)
673: 1H-NMR(400.0 MHz, d6-DMSO):
δ= 9.0829(2.0);9.0626(2.0);8.4835(6.9);8.4575(1.2);8.4426(1.3);8.4336(1.3);8.4188(1.2);7.8687(0.8);7.8560(1.6);7.8426(0.8);7.6931
(16.0);7.5995(1.6);7.5762(3.1);7.5529(2.2);7.5258(0.6);7.5058(0.5);7.4980(0.5);7.4886(0.4);7.4803(0.5);7.4548(3.8);7.4504(3.9);7.2
728(1.8);7.2546(1.9);7.1790(0.9);7.1752(0.9);7.1581(1.8);7.1405(1.2);7.1365(1.1);6.9004(1.4);6.8818(2.3);6.8654(1.0);6.8631(1.1);6
673 2.73 .7942(2.6);6.7756(2.3);6.2176(2.4);6.2126(4.3);6.2077(2.5);5.7555(10.1);5.2284(0.5);5.2139(1.2);5.1949(1.2);5.1806(0.5);4.4965(0.
6);4.4922(0.6);4.4773(1.9);4.4617(4.2);4.4463(2.1);4.2421(1.9);4.2296(3.2);4.2156(2.5);3.8610(1.0);3.8460(2.6);3.8316(2.5);3.8166(
0.9);3.3249(29.4);2.6705(0.3);2.5239(0.8);2.5189(1.2);2.5103(18.1);2.5061(37.6);2.5017(50.5);2.4972(37.0);2.4929(18.4);2.1465(0.
6);2.1327(0.6);2.1260(0.6);2.1119(0.9);2.0972(0.9);2.0828(0.3);2.0328(0.4);2.0199(0.8);2.0077(0.9);1.9943(0.6);1.9858(0.6);1.9715(
0.5);1.3520(0.8);1.2586(0.4);1.2276(0.9);0.0072(2.0);-0.0002(60.0);-0.0084(2.8)
674: (400.0 MHz, d6-DMSO):
δ= 9.2997(1.7);9.2792(1.7);8.6010(6.9);8.3134(2.8);8.2904(3.1);7.7458(3.3);7.7229(3.2);7.6789(2.2);7.6743(4.1);7.6696(2.4);7.6590
(0.4);7.6355(0.7);7.5524(0.4);7.3767(1.8);7.3464(1.8);7.3278(1.8);7.1892(0.9);7.1856(0.9);7.1683(1.7);7.1509(1.1);7.1473(1.0);6.92
39(1.2);6.9054(2.1);6.8889(1.0);6.8866(1.0);6.8042(2.4);6.7835(2.0);5.7555(1.3);5.2834(0.5);5.2687(1.0);5.2494(1.1);5.2346(0.6);5.
674 4.13 .1);5.1071(2.5);5.0920(1.1);4.2941(0.5);4.2867(0.5);4.2744(1.1);4.2654(1.0);4.2580(1.2);4.2502(1.4);4.2432(1.2);4.2303(0.9);
4.2227(1.1);4.2024(0.4);4.1950(0.3);3.7342(0.3);3.7229(0.4);3.7106(0.4);3.6435(0.8);3.6309(2.1);3.6172(2.4);3.6039(1.3);3.5678(16
5277(2.0);3.5149(2.7);3.5038(1.3);3.3194(58.5);3.0752(0.5);3.0653(1.3);3.0459(13.7);2.6748(0.7);2.6702(1.0);2.6658(0.7);2.50
97(63.1);2.5057(123.7);2.5013(161.6);2.4968(118.2);2.3325(0.7);2.3281(0.9);2.3237(0.7);2.2229(0.5);2.2097(0.7);2.2002(0.7);2.188
2(0.8);2.1771(0.6);2.1664(0.4);2.0605(0.7);2.0529(0.8);2.0428(0.6);2.0365(0.6);2.0267(0.6);2.0185(0.6);1.2586(0.5);1.2492(0.6);1.2
355(1.6);0.1461(0.6);0.0077(5.9);0.0000(131.3);-0.0081(7.0);-0.1495(0.6)
1H-NMR (400 MHz, Chloroform-d) δ 8.97 (s, 1H), 8.22 (m, 1H), 8.09 (d, J = 1.1 Hz, 1H), 7.68 (d, J = 6.3 Hz, 1H), 7.60 (m, 1H), 7.29
377 LC-MS (Method L2): Rt = 2.83
(d, J = 7.4 Hz, 1H), 7.26 – 7.16 (m, 2H), 6.96 – 6.81 (m, 3H), 5.41 – 5.33 (m, 1H), 4.34 (m, 1H), 4.19 (m, 1H), 3.96 (s, 3H), 3.13 (s,
min; m/z = 473 (M+H)+.
6H), 2.44 – 2.33 (m, 1H), 2.25 – 2.15 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.91 (s, 1H), 8.77 (d, J = 5.0 Hz, 1H), 8.25 (m, 1H), 8.03 (s, 1H), 7.79 (m, 1H), 7.72 (m, 1H),
378 LC-MS (Method L2): Rt = 2.82
7.67 – 7.59 (m, 1H), 7.31 (d, J = 7.3 Hz, 1H), 7.24 – 7.17 (m, 1H), 7.13 (d, J = 7.5 Hz, 1H), 6.98 – 6.90 (m, 1H), 6.87 (d, J = 8.2 Hz,
min; m/z = 450 (M+H)+.
1H), 5.37 (q, J = 5.4 Hz, 1H), 4.35 (m, 1H), 4.21 (m, 1H), 3.15 (s, 6H), 2.46 – 2.34 (m, 1H), 2.22 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.01 (s, 1H), 8.15 (t, J = 6.3 Hz, 2H), 7.68 (d, J = 6.3 Hz, 1H), 7.62 – 7.54 (m, 1H), 7.41 (d, J =
379 LC-MS (Method L2): Rt = 2.08
7.3 Hz, 1H), 7.30 (d, J = 7.5 Hz, 1H), 7.21 (t, J = 7.7 Hz, 1H), 6.90 (m, 3H), 6.76 (s, 1H), 5.38 (q, J = 5.4 Hz, 1H), 4.48 (s, 2H), 4.35
min; m/z = 440 (M+H)+.
(m, 1H), 4.25 – 4.16 (m, 1H), 3.12 (s, 6H), 2.39 (m, 1H), 2.21 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.00 (s, 1H), 8.58 (d, J = 5.1 Hz, 1H), 8.18 (m, 1H), 7.69 (m, 1H), 7.59 (m, 1H), 7.43 – 7.28 (m,
380 LC-MS (Method L2): Rt = 2.24
4H), 7.24 – 7.17 (m, 1H), 6.97 – 6.83 (m, 2H), 5.38 (q, J = 5.4 Hz, 1H), 4.35 (m, 1H), 4.20 (m, 1H), 3.13 (s, 6H), 2.63 (s, 3H), 2.45 –
min; m/z = 439 (M+H)+.
2.34 (m, 1H), 2.22 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.92 (s, 1H), 8.52 – 8.43 (m, 2H), 8.20 (m, 1H), 7.63 – 7.56 (m, 1H), 7.52 (m, 1H), 7.31 (m, 2H),
381 LC-MS (Method L2): Rt = 2.26
7.23 – 7.17 (m, 1H), 7.14 (d, J = 4.8 Hz, 1H), 6.96 – 6.82 (m, 2H), 5.37 (q, J = 5.4 Hz, 1H), 4.34 (m, 1H), 4.19 (m, 1H), 3.15 (s, 6H),
min; m/z = 439 (M+H)+.
2.38 (m 1H), 2.26 – 2.15 (m, 1H), 2.01 (s, 3H).
1H-NMR (400 MHz, Chloroform-d) δ 8.91 (s, 1H), 8.70 (s, 1H), 8.55 (d, J = 4.9 Hz, 1H), 8.28 – 8.20 (m, 1H), 7.65 – 7.57 (m, 2H),
382 LC-MS (Method L2): Rt = 2.63
7.35 – 7.27 (m, 2H), 7.24 – 7.14 (m, 2H), 6.92 (m, 1H), 6.86 (d, J = 8.2 Hz, 1H), 5.41 – 5.33 (m, 1H), 4.39 – 4.29 (m, 1H), 4.19 (m,
min; m/z = 259 (M+H)+.
1H), 3.15 (s, 6H), 2.44 – 2.33 (m, 1H), 2.20 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.94 (s, 1H), 8.55 (s, 1H), 8.49 (d, J = 4.8 Hz, 1H), 8.23 (m, 1H), 7.70 (d, J = 6.9 Hz, 1H), 7.61
383 LC-MS (Method L2): Rt = 2.59
(m, 1H), 7.45 – 7.38 (m, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 6.5 Hz, 1H), 7.23 – 7.16 (m, 1H), 6.92 (m, 1H), 6.86 (d, J = 8.2
min; m/z = 443 (M+H)+.
Hz, 1H), 5.41 – 5.32 (m, 1H), 4.34 (m, 1H), 4.19 (m, 1H), 3.14 (s, 6H), 2.44 – 2.33 (m, 1H), 2.21 (m, 1H).
1H-NMR (400 MHz, 6): δ [ppm] = 2.05-2.10 (m, 1H), 2.19-2.24 (m, 1H), 2.44 (s, 3H), 3.09 (s, 6H), 4.23-4.30 (m, 2H), 5.26
387 LC-MS (Method M14): Rt =
(q, 1H), 6.81 (d, 1H), 6.94 (t, 1H), 7.19 (t, 1H), 7.39 (d, 1H), 7.66 (t, 1H), 7.99 (s, 1H), 8.20 (d, 1H), 8.46 (d, 1H), 8.73 (s, 1H), 9.17 (d,
1.40 min; m/z = 469 (M+H)+
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.04-2.08 (m, 1H), 2.16-2.23 (m, 4H), 2.41 (s, 3H), 3.05 (s, 6H), 4.22-4.30 (m, 2H), 5.26
388 LC-MS (Method M24): Rt =
(q, 1H), 6.72 (s, 1H), 6.80 (s, 1H), 6.94 (t, 1H), 7.17 (t, 1H), 7.36 (d, 1H), 7.58-7.62 (m, 2H), 7.13-7.17 (m, 1H), 8.56 (s, 1H), 9.09 (d,
1.27 min; m/z = 458 (M+H)+
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.06-2.09 (m, 1H), 2.20-2.22 (m, 1H), 3.10 (s, 6H), 4.25-4.29 (m, 2H), 5.26 (q, 1H), 6.81
389 LC-MS (Method M23): Rt =
(d, 1H), 6.96 (t, 1H), 7.18 (t, 1H), 7.40 (d, 1H), 7.67 (t, 1H), 7.97 (d, 1H), 8.11 (d, 1H), 8.21 (d, 1H), 8.53 (d, 1H), 8.75 (s, 1H), 9.18
1.65 min; m/z = 455 (M+H)+
(d, 1H).
390 LC-MS (Method M23): Rt = 1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.08-2.09 (m, 1H), 2.20-2.23 (m, 1H), 3.07 (s, 6H), .30 (m, 2H), 5.26 (q, 1H), 6.81
1.67 min; m/z = 464 (M+H)+ (d, 1H), 6.94 (t, 1H), 7.16-7.21 (m, 2H), 7.40 (d, 1H), 7.61 (t, 1H), 7.81 (d, 1H), 8.10 (d, 1H), 8.33 (d, 1H), 8.70 (s, 1H), 9.15 (d, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.05-2.10 (m, 1H), 2.18-2.24 (m, 1H), 2.49 (s, 3H), 3.05 (s, 6H), 4.25-4.30 (m, 2H), 5.27
391 LC-MS (Method M14): Rt =
(q, 1H), 6.80-6.85 (m, 2H), 6.95 (t, 1H), 7.19 (t, 1H), 7.39 (d, 1H), 7.57 (t, 1H), 7.66 (d, 1H), 8.05 (d, 1H), 8.15 (d, 1H), 8.67 (s, 1H),
1.01 min; m/z = 444 (M+H)+
9.14 (d, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.02 (s, 1H), 8.29 (d, J = 5.1 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 7.0 Hz, 1H), 7.63 –
399 LC-MS (Method L2): Rt = 2.31
7.54 (m, 1H), 7.33 (m, 2H), 7.21 (t, J = 7.7 Hz, 1H), 6.91 (m, 4H), 5.38 (q, J = 5.4 Hz, 1H), 4.40 – 4.31 (m, 1H), 4.26 – 4.16 (m, 1H),
min; m/z = 510 (M+H)+.
3.88 – 3.79 (m, 4H), 3.59 – 3.51 (m, 4H), 3.13 (s, 6H), 2.40 (m, 1H), 2.27 – 2.17 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.95 (s, 1H), 8.27 – 8.18 (m, 2H), 7.58 (q, J = 4.5 Hz, 2H), 7.29 (d, J = 7.6 Hz, 1H), 7.20 (t, J =
400 LC-MS d L2): Rt = 2.86
7.2 Hz, 2H), 6.92 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 6.78 (s, 1H), 5.37 (q, J = 5.4 Hz, 1H), 4.33 (m, 1H), 4.24 – 4.13 (m,
min; m/z = 489 .
1H), 3.96 (s, 3H), 3.14 (s, 6H), 2.44 – 2.33 (m, 1H), 2.25 – 2.14 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.96 (s, 1H), 8.41 – 8.25 (m, 2H), 8.18 (d, J = 8.2 Hz, 1H), 7.59 (m, 3H), 7.30 (d, J = 7.6 Hz,
401 LC-MS (Method L9): Rt = 3.59
1H), 7.21 (m, 2H), 6.97 – 6.83 (m, 2H), 5.37 (q, J = 5.4 Hz, 1H), 4.34 (m, 1H), 4.25 – 4.16 (m, 1H), 3.77 (s, 3H), 3.13 (s, 6H), 2.39
min; m/z = 455 (M+H)+.
(m, 1H), 2.26 – 2.15 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.96 (s, 1H), 8.63 (d, J = 5.0 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.0 Hz, 1H), 7.60 (t, J
402 LC-MS (Method L2): Rt = 2.25 = 7.8 Hz, 1H), 7.50 (s, 1H), 7.47 (d, J = 5.0 Hz, 1H), 7.30 (d, J = 7.5 Hz, 2H), 7.21 (t, J = 7.7 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.86
min; m/z = 455 (M+H)+. (d, J = 8.2 Hz, 1H), 5.42 – 5.33 (m, 1H), 4.83 (s, 2H), 4.39 – 4.30 (m, 1H), 4.25 – 4.15 (m, 1H), 3.14 (s, 6H), 2.39 (m, 1H), 2.26 –
2.16 (m, 1H), 1.68 (s, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.91 (s, 1H), 8.46 (s, 2H), 8.28 (d, J = 8.5 Hz, 1H), 7.71 (d, J = 6.9 Hz, 1H), 7.68 – 7.60 (m, 1H),
403 LC-MS (Method L2): Rt = 2.89
7.29 (d, J = 7.6 Hz, 1H), 7.24 – 7.12 (m, 2H), 6.92 (t, J = 7.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 5.37 (q, J = 5.4 Hz, 1H), 4.34 (m, 1H),
min; m/z = 461 (M+H)+.
4.24 – 4.14 (m, 1H), 3.15 (s, 6H), 2.38 (m, 1H), 2.21 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.94 (s, 1H), 8.24 (m, 1H), 7.72 (m, 1H), 7.65 – 7.57 (m, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.25 –
413 LC-MS (Method L2): Rt = 3.02
7.17 (m, 1H), 7.12 (s, 3H), 6.94 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 5.38 (q, J = 5.4 Hz, 1H), 4.35 (m, 1H), 4.21 (m, 1H), 3.15
min; m/z = 461 (M+H)+.
(s, 6H), 2.46 – 2.34 (m, 1H), 2.22 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.91 (s, 1H), 8.32 – 8.22 (m, 2H), 7.70 (d, J = 6.9 Hz, 1H), 7.66 – 7.58 (m, 1H), 7.36 (t, J = 4.8
414 LC-MS (Method L2): Rt = 2.97
Hz, 1H), 7.30 (d, J = 7.5 Hz, 1H), 7.25 – 7.17 (m, 1H), 7.12 (d, J = 7.4 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 5.37
min; m/z = 477 (M+H)+.
(q, J = 5.3 Hz, 1H), 4.35 (m, 1H), 4.20 (m, 1H), 3.15 (s, 6H), 2.39 (m, 1H), 2.21 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.88 (s, 1H), 8.47 (s, 1H), 8.25 (m, 1H), 7.65 – 7.56 (m, 2H), 7.36 (s, 1H), 7.29 (d, J = 7.5 Hz,
415 LC-MS (Method L2): Rt = 3.02
1H), 7.24 – 7.17 (m, 1H), 7.09 (d, J = 7.5 Hz, 1H), 6.92 (t, J = 7.2 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 5.37 (q, J = 5.3 Hz, 1H), 4.34 (m,
min; m/z = 493 (M+H)+.
1H), 4.19 (m, 1H), 3.16 (s, 6H), 2.39 (m, 1H), 2.20 (m, 1H).
1H-NMR (400 MHz, form-d) δ 8.98 (s, 1H), 8.21 (m, 1H), 8.09 – 8.03 (m, 1H), 7.67 (d, J = 6.3 Hz, 1H), 7.63 – 7.55 (m, 1H),
416 LC-MS (Method L2): Rt = 3.14
7.30 (d, J = 7.6 Hz, 1H), 7.25 – 7.16 (m, 2H), 6.96 – 6.83 (m, 2H), 6.76 (d, J = 4.8 Hz, 1H), 5.37 (q, J = 5.4 Hz, 1H), 5.27 (m, 1H),
min; m/z = 501 (M+H)+.
4.34 (m, 1H), 4.19 (m, 1H), 3.13 (s, 6H), 2.38 (m, 1H), 2.20 (m, 1H), 1.37 (d, J = 6.2 Hz, 6H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.07 (d, J = 8.2 Hz, 1H), 8.44 (s, 1H), 7.69 – 7.55 (m, 3H), 7.49 (d, J = 2.6 Hz, 1H),
429 3.017 min; m/z = 508/510/512 7.36 (d, J = 7.5 Hz, 1H), 7.31 (d, J = 2.6 Hz, 1H), 7.17 (t, J = 7.3 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.24 (q, J
(M+H) +. = 5.9 Hz, 1H), 4.29 – 4.15 (m, 2H), 2.99 (s, 6H), 2.29 – 2.12 (m, 1H), 2.10 – 1.96 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 0.8 Hz, 1H), 8.29 – 8.21 (m, 1H), 7.95 – 7.87 (m, 1H), 7.66 –
433 LC-MS d L2): Rt =
7.58 (m, 2H), 7.52 – 7.43 (m, 1H), 7.33 (d, J = 7.7 Hz, 1H), 7.27 – 7.19 (m, 1H), 7.15 (t, J = 7.1 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H),
3.189 min; m/z = 560 (M+H) +.
6.78 (d, J = 8.0 Hz, 1H), 5.27 – 5.17 (m, 1H), 4.32 – 4.16 (m, 2H), 3.07 (s, 6H), 2.24 – 2.12 (m, 1H), 2.08 – 1.96 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.1 Hz, 1H), 8.50 (d, J = 0.8 Hz, 1H), 8.29 – 8.21 (m, 1H), 7.95 – 7.87 (m, 1H), 7.66 –
434 LC-MS (Method L2): Rt =
7.58 (m, 2H), 7.52 – 7.43 (m, 1H), 7.33 (d, J = 7.7 Hz, 1H), 7.27 – 7.19 (m, 1H), 7.15 (t, J = 7.1 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H),
2.894 min; m/z = 510 (M+H) +.
6.78 (d, J = 8.0 Hz, 1H), 5.27 – 5.17 (m, 1H), 4.32 – 4.16 (m, 2H), 3.07 (s, 6H), 2.24 – 2.12 (m, 1H), 2.08 – 1.96 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, 6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.53 (s, 1H), 8.32 – 8.23 (m, 1H), 7.96 – 7.84 (m, 2H), 7.80 (d, J = 8.3 Hz,
435 2.808 min; m/z = 483/485 1H), 7.71 – 7.62 (m, 2H), 7.34 (d, J = 7.4 Hz, 1H), 7.16 (t, 1H), 6.91 (t, 1H), 6.79 (d, 1H), 5.29 – 5.17 (m, 1H), 4.33 – 4.17 (m, 2H),
(M+H) +. 3.08 (s, 6H), 2.25 – 2.13 (m, 1H), 2.10 – 1.95 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.53 (s, 1H), 8.22 (dd, J = 8.4, 1.4 Hz, 1H), 7.66 – 7.60 (m, 1H), 7.59 –
436 LC-MS (Method L2): Rt =
7.53 (m, 1H), 7.37 – 7.26 (m, 2H), 7.20 – 7.07 (m, 2H), 6.97 (d, J = 9.3 Hz, 1H), 6.91 (t, J = 7.5, 1.0 Hz, 1H), 6.79 (d, 1H), 5.28 –
2.711 min; m/z = 456 (M+H) +.
.19 (m, 1H), 4.32 – 4.18 (m, 2H), 3.07 (s, 6H), 2.25 – 2.13 (m, 1H), 2.11 – 1.97 (m, 1H), 1.90 (s, 3H).
1H-NMR (400 MHz, DMSO-d6) δ 9.08 (d, J = 8.2 Hz, 1H), 8.54 (s, 1H), 8.22 (dd, J = 8.0, 2.0 Hz, 1H), 7.69 – 7.59 (m, 2H), 7.35 (d, J
437 LC-MS (Method L2): Rt =
= 7.5 Hz, 1H), 7.28 – 7.07 (m, 4H), 6.91 (t, J = 7.5, 1.1 Hz, 1H), 6.79 (d, J = 8.2, 0.9 Hz, 1H), 5.29 – 5.20 (m, 1H), 4.33 – 4.19 (m,
2.763 min; m/z = 456 (M+H) +.
2H), 3.07 (s, 6H), 2.34 (s, 3H), 2.26 – 2.13 (m, 1H), 2.11 – 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.03-2.09 (m, 1H), 2.20-2.25 (m, 1H), 3.27-3.29 (m, 4H), 3.86-3.88 (m, 4H), 4.21-4.29 (m,
441 LC-MS (Method M22): Rt =
2H), 5.26 (q, 1H), 6.80 (d, 1H), 6.94 (t, 1H), 7.18 (t, 1H), 7.24 (s, 1H), 7.38 (d, 1H), 7.70 (t, 1H), 7.79 (d, 1H), 8.28 (d, 1H), 8.67 (s,
1.67 min; m/z = 540 (M+H)+
1H), 9.19 (d, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.07-2.08 (m, 1H), 2.21-2.23 (m, 1H), 3.29-3.31 (m, 4H), 3.87-3.88 (m, 4H), 4.22-4.31 (m,
442 LC-MS (Method M22): Rt =
2H), 5.27 (q, 1H), 6.80 (d, 1H), 6.93 (t, 1H), 7.17-7.20 (m, 2H), 7.39 (d, 1H), 7.71 (t, 1H), 7.81 (d, 1H), 7.92 (d, 1H), 8.30 (d, 1H),
1.46 min; m/z = 506 (M+H)+
8.67 (s, 1H), 9.21 (d, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.07-2.12 (m, 1H), 2.21-2.26 (m, 1H), 3.28-3.30 (m, 4H), 3.87-3.90 (m, 4H), 4.23-4.31 (m,
443 LC-MS (Method M22): Rt =
2H), 5.28 (q, 1H), 6.81 (d, 1H), 6.96 (t, 1H), 7.17-7.21 (m, 2H), 7.42 (d, 1H), 7.67 (t, 1H), 7.83 (d, 1H), 8.14 (d, 1H), 8.37 (d, 1H),
1.84 min; m/z = 506 (M+H)+
8.77 (s, 1H), 9.24 (d, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 8.2 Hz, 1H), 8.67 (s, 1H), 8.38 (s, 1H), 8.28 (d, J = 7.3 Hz, 1H), 8.13 (d, J = 8.4 Hz,
456 LC-MS (Method L2): Rt = 2.76
1H), 7.65 – 7.57 (m, 1H), 7.39 (d, J = 7.2 Hz, 1H), 7.22 – 7.15 (m, 1H), 6.95 (t, J = 7.4 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 5.30 – 5.22
min, m/z = 445 (M+H)+.
(m, 1H), 4.34 – 4.21 (m, 2H), 3.07 (s, 6H), 2.68 (s, 3H), 2.27 – 2.16 (m, 1H), 2.12 – 2.01 (m, 1H).
LC-MS (Method L2): Rt = 3.33 1H-NMR (400 MHz, Chloroform-d) δ 9.05 (s, 1H), 8.03 (m, 2H), 7.58 (d, J = 1.5 Hz, 1H), 7.53 (m, 1H), 7.39 (d, J = 7.4 Hz, 1H), 7.32
457 min; m/z = 464 (M+H)+ with Cl (d, J = 7.6 Hz, 1H), 7.26 – 7.17 (m, 2H), 6.95 (m, 1H), 6.88 (d, J = 8.2 Hz, 1H), 5.38 (q, J = 5.3 Hz, 1H), 4.41 – 4.31 (m, 1H), 4.22
pattern. (m, 1H), 3.11 (s, 6H), 2.45 – 2.34 (m, 1H), 2.23 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.02 (s, 1H), 8.14 – 8.04 (m, 2H), 7.66 – 7.59 (m, 1H), 7.55 (m, 1H), 7.48 – 7.41 (m, 1H), 7.32
458 LC-MS (Method L2): Rt = 3.82
(d, J = 7.7 Hz, 1H), 7.26 – 7.17 (m, 2H), 6.95 (m, 1H), 6.91 – 6.84 (m, 1H), 5.42 – 5.33 (m, 1H), 4.41 – 4.32 (m, 1H), 4.22 (m, 1H),
min; m/z = 498 (M+H)+.
3.12 (s, 6H), 2.46 – 2.34 (m, 1H), 2.28 – 2.16 (m, 1H); contains 2.6% (w/w) EtOAc and 0.2% (w/w) DIP.
1H-NMR (400 MHz, form-d) δ 9.04 (s, 1H), 8.00 (m, 2H), 7.56 – 7.49 (m, 1H), 7.46 (d, J = 7.4 Hz, 1H), 7.36 – 7.29 (m, 2H),
459 LC-MS (Method L2): Rt = 3.26
7.25 – 7.17 (m, 1H), 6.95 (m, 1H), 6.88 (d, J = 8.2 Hz, 1H), 6.52 (m, 1H), 5.38 (q, J = 5.3 Hz, 1H), 4.41 – 4.31 (m, 1H), 4.22 (m, 1H),
min; m/z = 448 (M+H)+.
3.10 (s, 6H), 2.45 – 2.34 (m, 1H), 2.28 – 2.17 (m, 1H).
LC-MS (Method L2): Rt = 2.96 1H-NMR (400 MHz, Chloroform-d) δ 8.86 (s, 1H), 8.65 – 8.59 (m, 2H), 8.27 (m, 1H), 7.64 (m, 1H), 7.55 (m, 1H), 7.28 (d, J = 7.8 Hz,
460 min; m/z = 493 (M+H)+ with 1H), 7.24 – 7.17 (m, 1H), 7.06 (d, J = 7.5 Hz, 1H), 6.92 (m, 1H), 6.86 (d, J = 8.3 Hz, 1H), 5.37 (q, J = 5.3 Hz, 1H), 4.38 – 4.30 (m,
2*Cl pattern. 1H), 4.19 (m, 1H), 3.17 (s, 6H), 2.44 – 2.33 (m, 1H), 2.20 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.19 (t, 1H), 8.57 (d, J = 2.4 Hz, 1H), 8.35 – 8.28 (m, 1H), 8.15 – 8.08 (m, 1H), 8.06 – 8.00 (m, 1H),
461 LC-MS (Method L2): Rt = 7.74 – 7.65 (m, 3H), 7.35 (d, J = 7.7 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.27 – 5.19
3.774 min; m/z = 602 (M+H) +. (m, 1H), 4.31 – 4.17 (m, 2H), 3.94 - 3.85 (m, 4H), 3.37 – 3.22 (m, 4H; coinicdes with water ), 2.26 – 2.15 (m, 1H), 2.09 – 1.97
(m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.33 – 8.25 (m, 1H), 7.73 – 7.66 (m, 2H), 7.62 – 7.56 (m,
LC-MS d L2): Rt =
462 1H), 7.52 (dd, J = 8.6, 2.5 Hz, 1H), 7.44 (bs, 1H), 7.37 (d, J = 7.3 Hz, 1H), 7.16 (t, 1H), 6.92 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.1 Hz,
3.556 min; m/z = 534/536/538
1H), 5.29 – 5.20 (m, 1H), 4.33 – 4.19 (m, 2H), 3.94 – 3.81 (m, 4H), 3.36 – 3.22 (m, 4H; coincides with water signal), 2.27 – 2.15 (m,
(M+H) +.
1H), 2.11 – 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 8.2 Hz, 1H), 8.57 (d, J = 2.4 Hz, 1H), 8.29 (dd, J = 7.8, 2.1 Hz, 1H), 7.92 (dt, J = 9.2,
463 LC-MS (Method L2): Rt = 4.9 Hz, 1H), 7.71 – 7.62 (m, 2H), 7.49 (td, J = 8.5, 2.3 Hz, 1H), 7.35 (dd, J = 7.1, 2.8 Hz, 1H), 7.24 (ddd, J = 17.1, 9.3, 2.5 Hz, 1H),
3.464 min; m/z = 552 (M+H) +. 7.18 – 7.11 (m, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.28 – 5.20 (m, 1H), 4.32 – 4.18 (m, 2H), 3.94 – 3.82 (m, 4H),
3.37 – 3.21 (m, 4H; coincides with water signal), 2.28 – 2.15 (m, 1H), 2.09 – 1.98 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 8.35 – 8.28 (m, 1H), 7.93 (dd, J = 8.3, 2.0 Hz, 1H), 7.89 (s,
LC-MS d L2): Rt =
464 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 5.1 Hz, 2H), 7.36 (d, J = 7.2 Hz, 1H), 7.16 (t, 1H), 6.91 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.1
3.359 min; m/z = 525/527
Hz, 1H), 5.25 (q, J = 5.8 Hz, 1H), 4.33 – 4.19 (m, 2H), 3.94 – 3.85 (m, 4H), 3.37 – 3.22 (m, 4H; coincides with water signal), 2.27 –
(M+H) +.
2.16 (m, 1H), 2.10 – 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 8.0 Hz, 1H), 8.58 (s, 1H), 8.26 (dd, J = 8.4, 1.3 Hz, 1H), 7.72 – 7.64 (m, 1H), 7.64 –
465 LC-MS (Method L2): Rt = 7.59 (m, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 7.3 Hz, 1H), 7.24 (dd, J = 8.3, 1.8 Hz, 1H), 7.21 – 7.11 (m, 2H), 6.91 (t, J = 7.3
3.263 min; m/z = 514/516 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.30 – 5.21 (m, 1H), 4.33 – 4.19 (m, 2H), 3.93 – 3.80 (m, 4H), 3.36 – 3.21 (m, 4H; coincides with
(M+H) +. water signal), 2.33 (s, 3H), 2.27 – 2.15 (m, 1H), 2.10 – 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 8.2 Hz, 1H), 8.59 (s, 1H), 8.26 (dd, J = 8.4, 1.3 Hz, 1H), 7.72 – 7.64 (m, 1H), 7.64 –
466 LC-MS (Method L2): Rt = 7.57 (m, 1H), 7.36 (d, J = 7.2 Hz, 1H), 7.31 (dd, J = 8.3, 6.2 Hz, 1H), 7.20 – 7.09 (m, 2H), 6.97 (d, J = 8.5 Hz, 1H), 6.91 (t, 1H), 6.79
3.112 min; m/z = 498 (M+H) +. (d, J = 8.1 Hz, 1H), 5.29 – 5.21 (m, 1H), 4.33 – 4.19 (m, 2H), 3.93 – 3.82 (m, 4H), 3.36 – 3.22 (m, 4H; coincides with water peak),
2.27 – 2.16 (m, 1H), 2.10 – 2.00 (m, 1H), 1.89 (s, 3H).
1H-NMR (400 MHz, DMSO-d6) δ 9.17 (d, J = 8.2 Hz, 1H), 8.60 (s, 1H), 8.27 (dd, J = 7.4, 2.6 Hz, 1H), 7.74 – 7.65 (m, 2H), 7.37 (d, J
467 LC-MS (Method L2): Rt =
= 7.1 Hz, 1H), 7.28 – 7.22 (m, 1H), 7.22 – 7.10 (m, 3H), 6.92 (t, J = 7.5, 1.0 Hz, 1H), 6.80 (d, 1H), 5.30 – 5.22 (m, 1H), 4.33 – 4.19
3.239 min; m/z = 498 (M+H) +.
(m, 2H), 3.93 – 3.84 (m, 4H), 3.36 – 3.22 (m, 6H; coincides with water signal), 2.34 (s, 3H), 2.27 – 2.16 (m, 1H), 2.11 – 2.01 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.15 (d, J = 8.1 Hz, 1H), 8.56 (s, 1H), 8.23 (dd, J = 8.5, 1.2 Hz, 1H), 7.66 (dd, J = 8.3, 7.1 Hz, 1H),
468 LC-MS (Method L2): Rt = 7.56 (dd, J = 7.0, 1.2 Hz, 1H), 7.36 (d, J = 7.4 Hz, 1H), 7.21 – 7.12 (m, 2H), 7.12 – 7.05 (m, 1H), 6.98 – 6.87 (m, 2H), 6.79 (d, J = 8.1
3.043 min; m/z = 494 (M+H) +. Hz, 1H), 5.31 – 5.20 (m, 1H), 4.34 – 4.18 (m, 2H), 3.87 (s, 4H), 3.36 – 3.22 (m, 4H; coincides with water signal), 2.29 (s, 3H), 2.26 –
2.15 (m, 1H), 2.11 – 1.99 (m, 1H), 1.87 (d, J = 6.7 Hz, 3H).
LC-MS d L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.09 (d, J = 8.2 Hz, 1H), 8.53 (s, 1H), 8.30 – 8.20 (m, 1H), 7.65 (d, J = 5.1 Hz, 2H), 7.59 (d, J = 8.6
469 2.944 min; m/z = 492/494/496 Hz, 1H), 7.51 (dd, J = 8.6, 2.6 Hz, 1H), 7.43 (bs, 1H), 7.34 (d, J = 7.4 Hz, 1H), 7.17 (t, 1H), 6.91 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.1
(M+H) +. Hz, 1H), 5.27 – 5.19 (m, 1H), 4.32 – 4.18 (m, 2H), 3.07 (s, 6H), 2.26 – 2.13 (m, 1H), 2.10 – 1.96 (m, 1H).
LC-MS (Method L9): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.09 (d, J = 8.1 Hz, 1H), 8.51 (s, 1H), 8.22 (dd, J = 8.3, 1.4 Hz, 1H), 7.67 – 7.55 (m, 2H), 7.40 (d, J
470 2.815 min; m/z = 472/474 = 8.0 Hz, 1H), 7.34 (d, J = 7.5 Hz, 1H), 7.23 (d, J = 8.2, 1.8 Hz, 1H), 7.20 – 7.10 (m, 2H), 6.91 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.1 Hz,
(M+H) +. 1H), 5.28 – 5.19 (m, 1H), 4.32 – 4.19 (m, 2H), 3.07 (s, 6H), 2.33 (s, 3H), 2.25 – 2.14 (m, 1H), 2.09 – 1.97 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.07 (d, J = 8.2 Hz, 1H), 8.50 (s, 1H), 8.19 (d, J = 7.6 Hz, 1H), 7.61 (t, 1H), 7.52 (d, J = 6.1 Hz, 1H),
471 LC-MS (Method L2): Rt =
7.34 (d, J = 7.5 Hz, 1H), 7.21 – 7.12 (m, 2H), 7.09 (d, J = 7.9 Hz, 1H), 6.98 – 6.86 (m, 2H), 6.79 (d, J = 8.1 Hz, 1H), 5.29 – 5.18 (m,
2.770 min; m/z = 452 (M+H) +.
1H), 4.32 – 4.17 (m, 2H), 3.06 (s, 6H), 2.29 (s, 3H), 2.25 – 2.13 (m, 1H), 2.09 – 1.97 (m, 1H), 1.88 (d, J = 7.0 Hz, 3H).
1H-NMR (400 MHz, Chloroform-d) δ 9.03 (s, 1H), 8.15 (m, 1H), 7.68 (m, 1H), 7.57 (m, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.30 (d, J = 7.6
472 LC-MS (Method L2): Rt = 2.75
Hz, 1H), 7.24 – 7.17 (m, 1H), 6.93 (m, 1H), 6.87 (m, 1H), 6.55 (s, 2H), 5.38 (q, J = 5.4 Hz, 1H), 4.35 (m, 1H), 4.20 (m, 1H), 3.96 (s,
min; m/z = 485 .
6H), 3.12 (s, 6H), 2.45 – 2.34 (m, 1H), 2.21 (m, 1H).
LC-MS (Method L2): Rt = 2.76 1H-NMR (400 MHz, Chloroform-d) δ 8.97 (s, 1H), 8.20 (m, 1H), 7.68 (m, 1H), 7.59 (m, 1H), 7.40 (s, 1H), 7.34 (s, 1H), 7.31 (d, J = 7.7
473 min; m/z = 473 (M+H)+ with Cl Hz, 1H), 7.24 – 7.16 (m, 2H), 6.94 (m, 1H), 6.90 – 6.84 (m, 1H), 5.38 (q, J = 5.3 Hz, 1H), 4.40 – 4.31 (m, 1H), 4.21 (m, 1H), 3.14 (s,
pattern. 6H), 2.61 (s, 3H), 2.46 – 2.34 (m, 1H), 2.22 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.00 (s, 1H), 8.17 (m, 1H), 7.96 (d, J = 5.1 Hz, 1H), 7.65 (m, 1H), 7.58 (m, 1H), 7.42 (d, J = 7.5
474 LC-MS (Method L2): Rt = 2.54
Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.24 – 7.16 (m, 1H), 6.92 (m, 1H), 6.89 – 6.83 (m, 2H), 5.37 (q, J = 5.4 Hz, 1H), 4.34 (m, 1H), 4.19
min; m/z = 485 (M+H)+.
(m, 1H), 4.06 (s, 3H), 3.57 (s, 3H), 3.13 (s, 6H), 2.45 – 2.33 (m, 1H), 2.21 (m, 1H).
LC-MS (Method L2): Rt = 2.76 1H-NMR (400 MHz, form-d) δ 8.94 (s, 1H), 8.25 – 8.18 (m, 1H), 8.13 (d, J = 5.1 Hz, 1H), 7.64 – 7.56 (m, 2H), 7.28 (d, J = 7.7
475 min; m/z = 489 (M+H)+ with Cl Hz, 1H), 7.26 – 7.15 (m, 2H), 6.95 – 6.89 (m, 2H), 6.86 (d, J = 8.2 Hz, 1H), 5.37 (q, J = 5.4 Hz, 1H), 4.34 (m, 1H), 4.19 (m, 1H), 4.08
pattern. (s, 3H), 3.14 (s, 6H), 2.44 – 2.32 (m, 1H), 2.20 (m, 1H).
LC-MS (Method L2): Rt = 2.91 1H-NMR (400 MHz, Chloroform-d) δ 8.88 (s, 1H), 8.36 (d, J = 4.8 Hz, 1H), 8.25 (m, 1H), 7.65 – 7.56 (m, 2H), 7.29 (d, J = 7.7 Hz,
476 min; m/z = 493 (M+H)+ with 1H), 7.25 (d, J = 4.8 Hz, 1H), 7.23 – 7.16 (m, 1H), 7.10 (d, J = 6.5 Hz, 1H), 6.92 (m, 1H), 6.89 – 6.83 (m, 1H), 5.37 (q, J = 5.3 Hz,
2*Cl pattern. 1H), 4.38 – 4.30 (m, 1H), 4.19 (m, 1H), 3.16 (s, 6H), 2.44 – 2.33 (m, 1H), 2.20 (m, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.05-2.06 (m, 1H), 2.16 (s, 3H), 2.19-2.21 (m, 1H), 2.42 (s, 3H), 3.26-3.30 (m, 4H), 3.85-
480 LC-MS (Method M22): Rt =
3.88 (m, 4H), 4.24-4.28 (m, 2H), 5.25 (q, 1H), 6.72 (d, 1H), 6.80 (d, 1H), 6.94 (t, 1H), 7.18 (t, 1H), 7.38 (d, 1H), 7.62-7.65 (m, 2H),
1.26 min; m/z = 500 (M+H)+
8.20 (d, 1H), 8.63 (s, 1H), 9.16 (d, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.82 (d, J = 2.4 Hz, 1H), 8.29 (m, 1H), 7.56 (m, 1H), 7.44 (t, J = 8.8 Hz, 1H), 7.34 (m, 2H), 7.28
491 LC-MS (Method L2): Rt = 3.75
(s, 2H), 7.24 (m, 2H), 6.50 (d, J = 6.1 Hz, 1H), 5.72 (m, 1H), 3.94 (t, J = 3.9 Hz, 4H), 3.43 (m, 4H), 3.10 – 2.90 (m, 2H), 2.74 (m, 1H),
min; m/z = 536 (M+H)+.
1.96 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.83 (d, J = 1.1 Hz, 1H), 8.29 (m, 1H), 7.56 (m, 1H), 7.44 (t, J = 8.8 Hz, 1H), 7.33 (m, 2H), 7.25
492 LC-MS (Method L2): Rt = 3.87
– 7.08 (m, 4H), 6.65 – 6.54 (m, 1H), 5.45 – 5.36 (m, 1H), 4.12 (q, J = 7.2 Hz, 0H), 3.92 (m, 4H), 3.43 (m, 4H), 2.89 – 2.74 (m, 2H),
min; m/z = 550 (M+H)+.
2.24 – 2.11 (m, 1H), 2.09 – 1.98 (m, 1H), 1.97 – 1.77 (m, 2H).
1H-NMR (400 MHz, Chloroform-d) δ 8.90 (d, J = 3.7 Hz, 1H), 7.55 – 7.47 (m, 2H), 7.36 (dd, J = 21.1, 7.6 Hz, 1H), 7.29 (d, J = 9.6
LC-MS (Method L2): Rt = 2.93
496 Hz, 2H), 7.24 – 7.18 (m, 2H), 6.99 (d, J = 8.1 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.3 Hz, 1H), 5.39 (q, J = 5.5 Hz, 1H), 4.39
min, m/z = 564/566 (M+H)+;
– 4.30 (m, 1H), 4.24 – 4.16 (m, 1H), 4.06 (s, 3H), 3.76 (d, J = 4.1 Hz, 4H), 3.36 (d, J = 4.3 Hz, 4H), 2.49 – 2.32 (m, 1H), 2.28 – 2.16
Cl2 pattern.
(m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.93 (s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.42 – 7.35 (m, 2H), 7.35 – 7.28 (m, 2H), 7.21 (t, J = 7.1
LC-MS (Method L2): Rt = 2.92
497 Hz, 1H), 7.10 (t, J = 8.9 Hz, 1H), 6.99 (d, J = 8.2 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 5.39 (q, J = 5.2 Hz, 1H),
min, m/z = 548 (M+H)+; Cl
4.39 – 4.31 (m, 1H), 4.25 – 4.15 (m, 1H), 4.06 (s, 3H), 3.76 (d, J = 11.3, 6.7, 5.6 Hz, 4H), 3.34 (t, J = 4.3 Hz, 4H), 2.47 – 2.34 (m,
pattern.
1H), 2.27 – 2.15 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 8.2 Hz, 1H), 8.56 (s, 1H), 7.65 (d, J = 2.3 Hz, 3H), 7.53 (dd, J = 13.3, 2.7 Hz, 2H), 7.38
498 LC-MS (Method L2): Rt = 3.98
(d, J = 7.4 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 5.26 (q, J = 5.9 Hz, 1H), 4.34 – 4.20 (m,
min; m/z = 6 (M+H)+.
2H), 3.98 (s, 3H), 3.88 (t, J = 4.0 Hz, 4H), 3.31 – 3.20 (m, 4H), 2.28 – 2.16 (m, 1H), 2.12 – 2.01 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.22 – 9.11 (m, 1H), 8.45 (d, J = 1.6 Hz, 1H), 7.73 – 7.67 (m, 1H), 7.53 (d, J = 2.7 Hz, 1H), 7.47 –
499 LC-MS (Method L2): Rt = 3.61
7.40 (m, 1H), 7.35 (d, J = 7.1 Hz, 3H), 7.16 (t, J = 7.6 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.2 Hz, 1H), 5.25 (d, J = 6.2 Hz,
min; m/z = 564/566 (M+H)+.
1H), 4.25 (dt, J = 7.8, 4.6 Hz, 2H), 3.97 (s, 3H), 3.88 (s, 4H), 3.30 – 3.19 (m, 4H), 2.26 – 2.15 (m, 1H), 2.09 – 2.00 (m, 1H).
1H-NMR (400 MHz, 6) δ 9.17 (d, J = 8.2 Hz, 1H), 8.49 (s, 1H), 7.58 – 7.49 (m, 3H), 7.45 (d, J = 2.7 Hz, 1H), 7.39 – 7.31 (m,
500 LC-MS (Method L2): Rt = 3.65
2H), 7.17 (t, J = 7.2 Hz, 1H), 6.92 (t, J = 7.2 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.26 (q, J = 5.9 Hz, 1H), 4.33 – 4.19 (m, 2H), 3.97 (s,
min; m/z = 548/550 (M+H)+.
3H), 3.88 (t, J = 4.2 Hz, 4H), 3.31 – 3.21 (m, 4H), 2.29 – 2.15 (m, 1H), 2.11 – 2.00 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 8.2 Hz, 1H), 8.51 (s, 1H), 7.64 (s, 3H), 7.52 – 7.46 (m, 2H), 7.37 (d, J = 7.5 Hz, 1H),
501 LC-MS (Method L2): Rt = 3.42
7.17 (t, J = 7.1 Hz, 1H), 6.93 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 5.25 (q, J = 5.8 Hz, 1H), 4.34 – 4.20 (m, 2H), 3.96 (s, 3H),
min; m/z = 4 (M+H)+.
3.03 (s, 6H), 2.26 – 2.15 (m, 1H), 2.09 – 2.01 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.09 (dd, J = 8.0, 5.0 Hz, 1H), 8.40 (s, 1H), 7.69 (dd, J = 8.0, 1.4 Hz, 1H), 7.50 (d, J = 2.8 Hz, 1H),
502 LC-MS (Method L2): Rt = 3.09
7.47 – 7.40 (m, 1H), 7.32 (dd, J = 11.9, 5.4 Hz, 3H), 7.16 (t, J = 7.2 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 5.23
min; m/z = 522/524 (M+H)+
(d, J = 5.9 Hz, 1H), 4.31 – 4.19 (m, 2H), 3.96 (s, 3H), 3.04 (s, 6H), 2.25 – 2.13 (m, 1H), 2.06 (d, J = 15.1 Hz, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.44 (s, 1H), 7.56 – 7.48 (m, 3H), 7.42 (d, J = 2.8 Hz, 1H), 7.34 (t, J = 8.9
503 LC-MS (Method 2): Rt = 3.15
Hz, 2H), 7.20 – 7.12 (m, 1H), 6.91 (t, J = 7.1 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 5.24 (q, J = 5.8 Hz, 1H), 4.31 – 4.19 (m, 2H), 3.96 (s,
min; m/z = 506 (M+H)+.
3H), 3.04 (s, 6H), 2.25 – 2.14 (m, 1H), 2.09 – 1.98 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.15 (s, 1H), 8.20 (d, J = 7.4 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.46 (d, J = 1.8 Hz, 2H), 7.37 –
504 LC-MS (Method L9): Rt = 4.28
7.29 (m, 2H), 7.21 (t, J = 7.2 Hz, 1H), 6.90 (dd, J = 26.6, 8.1 Hz, 3H), 5.40 (q, J = 5.3 Hz, 1H), 4.40 – 4.31 (m, 1H), 4.26 – 4.16 (m,
min, m/z = 522/524 (M+H)+.
1H), 4.04 (s, 3H), 2.89 (s, 6H), 2.44 – 2.33 (m, 1H), 2.27 – 2.16 (m, 1H).
LC-MS (Method L9): Rt = 4.00 1H-NMR (400 MHz, Chloroform-d) δ 9.14 (d, J = 5.6 Hz, 1H), 8.33 (dd, J = 21.9, 7.3 Hz, 1H), 7.55 – 7.47 (m, 2H), 7.34 – 7.27 (m,
505 min, m/z = 522/524 (Cl2 2H), 7.21 (dd, J = 16.7, 8.0 Hz, 2H), 7.01 – 6.77 (m, 3H), 5.44 – 5.32 (m, 1H), 4.38 – 4.30 (m, 1H), 4.25 – 4.16 (m, 1H), 4.05 (s, 3H),
pattern; (M+H)+) 2.89 (s, 6H), 2.37 (td, J = 9.7, 4.7 Hz, 1H), 2.27 – 2.15 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 9.17 (s, 1H), 8.33 (d, J = 7.5 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.40 (dd, J = 6.2, 2.6 Hz, 1H),
506 LC-MS (Method L2): Rt = 2.74
7.32 (dd, J = 8.5, 4.4 Hz, 2H), 7.24 – 7.16 (m, 1H), 7.10 (t, J = 8.9 Hz, 1H), 7.01 – 6.84 (m, 3H), 5.39 (q, J = 5.3 Hz, 1H), 4.39 – 4.30
min, m/z = 506/508 .
(m, 1H), 4.25 – 4.16 (m, 1H), 4.04 (s, 3H), 2.88 (s, 6H), 2.43 – 2.32 (m, 1H), 2.26 – 2.16 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.67 (s, 1H), 7.57 – 7.49 (m, 2H), 7.45 (d, J = 1.8 Hz, 2H), 7.38 (t, J = 1.9 Hz, 1H), 7.30 (dd, J =
507 LC-MS (Method L2): Rt = 3.29
7.7, 1.6 Hz, 1H), 7.21 (dd, J = 15.4, 1.7 Hz, 1H), 6.98 – 6.90 (m, 1H), 6.86 (dd, J = 8.3, 1.2 Hz, 1H), 6.24 (d, J = 7.7 Hz, 1H), 5.38 (q,
min, m/z = 526/528.
J = 5.6 Hz, 1H), 4.40 – 4.31 (m, 1H), 4.25 – 4.15 (m, 1H), 3.06 (s, 6H), 2.46 – 2.34 (m, 1H), 2.27 – 2.16 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.64 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.51 (dd, J = 8.0, 1.7 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H),
508 LC-MS (Method L2): Rt = 3.06
7.29 (d, J = 7.4 Hz, 2H), 7.24 – 7.16 (m, 2H), 6.91 (t, J = 7.5 Hz, 1H), 6.85 (dd, J = 8.3, 1.2 Hz, 1H), 6.31 – 6.15 (m, 1H), 5.41 – 5.30
min, m/z = 526/528.
(m, 1H), 4.39 – 4.26 (m, 1H), 4.18 (t, J = 9.3 Hz, 1H), 3.06 (s, 6H), 2.44 – 2.33 (m, 1H), 2.25 – 2.14 (m, 1H).
LC-MS (Method L2): Rt = 3.07 1H-NMR (400 MHz, Chloroform-d) δ 8.66 (s, 1H), 7.59 – 7.49 (m, 2H), 7.41 – 7.31 (m, 2H), 7.29 (dd, J = 7.7, 1.7 Hz, 1H), 7.24 –
509 min, m/z = 510/512 (Cl2 7.16 (m, 1H), 7.11 (t, J = 8.9 Hz, 1H), 6.96 – 6.89 (m, 1H), 6.85 (dd, J = 8.3, 1.2 Hz, 1H), 6.23 (d, J = 7.6 Hz, 1H), 5.37 (q, J = 5.7
pattern, M+H)+. Hz, 1H), 4.39 – 4.30 (m, 1H), 4.23 – 4.14 (m, 1H), 3.06 (s, 6H), 2.44 – 2.33 (m, 1H), 2.25 – 2.15 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.23 – 9.11 (m, 1H), 8.65 (s, 1H), 8.54 (s, 1H), 7.93 (s, 1H), 7.73 (d, 1H), 7.50 – 7.43 (m, 1H), 7.43
510 3.828 min; m/z = 560/562/564 – 7.31 (m, 2H), 7.16 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.28 – 5.19 (m, 1H), 4.32 – 4.17 (m, 2H),
(M+H) +. 3.11 (s, 6H), 2.25 – 2.14 (m, 1H), 2.09 – 1.97 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.18 (d, J = 8.1 Hz, 1H), 8.68 (s, 1H), 8.54 (s, 1H), 8.03 (s, 1H), 7.62 – 7.53 (m, 2H), 7.41 – 7.32
511 3.897 min; m/z = 544/546 (m, 2H), 7.17 (t, J = 7.5 Hz, 1H), 6.92 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.24 (q, J = 5.6 Hz, 1H), 4.33 – 4.17 (m, 2H), 3.11
(M+H) +. (s, 6H), 2.26 – 2.14 (m, 1H), 2.11 – 1.98 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.28 (d, J = 8.1 Hz, 1H), 8.85 (s, 1H), 8.53 (s, 1H), 8.11 (s, 1H), 7.70 (s, 3H), 7.40 (d, J = 7.3 Hz,
512 4.340 min; m/z = 602/604/606 1H), 7.18 (t, J = 7.2 Hz, 1H), 6.94 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 5.26 (q, J = 5.6 Hz, 1H), 4.35 – 4.17 (m, 2H), 3.95 –
(M+H) +. 3.83 (m, 4H), 3.37 – 3.25 (m, 4H; coincides with water signal, 2.29 – 2.16 (m, 1H), 2.14 – 2.02 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.31 – 9.22 (m, 1H), 8.75 (d, J = 3.2 Hz, 1H), 8.55 (s, 1H), 7.98 (s, 1H), 7.74 (dd, J = 8.0, 1.4 Hz,
513 1H), 7.52 – 7.44 (m, 1H), 7.44 – 7.33 (m, 2H), 7.17 (t, J = 7.6 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.30 – 5.19
4.099 min; m/z = 602/604/606
(m, 1H), 4.34 – 4.17 (m, 2H), 3.96 – 3.82 (m, 4H), 3.40 – 3.23 (m, 4H; coincides with water signal), 2.29 – 2.15 (m, 1H), 2.12 – 1.97
(M+H) +.
(m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 8.1 Hz, 1H), 8.78 (s, 1H), 8.55 (s, 1H), 8.08 (s, 1H), 7.65 – 7.54 (m, 2H), 7.44 – 7.33
514 (m, 2H), 7.17 (t, J = 7.2 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 5.26 (q, J = 5.7 Hz, 1H), 4.34 – 4.16 (m, 2H), 3.95
– 3.82 (m, 4H), 3.39 – 3.23 (m, 4H; des with water signal), 2.29 – 2.16 (m, 1H), 2.13 – 2.00 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.17 – 9.07 (m, 1H), 8.37 (d, J = 2.2 Hz, 1H), 7.69 (dd, J = 8.0, 1.5 Hz, 1H), 7.53 (d,
517 3.180 min; m/z = 2/554 J = 2.7 Hz, 1H), 7.47 – 7.38 (m, 1H), 7.38 – 7.26 (m, 2H), 7.22 – 7.11 (m, 2H), 6.91 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.24
(M+H) +. (q, 1H), 4.34 – 4.18 (m, 2H), 3.92 – 3.77 (m, 4H), 3.30 – 3.16 (m, 4H), 2.28 – 2.12 (m, 1H), 2.11 – 1.95 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 8.91 (d, J = 8.3 Hz, 1H), 8.29 (s, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.50 – 7.41 (m, 1H), 7.35 – 7.29 (m,
528 2.588 min; m/z = 491/493 2H), 7.29 – 7.19 (m, 1H), 7.19 – 7.08 (m, 2H), 6.89 (t, J = 7.5 Hz, 1H), 6.77 (d, J = 8.0 Hz, 1H), 5.47 (s, 2H), 5.25 – 5.15 (m, 1H),
(M+H) +. 4.30 – 4.17 (m, 2H), 2.99 (s, 6H), 2.21 – 2.10 (m, 1H), 2.06 – 1.93 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 8.91 (d, J = 8.2 Hz, 1H), 8.31 (s, 1H), 7.91 (d, J = 9.2 Hz, 1H), 7.56 (t, J = 1.7 Hz, 1H), 7.31 (d, J =
529 2.722 min; m/z = 507/509/511 7.5 Hz, 1H), 7.22 (d, J = 1.6 Hz, 2H), 7.19 – 7.07 (m, 2H), 6.90 (t, J = 7.3 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.48 (s, 2H), 5.20 (q, J =
(M+H) +. 6.0 Hz, 1H), 4.27 – 4.19 (m, 2H), 2.98 (s, 6H), 2.21 – 2.10 (m, 1H), 2.05 – 1.95 (m, 1H).
1H-NMR (400 MHz, form-d) δ 8.93 (s, 1H), 7.59 (d, J = 8.2 Hz, 1H), 7.44 (d, J = 1.9 Hz, 2H), 7.39 – 7.28 (m, 4H), 7.26 – 7.16
530 LC-MS (Method L10) Rt =
(m, 2H), 7.01 – 6.82 (m, 3H), 5.51 – 5.20 (m, 1H), 4.48 – 4.28 (m, 1H), 4.28 – 4.12 (m, 1H), 4.05 (s, 3H), 3.76 (dt, J = 8.1, 4.7 Hz,
1.91 min, m/z = 564 (M+H)+.
6H), 3.34 (t, J = 4.5 Hz, 6H), 2.55 – 2.33 (m, 1H), 2.33 – 2.14 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.63 (s, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.36 (dd, J = 7.8, 4.8 Hz, 2H),
LC-MS (Method L2): Rt = 3.76
531 7.30 (dd, J = 7.8, 1.6 Hz, 1H), 7.23 – 7.17 (m, 1H), 7.15 – 7.07 (m, 1H), 6.93 (td, J = 7.5, 1.2 Hz, 1H), 6.86 (dd, J = 8.1, 1.2 Hz, 1H),
min, m/z = 4 (Cl2
6.20 (d, J = 7.6 Hz, 1H), 5.38 (q, J = 5.6 Hz, 1H), 4.40 – 4.31 (m, 1H), 4.24 – 4.14 (m, 1H), 4.15 – 3.75 (m, 4H), 3.43 (s, 4H), 2.46 –
pattern, M+H)+.
2.35 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.61 (d, J = 3.9 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.52 (dd, J = 8.0, 1.6 Hz, 1H), 7.47 (d, J = 7.7
532 LC-MS (Method L2): Rt = 3.74
Hz, 1H), 7.33 – 7.27 (m, 2H), 7.20 (td, J = 7.6, 1.7 Hz, 2H), 6.96 – 6.82 (m, 2H), 6.20 (t, J = 6.5 Hz, 1H), 5.42 – 5.33 (m, 1H), 4.39 –
min, m/z = 568/570 (M+H)+.
4.31 (m, 1H), 4.23 – 4.13 (m, 1H), 3.99 (d, J = 50.2 Hz, 4H), 3.44 (s, 4H), 2.46 – 2.34 (m, 1H), 2.26 – 2.16 (m, 1H).
1H-NMR (400 MHz, form-d) δ 8.65 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 1.9 Hz, 2H), 7.39 (t, J
533 LC-MS (Method L9): Rt = 4.38 = 1.9 Hz, 1H), 7.31 (dd, J = 7.6, 1.6 Hz, 1H), 7.21 (dd, J = 15.6, 1.7 Hz, 1H), 6.98 – 6.91 (m, 1H), 6.86 (dd, J = 8.3, 1.2 Hz, 1H), 6.20
min, m/z = 568/570 (M+H)+. (d, J = 7.6 Hz, 1H), 5.39 (q, J = 5.6 Hz, 1H), 4.41 – 4.33 (m, 1H), 4.25 – 4.16 (m, 1H), 3.95 (s, 4H), 3.43 (s, 4H), 2.47 – 2.36 (m, 1H),
2.29 – 2.19 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 8.99 (d, J = 8.3 Hz, 1H), 8.33 (s, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.50 – 7.43 (m, 1H), 7.33 (dt, J =
536 LC-MS (Method L2): Rt = 2.60
7.8, 4.6 Hz, 2H), 7.28 – 7.22 (m, 1H), 7.15 (t, J = 7.9 Hz, 2H), 6.90 (t, J = 7.0 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.52 (s, 2H), 5.27 –
min; m/z = 533/535 (M+H)+.
.17 (m, 1H), 4.24 (dt, J = 8.6, 4.0 Hz, 2H), 3.83 (s, 4H), 3.28 – 3.15 (m, 4H), 2.24 – 2.12 (m, 1H), 2.06 – 1.95 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.00 (dd, J = 8.3, 2.3 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.64 (dd, J = 8.1,
537 LC-MS (Method L2): Rt = 2.67 1.4 Hz, 1H), 7.41 (td, J = 7.8, 5.9 Hz, 1H), 7.32 (d, J = 7.3 Hz, 1H), 7.21 – 7.11 (m, 3H), 6.89 (t, J = 7.4 Hz, 1H), 6.77 (d, J = 8.1 Hz,
min; m/z = 549/551 (M+H)+. 1H), 5.37 (s, 2H), 5.21 (q, J = 6.0 Hz, 1H), 4.25 (t, J = 8.5 Hz, 2H), 3.82 (s, 4H), 3.28 – 3.16 (m, 4H), 2.23 – 2.12 (m, 1H), 2.06 –
1.95 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 8.98 (d, J = 8.3 Hz, 1H), 8.36 (s, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.57 (t, J = 1.9 Hz, 1H), 7.33 (d, J =
538 LC-MS (Method L2): Rt = 2.72
7.3 Hz, 1H), 7.22 (d, J = 1.8 Hz, 2H), 7.18 – 7.11 (m, 2H), 6.95 – 6.87 (m, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.54 (s, 2H), 5.22 (q, J = 5.9
min; m/z = 549/551 (M+H)+.
Hz, 1H), 4.31 – 4.18 (m, 2H), 3.82 (s, 4H), 3.28 – 3.14 (m, 4H), 2.19 (dq, J = 13.4, 4.8 Hz, 1H), 2.02 (dq, J = 10.4, 3.7, 3.3 Hz, 1H).
1H-NMR (400 MHz, 6) δ 8.92 (dd, J = 8.4, 2.4 Hz, 1H), 8.27 (s, 1H), 7.93 (d, J = 9.3 Hz, 1H), 7.63 (dd, J = 8.1, 1.7 Hz, 1H),
551 LC-MS (Method L2): 2.66 min,
7.47 – 7.37 (m, 1H), 7.30 (dd, J = 7.6, 1.6 Hz, 1H), 7.23 – 7.07 (m, 3H), 6.88 (t, J = 7.4 Hz, 1H), 6.77 (dd, J = 8.3, 1.2 Hz, 1H), 5.31
; m/z = 507/509 (M+1)+.
(d, J = 2.5 Hz, 2H), 5.20 (q, J = 6.2 Hz, 1H), 4.24 (t, J = 5.9 Hz, 2H), 2.99 (s, 6H), 2.23 – 2.10 (m, 1H), 2.06 – 1.92 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 10.37 (s, 1H), 8.98 (d, J = 8.3 Hz, 1H), 8.41 (s, 1H), 8.09 (d, J = 9.2 Hz, 1H), 7.48 – 7.40 (m, 1H),
559 LC-MS (Method L2): Rt = 2.60
7.35 – 7.24 (m, 4H), 7.18 – 7.12 (m, 1H), 6.90 (t, J = 7.3 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.21 (dd, J = 7.9, 5.1 Hz, 1H), 4.30 – 4.18
min; m/z = 492 (M+H)+.
(m, 2H), 3.03 (s, 6H), 2.22 – 2.12 (m, 1H), 2.06 – 1.96 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 8.98 (dd, J = 8.3, 2.4 Hz, 1H), 8.37 (s, 1H), 8.08 (d, J = 9.2 Hz, 1H), 7.61 (dd, J =
560 LC-MS (Method L2): Rt = 2.66
8.0, 1.5 Hz, 1H), 7.41 – 7.27 (m, 3H), 7.23 – 7.11 (m, 2H), 6.89 (t, J = 7.4 Hz, 1H), 6.77 (d, J = 8.1 Hz, 1H), 5.21 (q, J = 6.4 Hz, 1H),
min; m/z = 508/510 (M+H)+.
4.25 (td, J = 9.4, 8.0, 5.5 Hz, 2H), 3.03 (s, 6H), 2.22 – 2.11 (m, 1H), 2.06 – 1.94 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 10.33 (s, 1H), 8.98 (d, J = 8.2 Hz, 1H), 8.44 (s, 1H), 8.07 (d, J = 9.3 Hz, 1H), 7.54 (t, J = 2.0 Hz,
561 LC-MS (Method L2): Rt = 2.74
1H), 7.37 – 7.28 (m, 4H), 7.19 – 7.13 (m, 1H), 6.91 (td, J = 7.5, 1.2 Hz, 1H), 6.78 (dd, J = 8.2, 1.1 Hz, 1H), 5.26 – 5.18 (m, 1H), 4.30
min; m/z = 0 (M+H)+.
– 4.19 (m, 2H), 3.02 (s, 6H), 2.23 – 2.12 (m, 1H), 2.07 – 1.97 (m, 1H).
580 LC-MS (Method M11): Rt = 1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.04-2.09 (m, 1H), 2.17-2.30 (m, 1H), 3.07 (s, 6H), 4.22-4.32 (m 2H), 5.21-5.26 (m, 1H),
1.52 min; m/z = 570 (M+H)+ 6.79 (d, 1H), 7.33 (dd, 1H), 7.53 (d, 1H), .68 (m, 4H), 7.81 (dd, 1H), 8.25 (dd, 1H), 8.66 (s, 1H), 9.13 (d, 1H).
581 LC-MS (Method M11): Rt = 1H-NMR (300 MHz, DMSO-d6): δ [ppm] = 3.06 (s, 6H), 3.87 (dd, 1H), 4.05 (dd, 1H), 4.75 (d, 2H), 5.18-5.21 (m, 1H), 7.09-7.13 (m,
1.29 min; m/z = 492 (M+H)+ 1H), .30 (m, 2H), 7.47-7.50 (m, 1H), 7.62-7.67 (m, 4H), 7.80 (dd, 1H), 8.23 (dd, 1H), 8.62 (s, 1H), 9.11 (d, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.90 (d, J = 2.5 Hz, 1H), 8.21 (d, J = 9.3 Hz, 1H), 7.47 – 7.40 (m, 1H), 7.40 – 7.34 (m, 1H), 7.34
584 LC-MS (Method L2): Rt = 2.79
– 7.27 (m, 2H), 7.25 – 7.17 (m, 3H), 6.92 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 5.46 (s, 1H), 5.36 (dd, J = 7.6, 4.4 Hz, 1H),
min, m/z = 534 (M+H)+.
4.38 – 4.30 (m, 1H), 4.22 – 4.14 (m, 1H), 3.84 (q, J = 5.9 Hz, 4H), 3.40 (q, J = 4.4 Hz, 4H), 2.43 – 2.33 (m, 1H), 2.27 – 2.16 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.19 (dd, J = 8.1, 2.7 Hz, 1H), 8.68 (d, J = 1.9 Hz, 1H), 8.44 (d, J = 9.5 Hz, 1H), 7.77 (dt, J = 9.3,
609 LC-MS (Method L10): Rt =
1.6 Hz, 1H), 7.62 – 7.56 (m, 1H), 7.49 – 7.34 (m, 3H), 7.20 – 7.14 (m, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H),
3.98 min; m/z = 602 (M+H)+.
.37 – 5.10 (m, 1H), 4.32 – 4.18 (m, 2H), 3.88 (t, J = 4.8 Hz, 4H), 3.32 – 3.25 (m, 4H), 2.27 – 2.17 (m, 1H), 2.09 – 2.00 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.19 (dd, J = 8.1, 4.2 Hz, 1H), 8.65 (d, J = 3.7 Hz, 1H), 8.43 (d, J = 9.4 Hz, 1H), 7.76 (td, J = 8.8,
LC-MS (Method L10): Rt =
610 8.0, 1.6 Hz, 2H), 7.48 (td, J = 7.9, 5.1 Hz, 1H), 7.38 – 7.29 (m, 2H), 7.26 – 7.06 (m, 1H), 6.91 (tt, J = 7.5, 1.5 Hz, 1H), 6.79 (dd, J =
4.00 min; m/z = 618/620
8.3, 1.2 Hz, 1H), 5.23 (d, J = 6.5 Hz, 1H), 4.31 – 4.19 (m, 2H), 3.98 – 3.77 (m, 4H), 3.32 – 3.23 (m, 4H), 2.26 – 2.16 (m, 1H), 2.08 –
(M+H)+.
1.99 (m, 1H).
LC-MS (Method L10): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.19 (d, J = 8.1 Hz, 1H), 8.71 (s, 1H), 8.41 (d, J = 9.5 Hz, 1H), 7.84 – 7.66 (m, 2H), 7.39 (dd, J =
611 4.20 min; m/z = 618/620 19.0, 1.8 Hz, 3H), 7.22 – 7.13 (m, 1H), 6.96 – 6.88 (m, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.24 (q, J = 6.0 Hz, 1H), 4.32 – 4.19 (m, 2H),
(M+H)+. 3.98 – 3.71 (m, 4H), 3.32 – 3.22 (m, 4H), 2.27 – 2.17 (m, 1H), 2.10 – 2.01 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.10 (dd, J = 8.2, 2.8 Hz, 1H), 8.60 (s, 1H), 8.41 (d, J = 9.5 Hz, 1H), 7.71 (dq, J = 9.3, 1.5 Hz, 1H),
612 LC-MS (Method L10): Rt =
7.61 – 7.55 (m, 1H), 7.47 – 7.33 (m, 3H), 7.16 (td, J = 7.8, 1.6 Hz, 1H), 6.91 (td, J = 7.5, 1.2 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.22
3.67 min; m/z = 560 (M+H)+.
(dt, J = 8.4, 4.3 Hz, 1H), 4.31 – 4.18 (m, 2H), 3.09 (s, 6H), 2.25 – 2.14 (m, 1H), 2.09 – 1.91 (m, 1H).
LC-MS d L10): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.11 (dd, J = 8.2, 3.8 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.40 (d, J = 9.4 Hz, 1H), 7.76 – 7.68 (m,
613 3.60 min; m/z = 576/578 2H), 7.47 (td, J = 7.9, 5.1 Hz, 1H), 7.36 – 7.28 (m, 2H), 7.19 – 7.12 (m, 1H), 6.90 (tt, J = 7.3, 1.5 Hz, 1H), 6.78 (dd, J = 8.2, 1.2 Hz,
(M+H)+. 1H), 5.22 (d, J = 6.7 Hz, 1H), 4.31 – 4.17 (m, 2H), 3.09 (s, 6H), 2.19 (td, J = 9.1, 8.7, 3.9 Hz, 1H), 2.08 – 1.96 (m, 1H).
LC-MS (Method L10): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 9.10 (d, J = 8.2 Hz, 1H), 8.62 (s, 1H), 8.38 (d, J = 9.4 Hz, 1H), 7.70 (td, J = 4.4, 2.2 Hz, 2H), 7.40
614 3.82 min; m/z = 576/578 (d, J = 1.8 Hz, 2H), 7.35 (dd, J = 7.8, 1.6 Hz, 1H), 7.20 – 7.13 (m, 1H), 6.91 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.23 (q, J =
(M+H)+. 6.2 Hz, 1H), 4.31 – 4.19 (m, 2H), 3.08 (s, 6H), 2.24 – 2.14 (m, 1H), 2.08 – 1.99 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.06 (dd, J = 8.3, 2.9 Hz, 1H), 8.43 (d, J = 2.5 Hz, 1H), 8.13 (d, J = 9.3 Hz, 1H), 7.62
615 LC-MS (Method L2): Rt = 2.79
(dd, J = 7.9, 1.6 Hz, 1H), 7.45 – 7.30 (m, 3H), 7.24 – 7.11 (m, 2H), 6.90 (t, J = 7.5 Hz, 1H), 6.78 (dd, J = 8.3, 1.2 Hz, 1H), 5.22 (q, J
min, m/z = 550/552 (M+H)+.
= 6.3 Hz, 1H), 4.30 – 4.19 (m, 2H), 3.85 (q, J = 4.8, 3.8 Hz, 4H), 3.30 – 3.18 (m, 4H), 2.24 – 2.13 (m, 1H), 2.09 – 1.96 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 9.06 (d, J = 8.2 Hz, 1H), 8.51 (s, 1H), 8.13 (d, J = 9.3 Hz, 1H), 7.55 (d, J = 2.1 Hz,
616 LC-MS (Method L2): Rt = 2.92
1H), 7.41 – 7.30 (m, 4H), 6.92 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.23 (q, J = 5.9 Hz, 1H), 4.32 – 4.19 (m, 2H), 4.04 (s, 1H),
min, m/z = 550/552 (M+H)+.
3.90 – 3.79 (m, 4H), 3.24 (q, J = 5.3 Hz, 4H), 2.22 – 2.14 (m, 1H), 2.09 – 1.98 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 8.1 Hz, 1H), 8.67 (s, 1H), 8.36 (d, J = 8.6 Hz, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.77 (t, J =
617 LC-MS (Method L9): Rt = 4.03
1.9 Hz, 1H), 7.58 (s, 2H), 7.35 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.23 (q,
min; m/z = 9 (M+H)+.
J = 6.2 Hz, 1H), 4.31 – 4.19 (m, 2H), 3.08 (s, 6H), 2.25 – 2.14 (m, 1H), 2.09 – 1.98 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 9.06 (d, J = 8.2 Hz, 1H), 8.37 (s, 1H), 7.55 – 7.44 (m, 3H), 7.38 – 7.29 (m, 2H), 7.25
618 2.818 min; m/z = 492/494/496 (d, J = 2.6 Hz, 1H), 7.16 (t, J = 7.7 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 5.24 (q, J = 5.9 Hz, 1H), 4.31 – 4.17 (m,
(M+H) +. 2H), 3.00 (s, 6H), 2.26 – 2.13 (m, 1H), 2.09 – 1.95 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H), 9.10 – 9.00 (m, 1H), 8.33 (s, 1H), 7.68 (d, 1H), 7.48 (d, J = 2.6 Hz, 1H), 7.47 – 7.36
619 2.836 min; m/z = 508/510/512 (m, 1H), 7.36 – 7.27 (m, 2H), 7.20 – 7.10 (m, 2H), 6.90 (t, J = 7.4 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 5.29 – 5.16 (m, 1H), 4.31 – 4.15
(M+H) +. (m, 2H), 3.00 (s, 6H), 2.17 (dd, J = 8.6, 4.2 Hz, 1H), 2.01 (d, J = 13.7 Hz, 1H).
1H-NMR (400 MHz, CD3OD-d4): δ [ppm] = 2.22-2.25 (m, 1H), 2.31-2.35 (m, 1H), 3.18 (s, 6H), 4.29-4.34 (m, 1H), 4.38-4.43 (m, 1H),
620 LC-MS (Method M24): Rt =
.36 (t, 1H), 6.86-6.92 (m, 1H), 6.98-7.03 (m, 1H), 7.17 (d, 1H), 7.47 (t, 1H), 7.52 (d, 2H), 7.63 (dd, 1H), 7.71 (dd, 1H), 8.28 (dd, 1H),
1.34 min; m/z = 510 (M+H)+
8.55 (s,1H).
621 LC-MS (Method M47): Rt = 1H-NMR (400 MHz, CD3OD-d4): δ [ppm] = 2.20-2.26 (m, 1H), 2.29-2.35 (m, 1H), 3.19 (s, 6H), 4.33-4.39 (m, 1H), 4.43-4.48 (m, 1H),
2.86 min; m/z = 560 (M+H)+ 5.35 (t, 1H), 7.33-7.36 (m, 2H), 7.47 (t, 1H), 7.52 (d, 2H), 7.63 (dd, 1H), 7.72 (dd, 1H), 8.29 (dd, 1H), 8.56 (s, 1H).
622 LC-MS (Method M24): Rt = 1H-NMR (400 MHz, d4): δ [ppm] = .21 (m, 1H), .32 (m, 1H,), 3.19 (s, 6H), 4.23-4.34 (m, 2H), 5.32 (t, 1H), 6.80
1.43 min; m/z = 526 (M+H)+ (d, 1H), 7.15 (dd, 1H), 7.37 (d, 1H), 7.47 (t, 1H), 7.52 (d, 2H), 7.63 (dd, 1H), 7.72 (dd, 1H), 8.29 (dd, 1H), 8.56 (1 H, s).
623 LC-MS (Method M47): Rt = 1H-NMR (300 MHz, DMSO-d6): δ [ppm] = 1.99-2.05 (1 H, m), 2.18-2.21 (m, 1H), 3.06 (s, 6H), .27 (m, 2H), 5.19-5.24 (m, 1H),
2.86 min; m/z = 510 (M+H)+ 6.84 (dd, 1H), 7.00-7.07 (m, 1H), 7.17-7.22 (dd, 1H), 7.64-7.68 (m, 4H), 7.81 (dd, 1H), 8.24 (dd, 1H), 8.68 (s, 1H), 9.13 (d, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 9.12 (d, J = 8.2 Hz, 1H), 8.40 (s, 1H), 7.58 – 7.49 (m, 2H), 7.47 (dd, J = 6.2, 2.7 Hz,
626 3.240 min; m/z = 534/536/538 1H), 7.40 – 7.29 (m, 2H), 7.27 (d, J = 2.6 Hz, 1H), 7.16 (t, 1H), 6.92 (t, J = 7.5, 1.0 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 5.26 (q, 1H),
(M+H) +. 4.33 – 4.18 (m, 2H), 3.93 – 3.77 (m, 4H), 3.30 – 3.15 (m, 4H), 2.28 – 2.14 (m, 1H), 2.12 – 1.97 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 10.41 (s, 1H), 9.12 (d, J = 8.2 Hz, 1H), 8.46 (s, 1H), 7.63 (t, J = 1.9 Hz, 1H), 7.60 (d, J = 1.9 Hz,
627 3.529 min; m/z = 2/554 2H), 7.52 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 7.2 Hz, 1H), 7.32 (d, J = 2.6 Hz, 1H), 7.17 (t, 1H), 6.93 (t, 1H), 6.79 (d, J = 8.1 Hz, 1H),
(M+H) +. 5.25 (q, 1H), 4.33 – 4.18 (m, 2H), 3.89 – 3.74 (m, 4H), 3.27 – 3.13 (m, 4H), 2.29 – 2.12 (m, 1H), 2.12 – 1.98 (m, 1H).
632 LC-MS (Method M30): Rt = 1H-NMR (300 MHz, DMSO-d6): δ [ppm] = 2.07-2.11 (m, 1H), 2.23-2.27 (m,1 H), 3.06 (s, 6H), 4.31-4.45 (m, 2H), 5.28 (d, 1H), 6.94 (t,
1.65 min; m/z = 526 (M+H)+ 1H), 7.35 (t, 2H), 7.63-7.67 (m, 4H), 7.81 (d, 1H), 8.24 (d, 1H), 8.64 (s, 1H), 9.12 (d, 1H).
633 LC-MS (Method M14): Rt = 1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.06-2.10 (m, 1H), 2.20-2.24 (m, 1H), 3.06 (s, 6H), 4.31-4.44 (m,2H), 5.26-5.31 (m, 1H),
1.43 min; m/z = 570 (M+H)+ 6.88 (t, 1H), 7.40 (d, 1H), 7.48 (d, 1H), 7.63-7.67 (m, 4H), 7.80 (d, 1H), 8.24 (d, 1H), 8.64 (s, 1H), 9.13 (d, 1H).
634 LC-MS (Method M14): Rt = 1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.06-2.10 (m, 1H), 2.20-2.24 (m, 1H), 3.06 (s, 6H), 4.31-4.44 , 5.26-5.31 (m, 1H),
1.43 min; m/z = 570 (M+H)+ 6.88 (t, 1H), 7.40 (d, 1H), 7.48 (d, 1H), 7.63-7.67 (m, 4H), 7.80 (d, 1H), 8.24 (d, 1H), 8.64 (s, 1H), 9.13 (d, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.24 (dd, J = 8.1, 2.0 Hz, 1H), 8.74 (d, J = 2.7 Hz, 1H), 8.42 (d, J = 8.8 Hz, 1H), 8.04 (d, J = 8.8 Hz,
642 LC-MS (Method L9): Rt = 3.75 1H), 7.69 – 7.60 (m, 2H), 7.46 (td, J = 9.3, 7.0 Hz, 1H), 7.37 (dd, J = 7.6, 1.6 Hz, 1H), 7.20 – 7.14 (m, 1H), 6.92 (td, J = 7.5, 1.2 Hz,
min; m/z = 543/545 (M+H)+. 1H), 6.79 (d, J = 8.1 Hz, 1H), 5.24 (dq, J = 10.3, 5.4 Hz, 1H), 4.31 – 4.18 (m, 2H), 3.88 (t, J = 4.5 Hz, 4H), 3.29 (d, J = 4.8 Hz, 4H),
2.28 – 2.15 (m, 1H), 2.05 (s, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.80 (s, 1H), 8.11 (d, J = 7.4 Hz, 1H), 7.78 (d, J = 7.5 Hz, 1H), 7.45 – 7.37 (m, 2H), 7.31 (dd, J =
651 LC-MS (Method L2): Rt = 3.79 7.8, 1.7 Hz, 1H), 7.24 – 7.18 (m, 1H), 7.15 (t, J = 8.8 Hz, 1H), 6.97 – 6.91 (m, 1H), 6.87 (dd, J = 8.1, 1.2 Hz, 1H), 6.21 (d, J = 7.6 Hz,
min, m/z = 534 (M+H)+. 1H), 5.45 – 5.38 (m, 1H), 4.49 (s, 2H), 4.41 – 4.33 (m, 1H), 4.24 – 4.15 (m, 1H), 3.86 (s, 2H), 3.68 (s, 2H), 3.17 (s, 2H), 2.51 – 2.37
(m, 1H), 2.30 – 2.22 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 8.1 Hz, 1H), 8.76 (s, 1H), 8.39 (d, J = 8.8 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.78 (t, J =
652 LC-MS (Method L2): Rt = 3.88 1.9 Hz, 1H), 7.59 (d, J = 1.9 Hz, 2H), 7.37 (dd, J = 7.8, 1.6 Hz, 1H), 7.20 – 7.14 (m, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.79 (dd, J =
min; m/z = 559/661 (M+H)+. 8.1, 1.2 Hz, 1H), 5.28 – 5.21 (m, 1H), 4.32 – 4.18 (m, 2H), 3.88 (t, J = 4.8 Hz, 4H), 3.31 – 3.24 (m, 4H), 2.26 – 2.18 (m, 1H), 2.09 –
2.01 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.19 (d, J = 8.2 Hz, 1H), 8.69 (s, 1H), 8.51 (dd, J = 7.4, 1.4 Hz, 1H), 8.17 (dd, J =
LC-MS (Method L2): Rt =
656 8.5, 1.5 Hz, 1H), 7.65 (t, J = 8.4, 7.4 Hz, 1H), 7.36 (dd, J = 7.9, 1.6 Hz, 1H), 7.32 (s, 1H), 7.19 (ddd, J = 8.7, 7.4, 1.7 Hz, 1H), 6.95 (t,
2.697 min; m/z = 0
J = 7.5, 1.2 Hz, 1H), 6.82 (dd, J = 8.2, 1.1 Hz, 1H), 5.28 (q, J = 5.8 Hz, 1H), 4.34 – 4.19 (m, 2H), 3.09 (s, 6H), 2.28 – 2.16 (m, 1H),
(M+H)+.
2.12 – 2.00 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.77 (d, J = 4.0 Hz, 1H), 8.12 (d, J = 7.4 Hz, 1H), 7.70 (d, J = 7.3 Hz, 1H), 7.57 (dd, J = 8.1, 1.5
657 LC-MS d L2): Rt = 3.83 Hz, 1H), 7.36 – 7.27 (m, 2H), 7.24 – 7.17 (m, 2H), 6.93 (t, J = 7.3 Hz, 1H), 6.86 (dd, J = 8.3, 1.1 Hz, 1H), 6.21 (t, J = 6.6 Hz, 1H),
min, m/z = 559/561 (M+H)+. 5.41 (t, J = 6.2 Hz, 1H), 4.50 (s, 2H), 4.40 – 4.32 (m, 1H), 4.24 – 4.14 (m, 1H), 3.87 (s, 2H), 3.69 (s, 2H), 3.31 – 3.03 (m, 2H), 2.42
(dd, J = 12.0, 6.7 Hz, 1H), 2.31 – 2.18 (m, 1H).
1H-NMR (400 MHz, Chloroform-d) δ 8.83 (s, 1H), 8.10 (d, J = 7.4 Hz, 1H), 7.78 (d, J = 7.5 Hz, 1H), 7.47 – 7.39 (m, 2H), 7.31 (dd, J =
658 LC-MS (Method L2): Rt = 3.86 7.9, 1.6 Hz, 1H), 7.26 – 7.21 (m, 1H), 7.20 – 7.13 (m, 1H), 6.99 – 6.92 (m, 1H), 6.89 (dd, J = 8.3, 1.2 Hz, 1H), 6.23 (d, J = 7.7 Hz,
min, m/z = 501 (M+H)+. 1H), 5.41 (q, J = 5.6 Hz, 1H), 4.38 (dq, J = 10.3, 3.3 Hz, 1H), 4.26 – 4.18 (m, 1H), 3.08 (s, 6H), 2.48 – 2.38 (m, 1H), 2.30 – 2.21 (m,
1H-NMR (400 MHz, Chloroform-d) δ 8.78 (d, J = 1.3 Hz, 1H), 8.08 (d, J = 7.4 Hz, 1H), 7.67 (d, J = 7.4 Hz, 1H), 7.57 (dd, J = 8.1, 1.5
659 LC-MS (Method L2): Rt = 3.89
Hz, 1H), 7.36 – 7.29 (m, 1H), 7.28 (s, 1H), 7.24 – 7.17 (m, 2H), 6.96 – 6.89 (m, 1H), 6.86 (dd, J = 8.3, 1.1 Hz, 1H), 6.21 (t, J = 7.2
min, m/z = 517/519 (M+H)+.
Hz, 1H), 5.38 (s, 1H), 4.39 – 4.31 (m, 1H), 4.23 – 4.14 (m, 1H), 3.07 (s, 6H), 2.47 – 2.35 (m, 1H), 2.26 – 2.16 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.26 (d, J = 8.1 Hz, 1H), 8.87 (s, 1H), 7.91 – 7.87 (m, 1H), 7.84 – 7.73 (m, 2H), 7.70 – 7.57 (m,
660 LC-MS d L2): Rt = 3.65
1H), 7.35 (d, J = 7.8 Hz, 1H), 7.30 – 7.23 (m, 1H), 7.19 (t, J = 7.8 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 8.2 Hz, 1H), 5.31 –
min; m/z = 491 (M+H)+.
.11 (m, 4H), 4.84 – 4.70 (m, 2H), 4.34 – 4.21 (m, 2H), 2.25 – 2.15 (m, 1H), 2.08 – 2.01 (m, 1H).
1H-NMR (400 MHz, 6) δ 9.22 (d, J = 8.2 Hz, 1H), 8.66 (s, 1H), 8.29 (dd, J = 8.3, 1.7 Hz, 1H), 7.96 – 7.87 (m, 2H), 7.68 –
662 LC-MS (Method L2): Rt = 3.91
7.60 (m, 1H), 7.48 – 7.43 (m, 1H), 7.31 – 7.25 (m, 1H), 7.21 – 7.14 (m, 1H), 6.92 (td, J = 7.5, 1.2 Hz, 1H), 6.79 (dd, J = 8.2, 1.1 Hz,
min; m/z = 561 (M+H)+.
1H), 5.27 (q, J = 6.0 Hz, 1H), 4.34 – 4.19 (m, 2H), 2.23 (dp, J = 13.4, 4.3 Hz, 1H), 2.16 – 2.06 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.35 (d, J = 8.0 Hz, 1H), 8.87 (s, 1H), 8.28 (d, J = 7.6 Hz, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.72 (t, J =
663 LC-MS (Method L2): Rt = 4.04
1.9 Hz, 1H), 7.67 (d, J = 1.9 Hz, 2H), 7.45 – 7.38 (m, 1H), 7.22 – 7.15 (m, 1H), 6.94 (t, J = 7.4 Hz, 1H), 6.84 – 6.78 (m, 1H), 5.28 (q,
min, m/z = 559/561 (M+H)+.
J = 6.1 Hz, 1H), 4.34 – 4.17 (m, 4H), 3.78 (d, J = 10.9 Hz, 2H), 3.52 (s, 2H), 3.09 (s, 2H), 2.29 – 2.20 (m, 1H), 2.14 – 2.05 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.28 (d, J = 8.1 Hz, 1H), 8.86 (s, 1H), 8.26 (d, J = 7.6 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.72 (t, J =
664 LC-MS (Method L2): Rt = 4.11
2.0 Hz, 1H), 7.69 (d, J = 2.0 Hz, 2H), 7.39 (d, J = 7.3 Hz, 1H), 7.22 – 7.15 (m, 1H), 6.93 (t, J = 7.4 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H),
min, m/z = 517/519 (M+H)+.
.26 (q, J = 5.9 Hz, 1H), 4.31 – 4.22 (m, 2H), 2.91 (s, 6H), 2.27 – 2.15 (m, 1H), 2.14 – 2.01 (m, 1H).
665 LC-MS (Method M29): Rt = 1H-NMR (300 MHz, DMSO-d6): δ [ppm] = 3.05 (s, 6H), 3.88 (dd, 1H), 4.04 (dd, 1H), 4.79 (d, 2H), 5.19-5.22 (m, 1H), 7.11-7.17 (m,
2.82 min; m/z = 510 (M+H)+ 1H), 7.36 (dd, 2H), 7.62-7.67 (m, 4H), 7.80 (dd, 1H), 8.23 (dd, 1H), 8.63 (s, 1H), 9.14 (d, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.19 (dd, J = 8.3, 4.4 Hz, 1H), 8.80 – 8.67 (m, 2H), 7.83 (dd, J = 7.1, 1.2 Hz, 1H), 7.75 (dd, J = 8.6,
677 LC-MS (Method L2): Rt = 2.83 7.0 Hz, 1H), 7.61 (dtd, J = 11.0, 5.9, 3.0 Hz, 1H), 7.35 (dd, J = 7.7, 2.1 Hz, 1H), 7.22 (dp, J = 7.8, 2.4 Hz, 1H), 7.19 – 7.14 (m, 1H),
min; m/z = 504 (M+H)+. 6.92 (dd, J = 8.0, 6.8 Hz, 1H), 6.79 (dd, J = 8.2, 1.2 Hz, 1H), 5.29 (q, J = 6.4 Hz, 1H), 4.26 (td, J = 7.4, 7.0, 3.3 Hz, 2H), 3.99 (t, J =
8.9 Hz, 1H), 3.31 – 3.22 (m, 4H), 3.02 (q, J = 8.3 Hz, 1H), 2.26 – 2.10 (m, 3H), 2.09 – 2.00 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.29 – 9.14 (m, 1H), 8.75 (s, 1H), 8.53 – 8.19 (m, 1H), 7.97 – 7.71 (m, 2H), 7.61 (qd, J = 8.8, 3.3
LC-MS (Method L11): Rt =
678 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.20 (dt, J = 27.0, 6.7 Hz, 2H), 6.93 (tt, J = 7.5, 1.4 Hz, 1H), 6.79 (dd, J = 8.2, 1.2 Hz, 1H), 5.30 (q,
3.80 min and 3.84 min; m/z =
J = 6.2 Hz, 1H), 4.34 (p, J = 8.8, 8.2 Hz, 1H), 4.27 – 4.13 (m, 3H), 4.02 (dt, J = 29.8, 9.3 Hz, 1H), 3.87 – 3.56 (m, 1H), 3.25 – 3.15
505 (M+H)+.
(m, 1H), 2.44 – 2.36 (m, 1H), 2.32 – 2.18 (m, 2H), 2.10 – 2.01 (m, 1H).
1H-NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 8.3 Hz, 1H), 8.72 (s, 1H), 8.53 (d, J = 8.5 Hz, 1H), 7.80 (dt, J = 15.6, 7.2 Hz, 2H), 7.61
679 LC-MS d L2): Rt = 2.83 (dq, J = 12.7, 8.0, 6.9 Hz, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.25 – 7.13 (m, 2H), 6.93 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.3 Hz, 1H), 5.31
min; m/z = 532 (M+H)+. (q, J = 6.5 Hz, 1H), 4.31 – 4.19 (m, 2H), 2.94 (t, J = 11.7 Hz, 2H), 2.44 (d, J = 13.3 Hz, 3H), 2.25 (s, 4H), 2.00 (dt, J = 23.1, 11.4 Hz,
3H), 1.77 (dd, J = 22.3, 12.8 Hz, 2H).
1H-NMR (400 MHz, DMSO-d6) δ 13.95 (d, J = 7.7 Hz, 1H), 9.35 (dd, J = 8.2, 2.8 Hz, 1H), 8.67 (d, J = 3.3 Hz, 1H), 7.66 (dd, J = 8.0,
LC-MS (Method L9): Rt =
680 1.5 Hz, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.44 – 7.34 (m, 2H), 7.30 (t, J = 7.4, 1.5 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 6.96 (d, J = 8.0 Hz,
3.973 min; m/z = 550/552
1H), 6.92 (t, J = 7.7 Hz, 1H), 6.79 (dd, J = 8.2, 1.2 Hz, 1H), 5.25 (q, 1H), 4.35 – 4.15 (m, 2H), 3.85 (bs, 4H), 3.32 (bs, 4H; coincides
(M+H)+.
with water signal), 2.30 – 2.15 (m, 1H), 2.13 – 1.99 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 14.16 (s, 1H), 9.36 (d, J = 8.0 Hz, 1H), 8.79 (d, J = 1.6 Hz, 1H), 7.75 (dd, J = 8.1, 1.6 Hz, 1H), 7.61
681 4.067 min; m/z = 550/552 – 7.54 (m, 3H), 7.41 (d, J = 7.8 Hz, 1H), 7.22 – 7.14 (m, 1H), 6.99 – 6.90 (m, 2H), 6.81 (dd, J = 8.2, 1.4 Hz, 1H), 5.28 (q, J = 6.3 Hz,
(M+H)+. 1H), 4.35 – 4.18 (m, 2H), 3.85 (bs, 4H), 3.32 (bs, 4H; coincides with water peak), 2.29 – 2.17 (m, 1H), 2.14 – 2.02 (m, 1H).
LC-MS (Method L9): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 14.15 (s, 1H), 9.30 (d, J = 8.0 Hz, 1H), 8.67 (d, J = 2.4 Hz, 1H), 7.65 (dd, J = 8.0, 1.6 Hz, 1H), 7.53
682 4.036 min; m/z = 508/510 (d, J = 8.0 Hz, 1H), 7.44 – 7.33 (m, 2H), 7.33 – 7.26 (m, 1H), 7.17 (t, J = 7.6 Hz, 1H), 6.92 (dd, J = 7.9, 2.9 Hz, 2H), 6.79 (dd, J =
(M+H)+. 8.3, 1.2 Hz, 1H), 5.24 (q, J = 6.0 Hz, 1H), 4.31 – 4.20 (m, 2H), 2.99 (s, 6H), 2.23 – 2.15 (m, 1H), 2.09 – 1.99 (m, 1H).
LC-MS (Method L2): Rt = 1H-NMR (400 MHz, DMSO-d6) δ 14.36 (s, 1H), 9.32 (d, J = 8.0 Hz, 1H), 8.79 (s, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.61 – 7.57 (m, 2H),
683 3.335 min; m/z = 508/510 7.57 – 7.54 (m, 1H), 7.39 (dd, J = 7.8, 1.6 Hz, 1H), 7.18 (td, J = 7.8, 7.3, 1.7 Hz, 1H), 6.97 – 6.90 (m, 2H), 6.81 (d, J = 8.2, 1.2 Hz,
(M+H)+. 1H), 5.26 (q, J = 5.9 Hz, 1H), 4.33 – 4.18 (m, 2H), 2.99 (s, 6H), 2.27 – 2.16 (m, 1H), 2.13 – 2.02 (m, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.10-2.11 (m, 1H), 2.20-2.25 (m, 1H), 3.20-3.25 (m, 4H), 3.73-3.74 (m, 4H), 4.24-4.32 (m,
689 LC-MS (Method M48): Rt =
2H), 5.24 (q, 1H), 6.81 (dd, 1H), 6.95 (t, 1H), 7.19 (t, 1H), 7.39 (d, 1H), 7.54-7.55 (m, 1H), 7.77-7.83 (m, 2H), 8.68 (s, 1H), 9.24 (d,
2.70 min; m/z = 556 (M+H)+
690 LC-MS (Method M29): Rt = 1H-NMR (400 MHz, DMSO-d6): δ [ppm] = .10 (m, 1H), 2.19-2.22 (m, 1H), 2.97 (s, 6H), 4.23-4.29 (m, 2H), 5.22-5.24 (m, 1H),
2.91 min; m/z = 514 (M+H)+ 6.81 (d, 1H), 6.94 (t, 1H), 7.17-7.21 (m, 1H), 7.36 (d, 1H), 7.52 (s, 1H), 7.72-7.75 (m, 2H), 8.59 (s, 1H), 9.14 (d, 1H).
691 LC-MS (Method M48): Rt = 1H-NMR (400 MHz, DMSO-d6): δ [ppm] = 2.06-2.10 (m, 1H), 2.20-2.24 (m, 1H), 3.27-3.32 (m, 4H), 3.72-3.73 (m, 4H), .29 (m,
2.41 min; m/z = 570 (M+H)+ 2H), 5.24 (q, 1H), 6.81 (d, 1H), 6.95-6.97 (m, 1H), 7.17-7.19 (m, 1H), 7.38-7.40 (m, 1H), 7.70-7.78 (m,4H), 8.65 (s, 1H), 9.24 (d, 1H).
692 LC-MS (Method M7): Rt = 1H-NMR (400 MHz, CD3OD-d4): δ [ppm] = 2.18-2.23 (m, 1H), 2.26-2.33 (m, 1H), 3.09 (d, 6H), 4.24-4.32 (m, 2H), 5.30 (t, 1H), 6.80-
1.67 min; m/z = 528 (M+H)+ 6.83 (m, 1H), 6.91-6.96 (m, 1H),7.15-7.20 (m, 1H), 7.33-7.36 (m, 1H), 7.50-7.58 (m, 4H), 8.50 (s, 1H).
1H-NMR (400 MHz, 6): δ [ppm]= 2.08-2.10 (m, 1H), 2.22-2.25 (m,1 H), 3.20-3.32 (m, 4H), 3.70 (s, 4H), 4.23-4.30 (m, 2H),
693 LC-MS (Method M7): Rt =
.24 (q, 1H), 6.81 (d, 1H), 6.94 (t,1H), 7.19 (t, 1H), 7.39 (d, 1H), 7.57 (t, 1H), 7.63-7.65 (m, 1H), 7.78-7.85 (m, 2H), 8.68 (s, 1H), 9.22
1.71 min; m/z = 570 (M+H)+
(t, 1H).
1H-NMR (400 MHz, DMSO-d6): δ [ppm]=2.05-2.07 (m, 1H), 2.18-2.21 (m,1H), 2.97 (s, 6H), .29 (m, 2H), 5.21 (q, 1H), 6.81 (d,
694 LC-MS (Method M7): Rt =
1H), 6.94 (t, 1H), 7.19 (t, 1H), 7.36 (d, 1H), 7.53-7.57 (m, 1H), 7.63-7.64 (m,1H), 7.72 (d, 1H), 7.81-7.84 (m, 1H), 8.58 (s, 1H), 9.12-
1.61 min; m/z = 528 (M+H)+
9.14 (m, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.57), -0.008 (14.94), 0.008 (13.32), 0.146 (1.57), 2.038 (0.71), 2.103 (0.71), 2.179
(0.86), 2.214 (1.11), 2.327 (1.52), 2.366 (1.11), 2.523 (4.71), 2.670 (1.62), 2.694 (1.01), 2.709 (1.16), 3.363 (2.08), 3.379 (1.47),
3.405 (1.47), 3.436 (1.52), 3.462 , 3.490 (0.76), 4.120 (3.70), 4.204 (0.96), 4.258 (1.67), 4.278 (1.92), 4.287 (1.97), 4.645
374 LC-MS (Method L1): Rt = 1.38
(0.96), 5.243 (1.06), 5.285 (0.96), 6.798 (3.54), 6.818 (4.00), 6.861 (0.86), 6.879 (1.77), 6.899 , 6.924 , 6.945 (1.82),
min; m/z = 602 [M+H]⁺
6.961 (1.11), 7.160 (1.06), 7.178 , 7.188 (1.77), 7.285 (1.47), 7.304 (1.32), 7.418 (1.57), 7.435 (1.52), 7.646 (14.89), 7.648
(16.00), 7.681 (0.86), 7.717 (2.43), 7.735 (3.49), 7.756 (3.14), 7.868 (4.00), 7.886 (3.19), 8.329 (1.87), 8.346 (2.53), 8.363 (1.57),
8.773 , 8.786 (6.73), 8.962 (0.61), 9.262 (1.82), 9.282 (3.29), 9.303 (1.57).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.028 (0.47), 2.050 (0.77), 2.065 (0.73), 2.132 (0.72), 2.145 (0.85), 2.160 (0.51), 3.644
(16.00), 4.253 (1.62), 4.264 (2.51), 4.279 (1.47), 4.388 (1.53), 4.404 (1.52), 4.412 (1.50), 4.429 (1.52), 5.206 (0.44), 5.221 (0.97),
LC-MS d L1): Rt =
375 5.240 (0.94), 5.255 (0.45), 5.754 , 6.782 (1.85), 6.802 (2.07), 6.891 (0.88), 6.910 , 6.928 (1.09), 7.147 (0.94), 7.165
0.93 min; MS s): m/z =
(1.54), 7.183 (0.71), 7.302 , 7.321 (1.48), 7.575 (1.18), 7.594 (1.75), 7.616 (3.91), 7.626 (8.51), 7.631 (4.90), 7.769 (2.16),
536 [M+H]⁺
7.787 (1.79), 8.075 , 8.091 (1.40), 8.106 (0.67), 8.160 , 8.351 (1.65), 8.372 (1.58), 8.522 (5.37), 9.077 (1.61), 9.098
(1.57).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 2.074 (0.92), 2.081 (0.95), 2.090 (1.23), 2.099 (1.37), 2.107 (1.62), 2.115
(1.60), 2.167 (1.52), 2.189 (1.28), 2.328 , 2.671 (0.49), 4.258 (0.94), 4.276 (2.38), 4.286 (2.24), 4.307 (2.99), 4.317 (2.25),
LC-MS Method L1): Rt = 1.21 4.325 (2.52), 4.345 (0.91), 5.311 (1.02), 5.327 (2.32), 5.344 (2.34), 5.361 (1.07), 6.814 (4.66), 6.835 (5.19), 6.877 (2.09), 6.894
376 min; MS (ESIpos): m/z = 449 (4.48), 6.912 (2.65), 7.163 (2.38), 7.181 (3.70), 7.202 (1.79), 7.253 (3.98), 7.272 (3.65), 7.400 (3.14), 7.405 (3.55), 7.420 ,
[M+H]+ 7.424 (5.83), 7.457 (5.34), 7.477 , 7.496 (3.47), 7.718 (5.20), 7.723 (5.42), 7.738 (4.66), 7.742 (4.46), 7.755 (1.40), 7.772
(6.63), 7.781 , 7.789 (16.00), 7.798 , 8.164 (3.15), 8.173 (2.91), 8.180 (2.79), 8.188 , 8.943 (7.32), 8.948 (7.68),
9.208 (4.01), 9.217 (9.88), 9.222 (9.87), 9.228 (4.19).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.19), -0.008 (9.91), 0.146 (1.21), 1.523 (9.91), 1.529 (10.20), 1.541 (11.31), 1.552
(14.84), 1.572 ), 2.009 (1.32), 2.018 (1.45), 2.028 , 2.045 (2.19), 2.052 (1.79), 2.072 (1.11), 2.178 (1.87), 2.190 (1.79),
LC-MS (Method L1): Rt = 2.200 (1.69), 2.327 (1.11), 2.366 (1.08), 2.669 (1.16), 2.709 (1.08), 3.848 (1.69), 4.207 (1.05), 4.226 (3.16), 4.234 (2.79), 4.245
386 1.36 min; MS (ESIpos): m/z = (4.93), 4.254 (5.27), 4.270 (2.85), 4.289 (0.90), 5.243 (1.19), 5.258 (2.66), 5.276 (2.74), 5.292 (1.13), 5.753 (6.70), 6.771 (5.67),
526 [M+H]⁺ 6.791 , 6.895 (2.45), 6.914 (5.22), 6.933 (3.03), 7.141 , 7.159 (4.56), 7.176 (2.19), 7.327 (2.64), 7.334 (2.87), 7.353
, 7.465 (3.58), 7.471 (3.85), 7.489 , 7.495 , 7.736 (16.00), 7.745 (7.93), 7.752 (7.78), 7.769 (1.27), 7.911 (8.30),
7.918 (8.20), 8.473 (3.87), 8.483 (3.43), 8.489 (3.37), 8.498 , 8.669 (7.54), 8.679 (8.20), 9.119 (5.19), 9.139 (5.06).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.44), -0.008 (3.87), 0.008 (3.75), 0.146 (0.44), 1.235 (0.52), 2.012 (0.57), 2.023
(0.75), 2.033 (0.65), 2.046 (1.16), 2.060 (1.08), 2.073 (1.84), 2.135 (0.41), 2.149 (1.12), 2.163 (1.23), 2.181 (0.72), 2.199 (0.67),
2.327 (0.42), 2.366 (0.41), 2.523 (1.29), 2.670 (0.43), 2.710 (0.44), 4.252 (2.47), 4.264 (4.03), 4.278 (2.39), 4.512 (0.46), 4.544
LC-MS (Method L1): Rt =
392 (1.08), 4.577 (2.07), 4.606 (1.41), 4.637 (1.95), 4.647 (2.10), 4.661 (0.77), 4.676 (0.74), 4.691 , 4.705 (0.72), 4.718 (0.44),
0.85 min; MS (ESIpos): m/z =
.178 (0.62), 5.193 (1.42), 5.212 (1.43), 5.226 (0.63), 5.411 (0.80), 5.557 (0.79), 5.754 (4.87), 6.791 (2.68), 6.812 (2.97), 6.894
522 [M+H]⁺
(1.29), 6.897 (1.35), 6.915 (2.76), 6.931 (1.62), 6.934 (1.63), 7.150 (1.32), 7.154 , 7.171 (2.22), 7.189 (1.09), 7.192 (1.09),
7.314 (2.35), 7.331 (2.17), 7.472 (1.95), 7.490 (2.54), 7.493 (2.57), 7.511 (2.33), 7.614 (16.00), 7.737 (3.27), 7.753 (2.63), 7.755
(2.75), 8.065 (2.69), 8.084 (2.39), 8.181 (0.62), 8.488 (9.91), 9.045 (2.49), 9.065 (2.43).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.46), 0.146 , 2.004 (1.48), 2.054 (1.02), 2.073 (1.42), 2.129 , 2.179
(1.60), 2.192 (1.83), 2.203 (1.71), 2.214 (1.57), 2.327 (0.49), 2.366 (0.54), 2.669 (0.51), 2.710 (0.49), 3.015 (0.72), 3.192 ,
LC-MS (Method L1): Rt =
393 3.220 , 3.403 (0.84), 3.429 , 3.454 (1.45), 4.219 (0.48), 4.240 (1.51), 4.248 (1.25), 4.261 (2.24), 4.270 (2.16), 4.287
1.31 min; MS (ESIpos): m/z =
, 4.306 (0.49), 4.909 (0.62), 5.030 (0.63), 5.226 (0.65), 5.241 (1.44), 5.260 (1.43), 5.274 (0.66), 6.787 (2.64), 6.807 (2.91),
550 [M+H]⁺
6.912 (1.29), 6.931 (2.76), 6.950 (1.60), 7.156 , 7.174 (2.28), 7.195 (1.06), 7.368 (2.41), 7.386 (2.21), 7.636 (16.00), 7.682
(1.66), 7.701 (2.56), 7.721 (2.23), 7.826 (3.11), 7.844 (2.39), 8.205 (2.59), 8.225 (2.30), 8.680 (8.42), 9.126 (2.54), 9.147 (2.47).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.00), 0.008 (2.42), 2.044 (0.47), 2.054 (0.42), 2.066 (0.71), 2.080 (0.65), 2.169
LC-MS (Method L1): Rt = (0.68), 2.183 (0.74), 2.202 (0.45), 2.219 (0.41), 2.523 (0.83), 4.253 (1.55), 4.266 , 4.279 (1.48), 4.798 (2.52), 4.830 (5.19),
394 1.00 min; MS (ESIpos): m/z = 4.861 (2.27), 5.198 (0.90), 5.217 (0.92), 5.754 (0.78), 6.795 , 6.815 (1.81), 6.902 (0.81), 6.918 (1.67), 6.937 (0.99), 7.155
540 [M+H]⁺ (0.84), 7.159 (0.87), 7.176 (1.38), 7.194 (0.66), 7.340 (1.43), 7.359 (1.33), 7.517 (1.16), 7.535 (1.55), 7.538 (1.50), 7.556 (1.38),
7.620 (16.00), 7.779 (1.90), 7.795 (1.64), 8.074 , 8.093 (1.48), 8.170 (0.52), 8.557 (5.90), 9.136 , 9.156 (1.43).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (3.25), 1.618 , 1.631 (0.69), 1.648 (0.77), 1.909 (0.75), 1.922 (0.75), 1.930
(0.75), 1.943 (0.59), 2.327 (0.50), 2.366 , 2.669 (0.53), 2.710 (0.51), 3.929 (0.61), 3.951 (1.23), 3.972 (0.85), 4.084 (0.88),
LC-MS (Method L1): Rt =
396 4.094 (0.85), 4.102 (1.06), 4.122 (0.64), 4.979 (0.55), 4.994 (1.22), 5.013 (1.22), 5.028 (0.55), 6.717 (2.55), 6.737 (2.73), 6.787
1.18 min; MS (ESIpos): m/z =
(5.10), 6.797 (4.07), 7.101 (0.99), 7.113 (1.39), 7.123 (1.52), 7.134 (1.07), 7.144 (0.75), 7.421 (1.35), 7.489 (1.36), 7.580 (1.91),
526 [M+H]⁺
7.601 (2.47), 7.699 (16.00), 7.717 (2.39), 7.739 (1.49), 7.940 (2.48), 7.956 (2.12), 8.753 (1.33), 8.764 (1.43), 8.806 (1.46), 8.817
(1.31), 8.867 , 8.888 (1.86), 9.071 (6.62).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.62), 0.844 (1.37), 0.859 (1.40), 1.235 (0.54), 1.800 , 2.047 (0.57), 2.523
LC-MS (Method L1): Rt =
397 (1.33), 2.670 (0.42), 4.167 (0.67), 5.116 (0.76), 6.516 (0.46), 6.737 (2.19), 6.757 (2.43), 6.847 (1.09), 6.865 , 7.118 (1.00),
1.05 min; MS (ESIpos): m/z =
7.136 (1.73), 7.154 (0.84), 7.465 , 7.679 (16.00), 7.726 (1.42), 7.747 (2.19), 7.765 (2.16), 7.869 , 7.890 , 7.917
541 [M+H]⁺
(2.54), 7.920 (2.39), 7.934 (2.12), 8.852 (1.93), 8.873 , 8.981 (6.99).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.48), 0.008 (2.72), 2.032 (0.71), 2.039 (0.77), 2.052 (0.85), 2.067 (1.16), 2.074
(0.99), 2.082 (0.73), 2.181 (0.77), 2.192 (1.10), 2.204 (1.13), 2.214 (1.15), 2.251 (1.94), 2.289 (2.48), 2.322 (1.97), 2.366 (0.45),
LC-MS (Method L1): Rt = 3.331 (1.13), 3.348 , 3.364 (4.98), 3.378 (4.86), 3.393 (2.42), 3.410 (0.88), 4.210 (0.45), 4.217 (0.58), 4.238 (1.67), 4.245
398 1.38 min; MS (ESIpos): m/z = (1.31), 4.259 (1.70), 4.266 , 4.275 (1.76), 4.281 (1.44), 4.290 (1.42), 4.303 (0.49), 4.309 (0.58), 5.228 (0.69), 5.243 (1.61),
568 [M+H]⁺ 5.262 (1.61), 5.276 (0.71), 6.789 (3.07), 6.810 (3.40), 6.911 (1.52), 6.929 (3.14), 6.948 (1.84), 7.156 (1.45), 7.159 (1.59), 7.176
(2.50), 7.194 (1.18), 7.198 (1.22), 7.367 (2.67), 7.384 (2.44), 7.636 (5.96), 7.639 (16.00), 7.692 , 7.713 , 7.731 (2.60),
7.847 , 7.864 (2.74), 8.262 (3.00), 8.283 (2.65), 8.719 (10.73), 9.173 (2.85), 9.193 (2.80).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.92), -0.008 (7.44), 0.008 (8.20), 0.146 (0.97), 1.759 , 1.783 (1.32), 1.806
(1.48), 1.830 (0.56), 2.045 (1.32), 2.071 (2.55), 2.096 (1.99), 2.117 (0.82), 2.179 (1.12), 2.191 , 2.201 (1.07), 2.270 (0.97),
LC-MS (Method L1): Rt = 2.295 (1.43), 2.322 (2.50), 2.327 (2.39), 2.347 (1.43), 2.366 (1.99), 2.523 (4.48), 2.605 (1.22), 2.626 (2.60), 2.650 (2.45), 2.669
404 1.37 min; MS (ESIpos): m/z = (2.29), 2.710 (1.58), 4.221 (0.61), 4.241 (1.89), 4.249 (1.68), 4.260 (2.80), 4.269 (3.26), 4.283 (1.73), 4.301 , 4.343 (0.41),
503 [M+H]⁺ 4.366 (1.02), 4.387 (1.63), 4.407 (0.97), 5.218 (0.82), 5.233 , 5.252 (1.78), 5.266 (0.82), 6.781 (3.26), 6.801 (3.62), 6.902
(1.68), 6.921 (3.46), 6.940 , 7.145 (1.68), 7.149 , 7.166 (2.75), 7.187 (1.38), 7.342 (2.90), 7.359 (2.70), 7.630 (8.76),
7.635 (16.00), 7.645 (4.54), 7.649 (3.52), 7.654 , 7.684 (2.39), 7.702 (3.26), 7.705 , 7.723 (3.11), 7.828 (3.87), 7.831
(4.23), 7.846 (3.16), 7.849 (3.26), 8.185 , 8.203 (2.96), 8.747 (11.87), 9.091 (3.11), 9.111 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.56), 0.008 (1.55), 1.529 (14.85), 1.546 (16.00), 1.555 (15.65), 1.573 (14.94), 2.014
(0.47), 2.030 (1.05), 2.038 (1.09), 2.048 (1.15), 2.056 (1.17), 2.065 (1.65), 2.072 (1.41), 2.080 (1.01), 2.089 (0.68), 2.171 (0.64),
2.181 (1.09), 2.193 (1.44), 2.204 (1.41), 2.214 (1.31), 2.228 (0.85), 2.236 (0.73), 2.248 (0.47), 3.830 (0.61), 3.848 (1.53), 3.866
(2.04), 3.884 (1.51), 3.902 (0.60), 4.211 (0.53), 4.219 (0.74), 4.239 (2.42), 4.247 (2.13), 4.258 , 4.267 (4.11), 4.282 (2.22),
LC-MS (Method L1): Rt =
406 4.294 (0.55), 4.301 (0.71), 4.310 (0.46), 5.261 (1.00), 5.276 (2.23), 5.296 (2.26), 5.310 (1.00), 6.781 (4.24), 6.801 (4.69), 6.910
1.27 min; MS (ESIpos): m/z =
(2.06), 6.912 (2.10), 6.928 (4.40), 6.930 (4.40), 6.947 (2.64), 6.949 (2.57), 7.146 (2.14), 7.149 (2.30), 7.167 (3.62), 7.185 (1.70),
457 [M+H]⁺
7.188 , 7.348 (3.81), 7.366 (3.51), 7.449 (0.88), 7.454 , 7.459 (1.26), 7.468 (3.22), 7.473 (6.43), 7.478 (6.93), 7.497
(7.07), 7.516 (3.62), 7.521 (3.95), 7.525 (5.85), 7.529 (3.35), 7.539 (1.50), 7.542 (2.10), 7.547 (1.25), 7.624 (6.23), 7.709 (2.59),
7.726 (4.37), 7.748 (4.22), 7.789 , 7.791 (5.67), 7.806 (3.43), 7.809 (3.21), 8.415 (3.92), 8.434 (3.66), 8.730 ), 9.099
(3.83), 9.120 (3.74).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.46), 0.008 , 0.146 (0.51), 1.530 (14.63), 1.548 (16.00), 1.557 ), 1.575
(14.69), 2.030 (1.04), 2.039 (1.13), 2.056 (1.22), 2.065 (1.66), 2.073 (1.40), 2.081 (1.00), 2.172 , 2.181 (1.08), 2.193 (1.51),
2.205 , 2.214 , 2.229 (0.87), 2.248 (0.49), 2.327 , 2.366 (0.53), 2.670 (0.66), 2.710 (0.58), 3.830 (0.62), 3.849
LC-MS (Method L1): Rt =
407 , 3.866 (2.02), 3.885 (1.48), 3.903 (0.58), 4.217 (0.77), 4.237 (2.46), 4.245 (2.06), 4.257 (3.81), 4.266 (3.83), 4.283 (2.19),
1.31 min; MS (ESIpos): m/z =
4.302 (0.77), 5.262 (1.00), 5.276 (2.28), 5.296 (2.28), 5.310 (1.00), 6.781 (4.30), 6.802 (4.74), 6.912 (2.10), 6.928 (4.43), 6.947
507 [M+H]⁺
(2.61), 7.147 (2.22), 7.150 , 7.167 (3.61), 7.185 (1.73), 7.189 (1.71), 7.344 (3.83), 7.362 (3.72), 7.399 (2.33), 7.415 ,
7.478 (0.44), 7.498 (0.67), 7.561 (4.92), 7.579 (1.68), 7.598 (6.14), 7.608 (4.99), 7.615 (10.39), 7.627 (1.57), 7.706 (0.73), 7.720
(3.01), 7.738 (4.46), 7.760 (4.03), 7.815 (5.50), 7.830 (3.57), 8.429 (3.90), 8.448 (3.68), 8.717 (14.67), 9.099 (3.86), 9.120 (3.81).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.533 (14.48), 1.551 (16.00), 1.559 ), 1.577 (14.51), 2.019 (1.10), 2.027 (1.16), 2.037
(1.29), 2.043 (1.30), 2.053 (1.77), 2.061 (1.48), 2.069 (1.06), 2.170 , 2.182 (1.57), 2.193 , 2.204 (1.42), 2.216 (0.97),
2.669 (0.41), 3.835 (0.65), 3.852 (1.60), 3.870 (2.11), 3.888 , 3.906 (0.64), 4.206 (0.81), 4.227 , 4.234 (2.16), 4.247
LC-MS (Method L1): Rt =
408 (3.95), 4.256 (3.84), 4.273 (2.27), 4.292 (0.78), 5.247 (1.07), 5.261 (2.45), 5.280 (2.43), 5.295 (1.05), 6.773 (4.46), 6.793 (5.02),
1.26 min; MS (ESIpos): m/z =
6.899 (2.19), 6.917 (4.73), 6.936 (2.74), 7.142 (2.33), 7.161 (3.88), 7.179 , 7.338 (4.13), 7.357 (3.80), 7.499 (2.10), 7.518
509 [M+H]⁺
(4.65), 7.538 (2.73), 7.571 (0.56), 7.591 (1.20), 7.610 (0.68), 7.746 (2.26), 7.763 (5.20), 7.774 (3.98), 7.784 (4.83), 7.806 (5.93),
7.826 (3.63), 7.848 (3.46), 7.865 (1.75), 7.910 (0.66), 7.926 (0.75), 7.945 , 8.492 (3.95), 8.513 (3.73), 8.684 (13.95), 9.126
(4.03), 9.147 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.49), -0.008 (4.30), 0.008 (4.43), 0.146 (0.48), 1.531 (14.92), 1.549 (16.00), 1.558
(15.65), 1.576 (14.94), 2.016 , 2.025 (1.12), 2.034 (1.15), 2.041 (1.17), 2.051 (1.63), 2.059 (1.41), 2.067 (1.01), 2.163 (0.62),
2.172 (1.08), 2.184 (1.45), 2.196 , 2.205 (1.30), 2.219 (0.84), 2.226 (0.75), 2.239 (0.48), 2.327 (0.49), 2.366 , 2.669
(0.59), 2.709 (0.71), 3.828 (0.60), 3.845 , 3.863 (1.98), 3.881 (1.45), 3.899 (0.57), 4.202 (0.55), 4.210 (0.79), 4.230 (2.42),
LC-MS (Method L1): Rt =
409 4.238 , 4.249 (3.86), 4.258 (3.99), 4.275 (2.18), 4.286 (0.59), 4.294 (0.75), 4.302 (0.48), 5.250 (0.99), 5.264 (2.18), 5.284
1.24 min; MS (ESIpos): m/z =
(2.22), 5.298 (0.99), 6.774 (4.12), 6.792 (4.36), 6.795 (4.54), 6.900 (2.03), 6.902 , 6.919 (4.30), 6.921 (4.32), 6.937 (2.60),
475 [M+H]⁺
6.940 (2.56), 7.140 (2.12), 7.144 (2.29), 7.161 (3.50), 7.179 (1.70), 7.182 , 7.309 (2.18), 7.329 (5.82), 7.339 (3.97), 7.348
(4.54), 7.357 (3.62), 7.384 (2.38), 7.388 (2.82), 7.399 (2.69), 7.403 (3.70), 7.418 (1.65), 7.423 (1.54), 7.628 , 7.633 (2.05),
7.648 (3.06), 7.666 (1.81), 7.670 , 7.730 (2.00), 7.748 , 7.768 (6.90), 7.771 (6.96), 7.776 (6.74), 7.788 (2.22), 7.793
(1.39), 8.470 (3.41), 8.475 (3.42), 8.491 (3.33), 8.495 (3.17), 8.692 (14.76), 9.114 (3.73), 9.135 (3.70).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.13), 0.008 (3.29), 0.146 (0.40), 1.528 (14.85), 1.546 (16.00), 1.555 (15.61), 1.573
(15.00), 2.001 (0.49), 2.016 , 2.025 (1.11), 2.035 (1.18), 2.042 (1.17), 2.052 (1.64), 2.059 (1.39), 2.067 (1.00), 2.163 (0.65),
2.173 (1.07), 2.185 (1.47), 2.197 (1.40), 2.207 (1.31), 2.218 (0.85), 2.327 (0.48), 2.366 (0.42), 2.669 (0.53), 2.709 (0.46), 3.821
(0.64), 3.839 (1.49), 3.857 (1.95), 3.874 (1.44), 3.892 (0.60), 4.202 (0.56), 4.210 (0.78), 4.230 (2.43), 4.238 (2.08), 4.249 (3.91),
LC-MS (Method L1): Rt =
410 4.259 (3.92), 4.275 (2.22), 4.294 (0.76), 5.251 (1.01), 5.265 , 5.285 (2.26), 5.300 (0.99), 6.774 (4.47), 6.795 (4.89), 6.900
1.26 min; MS (ESIpos): m/z =
(2.08), 6.903 , 6.921 , 6.937 , 6.940 (2.65), 7.141 (2.17), 7.144 (2.30), 7.162 (3.63), 7.179 (1.71), 7.183 (1.71),
475 [M+H]⁺
7.323 (3.21), 7.338 (4.16), 7.345 (6.69), 7.355 (3.75), 7.368 (3.97), 7.485 (2.85), 7.492 (4.04), 7.500 (2.96), 7.507 , 7.515
(2.58), 7.522 (2.10), 7.525 , 7.533 (1.86), 7.536 (2.35), 7.544 , 7.547 (2.22), 7.554 (1.51), 7.721 (2.43), 7.739 (4.57),
7.760 (4.71), 7.785 , 7.799 (2.83), 8.463 (3.64), 8.466 (3.77), 8.484 (3.54), 8.487 (3.37), 8.687 (15.55), 9.113 (3.86), 9.133
(3.75).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.52), -0.008 (4.69), 0.008 , 0.146 (0.52), 1.534 (14.70), 1.552 (16.00), 1.560
(15.73), 1.578 (14.85), 2.031 (1.01), 2.039 (1.07), 2.056 (1.17), 2.066 (1.67), 2.074 (1.42), 2.170 (0.64), 2.191 (1.44), 2.203 (1.40),
2.213 (1.34), 2.225 (0.87), 2.328 (0.66), 2.366 (0.78), 2.670 (0.70), 2.710 (0.72), 3.840 (0.62), 3.856 (1.50), 3.874 , 3.892
LC-MS (Method L1): Rt =
411 (1.50), 3.909 (0.58), 4.216 (0.76), 4.236 (2.41), 4.245 (2.10), 4.256 (3.85), 4.265 (3.95), 4.282 (2.20), 4.300 (0.76), 5.259 (0.97),
1.31 min; MS (ESIpos): m/z =
.274 (2.22), 5.293 (2.27), 5.308 (1.01), 6.781 (4.32), 6.801 (4.72), 6.910 (2.06), 6.928 (4.39), 6.945 (2.59), 7.145 (2.20), 7.149
491 [M+H]⁺
(2.33), 7.167 (3.62), 7.184 (1.71), 7.188 (1.69), 7.347 (3.77), 7.364 (3.48), 7.511 (0.54), 7.694 (1.57), 7.713 (4.35), 7.732 (6.71),
7.750 (4.76), 7.754 (5.35), 7.759 (5.37), 7.771 (4.57), 7.836 (5.46), 7.852 , 7.874 (3.95), 7.897 (7.35), 8.441 , 8.461
(3.67), 8.721 (15.16), 9.107 (3.85), 9.128 (3.77).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.146 (0.43), 1.233 (0.49), 1.756 (0.67), 1.768 (0.74), 1.784 (0.78), 2.002 , 2.015
(0.83), 2.023 (0.78), 2.037 (0.56), 2.327 (0.67), 2.366 (0.58), 2.669 , 2.709 , 3.946 (0.74), 3.967 (1.32), 3.988 (0.85),
LC-MS (Method L1): Rt =
412 4.134 (0.94), 4.152 (1.10), 4.171 (0.72), 5.059 (0.65), 5.074 (1.28), 5.093 (1.21), 5.107 (0.54), 6.729 (2.29), 6.749 (2.44), 6.854
1.12 min; MS (ESIpos): m/z =
(0.94), 6.874 (2.31), 6.892 (1.77), 6.932 (2.42), 6.949 (1.39), 7.094 (5.94), 7.108 (1.79), 7.130 (1.99), 7.147 (1.01), 7.685 (16.00),
542 [M+H]⁺
7.719 (1.55), 7.738 (2.20), 7.758 (2.11), 7.861 (2.62), 7.880 (1.93), 7.921 (2.62), 7.938 (2.15), 8.272 (1.86), 8.864 (2.29), 8.884
(2.13), 8.993 (6.79).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (1.65), 0.008 (1.55), 1.529 (9.91), 1.546 (10.68), 1.556 (11.45), 1.574 (10.97), 2.011
(0.79), 2.019 (0.83), 2.029 (0.86), 2.036 (0.88), 2.046 (1.25), 2.054 (1.05), 2.061 (0.78), 2.070 , 2.085 (16.00), 2.158 (0.47),
2.167 (0.82), 2.180 (1.09), 2.191 (1.07), 2.201 (0.98), 2.212 (0.63), 2.523 (0.80), 3.816 (0.45), 3.833 (1.04), 3.851 (1.38), 3.869
LC-MS (Method L1): Rt = (1.03), 3.887 (0.42), 4.208 (0.56), 4.228 (1.84), 4.236 (1.62), 4.247 (2.92), 4.255 (3.09), 4.271 (1.69), 4.283 , 4.290 (0.53),
418 1.23 min; MS (ESIpos): m/z = 5.247 (0.74), 5.261 (1.64), 5.281 (1.65), 5.295 (0.75), 6.771 (3.27), 6.791 (3.58), 6.894 (1.53), 6.897 (1.53), 6.913 (3.26), 6.932
475 [M+H]⁺ (1.99), 6.934 (1.87), 7.137 (1.66), 7.141 (1.75), 7.158 (2.68), 7.175 (1.32), 7.179 (1.28), 7.258 (1.26), 7.279 (1.22), 7.293 (1.89),
7.301 (1.38), 7.315 (2.98), 7.323 (2.78), 7.331 (2.81), 7.336 (2.95), 7.344 (2.35), 7.349 (2.44), 7.577 (1.76), 7.590 (1.90), 7.599
, 7.612 (1.58), 7.682 , 7.686 (2.13), 7.700 (4.61), 7.703 (4.23), 7.717 (3.84), 7.738 (3.71), 7.756 (1.81), 8.452 (2.70),
8.456 (2.79), 8.473 (2.60), 8.477 (2.48), 8.660 (9.72), 9.115 (2.91), 9.136 (2.80).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.50), -0.008 (4.19), 0.008 (4.14), 0.146 (0.48), 1.525 (14.78), 1.543 ), 1.552
(15.64), 1.569 (14.85), 2.030 (1.00), 2.038 (1.03), 2.048 (1.12), 2.055 (1.12), 2.065 (1.63), 2.073 , 2.081 (1.00), 2.171 (0.65),
2.180 (1.08), 2.192 (1.46), 2.204 (1.39), 2.214 (1.24), 2.228 (0.84), 2.327 , 2.366 (0.62), 2.669 , 2.709 (0.67), 3.832
LC-MS d L1): Rt = (0.62), 3.848 , 3.866 (2.03), 3.884 (1.48), 3.902 (0.60), 4.210 , 4.219 (0.79), 4.239 , 4.247 (2.06), 4.258 (3.87),
419 1.30 min; MS (ESIpos): m/z = 4.267 (3.99), 4.283 (2.18), 4.302 (0.72), 4.311 , 5.260 (0.96), 5.275 (2.20), 5.294 (2.22), 5.309 (0.98), 6.781 (4.28), 6.802
475 [M+H]⁺ (4.71), 6.911 (2.01), 6.913 (2.08), 6.932 (4.35), 6.948 (2.63), 6.951 (2.58), 7.147 , 7.151 (2.32), 7.169 (3.54), 7.186 (1.70),
7.190 , 7.350 , 7.368 (3.44), 7.419 (3.16), 7.423 (2.92), 7.444 (3.09), 7.447 (3.04), 7.457 (2.15), 7.462 (3.32), 7.467
(2.25), 7.479 (1.87), 7.484 (3.52), 7.489 (2.87), 7.496 (5.60), 7.500 (7.01), 7.624 (0.55), 7.717 (2.82), 7.735 (4.69), 7.756 (4.26),
7.838 , 7.854 (3.78), 7.856 (3.73), 8.442 (3.97), 8.461 (3.61), 8.753 (15.50), 9.106 (3.90), 9.126 (3.80).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.45), 0.008 (3.55), 0.146 (0.41), 1.529 (9.38), 1.539 (9.80), 1.547 (11.02), 1.559
(16.00), 1.578 (11.91), 1.581 (11.87), 2.011 (1.20), 2.030 (1.39), 2.039 (1.60), 2.046 (1.79), 2.054 (1.43), 2.085 (5.81), 2.174 (1.52),
2.186 , 2.196 (1.37), 2.327 (0.68), 2.366 (0.75), 2.669 (0.68), 2.710 (0.73), 3.848 (1.31), 3.865 (1.68), 3.878 (1.31), 4.199
(0.71), 4.219 (1.78), 4.227 (2.57), 4.241 (3.61), 4.250 (4.05), 4.267 (2.68), 4.285 (0.85), 5.257 (2.24), 5.271 (2.20), 5.754 (2.22),
LC-MS (Method L1): Rt =
420 6.767 (5.06), 6.788 (5.62), 6.888 (1.37), 6.892 (1.52), 6.906 (2.91), 6.911 (3.15), 6.925 (1.81), 6.929 (1.89), 7.135 , 7.155
1.27 min; MS (ESIpos): m/z =
(4.03), 7.174 (2.05), 7.319 (2.22), 7.337 (4.15), 7.354 , 7.424 (0.50), 7.440 , 7.444 (0.87), 7.458 (0.42), 7.475 (0.42),
525 [M+H]⁺
7.487 (0.77), 7.505 (0.62), 7.609 (0.89), 7.627 (2.80), 7.640 (3.51), 7.646 (3.20), 7.658 (5.83), 7.677 (3.53), 7.680 , 7.700
(1.81), 7.706 (2.86), 7.709 (3.38), 7.723 (7.68), 7.727 (7.16), 7.736 (5.71), 7.757 , 7.775 (2.37), 7.894 (0.44), 7.916 (4.48),
7.921 (4.48), 7.935 (3.88), 7.940 (3.80), 8.475 (4.00), 8.479 (4.25), 8.496 (3.88), 8.500 (3.84), 8.649 (8.55), 8.658 (9.36), 9.107
(2.39), 9.126 (3.82), 9.145 (2.35).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.74), 0.008 (0.66), 1.398 (16.00), 1.531 (2.32), 1.549 (2.57), 1.558 (3.55), 1.576
(3.28), 2.044 (0.42), 3.853 (0.41), 4.226 (0.60), 4.235 (0.52), 4.245 (0.96), 4.254 (1.03), 4.270 (0.56), 5.259 (0.53), 5.278 (0.54),
LC-MS (Method L1): Rt =
421 6.770 (1.05), 6.790 (1.17), 6.894 (0.43), 6.913 (0.95), 6.931 (0.55), 7.136 (0.49), 7.139 (0.53), 7.157 , 7.175 (0.41), 7.178
1.22 min; MS (ESIpos): m/z =
(0.42), 7.223 (0.50), 7.329 (0.63), 7.348 (0.59), 7.451 , 7.460 (1.29), 7.472 (1.04), 7.479 (1.04), 7.685 , 7.688 (0.73),
475 [M+H]⁺
7.702 (1.46), 7.706 (1.42), 7.723 (1.24), 7.744 (1.24), 7.762 (0.62), 8.461 , 8.464 (0.98), 8.482 (0.88), 8.485 , 8.653
(1.41), 9.113 (0.66), 9.133 (0.64).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.40), 0.008 (2.26), 1.141 , 1.520 (7.81), 1.537 (8.37), 1.547 , 1.564
(7.78), 2.023 , 2.031 (0.58), 2.048 (0.63), 2.058 (0.85), 2.066 (0.74), 2.075 (0.59), 2.085 (6.90), 2.161 (16.00), 2.177 (0.76),
2.189 , 2.201 (0.76), 2.211 (0.70), 2.327 (0.45), 2.386 (0.52), 2.395 (0.44), 2.416 (12.94), 2.670 (0.45), 3.822 (0.75), 3.841
LC-MS (Method L1): Rt =
422 (1.02), 3.858 (0.72), 4.238 (1.26), 4.246 (1.09), 4.257 (2.03), 4.265 (2.14), 4.282 , 5.259 , 5.273 (1.16), 5.293 (1.14),
1.26 min; MS (ESIpos): m/z =
.307 (0.53), 5.754 (0.60), 6.710 , 6.712 (3.83), 6.779 (2.31), 6.799 (2.52), 6.911 (1.13), 6.927 (2.33), 6.946 (1.40), 7.145
457 [M+H]⁺
, 7.149 (1.23), 7.167 (1.85), 7.184 (0.91), 7.341 (1.95), 7.359 (1.78), 7.624 (1.06), 7.628 (1.41), 7.642 (3.30), 7.646 ,
7.655 (2.78), 7.676 (2.61), 7.694 (1.18), 8.342 (1.79), 8.346 (1.89), 8.363 (1.74), 8.367 (1.66), 8.686 (8.47), 9.079 , 9.100
(1.92).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.141 (0.76), 1.356 (1.34), 1.519 (14.63), 1.537 (16.00), 1.546 (15.53), 1.564 (14.65), 2.023
(1.05), 2.031 (1.09), 2.049 (1.27), 2.058 (1.67), 2.066 (1.49), 2.085 ), 2.183 (1.31), 2.191 (1.53), 2.203 (1.48), 2.212 (1.37),
LC-MS (Method L1): Rt = 2.327 (0.60), 2.366 (0.65), 2.670 (0.66), 2.709 (0.66), 3.811 (0.65), 3.829 (1.53), 3.847 (2.05), 3.865 (1.54), 3.881 (0.61), 4.215
423 1.35 min; MS (ESIpos): m/z = (0.80), 4.235 (2.49), 4.243 (2.19), 4.255 (3.96), 4.264 (3.93), 4.281 (2.31), 4.300 (0.76), 5.257 (1.04), 5.273 , 5.292 (2.38),
497 [M+H]⁺ 5.306 (1.02), 5.754 (1.15), 6.779 (4.42), 6.799 (4.85), 6.912 (2.14), 6.930 (4.56), 6.947 , 7.149 (2.39), 7.167 (3.78), 7.188
(1.87), 7.231 (13.75), 7.346 (3.92), 7.364 , 7.716 (2.56), 7.734 (4.37), 7.755 , 7.800 (5.63), 7.815 (3.43), 8.454 (3.95),
8.473 (3.67), 8.737 (14.24), 9.105 , 9.125 (3.71).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.149 (0.62), 0.146 (0.58), 2.082 (0.85), 2.092 (0.94), 2.118 (1.45), 2.126 , 2.220
(1.28), 2.232 (1.23), 2.242 (1.10), 2.328 (0.69), 2.366 (0.74), 2.670 (0.75), 2.710 , 3.046 (2.57), 3.168 (0.82), 3.426 (3.56),
LC-MS (Method L1): Rt =
424 3.443 (4.68), 4.227 (0.88), 4.247 (2.21), 4.256 (1.97), 4.267 (3.31), 4.275 (3.45), 4.292 (1.93), 4.310 (0.72), 5.298 , 5.314
0.83 min; MS s): m/z =
, 6.790 (3.71), 6.811 (4.03), 6.913 (1.81), 6.931 (3.79), 6.949 (2.21), 7.158 (1.97), 7.176 (3.10), 7.196 (1.57), 7.376 ,
492 [M+H]⁺
7.394 (2.97), 7.646 (8.78), 7.650 (16.00), 7.658 (5.74), 7.662 (4.49), 7.772 (1.84), 7.790 (3.18), 7.811 (2.48), 7.898 (4.35), 7.915
(3.20), 8.337 (0.98), 8.400 (2.78), 8.421 (2.49), 8.895 (10.41), 9.594 (1.37).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.52), 0.008 (1.58), 1.509 (12.78), 1.527 (13.71), 1.536 ), 1.554 (12.80), 2.013
(0.92), 2.022 (1.01), 2.032 (1.08), 2.039 , 2.049 (1.52), 2.056 (1.44), 2.085 (7.75), 2.172 (0.94), 2.184 (1.30), 2.196 (1.24),
2.206 (1.19), 2.219 (0.80), 2.240 (0.47), 2.327 (0.45), 2.366 (0.47), 2.423 (16.00), 2.669 (0.46), 2.710 (0.40), 3.804 (0.54), 3.823
LC-MS (Method L1): Rt =
425 (1.32), 3.840 (1.76), 3.859 (1.30), 3.876 (0.52), 4.201 (0.51), 4.208 (0.72), 4.228 (2.09), 4.236 (1.71), 4.249 (2.84), 4.259 (2.77),
1.26 min; MS (ESIpos): m/z =
4.267 (1.88), 4.277 (1.91), 4.288 (0.56), 4.295 (0.68), 4.304 (0.47), 5.246 , 5.260 (1.95), 5.280 (1.96), 5.294 (0.85), 5.754
475 [M+H]⁺
(7.58), 6.631 (2.13), 6.777 (3.89), 6.797 (4.26), 6.902 (1.75), 6.904 (1.90), 6.923 (3.94), 6.939 (2.29), 6.942 (2.32), 7.143 (1.85),
7.147 (2.06), 7.164 (3.17), 7.182 (1.50), 7.185 (1.53), 7.334 (3.33), 7.352 (3.03), 7.618 (2.57), 7.641 (4.67), 7.664 (2.68), 8.442
(2.31), 8.457 (2.47), 8.465 (2.46), 8.481 (2.28), 8.709 (12.28), 9.081 (3.16), 9.102 (3.09).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.83), -0.008 (6.50), 0.008 (7.02), 0.146 (0.83), 1.235 (0.67), 1.508 (14.93), 1.526
(15.98), 1.534 (16.00), 1.552 (15.19), 2.051 (1.31), 2.073 (1.29), 2.085 (2.88), 2.185 (1.50), 2.198 (1.48), 2.207 (1.40), 2.220 (0.98),
LC-MS (Method L1): Rt = 2.327 (0.90), 2.366 (0.95), 2.669 (0.93), 2.710 (0.93), 3.828 (1.33), 3.846 (1.74), 3.863 (1.31), 4.206 , 4.225 (2.29), 4.233
426 1.32 min; MS (ESIpos): m/z = (1.88), 4.252 (2.95), 4.259 (2.71), 4.267 (2.05), 4.276 (2.19), 4.295 (0.83), 5.245 (0.93), 5.259 (2.12), 5.278 , 5.292 (0.98),
515 [M+H]⁺ 6.776 (4.48), 6.796 (4.88), 6.905 , 6.924 (4.50), 6.940 (2.71), 7.144 (2.24), 7.147 (2.40), 7.165 (3.71), 7.186 (1.83), 7.205
(3.79), 7.230 (3.98), 7.333 (1.83), 7.346 (2.26), 7.362 (1.69), 7.687 (2.98), 7.710 (5.17), 7.732 (3.05), 8.553 (2.71), 8.568 (2.88),
8.577 , 8.593 (2.71), 8.764 (7.26), 9.111 (3.05), 9.132 (3.05).
1H-NMR (400 MHz, DMSO-d6) δ 9.16 (d, J = 8.1 Hz, 1H), 8.72 (s, 1H), 8.69 (d, J = 1.9 Hz, 1H), 8.14 (d, J = 1.8 Hz, 1H), 7.71 – 7.66
428 LC-MS (L2): Rt = 3.893 min;
(m, 3H), 7.37 (d, J = 7.9, 1.7 Hz, 1H), 7.17 (t, J = 8.5, 7.4, 1.7 Hz, 1H), 6.92 (t, J = 7.4, 1.2 Hz, 1H), 6.80 (d, J = 8.3, 1.2 Hz, 1H),
m/z = 517/5519 (M+H)+
.23 (q, J = 5.8 Hz, 1H), 4.32 – 4.17 (m, 2H), 3.12 (s, 6H), 2.26 – 2.14 (m, 1H), 2.10 – 1.99 (m, 1H).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.38), 1.526 (14.80), 1.543 (16.00), 1.552 (15.65), 1.570 (14.87), 2.029 (1.04), 2.038
, 2.047 (1.19), 2.055 (1.21), 2.064 (1.68), 2.072 (1.42), 2.080 (1.02), 2.087 (0.71), 2.172 (0.65), 2.181 , 2.193 (1.48),
LC-MS (Method L1): Rt = 2.205 (1.42), 2.215 (1.36), 2.228 , 3.828 (0.64), 3.845 (1.58), 3.863 (2.07), 3.881 (1.54), 3.899 , 4.211 (0.56), 4.219
430 1.23 min; MS (ESIpos): m/z = (0.77), 4.239 (2.44), 4.247 (2.13), 4.258 (3.96), 4.267 (4.09), 4.283 (2.26), 4.302 (0.73), 5.262 (1.01), 5.277 (2.33), 5.296 (2.31),
459 [M+H]⁺ 5.311 (1.05), 6.781 (4.65), 6.801 (5.20), 6.912 (2.17), 6.930 (4.68), 6.949 (2.74), 7.150 (2.33), 7.168 (3.75), 7.189 (1.74), 7.252
(1.63), 7.258 (1.26), 7.276 (3.15), 7.282 (3.16), 7.301 (6.35), 7.318 (6.19), 7.334 (1.02), 7.348 (4.05), 7.366 (3.67), 7.716 (2.63),
7.734 (4.12), 7.755 (3.67), 7.834 , 7.851 (4.00), 8.438 (4.18), 8.459 (3.86), 8.750 (14.88), 9.106 (3.97), 9.126 (3.90).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.75), 1.530 (14.75), 1.548 (16.00), 1.556 (15.84), 1.574 (14.95), 2.034 (1.00), 2.043
(1.11), 2.053 (1.16), 2.059 (1.19), 2.069 (1.70), 2.077 (1.41), 2.085 (1.05), 2.191 , 2.203 (1.47), 2.213 , 2.226 ,
LC-MS (Method L1): Rt = 2.328 (0.61), 2.366 (0.66), 2.670 (0.63), 2.710 (0.66), 3.843 (0.64), 3.860 (1.58), 3.878 , 3.896 (1.53), 3.914 (0.61), 4.209
431 1.37 min; MS (ESIpos): m/z = (0.61), 4.217 (0.75), 4.237 (2.49), 4.245 (2.13), 4.257 (3.91), 4.266 (4.02), 4.282 , 4.301 (0.75), 5.258 (1.02), 5.273 (2.30),
525 [M+H]⁺ 5.292 (2.31), 5.307 (1.03), 6.782 (4.49), 6.802 (4.96), 6.913 (2.21), 6.931 , 6.950 (2.69), 7.151 (2.39), 7.168 (3.68), 7.190
, 7.351 (3.93), 7.370 (3.58), 7.740 (2.83), 7.758 , 7.761 , 7.779 (3.71), 7.891 (10.85), 7.902 (6.54), 7.909 (5.57),
7.968 (6.30), 8.471 (4.19), 8.492 (3.75), 8.752 (15.12), 9.117 (4.02), 9.138 (3.91).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 2.063 (0.44), 2.074 (1.74), 2.085 (0.57), 2.091 (0.49), 2.154 (16.00), 2.213 (0.54), 2.223
, 2.230 (0.52), 3.994 , 4.221 (0.41), 4.226 (0.88), 4.232 (0.59), 4.243 (0.65), 4.249 (0.52), 4.271 (0.53), 4.278 (0.67),
LC-MS (Method L1): Rt = 4.284 (0.59), 4.291 (0.69), 5.297 (0.75), 5.313 (0.74), 6.792 (1.44), 6.793 , 6.808 (1.59), 6.810 (1.58), 6.918 (0.74), 6.920
432 0.93 min; MS (ESIpos): m/z = (0.73), 6.933 (1.47), 6.935 (1.43), 6.948 (0.86), 6.950 (0.81), 7.160 (0.72), 7.163 (0.74), 7.177 (1.18), 7.191 (0.60), 7.194 ,
506 [M+H]⁺ 7.404 (1.21), 7.418 (1.15), 7.646 (0.87), 7.655 (9.82), 7.725 , 7.739 (1.43), 7.741 (1.26), 7.756 (1.25), 7.863 (1.61), 7.866
(1.64), 7.877 (1.33), 7.880 (1.26), 8.164 (1.66), 8.523 (1.33), 8.526 (1.33), 8.540 (1.27), 8.543 (1.20), 8.920 , 9.432 (1.31),
9.448 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.41), -0.008 (3.62), 0.008 , 1.356 (1.83), 1.523 (14.77), 1.541 (16.00), 1.550
(15.57), 1.568 (14.88), 2.032 (1.00), 2.041 (1.04), 2.051 (1.14), 2.058 (1.11), 2.067 (1.68), 2.073 , 2.084 (1.01), 2.170 (0.66),
2.183 (1.20), 2.192 (1.42), 2.203 (1.34), 2.213 (1.30), 2.225 (0.81), 2.323 (0.49), 2.327 (0.62), 2.366 (0.55), 2.523 (1.52), 2.670
LC-MS (Method L1): Rt = (0.68), 2.709 (0.55), 3.833 (0.60), 3.851 (1.50), 3.869 (2.02), 3.887 (1.45), 3.905 (0.60), 4.211 (0.54), 4.219 (0.74), 4.239 (2.40),
438 1.37 min; MS (ESIpos): m/z = 4.247 (2.04), 4.258 (3.83), 4.267 (3.95), 4.283 (2.15), 4.301 (0.70), 5.260 (0.98), 5.274 , 5.294 (2.20), 5.308 (0.96), 5.754
509 [M+H]⁺ (6.17), 6.780 (4.02), 6.782 (4.25), 6.800 (4.58), 6.803 , 6.912 (2.09), 6.915 , 6.931 (4.36), 6.933 (4.28), 6.949 (2.67),
6.952 (2.58), 7.148 (2.17), 7.152 (2.29), 7.169 (3.48), 7.187 (1.71), 7.190 (1.68), 7.351 (3.62), 7.370 (3.40), 7.717 (2.99), 7.735
(4.36), 7.738 (3.68), 7.756 (4.00), 7.786 (15.35), 7.802 (15.29), 7.853 (5.04), 7.855 (5.31), 7.870 (4.03), 7.873 (3.81), 7.907 (0.55),
7.923 (0.54), 8.444 (3.89), 8.464 (3.67), 8.762 (15.95), 9.108 (3.86), 9.129 (3.76).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (3.10), 1.826 (0.43), 2.073 (1.46), 2.086 (0.91), 2.327 (0.43), 2.366
LC-MS (Method L1): Rt = (0.59), 2.670 (0.47), 2.710 (0.59), 4.178 (0.90), 5.127 (1.22), 5.141 (1.19), 6.747 (2.96), 6.767 (3.31), 6.836 , 6.920 (0.57),
439 1.10 min; MS s): m/z = 7.045 (0.47), 7.124 (1.50), 7.145 (2.50), 7.162 (1.27), 7.258 (0.57), 7.333 (0.67), 7.467 (0.72), 7.672 , 7.676 (16.00), 7.682
560 [M+H]⁺ (6.08), 7.685 (3.72), 7.732 (2.26), 7.750 (2.96), 7.753 (3.13), 7.771 (3.12), 7.911 (3.10), 7.929 (5.80), 7.932 (5.43), 7.946 ,
8.870 (1.48), 8.885 (1.41), 9.005 (5.27), 12.563 (0.65).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (3.30), 0.008 (2.88), 1.528 , 1.546 (10.48), 1.555 (10.17), 1.573 (9.77), 2.017
(0.68), 2.025 (0.71), 2.035 (0.76), 2.043 (0.78), 2.052 (1.09), 2.060 (0.90), 2.068 (0.66), 2.162 (0.45), 2.171 (0.73), 2.184 (1.01),
2.196 (0.94), 2.205 (0.87), 2.219 , 2.327 (0.73), 2.346 (16.00), 2.366 (0.80), 2.523 , 2.665 (0.40), 2.669 (0.54), 2.710
LC-MS (Method L1): Rt = (0.61), 3.841 (0.97), 3.859 (1.27), 3.877 (0.94), 4.211 (0.50), 4.231 (1.58), 4.239 (1.35), 4.250 (2.53), 4.259 (2.64), 4.275 (1.46),
444 1.30 min; MS (ESIpos): m/z = 4.294 (0.47), 5.249 (0.64), 5.264 (1.44), 5.283 , 5.297 (0.61), 6.775 (2.69), 6.793 (2.86), 6.795 (2.95), 6.901 (1.37), 6.904
489 [M+H]⁺ (1.39), 6.920 (2.83), 6.922 (2.83), 6.938 (1.75), 6.941 (1.70), 7.141 (1.39), 7.145 (1.49), 7.162 (2.34), 7.180 (2.86), 7.183 (2.93),
7.195 , 7.199 (1.79), 7.340 , 7.357 (2.27), 7.451 (1.63), 7.455 (1.58), 7.468 (1.65), 7.472 (1.56), 7.716 (1.16), 7.734
(3.42), 7.753 (6.32), 7.756 (5.45), 7.768 (1.30), 8.457 (2.15), 8.462 (2.08), 8.476 (2.08), 8.482 (1.96), 8.687 (9.91), 9.113 (2.57),
9.133 (2.50).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.006 (0.83), 1.528 (15.59), 1.542 (16.00), 1.554 (15.53), 1.569 (15.22), 2.022 (0.59), 2.029
(0.75), 2.035 (1.20), 2.042 (1.26), 2.049 (1.35), 2.055 (1.35), 2.063 (1.74), 2.069 (1.50), 2.076 (1.05), 2.082 , 2.178 (0.75),
2.185 (1.16), 2.195 (1.62), 2.205 (1.56), 2.212 (1.50), 2.222 (1.07), 2.229 (0.80), 2.239 (0.53), 3.836 (0.65), 3.851 , 3.865
LC-MS d L1): Rt = (1.95), 3.879 (1.44), 3.893 , 4.218 (0.74), 4.224 (0.93), 4.240 (2.73), 4.246 (2.13), 4.256 (2.85), 4.261 (3.43), 4.268 (2.78),
446 1.28 min; MS (ESIpos): m/z = 4.274 (2.18), 4.281 (2.36), 4.290 (0.72), 4.296 (0.86), 4.303 , 5.266 (1.16), 5.278 (2.45), 5.293 (2.39), 5.305 (1.07), 5.753
475 [M+H]⁺ (2.04), 6.783 (4.78), 6.799 (5.11), 6.916 (2.31), 6.931 (4.75), 6.945 (2.64), 7.151 (2.25), 7.154 (2.34), 7.168 (3.85), 7.182 ,
7.184 (1.80), 7.350 (4.06), 7.364 (3.73), 7.492 , 7.509 (5.77), 7.528 (4.33), 7.571 (2.42), 7.575 (2.60), 7.581 (2.67), 7.585
(2.75), 7.593 , 7.598 (1.61), 7.602 (1.61), 7.712 (2.90), 7.726 (4.39), 7.743 (3.94), 7.772 (3.91), 7.776 (3.80), 7.786 (3.97),
7.790 (3.76), 7.806 (5.60), 7.819 (3.92), 8.418 (4.24), 8.434 , 8.736 (14.80), 9.100 (4.07), 9.116 (3.94).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.67), 0.008 (1.74), 1.531 (11.51), 1.549 (12.60), 1.558 (16.00), 1.576 (15.03), 1.860
(10.28), 1.875 (10.05), 2.011 (1.17), 2.019 (1.28), 2.028 (1.43), 2.035 (1.35), 2.045 (1.78), 2.053 (1.52), 2.061 (1.12), 2.069 (0.78),
2.085 (3.05), 2.168 (3.67), 2.179 (1.64), 2.191 , 2.201 (1.41), 2.214 , 2.234 (0.57), 2.285 (12.65), 2.292 (14.54), 2.327
LC-MS (Method L1): Rt = (0.48), 2.669 (0.41), 3.818 , 3.835 (1.53), 3.853 (2.04), 3.871 (1.49), 3.888 (0.61), 4.199 (0.69), 4.207 (0.86), 4.227 (2.74),
447 1.27 min; MS (ESIpos): m/z = 4.235 (2.35), 4.247 (4.38), 4.256 (4.48), 4.272 (2.50), 4.284 (0.69), 4.290 , 4.299 (0.59), 5.246 (1.09), 5.260 (2.43), 5.280
451 [M+H]⁺ (2.46), 5.294 (1.09), 5.754 , 6.772 (4.79), 6.792 (5.26), 6.894 (1.96), 6.912 (4.26), 6.932 (4.96), 6.950 (2.92), 7.005 (0.53),
7.090 (2.60), 7.109 (4.90), 7.141 (3.48), 7.155 (5.80), 7.175 (3.08), 7.303 (0.65), 7.324 (3.77), 7.343 (2.96), 7.412 (0.62), 7.431
(0.77), 7.562 (4.28), 7.565 , 7.580 (5.85), 7.582 (5.76), 7.673 , 7.691 (3.82), 7.694 (4.77), 7.712 (3.30), 8.378 (4.53),
8.397 (4.13), 8.616 ), 9.077 (4.12), 9.098 (4.04).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.15), 0.008 (2.01), 1.526 (8.21), 1.543 , 1.552 (8.65), 1.570 (8.25), 2.028
(0.57), 2.037 (0.60), 2.047 (0.61), 2.053 (0.63), 2.063 (0.89), 2.071 (0.76), 2.079 (0.53), 2.179 (0.59), 2.192 (0.77), 2.203 (0.76),
2.213 (0.69), 2.227 , 2.366 (0.49), 2.388 (16.00), 3.842 (0.82), 3.860 (1.10), 3.878 (0.79), 4.239 (1.31), 4.248 (1.14), 4.258
LC-MS (Method L1): Rt =
448 (2.05), 4.267 (2.19), 4.282 (1.16), 5.261 (0.56), 5.276 (1.18), 5.295 (1.18), 5.310 (0.53), 6.778 (2.20), 6.781 (2.35), 6.799 (2.50),
1.27 min; MS (ESIpos): m/z =
6.801 (2.55), 6.909 (1.16), 6.912 (1.18), 6.928 (2.39), 6.930 (2.36), 6.946 (1.47), 6.949 (1.40), 7.052 (1.36), 7.076 , 7.146
455 [M+H]⁺
(1.22), 7.150 (1.28), 7.167 , 7.190 (2.18), 7.204 (3.78), 7.346 (1.99), 7.365 (1.85), 7.691 (1.43), 7.709 (2.47), 7.731 (2.48),
7.763 (2.94), 7.766 (3.19), 7.781 (1.79), 7.784 (1.62), 8.393 (2.00), 8.396 (2.06), 8.415 (1.96), 8.418 (1.84), 8.721 (8.75), 9.097
(2.09), 9.117 (2.02).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.44), -0.008 (3.46), 0.008 (3.37), 0.146 (0.41), 1.522 (14.76), 1.540 (16.00), 1.548
(15.61), 1.566 (14.88), 2.014 (0.46), 2.030 (1.02), 2.038 (1.07), 2.048 (1.14), 2.055 (1.14), 2.064 (1.61), 2.072 (1.35), 2.080 (0.98),
2.088 (0.68), 2.171 (0.62), 2.181 (1.07), 2.193 (1.41), 2.205 (1.37), 2.214 (1.27), 2.229 (0.85), 2.235 (0.72), 2.248 (0.46), 2.327
LC-MS (Method L1): Rt = (0.52), 2.366 (0.54), 2.669 , 2.710 (0.55), 3.826 (0.62), 3.843 (1.51), 3.861 (2.02), 3.879 (1.48), 3.896 (0.57), 4.210 (0.55),
449 1.27 min; MS (ESIpos): m/z = 4.218 (0.76), 4.238 (2.44), 4.246 (2.05), 4.258 (3.89), 4.267 (3.93), 4.283 (2.16), 4.295 (0.59), 4.302 (0.73), 5.261 (0.98), 5.276
477 [M+H]⁺ (2.18), 5.296 (2.20), 5.310 (0.99), 6.782 (4.05), 6.802 (4.47), 6.911 (2.03), 6.914 (2.08), 6.930 (4.31), 6.932 (4.24), 6.948 (2.63),
6.951 (2.50), 7.148 (2.11), 7.152 (2.23), 7.169 (3.50), 7.187 (1.71), 7.190 (1.69), 7.348 (3.67), 7.366 (3.41), 7.538 (4.10), 7.546
(1.25), 7.555 (4.44), 7.561 , 7.578 (4.34), 7.587 (0.80), 7.594 (0.47), 7.716 (2.81), 7.734 (4.18), 7.737 (3.56), 7.756 (3.90),
7.834 (4.93), 7.836 , 7.851 (3.82), 8.441 (3.93), 8.460 , 8.754 (14.49), 9.107 (3.76), 9.128 (3.64).
¹H-NMR (400 MHz, 6) δ [ppm]: -0.008 (3.44), 0.008 (2.25), 1.528 ), 1.546 (16.00), 1.555 (15.22), 1.573 (14.27), 2.003
(0.56), 2.018 (1.14), 2.027 (1.17), 2.036 (1.20), 2.044 (1.21), 2.053 (1.64), 2.061 (1.36), 2.069 (0.97), 2.077 (0.66), 2.165 (0.73),
2.174 (1.14), 2.187 (1.49), 2.198 (1.42), 2.208 (1.32), 2.219 (0.87), 2.229 , 2.241 (0.45), 2.524 , 3.824 (0.68), 3.841
(1.51), 3.859 (1.93), 3.877 (1.40), 3.895 (0.55), 4.203 (0.69), 4.210 (0.92), 4.230 (2.57), 4.238 (2.17), 4.250 (3.83), 4.260 (3.63),
LC-MS d L1): Rt =
450 4.267 (2.17), 4.276 (2.10), 4.288 , 4.295 (0.73), 4.304 (0.47), 5.251 (1.07), 5.266 (2.23), 5.285 (2.13), 5.300 (0.94), 6.774
1.22 min; MS s): m/z =
, 6.776 (3.91), 6.794 (4.27), 6.796 (4.17), 6.902 (2.14), 6.905 (2.10), 6.921 (4.27), 6.923 (4.08), 6.939 (2.56), 6.942 (2.34),
477 [M+H]⁺
7.142 (2.24), 7.146 (2.30), 7.163 (3.45), 7.181 (1.81), 7.185 (1.77), 7.207 (1.78), 7.215 (1.67), 7.229 (1.65), 7.241 (0.79), 7.340
(3.62), 7.359 (3.30), 7.567 (0.70), 7.575 (0.84), 7.582 (0.97), 7.590 , 7.595 , 7.603 (1.42), 7.610 (1.33), 7.616 (1.34),
7.623 (0.84), 7.631 (0.75), 7.639 (0.66), 7.743 (2.63), 7.761 (4.44), 7.782 (4.33), 7.815 (5.04), 7.818 (5.19), 7.832 (3.04), 8.495
(3.72), 8.498 (3.67), 8.516 , 8.519 (3.18), 8.716 (13.80), 9.126 , 9.146 (3.50).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.87), 0.008 (2.99), 1.535 (13.93), 1.553 (15.28), 1.562 (16.00), 1.580 (15.01), 2.015
(11.45), 2.043 (1.86), 2.073 (0.70), 2.086 , 2.156 (0.80), 2.165 (1.28), 2.178 (1.76), 2.190 (1.65), 2.199 (1.57), 2.211 (1.06),
2.220 , 2.233 (0.55), 2.301 (1.08), 2.327 (0.40), 3.833 (0.67), 3.851 (1.64), 3.868 (2.17), 3.886 , 3.904 (0.65), 4.194
LC-MS (Method L1): Rt = (0.64), 4.202 (0.82), 4.222 (2.46), 4.230 (2.05), 4.244 (3.50), 4.254 (3.47), 4.261 (2.45), 4.271 (2.47), 4.282 (0.76), 4.289 (0.90),
451 1.32 min; MS (ESIpos): m/z = 4.298 (0.61), 5.241 (1.14), 5.256 (2.55), 5.275 (2.57), 5.290 (1.14), 5.754 (11.28), 6.769 (4.42), 6.771 (4.75), 6.789 (5.07), 6.792
505 [M+H]⁺ , 6.890 (2.32), 6.892 (2.35), 6.909 , 6.911 (4.82), 6.927 (2.95), 6.930 (2.82), 7.136 (2.44), 7.140 , 7.157 (4.04),
7.175 (2.01), 7.178 (1.96), 7.323 (4.16), 7.341 (3.86), 7.398 (0.50), 7.402 (0.46), 7.439 (2.71), 7.483 (0.53), 7.535 (2.86), 7.555
(3.81), 7.665 (5.56), 7.668 (4.53), 7.683 (8.94), 7.719 (5.14), 7.737 (3.59), 7.741 (5.33), 7.758 , 8.445 (4.24), 8.448 ,
8.467 (4.12), 8.469 (3.99), 8.640 (15.04), 9.087 (2.78), 9.107 (2.71).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.92), 0.008 (2.81), 1.528 (13.71), 1.546 ), 1.555 (16.00), 1.573 (15.23), 1.995
(0.48), 2.011 (1.10), 2.019 (1.19), 2.029 (1.25), 2.037 (1.25), 2.046 (1.76), 2.054 (1.47), 2.062 (1.08), 2.158 (0.66), 2.167 (1.14),
2.179 (1.56), 2.191 , 2.201 (1.38), 2.215 (0.95), 2.224 (0.79), 2.234 (0.51), 2.327 , 2.366 (0.64), 2.522 (1.30), 2.669
(0.57), 2.710 (0.64), 3.818 (0.59), 3.836 (1.47), 3.854 (1.91), 3.871 (1.43), 3.889 (0.57), 4.199 (0.57), 4.207 (0.81), 4.227 (2.55),
LC-MS d L1): Rt =
453 4.235 (2.24), 4.246 (4.18), 4.255 (4.37), 4.271 (2.40), 4.283 (0.66), 4.290 (0.79), 4.299 , 5.245 (1.03), 5.259 (2.33), 5.279
1.29 min; MS (ESIpos): m/z =
(2.42), 5.294 , 6.771 (4.44), 6.792 (4.88), 6.895 (2.11), 6.897 (2.18), 6.913 (4.53), 6.916 (4.55), 6.932 (2.84), 6.934 (2.70),
491 [M+H]⁺
7.137 (2.24), 7.141 (2.42), 7.158 (3.78), 7.176 , 7.179 , 7.331 , 7.349 (3.32), 7.446 (2.55), 7.457 (3.58), 7.470
, 7.478 (1.08), 7.484 (1.54), 7.489 (1.34), 7.495 (1.12), 7.505 (4.07), 7.511 (3.08), 7.526 (6.37), 7.533 (5.60), 7.585 (4.48),
7.599 (1.47), 7.607 (2.68), 7.622 (0.88), 7.693 (1.47), 7.698 (2.37), 7.711 (6.81), 7.716 (6.90), 7.719 (7.23), 7.739 (5.49), 7.757
(2.24), 8.456 (3.58), 8.460 (3.76), 8.476 (3.45), 8.480 , 8.661 (11.47), 8.729 (0.46), 9.113 (4.07), 9.134 (4.00).
LC-MS (Method L1): Rt = ¹H-NMR (500 MHz, DMSO-d6): δ [ppm] = 13.33 (br s, 1H), 8.92 (s, 1H), 8.75 (d, 1H), 8.12-7.96 (m, 2H), 7.90 (dd, 1H), .66 (m,
454 1.13 min; MS (ESIpos): m/z = 5H), 7.12 (t, 1H), 6.92 (d, 1H), 6.83 (t, 1H), 6.73 (dd, 1H), .06 (m, 1H), 4.18-4.07 (m, 1H), 3.99 (ddd, 1H), 2.56-2.52 (m, 1H),
515 [M+H]⁺ 2.09-1.96 (m, 1H), 1.78 (td, 1H)
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.81), 0.008 (2.57), 0.853 (0.46), 1.235 (2.17), 1.300 (0.52), 1.316 (0.51), 1.398
(1.60), 1.513 (14.80), 1.531 (16.00), 1.540 (15.55), 1.558 (14.28), 2.016 (1.21), 2.023 (1.32), 2.033 (1.33), 2.040 (1.33), 2.050
(1.72), 2.057 (1.47), 2.181 (1.67), 2.194 (1.60), 2.203 (1.49), 2.216 (1.01), 2.327 (0.52), 2.669 (0.63), 2.710 (0.49), 3.829 (0.77),
LC-MS (Method L1): Rt =
455 3.847 (1.66), 3.865 (2.13), 3.882 (1.55), 3.900 (0.64), 4.205 (1.06), 4.225 (2.72), 4.233 , 4.246 , 4.265 (2.32), 4.274
1.36 min; MS (ESIpos): m/z =
(2.31), 4.293 (0.84), 5.242 (1.17), 5.256 , 5.276 (2.34), 5.290 (1.06), 5.754 (5.78), 6.776 (4.38), 6.795 (4.71), 6.900 (2.25),
509 [M+H]⁺
6.919 (4.51), 6.937 (2.66), 7.146 (2.46), 7.164 (3.72), 7.181 (1.83), 7.335 (3.97), 7.353 (3.56), 7.505 (11.79), 7.509 (11.98), 7.682
(3.19), 7.692 (4.34), 7.697 (7.04), 7.702 (5.43), 7.705 (5.86), 7.728 , 8.525 (2.64), 8.540 (2.80), 8.549 (2.69), 8.564 (2.43),
8.745 (13.37), 9.099 (3.97), 9.120 (3.77).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.837 (0.43), 0.854 (0.54), 0.891 (0.49), 1.141 (0.54), 1.235 , 1.317 (0.60), 1.343
(0.89), 1.359 (1.03), 1.519 (11.49), 1.522 (11.46), 1.536 (12.92), 1.541 ), 1.548 (16.00), 1.566 (14.61), 2.000 , 2.008
(1.47), 2.024 (1.68), 2.035 (2.05), 2.174 (1.95), 2.186 (1.92), 2.196 , 2.210 (1.48), 2.328 (0.62), 2.366 (0.58), 2.669 (0.65),
LC-MS d L1): Rt = 2.710 (0.54), 3.849 (1.72), 3.858 (1.72), 4.196 (1.05), 4.216 (3.08), 4.224 , 4.240 (4.11), 4.265 (2.93), 4.284 (1.16), 5.232
477 1.26 min; MS (ESIpos): m/z = (1.14), 5.247 (2.57), 5.264 (2.59), 6.767 (4.85), 6.787 (5.50), 6.888 (2.50), 6.906 (5.25), 6.924 (3.19), 7.137 (2.79), 7.155 (4.52),
509 [M+H]⁺ 7.172 (2.28), 7.316 (2.70), 7.326 (2.95), 7.333 (2.84), 7.343 (2.62), 7.358 (2.21), 7.361 (2.23), 7.380 (4.65), 7.399 (3.04), 7.403
(2.97), 7.457 (2.43), 7.469 (2.86), 7.477 (4.20), 7.489 (4.31), 7.496 (2.32), 7.508 (2.35), 7.694 (3.04), 7.717 (5.27), 7.739 (7.60),
7.758 (4.31), 7.762 , 8.555 (2.91), 8.570 (3.22), 8.579 (3.15), 8.594 (2.82), 8.675 (6.93), 8.686 (7.13), 9.115 (4.16), 9.135
(3.98).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.30), 0.008 (1.39), 1.157 (0.78), 1.175 (1.56), 1.192 (0.80), 1.398 (0.65), 1.988
(3.13), 2.002 (0.44), 2.012 (0.46), 2.019 (0.47), 2.029 (0.65), 2.036 (0.56), 2.044 (0.40), 2.086 (1.10), 2.135 (0.42), 2.148 (0.61),
2.160 (0.56), 2.169 (0.53), 4.021 (0.69), 4.038 (0.69), 4.216 (0.98), 4.223 (0.77), 4.236 (1.07), 4.243 (1.18), 4.250 (1.04), 4.257
LC-MS (Method L1): Rt =
478 (0.80), 4.266 (0.84), 5.227 (0.88), 5.247 (0.89), 5.677 (1.55), 5.681 (1.65), 5.722 , 5.725 (1.76), 5.754 (2.74), 5.810 ,
1.31 min; MS (ESIpos): m/z =
.813 (1.59), 5.839 (1.68), 5.842 , 6.775 , 6.796 , 6.899 (0.83), 6.917 (1.72), 6.934 (1.01), 7.142 (0.82), 7.146
475 [M+H]⁺
(0.88), 7.163 (1.40), 7.180 (0.67), 7.184 (0.68), 7.305 (1.47), 7.324 (1.41), 7.331 (1.46), 7.360 (1.32), 7.376 (1.31), 7.405 (1.17),
7.664 ), 7.741 (1.18), 7.759 (1.71), 7.780 (1.56), 7.895 (1.87), 7.898 (2.02), 7.913 (1.52), 7.916 (1.50), 8.242 (1.70), 8.245
(1.76), 8.262 (1.59), 8.266 , 8.909 (5.42), 9.001 (1.53), 9.021 (1.48).
¹H-NMR (400 MHz, 6) δ [ppm]: 1.519 (14.64), 1.536 (16.00), 1.545 (15.88), 1.563 (14.91), 2.013 (1.08), 2.021 (1.17), 2.031
(1.28), 2.038 (1.29), 2.048 (1.72), 2.055 (1.49), 2.063 (1.07), 2.071 (0.76), 2.161 (0.68), 2.170 (1.10), 2.182 (1.58), 2.194 (1.51),
2.203 , 2.216 (1.01), 2.237 (0.51), 3.827 (0.66), 3.845 (1.63), 3.863 (2.19), 3.881 (1.61), 3.898 (0.66), 4.196 (0.63), 4.203
LC-MS (Method L1): Rt =
479 , 4.223 (2.53), 4.230 (2.07), 4.249 , 4.256 (2.97), 4.264 (2.19), 4.273 (2.28), 4.284 (0.71), 4.292 (0.84), 4.300 (0.57),
1.29 min; MS (ESIpos): m/z =
.244 (1.06), 5.258 (2.41), 5.277 (2.44), 5.292 (1.07), 6.774 (4.57), 6.795 (5.08), 6.898 (2.22), 6.916 (4.75), 6.935 (2.76), 7.143
525 [M+H]⁺
(2.39), 7.162 (3.87), 7.182 (1.81), 7.329 (4.15), 7.348 (3.78), 7.421 (5.41), 7.454 (3.25), 7.466 (3.77), 7.486 (4.52), 7.607 (4.06),
7.627 , 7.646 , 7.677 (2.67), 7.700 (5.22), 7.723 (2.75), 8.510 (2.55), 8.525 (2.75), 8.534 , 8.549 (2.46), 8.707
(13.60), 9.091 (4.09), 9.111 (3.99).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.50), 0.146 (0.45), 0.852 (0.69), 1.234 (3.42), 1.299 (0.54), 1.518 (13.51), 1.536
(14.79), 1.544 (16.00), 1.562 (14.83), 2.006 , 2.014 , 2.023 (1.45), 2.031 (1.35), 2.040 (1.61), 2.049 (1.65), 2.056 (1.35),
2.182 (1.69), 2.194 (1.63), 2.203 (1.56), 2.217 (1.13), 2.327 (0.52), 2.669 (0.48), 3.839 (1.13), 3.857 (1.54), 3.866 (1.54), 3.884
LC-MS (Method L12): Rt =
487 (1.08), 4.197 , 4.223 (2.32), 4.246 , 4.255 (2.97), 4.263 , 4.272 , 4.291 , 5.256 (2.25), 5.270 (2.26),
1.56 min; MS (ESIpos): m/z =
6.773 (4.60), 6.793 (5.14), 6.897 (2.13), 6.916 (4.58), 6.934 (2.71), 7.144 , 7.162 , 7.180 (1.89), 7.279 , 7.323
495 [M+H]⁺
(2.19), 7.342 (4.10), 7.360 (2.08), 7.638 , 7.646 (0.80), 7.661 (1.58), 7.674 (1.60), 7.687 (1.61), 7.702 (0.89), 7.710 (0.84),
7.724 (2.62), 7.747 (4.86), 7.770 (2.69), 8.596 (2.77), 8.611 (2.95), 8.620 (2.95), 8.635 (2.69), 8.736 (6.87), 8.747 (7.18), 9.121
(4.19), 9.142 (4.12).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.83), -0.008 (6.41), 0.008 , 0.146 (0.80), 1.141 (0.40), 1.157 (0.99), 1.175
(1.92), 1.193 (0.96), 1.235 (0.88), 1.398 (2.11), 1.522 ), 1.540 (16.00), 1.548 (15.71), 1.566 (14.90), 1.988 (3.66), 2.013
(1.04), 2.022 (1.15), 2.031 (1.20), 2.048 (1.63), 2.056 (1.39), 2.180 (1.52), 2.192 (1.44), 2.202 (1.39), 2.215 (0.91), 2.327 (0.75),
LC-MS (Method L12): Rt = 2.670 (0.83), 3.836 (0.59), 3.853 (1.50), 3.871 (2.03), 3.889 (1.44), 3.907 (0.59), 4.021 (0.83), 4.038 (0.83), 4.202 (0.85), 4.222
488 1.60 min; MS (ESIpos): m/z = (2.51), 4.230 (1.98), 4.248 (2.86), 4.255 (2.80), 4.263 (2.06), 4.272 (2.16), 4.291 (0.88), 5.240 (0.99), 5.255 (2.16), 5.275 (2.22),
509 [M+H]⁺ 5.290 , 6.774 (4.51), 6.795 (4.99), 6.895 (2.11), 6.897 (2.19), 6.916 (4.43), 6.932 (2.70), 6.935 (2.62), 7.140 (2.22), 7.143
(2.32), 7.161 (3.58), 7.178 (1.82), 7.182 (1.84), 7.330 (3.69), 7.348 (3.42), 7.691 (2.96), 7.714 (6.17), 7.737 (5.96), 7.752 (11.25),
7.767 (7.93), 7.802 (3.53), 7.817 (2.03), 8.524 (2.59), 8.538 (2.78), 8.547 (2.83), 8.563 (2.59), 8.710 (15.17), 9.096 (3.79), 9.117
(3.69).
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.670 (0.68), 1.681 (1.19), 1.688 (1.28), 1.692 , 1.700 (1.35), 1.704 (1.28), 1.710
(0.81), 1.938 (0.60), 1.946 (0.88), 1.952 (1.34), 1.960 (1.43), 1.966 (1.42), 1.975 , 1.980 (0.77), 1.983 (0.76), 1.988 (0.57),
LC-MS (Method L1): Rt = 3.957 (1.00), 3.961 (1.18), 3.975 (2.40), 3.989 (1.44), 3.993 (1.28), 4.105 (1.24), 4.110 (1.53), 4.116 (1.46), 4.122 (2.04), 4.128
489 1.38 min; MS (ESIpos): m/z = (1.21), 4.135 (1.18), 4.139 , 5.034 (0.99), 5.044 (2.14), 5.057 (2.17), 5.067 , 5.747 (5.67), 6.713 (4.06), 6.726 (4.34),
531 [M+H]⁺ 6.811 (1.78), 6.823 (4.08), 6.835 (2.55), 6.899 (3.76), 6.912 (2.80), 7.101 (1.95), 7.113 (3.41), 7.126 (1.67), 7.259 (4.11), 7.267
(4.21), 7.669 (9.16), 7.672 (9.94), 7.681 (16.00), 7.684 (12.40), 7.691 (2.86), 7.705 (4.02), 7.717 , 7.795 (5.01), 7.798 (4.25),
7.803 (4.06), 7.806 (6.59), 7.892 (4.03), 7.894 (4.31), 7.904 (3.65), 7.906 (3.78), 8.700 , 8.714 (3.63), 8.975 (11.32).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.23), 0.008 (1.23), 1.235 (0.64), 2.073 (0.59), 3.063 (16.00), 3.283 (0.84), 3.332
LC-MS (Method L1): Rt = (1.24), 3.707 (0.83), 3.726 (0.96), 3.735 , 3.754 (0.75), 5.790 (0.75), 5.810 (0.75), 7.121 (0.41), 7.124 (0.46), 7.140 (0.96),
493 1.07 min; MS (ESIpos): m/z = 7.143 (1.04), 7.158 (0.66), 7.161 (0.71), 7.229 (0.45), 7.248 (1.01), 7.266 (0.67), 7.288 (1.37), 7.306 (0.61), 7.389 (1.07), 7.408
494 [M+H]⁺ , 7.640 (7.94), 7.651 (2.13), 7.655 (2.38), 7.673 (1.13), 7.798 (1.17), 7.801 (1.35), 7.816 (1.24), 7.819 (1.23), 8.233 (0.99),
8.236 (1.09), 8.254 , 8.258 (0.98), 8.581 (0.48), 8.683 (3.65), 9.242 (0.98), 9.263 (0.98).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.50), 1.234 (1.19), 1.797 (2.72), 1.813 (2.16), 1.831 (1.22), 2.017 (3.78), 2.027
(5.23), 2.042 (4.61), 2.052 (4.11), 2.118 (2.71), 2.141 (2.97), 2.166 (2.48), 2.174 , 2.187 (2.12), 2.198 , 2.209 (1.47),
LC-MS d L1): Rt = 2.242 (0.49), 3.802 (1.35), 3.825 (1.96), 3.849 (1.31), 4.211 (0.45), 4.219 (0.64), 4.238 (2.26), 4.247 (2.23), 4.257 (3.32), 4.265
494 1.44 min; MS (ESIpos): m/z = (3.75), 4.279 (2.16), 4.297 (0.65), 4.306 , 5.268 (0.94), 5.283 (2.12), 5.303 (2.15), 5.317 (0.95), 5.754 , 6.780 (3.97),
517 [M+H]⁺ 6.800 (4.42), 6.906 (1.93), 6.924 (4.12), 6.943 (2.41), 7.146 (1.92), 7.150 (2.10), 7.167 (3.36), 7.185 (1.57), 7.188 (1.61), 7.334
(3.58), 7.352 (3.29), 7.615 (11.95), 7.620 (16.00), 7.643 (3.83), 7.648 (5.15), 7.652 (2.49), 7.709 (2.30), 7.728 (3.62), 7.749 (3.21),
7.835 (4.99), 7.853 (3.64), 8.277 , 8.297 (3.29), 8.751 (13.22), 9.097 (3.72), 9.117 (3.65).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.157 (2.50), 1.175 (5.02), 1.193 (2.67), 1.234 (1.23), 1.540 (3.03), 1.988 (9.10), 2.063
(2.50), 2.079 (2.80), 2.198 (2.93), 2.221 (2.26), 2.328 (0.95), 2.366 (0.77), 2.670 (0.84), 2.694 (0.44), 2.710 (0.45), 2.961 (1.24),
2.983 (1.72), 3.003 (1.27), 3.192 (2.79), 3.209 (2.69), 3.510 (0.78), 3.568 (1.00), 3.687 (1.02), 3.944 (1.29), 3.964 (1.72), 3.984
LC-MS (Method L1): Rt =
519 (1.23), 4.003 , 4.020 (2.57), 4.038 (2.55), 4.056 (1.22), 4.264 , 5.271 (1.44), 5.287 (3.19), 5.305 (3.16), 5.320 (1.42),
0.91 min; MS (ESIpos): m/z =
6.779 (5.67), 6.799 (6.10), 6.907 (2.67), 6.926 (5.43), 6.944 (3.19), 7.147 (3.24), 7.166 (5.08), 7.185 (2.43), 7.345 (4.52), 7.364
518 [M+H]⁺
, 7.621 (16.00), 7.641 (6.46), 7.646 (7.29), 7.666 (3.01), 7.691 (2.20), 7.711 , 7.731 (3.09), 7.832 (6.29), 7.849 (4.99),
7.890 (0.71), 7.908 (0.56), 8.417 (0.70), 8.654 (2.62), 8.675 (2.44), 8.759 (14.38), 8.912 (1.06), 9.129 (2.46), 9.139 (2.89), 9.149
(2.97), 9.159 (2.67).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.735 (0.54), 1.741 (0.60), 1.753 , 1.769 (0.75), 1.775 (0.68), 1.785 (0.45), 1.982
(0.46), 1.994 (0.70), 2.008 (0.73), 2.016 (0.72), 2.029 (0.56), 3.944 (0.51), 3.950 (0.61), 3.972 (1.26), 3.993 (0.80), 3.999 (0.65),
LC-MS (Method L1): Rt =
520 4.118 , 4.125 (0.83), 4.134 (0.77), 4.142 (0.98), 4.153 (0.60), 4.162 (0.60), 4.169 (0.47), 5.070 (0.51), 5.084 (1.14), 5.104
1.26 min; MS (ESIpos): m/z =
(1.15), 5.118 (0.50), 5.754 (1.74), 6.728 (2.15), 6.748 (2.40), 6.803 (0.98), 6.822 (2.24), 6.840 (1.42), 6.951 (2.12), 6.969 (1.59),
565 [M+H]⁺
7.106 (1.04), 7.127 (1.79), 7.145 , 7.684 (16.00), 7.737 (1.24), 7.757 (2.35), 7.776 (1.77), 7.862 (1.30), 7.929 (2.60), 7.940
(3.02), 7.943 (2.91), 7.961 (2.06), 8.010 (7.93), 8.156 (1.16), 8.519 (6.04), 8.866 (2.07), 8.886 (2.02), 8.999 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.51), 1.235 (0.43), 1.676 (1.54), 1.713 (2.60), 1.751 , 2.057 (0.97), 2.072
(1.11), 2.085 (1.87), 2.218 (1.33), 2.231 (1.31), 2.240 (1.26), 2.252 , 2.327 , 2.366 (0.60), 2.429 (2.14), 2.460 (2.25),
LC-MS d L1): Rt = 1.28 2.670 (0.69), 2.710 (0.67), 3.464 (1.07), 3.493 (1.97), 3.520 , 3.546 (2.15), 3.575 (1.18), 3.738 , 4.010 (3.17), 4.023
539 min; MS (ESIpos): m/z = 533 , 4.038 (2.85), 4.219 (0.82), 4.240 (2.21), 4.247 (1.78), 4.260 (2.15), 4.268 , 4.279 (2.21), 4.295 , 5.293 (0.94),
[M+H]+ 5.307 (2.08), 5.327 (2.08), 5.342 (0.90), 5.754 (5.00), 6.785 (3.97), 6.804 (4.38), 6.918 (1.97), 6.937 (4.07), 6.956 (2.40), 7.158
(2.10), 7.176 (3.37), 7.193 (1.61), 7.405 (3.52), 7.423 (3.20), 7.613 (13.15), 7.617 (16.00), 7.648 (4.20), 7.653 , 7.748 (2.29),
7.766 (3.65), 7.787 (3.20), 7.856 (4.95), 7.874 (3.52), 8.510 (3.43), 8.531 (3.17), 8.777 ), 9.140 (3.54), 9.161 (3.54).
¹H-NMR (500 MHz, 6) δ [ppm]: 0.006 (2.45), 2.035 , 2.042 (0.79), 2.050 (0.83), 2.056 (0.84), 2.063 (1.08), 2.070
(0.92), 2.076 (0.65), 2.084 (0.55), 2.177 (0.48), 2.184 , 2.194 (0.96), 2.204 (0.93), 2.212 (0.89), 2.222 (0.61), 2.361 (0.44),
2.635 (0.42), 2.784 (16.00), 4.218 (0.41), 4.240 (1.35), 4.253 (2.26), 4.260 (2.33), 4.273 (1.44), 4.289 (0.47), 5.276 (0.62), 5.288
LC-MS (Method L1): Rt =
552 (1.38), 5.303 (1.35), 5.315 (0.58), 5.753 (1.80), 6.779 (2.82), 6.795 (3.02), 6.899 (1.36), 6.913 (2.78), 6.928 (1.56), 7.147 (1.37),
1.16 min; MS (ESIpos): m/z =
7.161 (2.32), 7.175 (1.13), 7.336 (2.58), 7.342 (1.47), 7.351 (3.50), 7.367 (1.58), 7.434 (1.15), 7.440 , 7.450 (1.98), 7.456
463 [M+H]⁺
(2.00), 7.465 (1.00), 7.471 (0.96), 7.698 (2.97), 7.701 (2.98), 7.714 , 7.727 , 7.729 (3.39), 7.757 (2.79), 7.773 (3.09),
7.788 (1.77), 8.296 (2.65), 8.299 (2.73), 8.313 (2.51), 8.315 (2.43), 8.725 (3.78), 8.730 (3.80), 9.066 (1.31), 9.073 (1.41), 9.083
(1.35), 9.089 (1.27).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.040 (0.54), 2.049 (0.56), 2.058 (0.59), 2.066 (0.62), 2.075 (0.86), 2.084 (0.82), 2.199
(0.74), 2.211 (0.72), 2.221 (0.67), 2.791 (16.00), 4.239 (1.25), 4.248 , 4.258 (1.91), 4.266 (2.10), 4.281 (1.17), 5.278 (0.52),
LC-MS (Method L1): Rt =
554 5.292 (1.15), 5.311 (1.17), 5.326 (0.53), 5.754 (2.08), 6.782 (2.11), 6.802 (2.36), 6.902 (1.03), 6.921 (2.23), 6.939 (1.30), 7.149
1.11 min; MS (ESIpos): m/z =
(1.12), 7.167 (1.84), 7.184 (0.89), 7.228 (0.92), 7.240 (0.93), 7.250 , 7.346 (1.97), 7.365 (1.80), 7.584 (0.41), 7.599 (0.74),
449 [M+H]⁺
7.612 (0.76), 7.624 (0.74), 7.639 , 7.779 , 7.798 (2.28), 7.818 (2.13), 7.853 (2.63), 7.868 , 8.336 (2.03), 8.339
(2.04), 8.357 (1.93), 8.795 (6.37), 9.088 (1.87), 9.109 (1.81).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.81), 0.008 (0.91), 1.235 (0.83), 1.583 (5.80), 1.773 (0.41), 1.790 (0.55), 1.800
LC-MS (Method L1): Rt = (0.64), 2.756 (0.59), 2.782 (0.54), 2.812 (0.68), 2.820 (0.83), 2.977 (16.00), 7.042 (0.46), 7.061 (1.18), 7.070 (0.71), 7.072 (0.72),
555 1.11 min; MS (ESIpos): m/z = 7.087 (0.98), 7.090 (1.00), 7.106 (0.45), 7.109 (0.43), 7.131 (0.52), 7.150 (0.77), 7.502 (1.01), 7.520 , 7.610 (0.79), 7.628
504 [M+H]⁺ (1.21), 7.632 (1.38), 7.638 (10.75), 7.649 (1.14), 7.771 (1.14), 7.774 , 7.789 , 7.792 (0.96), 8.202 (1.03), 8.205 (1.09),
8.223 (0.99), 8.227 (0.96), 8.645 (3.75), 8.744 (1.76).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.58), -0.008 (5.47), 0.008 (4.38), 0.146 (0.61), 1.235 (1.34), 2.036 (1.59), 2.073
(0.95), 2.159 (1.17), 2.172 (1.51), 2.183 (1.48), 2.193 (1.40), 2.327 (1.17), 2.366 (0.64), 2.523 , 2.670 (1.31), 2.710 (0.67),
3.996 (0.51), 4.032 (9.72), 4.078 (0.42), 4.203 (0.70), 4.243 (3.57), 4.252 (4.02), 4.267 (2.26), 4.285 , 4.941 (4.22), 4.966
LC-MS (Method L1): Rt =
562 (2.98), 5.213 (0.97), 5.228 (2.18), 5.247 (2.17), 5.261 (0.90), 5.754 (8.48), 6.780 (4.08), 6.800 (4.58), 6.885 (1.79), 6.903 ,
0.74 min; MS (ESIpos): m/z =
6.922 (2.20), 7.146 (2.20), 7.164 (3.60), 7.182 (1.68), 7.304 (3.88), 7.322 (3.85), 7.353 (2.26), 7.415 (1.60), 7.427 (2.01), 7.435
533 [M+H]⁺
(2.80), 7.447 (3.08), 7.454 (1.54), 7.466 (1.53), 7.649 (1.29), 7.666 (5.30), 7.676 (5.97), 7.684 (13.71), 7.689 (6.43), 7.705 (4.35),
7.709 (4.08), 8.136 (4.77), 8.308 (0.72), 8.317 (3.74), 8.325 , 8.334 (3.46), 8.342 (3.29), 8.630 (16.00), 8.707 (5.45), 9.196
(1.74), 9.214 (2.90), 9.233 (1.90).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.20), -0.008 (9.34), 0.008 (9.02), 0.146 (1.08), 0.854 (0.58), 1.148 (0.41), 1.235
(3.04), 2.039 (1.61), 2.085 (3.50), 2.183 (1.52), 2.194 (1.37), 2.327 , 2.366 (0.93), 2.669 (2.04), 2.709 (1.02), 3.508 ,
LC-MS (Method L1): Rt =
563 4.039 (9.81), 4.253 (3.88), 4.268 (2.28), 4.948 , 4.972 (2.77), 5.225 , 5.243 (2.22), 5.754 (7.04), 6.782 (4.76), 6.803
0.85 min; MS (ESIpos): m/z =
(5.23), 6.888 (2.10), 6.907 , 6.925 (2.45), 7.149 (2.36), 7.167 (3.91), 7.184 (1.96), 7.305 (3.50), 7.325 (3.18), 7.454 (2.39),
567 [M+H]⁺
7.477 , 7.483 (2.60), 7.652 (2.51), 7.670 , 7.691 (4.44), 7.721 (5.26), 7.737 (2.92), 7.910 (8.35), 7.916 (8.23), 8.163
(2.04), 8.338 (4.35), 8.341 (4.50), 8.359 , 8.362 (3.94), 8.642 (16.00), 8.717 (5.69), 9.213 (2.63), 9.233 (2.51).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.40), 0.008 (2.06), 2.061 , 2.185 (1.12), 2.327 (0.94), 2.669 (0.87), 4.025
(5.86), 4.065 (0.57), 4.238 (1.84), 4.258 (2.64), 4.266 (2.99), 4.913 (1.72), 4.926 (3.39), 4.946 , 4.959 , 5.246 (1.74),
LC-MS (Method L1): Rt =
569 5.266 (1.56), 6.792 , 6.813 (3.85), 6.904 (1.66), 6.922 , 6.939 (2.06), 7.158 (1.80), 7.175 (2.74), 7.197 , 7.321
0.78 min; MS (ESIpos): m/z =
(2.74), 7.338 (2.56), 7.392 (1.86), 7.411 (2.11), 7.578 (2.92), 7.588 (4.18), 7.597 (5.85), 7.616 (4.05), 7.627 (5.32), 7.647 (1.93),
549 [M+H]⁺
7.652 (2.84), 7.670 (3.21), 7.691 , 7.814 (3.61), 7.817 (3.83), 7.832 (3.05), 8.291 (3.30), 8.310 (3.02), 8.706 (16.00), 9.217
(2.96), 9.237 (2.95).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.87), 0.008 (0.82), 1.308 , 1.327 (16.00), 1.345 (7.07), 2.024 (0.53), 2.039
, 2.049 , 2.058 (1.29), 2.066 (1.35), 2.075 (1.94), 2.083 (1.61), 2.090 (1.19), 2.099 (0.77), 2.180 (0.74), 2.190 (1.30),
2.203 (1.54), 2.213 (1.54), 2.225 (1.35), 2.243 (0.95), 2.256 (0.53), 3.233 (1.89), 3.252 (5.94), 3.271 (5.86), 3.289 (1.97), 4.220
LC-MS d L1): Rt =
570 (0.46), 4.229 (0.69), 4.249 (2.90), 4.258 (4.37), 4.268 (5.05), 4.275 (4.55), 4.284 (2.85), 4.302 (0.68), 5.294 (1.14), 5.309 (2.53),
1.27 min; MS (ESIpos): m/z =
.329 (2.56), 5.344 (1.15), 6.785 (4.65), 6.805 (5.16), 6.910 (2.22), 6.913 (2.38), 6.931 (4.95), 6.948 (2.88), 6.950 (2.91), 7.148
493 [M+H]⁺
(2.35), 7.152 (2.57), 7.169 (4.01), 7.187 , 7.190 (1.93), 7.348 (4.27), 7.366 (3.97), 7.402 (2.57), 7.421 (3.07), 7.587 (3.08),
7.606 ), 7.626 (5.62), 7.636 (4.50), 7.639 (7.18), 7.658 , 7.756 (2.88), 7.774 (4.86), 7.795 (4.63), 7.845 (5.60), 7.847
(6.27), 7.862 (3.86), 7.865 (3.83), 8.305 (4.57), 8.324 (4.08), 8.326 (4.06), 8.800 (15.69), 9.096 (4.36), 9.117 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.051 , 2.060 (0.52), 2.087 (0.83), 2.095 (0.71), 2.206 (0.69), 2.217 (0.69), 2.227
(0.59), 2.793 (16.00), 4.247 (1.21), 4.266 (1.74), 4.272 , 4.287 (1.09), 5.288 (0.50), 5.303 (1.10), 5.323 (1.10), 5.338 (0.49),
LC-MS (Method L1): Rt =
571 6.788 (2.15), 6.808 (2.34), 6.911 (1.04), 6.927 , 6.946 (1.29), 7.154 (1.12), 7.171 (1.74), 7.189 (0.83), 7.350 (1.84), 7.369
1.21 min; MS (ESIpos): m/z =
(1.70), 7.405 (1.21), 7.425 (1.42), 7.591 (1.39), 7.610 (5.39), 7.629 (2.38), 7.646 (3.07), 7.665 (1.25), 7.758 (1.35), 7.776 (2.19),
479 [M+H]⁺
7.797 (2.04), 7.857 (2.46), 7.860 (2.60), 7.875 (1.77), 7.878 (1.68), 8.268 (2.07), 8.271 (2.11), 8.289 (1.94), 8.292 (1.85), 8.810
(6.83), 9.075 (1.81), 9.095 (1.79).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.032 (0.65), 2.041 , 2.050 (0.76), 2.058 (0.79), 2.067 (1.04), 2.075 (0.91), 2.172
(0.41), 2.181 (0.73), 2.193 (0.92), 2.204 (0.91), 2.215 (0.83), 2.787 ), 4.216 (0.41), 4.236 (1.41), 4.254 (2.29), 4.261 (2.58),
LC-MS (Method L1): Rt =
572 4.276 (1.47), 4.294 (0.44), 5.271 (0.58), 5.286 (1.35), 5.304 (1.38), 5.320 (0.61), 6.778 , 6.799 , 6.897 (1.24), 6.915
1.26 min; MS (ESIpos): m/z =
(2.63), 6.934 (1.54), 7.145 (1.36), 7.163 (2.20), 7.184 (1.05), 7.337 (2.34), 7.355 (2.19), 7.495 (2.29), 7.502 (1.52), 7.657 (0.42),
497 [M+H]⁺
7.771 (6.93), 7.779 (3.68), 7.787 (3.32), 7.805 (0.67), 7.922 (2.71), 7.928 (2.67), 8.315 (1.92), 8.324 (1.81), 8.332 (1.66), 8.340
(1.74), 8.751 , 9.078 (2.11), 9.099 (2.06).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.08), 0.008 (1.69), 1.311 (7.04), 1.329 ), 1.348 (7.23), 2.018 , 2.028
(1.39), 2.037 (1.33), 2.053 , 2.062 (1.64), 2.188 (1.63), 2.198 (1.61), 2.210 (1.49), 2.229 (1.04), 2.241 (0.61), 2.327 ,
LC-MS (Method L1): Rt = 2.670 (0.76), 3.241 (3.86), 3.260 (3.83), 4.217 (0.70), 4.236 (2.98), 4.246 (4.20), 4.256 (5.08), 4.263 (4.65), 4.272 (2.85), 4.290
573 1.32 min; MS (ESIpos): m/z = (0.68), 5.274 (1.17), 5.289 (2.57), 5.308 (2.57), 5.323 , 6.776 (5.42), 6.796 , 6.897 (2.61), 6.899 (2.58), 6.915 (5.46),
511 [M+H]⁺ 6.934 (3.26), 7.140 (2.67), 7.144 (2.76), 7.161 (4.38), 7.179 , 7.332 (4.46), 7.351 (4.10), 7.492 (4.02), 7.498 , 7.504
(4.01), 7.755 (2.30), 7.767 (14.83), 7.772 (8.12), 7.785 , 7.803 (1.92), 7.919 (10.30), 7.925 (9.81), 8.348 (4.00), 8.355 (3.95),
8.367 (3.57), 8.373 (3.60), 8.742 (7.68), 8.747 (7.69), 9.108 (3.20), 9.127 (3.19).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.196 (5.36), 1.216 (11.90), 1.234 (5.37), 2.071 (0.42), 2.613 (1.31), 2.632 (3.68), 2.651
LC-MS (Method L1): Rt = (3.53), 2.669 (1.23), 3.055 (16.00), 4.243 (0.61), 4.251 (0.57), 4.262 (0.88), 4.270 (0.97), 4.284 , 5.245 (0.56), 5.264 ,
574 0.91 min; MS (ESIpos): m/z = 6.788 (1.10), 6.806 (1.17), 6.902 (0.54), 6.905 (0.53), 6.921 , 6.939 (0.67), 6.942 (0.61), 7.064 (1.62), 7.148 (0.57), 7.152
480 [M+H]⁺ , 7.169 (0.97), 7.191 (3.92), 7.351 (0.92), 7.368 (0.83), 7.588 (0.68), 7.606 (1.18), 7.626 (1.17), 7.657 (1.35), 7.661 (1.40),
7.675 (0.81), 7.679 (0.68), 8.153 (1.09), 8.156 (1.06), 8.173 (0.99), 8.177 (0.92), 8.573 (4.21), 9.076 (0.96), 9.096 (0.92).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.315 (7.37), 1.334 (16.00), 1.352 (7.13), 2.016 (1.34), 2.026 (1.38), 2.034 , 2.051
(2.04), 2.060 (1.67), 2.188 (1.64), 2.210 (1.45), 2.224 (1.01), 2.327 (0.50), 2.669 (0.61), 3.238 (3.99), 3.257 (4.06), 4.245 (4.33),
LC-MS (Method L1): Rt = 4.256 (5.35), 4.271 (2.97), 5.276 (1.22), 5.290 (2.56), 5.309 (2.47), 5.324 (1.11), 6.773 (5.14), 6.792 (5.52), 6.895 (2.45), 6.913
575 1.22 min; MS (ESIpos): m/z = (5.11), 6.932 (2.89), 7.141 (2.70), 7.159 (4.13), 7.176 (1.99), 7.330 (4.58), 7.349 (6.16), 7.359 (3.61), 7.363 (4.57), 7.425 (2.86),
477 [M+H]⁺ 7.431 (3.07), 7.444 (4.36), 7.451 (4.11), 7.464 , 7.470 (2.10), 7.693 (6.38), 7.697 (6.72), 7.702 (4.33), 7.705 (4.53), 7.713
(6.16), 7.717 (7.18), 7.719 (7.98), 7.723 (6.68), 7.752 (5.37), 7.772 (5.59), 7.790 (3.08), 8.326 (4.48), 8.329 , 8.347 (4.17),
8.718 (7.77), 8.724 (7.76), 9.099 (4.38), 9.120 .
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.161 (1.21), 1.180 , 1.196 (3.31), 1.216 (3.24), 1.230 (2.47), 1.235 (1.47), 1.249
(1.09), 1.356 (0.40), 2.044 (0.41), 2.184 (0.41), 2.595 (0.99), 2.609 (1.17), 2.628 , 2.728 (0.96), 2.745 (1.23), 2.763 (0.79),
LC-MS d L1): Rt =
582 3.065 (16.00), 4.229 (0.62), 4.237 (0.58), 4.248 (0.91), 4.256 (1.04), 4.270 (0.58), 5.227 (0.48), 5.241 (0.48), 6.774 , 6.794
0.99 min; MS (ESIpos): m/z =
(1.15), 6.883 (0.48), 6.902 (1.01), 6.920 (0.59), 6.967 (0.72), 6.972 (0.72), 6.996 (0.74), 7.001 (0.75), 7.138 (0.56), 7.156 (0.90),
514 [M+H]⁺
7.174 (0.45), 7.218 (1.64), 7.223 (1.57), 7.331 (0.76), 7.350 (0.71), 7.550 (0.70), 7.567 (1.32), 7.595 (1.22), 7.616 (1.30), 7.633
(0.71), 8.199 , 8.203 (1.13), 8.220 (1.01), 8.224 (1.00), 8.506 (2.86), 9.055 (0.47), 9.073 (0.74), 9.092 (0.49).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.62), 1.142 (0.89), 1.161 (6.60), 1.180 (13.02), 1.195 (16.00), 1.216 (15.26), 1.229
(11.19), 1.234 (6.42), 1.248 (5.03), 1.356 (2.57), 2.034 (1.17), 2.061 (1.72), 2.182 (1.53), 2.194 (1.58), 2.207 , 2.217 (1.57),
2.327 (0.56), 2.366 (0.40), 2.578 (1.59), 2.596 (4.14), 2.610 (4.95), 2.629 (4.33), 2.648 (1.32), 2.709 (1.71), 2.728 (3.88), 2.745
LC-MS (Method L1): Rt =
583 (4.90), 2.763 (3.19), 3.875 (11.89), 4.211 , 4.232 (2.57), 4.252 (3.80), 4.262 (3.67), 4.279 (2.36), 5.242 (2.14), 5.256 (2.13),
1.20 min; MS s): m/z =
6.776 (4.90), 6.796 (5.51), 6.892 (1.72), 6.910 (3.66), 6.929 (2.06), 6.969 (3.24), 6.974 (3.27), 7.000 (3.63), 7.005 (3.58), 7.141
556 [M+H]⁺
(2.39), 7.161 (3.89), 7.180 (2.02), 7.225 (7.39), 7.230 (6.95), 7.352 (4.16), 7.370 (3.84), 7.591 (3.42), 7.607 (5.69), 7.646 (5.21),
7.667 (5.45), 7.685 (3.27), 8.243 (4.62), 8.246 (4.72), 8.263 , 8.267 (4.07), 8.566 (8.87), 8.571 (9.34), 9.136 (2.13), 9.154
(3.49), 9.173 (2.18).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.77), 0.008 (0.70), 2.009 (0.45), 2.124 (0.42), 2.137 , 2.159 (0.67), 2.173
(0.54), 2.729 (16.00), 3.132 (8.33), 3.140 (9.59), 4.242 (1.09), 4.256 (1.79), 4.268 (1.30), 4.285 (0.74), 4.304 , 4.313 ,
LC-MS (Method L4): Rt = 5.228 (0.59), 5.244 (0.74), 5.261 (0.70), 5.277 , 5.754 (5.28), 6.788 (0.97), 6.800 (1.15), 6.807 (1.12), 6.818 (1.26), 6.861
585 3.93 min; MS (ESIpos): m/z = (0.47), 6.879 (1.00), 6.898 (0.64), 6.905 (0.63), 6.923 (1.16), 6.942 (0.70), 7.145 (0.53), 7.163 (1.32), 7.184 (1.31), 7.201 ,
520 [M+H]⁺ 7.217 (0.79), 7.322 (0.99), 7.341 , 7.673 (1.37), 7.677 , 7.682 (2.18), 7.707 , 7.712 (5.77), 7.789 (0.70), 7.809
(2.12), 7.827 (3.94), 7.832 (2.99), 7.849 (0.62), 7.852 (0.68), 7.975 (1.92), 7.980 (1.72), 7.991 (1.71), 7.996 (1.45), 9.158 (4.20),
9.183 (4.34), 9.199 (1.01).
LC-MS (Method L1): Rt = ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.313 (16.00), 2.359 (3.34), 3.056 (5.98), 4.262 (0.45), 4.271 (0.52), 6.788 (0.52), 6.809
586 0.98 min; MS (ESIpos): m/z = (0.57), 6.924 (0.54), 7.173 (1.16), 7.218 (0.69), 7.346 (0.96), 7.367 (0.45), 7.611 (0.52), 7.631 , 7.659 (0.59), 8.157 (0.42),
494 [M+H]⁺ 8.564 (1.24), 9.083 (0.42), 9.103 (0.42).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.295 , 1.313 (16.00), 2.360 (4.01), 3.276 (1.42), 3.287 (1.54), 3.875 (2.03), 4.268
LC-MS (Method L1): Rt =
587 (0.54), 6.789 (0.67), 6.810 (0.75), 6.932 (0.71), 6.950 (0.41), 7.156 (0.40), 7.175 (1.57), 7.225 (0.98), 7.349 (1.06), 7.373 (0.71),
1.18 min; MS (ESIpos): m/z =
7.392 (0.66), 7.659 (0.78), 7.679 (0.75), 7.698 (0.86), 7.712 (0.44), 8.213 (0.58), 8.230 (0.53), 8.623 (1.85), 9.157 (0.60), 9.178
536 [M+H]⁺
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.01), 0.008 (0.99), 1.197 (7.08), 1.216 (16.00), 1.234 (7.43), 2.089 , 2.096
(0.46), 2.208 (0.52), 2.220 (0.48), 2.230 (0.47), 2.327 (0.44), 2.522 (1.17), 2.615 (1.76), 2.634 (5.17), 2.653 (5.02), 2.671 (1.92),
LC-MS (Method L1): Rt = 3.243 (0.45), 3.262 (1.26), 3.275 (2.62), 3.287 (2.82), 3.874 (4.06), 4.245 (0.80), 4.253 (0.63), 4.267 (1.07), 4.277 (1.01), 4.293
588 1.14 min; MS (ESIpos): m/z = (0.68), 5.259 (0.75), 5.278 (0.75), 5.754 (1.39), 6.789 (1.42), 6.810 , 6.913 (0.73), 6.932 (1.50), 6.948 , 6.951 (0.88),
522 [M+H]⁺ 7.073 (2.20), 7.152 (0.74), 7.156 (0.80), 7.173 (1.25), 7.194 (5.31), 7.373 (1.25), 7.391 (1.18), 7.638 (0.84), 7.656 (1.64), 7.676
(1.69), 7.695 (1.79), 7.699 (2.07), 7.713 (0.99), 7.717 (0.85), 8.208 (1.34), 8.212 (1.38), 8.229 (1.26), 8.233 (1.22), 8.629 (5.50),
9.153 (1.39), 9.173 (1.34).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.234 (0.47), 2.106 (0.61), 2.117 (0.70), 2.129 (0.79), 2.134 (0.71), 2.262 (0.49), 2.273
(0.68), 2.283 (0.72), 2.290 (0.70), 2.301 (0.52), 4.035 (0.41), 4.195 , 4.200 (0.56), 4.218 (1.25), 4.235 (0.87), 4.240 (0.70),
LC-MS (Method L1): Rt = 4.289 (0.70), 4.295 (0.92), 4.301 (0.85), 4.308 (0.93), 4.318 , 4.323 (0.56), 4.330 , 4.742 (1.91), 5.390 (0.52), 5.400
592 1.14 min; MS (ESIpos): m/z = (1.12), 5.416 (1.11), 5.427 (0.51), 5.554 (0.98), 6.793 (2.09), 6.808 (2.27), 6.937 (1.02), 6.952 , 6.966 (1.23), 7.163 (1.03),
479 [M+H]⁺ 7.166 (1.07), 7.180 (1.76), 7.194 (0.87), 7.197 (0.82), 7.410 (1.80), 7.424 (1.69), 7.665 (16.00), 7.737 (1.30), 7.752 (2.11), 7.768
(1.83), 7.845 (2.28), 7.848 (2.39), 7.860 (1.82), 7.862 (1.73), 7.967 , 7.984 (1.29), 8.488 , 9.045 (5.88), 9.260 (1.85),
9.277 (1.82).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.190 (0.46), 2.062 (0.53), 2.068 (0.53), 2.076 , 2.090 , 2.096 (0.59), 2.213
(0.59), 2.223 , 2.230 (0.53), 2.362 (0.53), 2.519 (0.72), 2.522 (0.53), 2.636 (0.53), 3.460 (0.99), 3.473 (2.24), 3.487 (1.32),
3.780 (1.05), 3.790 (1.51), 3.799 (0.99), 4.230 (0.46), 4.246 (1.12), 4.253 (0.79), 4.263 (1.05), 4.268 (1.32), 4.275 (0.99), 4.281
593 1.18 min; MS s): m/z = (0.79), 4.288 (0.86), 5.091 (0.86), 5.101 (1.78), 5.111 (0.79), 5.286 (0.40), 5.297 (0.86), 5.314 , 6.786 (1.91), 6.789 (1.91),
493 [M+H]⁺ 6.803 (2.17), 6.805 (2.11), 6.906 (1.05), 6.908 (1.12), 6.921 (1.91), 6.923 (1.84), 6.935 (1.19), 6.938 (1.12), 7.153 (0.99), 7.156
(0.99), 7.170 , 7.184 , 7.352 (1.12), 7.359 (1.58), 7.374 (1.38), 7.537 (0.40), 7.648 (4.54), 7.651 (16.00), 7.654 (3.23),
7.659 (0.72), 7.693 (0.66), 7.754 (1.45), 7.769 (1.91), 7.771 (1.65), 7.786 (1.78), 7.877 (2.17), 7.880 (2.24), 7.891 , 7.894
(1.65), 8.359 (1.58), 8.362 (1.65), 8.377 (1.58), 8.869 (7.57), 9.225 (1.65), 9.242 (1.58).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.050 (0.60), 2.058 (0.65), 2.069 (0.70), 2.085 (0.97), 2.092 (0.83), 2.100 (0.60), 2.197
(0.65), 2.209 (0.88), 2.221 (0.86), 2.230 , 2.243 (0.56), 2.252 , 2.327 , 2.429 (16.00), 2.670 (0.44), 3.252 (0.90),
LC-MS (Method L1): Rt = 3.272 (2.69), 3.283 (5.98), 3.295 (7.10), 3.867 (4.41), 3.878 (7.26), 3.889 (4.17), 4.224 (0.46), 4.245 (1.41), 4.252 (1.14), 4.266
594 1.04 min; MS (ESIpos): m/z = (1.97), 4.275 (1.86), 4.292 (1.23), 4.311 (0.44), 5.243 (0.60), 5.257 (1.32), 5.276 , 5.290 (0.58), 6.788 (2.37), 6.809 (2.62),
505 [M+H]⁺ 6.914 (1.18), 6.916 (1.21), 6.933 (2.50), 6.951 (1.48), 7.153 (1.23), 7.156 (1.30), 7.174 (2.09), 7.192 (1.02), 7.195 (1.00), 7.376
(2.23), 7.394 (2.09), 7.685 (3.87), 7.702 (2.60), 7.723 , 7.741 (3.73), 7.802 (2.78), 7.805 (2.92), 7.820 (2.32), 7.823 ,
7.831 (3.66), 8.267 (2.32), 8.270 (2.39), 8.288 (2.20), 8.291 (2.13), 8.679 (8.26), 9.161 (2.34), 9.182 (2.30).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.75), 0.008 (0.48), 2.068 (0.58), 2.076 (0.47), 2.175 (0.42), 2.188 (0.51), 2.199
(0.49), 2.209 (0.45), 2.427 (9.40), 2.523 (1.01), 3.070 (16.00), 4.242 (0.87), 4.250 (0.80), 4.261 (1.24), 4.269 (1.37), 4.284 (0.72),
LC-MS (Method L1): Rt =
598 5.241 (0.79), 5.261 (0.75), 6.785 (1.39), 6.787 (1.45), 6.805 , 6.808 (1.54), 6.905 (0.76), 6.908 (0.76), 6.924 (1.51), 6.926
0.84 min; MS (ESIpos): m/z =
(1.43), 6.942 (0.91), 6.945 (0.84), 7.149 (0.77), 7.153 (0.79), 7.170 (1.19), 7.187 (0.59), 7.191 (0.55), 7.354 (1.25), 7.372 (1.15),
463 [M+H]⁺
7.632 (1.11), 7.650 (1.59), 7.654 (1.36), 7.672 (1.79), 7.680 (1.98), 7.737 (2.19), 7.739 (2.19), 7.762 (1.69), 7.766 (1.74), 7.780
, 7.783 (1.21), 7.828 (2.17), 8.220 (1.41), 8.223 (1.38), 8.241 (1.29), 8.244 (1.19), 8.613 (3.96), 9.082 (1.26), 9.103 (1.19).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.033 (0.49), 2.041 (0.52), 2.068 (0.76), 2.076 , 2.195 (0.64), 2.205 (0.65), 2.216
(0.57), 2.783 (16.00), 4.236 (1.14), 4.255 (1.65), 4.262 (1.79), 4.276 (1.08), 5.274 (0.47), 5.288 (1.06), 5.308 (1.05), 5.323 (0.49),
LC-MS (Method L1): Rt =
600 6.778 (2.06), 6.799 (2.26), 6.898 (1.00), 6.914 (2.08), 6.933 (1.25), 7.141 (1.01), 7.145 (1.08), 7.163 (1.66), 7.180 (0.81), 7.266
1.13 min; MS (ESIpos): m/z =
(1.14), 7.274 (1.67), 7.289 (1.20), 7.296 (1.69), 7.303 (1.14), 7.311 (0.77), 7.324 (1.88), 7.333 , 7.345 , 7.354 (2.23),
447 [M+H]⁺
7.584 (1.59), 7.597 , 7.606 (1.48), 7.619 (1.41), 7.717 (1.13), 7.720 (1.36), 7.734 , 7.738 (2.68), 7.753 (2.46), 7.773
(2.49), 7.791 (1.20), 8.293 (1.91), 8.297 (2.02), 8.314 (1.85), 8.318 (1.75), 8.738 , 9.072 (1.70), 9.093 (1.64).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.79), 0.008 (0.75), 1.270 ), 1.284 ), 2.388 (3.41), 2.401 (3.26), 2.523
(0.94), 3.065 (16.00), 4.232 (0.55), 4.245 (0.88), 4.255 (1.03), 4.270 (0.61), 5.224 (0.60), 5.243 (0.60), 5.754 (1.14), 6.774 (1.15),
LC-MS (Method L1): Rt =
601 6.795 (1.28), 6.885 , 6.903 (1.22), 6.922 (0.69), 7.096 (0.63), 7.102 (0.70), 7.123 (0.72), 7.128 , 7.135 (0.65), 7.139
1.01 min; MS (ESIpos): m/z =
(0.65), 7.156 (0.97), 7.178 , 7.331 (0.94), 7.350 (0.87), 7.411 (1.63), 7.416 (1.58), 7.550 (0.92), 7.565 (1.38), 7.601 (1.33),
528 [M+H]⁺
7.621 (1.46), 7.639 (0.85), 8.203 (1.13), 8.206 (1.22), 8.224 (1.07), 8.228 (1.06), 8.503 (1.65), 8.508 (1.79), 9.069 (1.03), 9.089
(1.02).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.43), 0.008 (2.43), 2.005 (1.56), 2.014 (1.65), 2.040 (2.57), 2.048 (2.04), 2.174
(2.09), 2.186 (2.16), 2.196 (2.02), 2.327 (0.80), 2.366 (0.85), 2.669 , 2.710 (0.83), 4.032 ), 4.207 (1.19), 4.227 (3.60),
LC-MS d L1): Rt = 4.235 (3.19), 4.246 (5.44), 4.254 (6.06), 4.270 , 4.287 (1.12), 4.938 (5.67), 4.956 (5.44), 5.217 (1.58), 5.231 , 5.251
602 0.72 min; MS (ESIpos): m/z = (3.28), 5.265 (1.40), 6.782 (6.82), 6.803 (7.51), 6.889 (3.33), 6.907 (6.61), 6.924 (4.02), 7.145 (3.35), 7.149 , 7.166 (5.42),
517 [M+H]⁺ 7.187 , 7.252 (2.89), 7.274 (2.87), 7.293 (2.71), 7.307 (6.36), 7.314 (5.28), 7.323 (7.92), 7.335 , 7.343 (2.32), 7.576
(3.70), 7.589 (4.11), 7.598 (3.56), 7.611 (3.28), 7.650 (2.62), 7.667 (7.67), 7.686 (13.61), 7.701 (2.46), 8.132 (3.35), 8.319 (5.26),
8.325 (4.96), 8.338 (4.77), 8.344 (4.55), 8.642 ), 8.708 (6.38), 9.213 (4.73), 9.234 (4.61).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.312 (7.07), 1.330 (16.00), 1.349 (7.30), 2.004 (0.55), 2.019 (1.26), 2.030 (1.33), 2.038
(1.35), 2.047 (1.47), 2.055 (2.00), 2.063 (1.72), 2.071 (1.26), 2.079 , 2.167 , 2.178 (1.39), 2.190 (1.60), 2.200 (1.63),
2.212 (1.45), 2.226 (1.03), 2.243 (0.57), 3.220 (1.71), 3.238 (4.68), 3.256 , 3.274 (1.72), 4.218 (0.71), 4.237 (3.03), 4.246
LC-MS (Method L1): Rt = (4.63), 4.256 (5.41), 4.263 (4.80), 4.272 (3.05), 4.291 , 5.278 (1.19), 5.293 , 5.312 (2.65), 5.328 (1.20), 6.775 (4.64),
603 1.20 min; MS (ESIpos): m/z = 6.795 , 6.897 (2.35), 6.900 (2.37), 6.916 (5.03), 6.934 (3.02), 7.139 (2.49), 7.143 (2.59), 7.160 (4.16), 7.178 (2.02), 7.181
461 [M+H]⁺ (1.96), 7.269 (2.88), 7.276 (4.09), 7.292 (3.57), 7.299 (6.76), 7.307 (2.30), 7.321 (4.84), 7.330 (5.77), 7.342 (3.34), 7.350 (5.55),
7.436 (0.55), 7.444 (0.73), 7.460 (2.03), 7.470 (1.50), 7.483 (0.63), 7.488 , 7.582 , 7.595 (3.67), 7.604 (3.36), 7.617
, 7.635 (0.42), 7.708 (2.96), 7.712 , 7.726 (6.55), 7.729 (6.17), 7.751 (5.10), 7.772 (5.47), 7.790 (2.85), 8.326 (4.37),
8.329 (4.51), 8.347 (4.16), 8.350 , 8.731 (14.58), 9.104 (4.09), 9.124 (3.99).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 , 0.008 (3.20), 2.011 (1.02), 2.020 (1.09), 2.046 (1.71), 2.054 (1.42), 2.167
(1.15), 2.178 (1.46), 2.189 (1.42), 2.200 (1.38), 2.327 (1.33), 2.366 (0.84), 2.523 (2.88), 2.669 (1.31), 2.710 (0.80), 3.998 (0.69),
4.038 (7.81), 4.078 (0.67), 4.210 (0.82), 4.230 (2.51), 4.238 (2.22), 4.249 (3.71), 4.258 (4.19), 4.272 , 4.927 (2.42), 4.940
LC-MS (Method L1): Rt = (4.59), 4.963 (4.55), 4.975 , 5.221 (1.04), 5.234 , 5.255 (2.20), 5.268 (0.95), 6.785 (4.62), 6.806 (4.88), 6.892 (2.31),
604 0.76 min; MS (ESIpos): m/z = 6.911 (4.53), 6.929 (2.71), 6.954 (0.51), 6.961 , 6.974 (0.51), 6.980 (0.47), 7.149 (2.60), 7.170 (3.77), 7.187 (1.84), 7.191
517 [M+H]⁺ (1.80), 7.200 (0.51), 7.313 , 7.320 (3.57), 7.330 (3.82), 7.342 (6.10), 7.365 (3.68), 7.486 (3.11), 7.493 (4.44), 7.502 (3.13),
7.508 (4.84), 7.522 (3.02), 7.529 (1.75), 7.533 (2.37), 7.540 (1.93), 7.544 (2.24), 7.551 (1.58), 7.650 (3.11), 7.667 (4.50), 7.671
(3.77), 7.688 (4.24), 7.776 (4.79), 7.791 (3.62), 8.133 , 8.323 (4.42), 8.326 (4.28), 8.344 , 8.347 , 8.661 (16.00),
8.710 (5.68), 9.208 , 9.228 (3.79), 10.355 (1.09).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.038 (0.55), 2.048 (0.59), 2.057 (0.62), 2.064 (0.65), 2.074 (0.89), 2.082 (0.75), 2.089
(0.55), 2.185 (0.61), 2.197 (0.74), 2.209 (0.73), 2.219 (0.68), 2.787 ), 4.239 (1.30), 4.248 (1.30), 4.258 (1.93), 4.265 (2.14),
LC-MS (Method L1): Rt =
605 4.279 (1.20), 5.277 (0.53), 5.292 , 5.311 (1.21), 5.326 (0.54), 6.780 (2.05), 6.800 (2.32), 6.901 (1.05), 6.920 (2.28), 6.938
1.16 min; MS (ESIpos): m/z =
(1.33), 7.148 (1.14), 7.166 (1.88), 7.183 (0.88), 7.333 (1.49), 7.343 (2.14), 7.356 (3.17), 7.378 (1.66), 7.505 (1.11), 7.511 (1.81),
447 [M+H]⁺
7.526 (2.33), 7.534 (1.46), 7.545 (1.03), 7.556 (1.03), 7.562 (0.70), 7.757 (1.11), 7.776 (2.36), 7.796 (2.24), 7.821 (2.68), 7.836
(1.38), 8.304 (2.03), 8.325 (1.92), 8.769 (6.05), 9.077 (1.92), 9.097 (1.89).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (3.63), 0.008 , 0.146 (0.46), 1.175 (0.42), 1.269 (14.91), 1.283
(16.00), 1.398 (0.57), 1.988 (0.79), 2.065 (0.44), 2.195 (0.48), 2.327 (0.69), 2.366 (0.79), 2.388 (4.14), 2.401 (3.93), 2.669 ,
LC-MS (Method L1): Rt =
607 2.709 (0.77), 3.283 (1.88), 3.876 (3.43), 4.231 (0.63), 4.252 (1.03), 4.279 (0.69), 5.238 (0.73), 5.258 (0.77), 5.754 (0.79), 6.776
1.26 min; MS s): m/z =
(1.43), 6.797 (1.53), 6.891 (0.65), 6.910 (1.35), 6.928 (0.81), 7.102 (0.85), 7.131 (0.91), 7.143 (0.77), 7.161 (1.15), 7.180 (0.54),
570 [M+H]⁺
7.353 (1.27), 7.370 (1.19), 7.418 (2.00), 7.424 (1.98), 7.590 , 7.607 (1.61), 7.652 (1.47), 7.673 (1.61), 7.690 (1.01), 8.250
(1.37), 8.267 (1.23), 8.564 (1.86), 8.572 (2.04), 9.148 (1.21), 9.168 (1.17).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.94), 0.008 (2.84), 2.026 (1.36), 2.034 (1.46), 2.045 (1.57), 2.061 (2.14), 2.068
(1.86), 2.076 (1.39), 2.183 (1.38), 2.196 (1.99), 2.207 (1.94), 2.217 (1.90), 2.230 (1.30), 2.252 , 2.327 (0.62), 2.366 ,
2.669 (0.72), 2.710 , 3.254 (1.39), 3.294 (9.84), 3.879 (15.30), 4.202 (0.81), 4.209 (1.06), 4.230 (3.23), 4.238 (2.57), 4.251
LC-MS (Method L1): Rt =
608 (4.00), 4.263 (3.86), 4.279 (2.90), 4.298 (1.09), 4.306 (0.75), 5.239 (2.49), 5.253 (2.51), 5.754 (2.12), 6.778 (5.59), 6.798 (6.16),
1.12 min; MS (ESIpos): m/z =
6.895 (2.42), 6.913 (5.26), 6.932 (3.13), 7.142 (2.78), 7.146 (3.03), 7.164 (4.72), 7.181 (2.33), 7.185 (2.30), 7.354 (5.00), 7.372
559 [M+H]⁺
(4.65), 7.706 (2.07), 7.724 (7.43), 7.737 (7.97), 7.742 (16.00), 7.754 (2.22), 7.888 (2.90), 7.892 (3.07), 7.917 (3.30), 7.921 (3.26),
8.052 (0.43), 8.297 (0.70), 8.310 (4.84), 8.316 (4.51), 8.328 (4.39), 8.334 (4.48), 8.342 (7.65), 8.347 (7.65), 8.604 (10.28), 8.706
(0.70), 9.165 (3.36), 9.184 (3.22).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.20), 0.008 (1.22), 2.044 (0.43), 2.185 (0.41), 2.195 (0.40), 3.080 (16.00), 4.227
LC-MS d L1): Rt = (0.67), 4.246 (1.04), 4.254 (1.15), 4.269 (0.62), 5.235 (0.51), 5.754 (3.68), 6.776 , 6.796 (1.47), 6.887 (0.57), 6.905 (1.24),
624 0.97 min; MS (ESIpos): m/z = 6.924 (0.75), 7.142 (0.65), 7.159 (1.03), 7.180 (0.52), 7.331 (0.80), 7.350 (0.73), 7.652 (0.64), 7.670 (1.58), 7.690 (2.46), 7.697
517 [M+H]⁺ (1.81), 7.710 , 7.882 (0.81), 7.908 (0.84), 8.278 (1.17), 8.283 (1.16), 8.298 (1.11), 8.303 (1.04), 8.333 (2.42), 8.337 (2.34),
8.531 (4.40), 9.078 (0.75), 9.098 (0.70).
¹H-NMR (400 MHz, 6) δ [ppm]: 1.308 (7.60), 1.326 (16.00), 1.345 (7.79), 2.061 (2.32), 2.203 (2.13), 2.327 (0.52), 2.670
LC-MS (Method L1): Rt = (0.63), 3.243 (6.84), 3.262 (6.74), 3.280 , 4.260 (6.66), 5.298 (3.26), 5.314 (3.18), 6.777 (5.35), 6.797 (5.91), 6.903 (2.66),
628 1.22 min; MS (ESIpos): m/z = 6.921 (5.56), 6.940 , 7.145 (3.07), 7.163 (4.94), 7.182 , 7.339 (6.05), 7.354 (9.10), 7.375 (3.63), 7.511 (5.22), 7.526
461 [M+H]⁺ (7.31), 7.550 (2.82), 7.756 (2.29), 7.774 (5.35), 7.794 (5.18), 7.810 (7.32), 7.827 (3.38), 8.338 (4.91), 8.358 (4.55), 8.763 ),
9.106 (4.65), 9.126 (4.63).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.091 (0.41), 1.235 (1.08), 1.259 (0.68), 1.299 (0.43), 2.066 (16.00), 2.100 (0.88), 2.214
(0.78), 2.226 (0.77), 2.235 (0.72), 2.268 (1.76), 2.328 (0.58), 2.669 (0.60), 2.750 ), 4.208 (0.55), 4.228 (1.45), 4.249 (1.16),
LC-MS Method L4): Rt = 3.90
631 4.258 , 4.269 (1.15), 4.286 (1.02), 5.143 , 5.250 (0.77), 5.282 (1.13), 5.301 (1.12), 6.790 (2.18), 6.810 (2.37), 6.917
min; MS (ESIpos): m/z = 534
(1.17), 6.935 (2.21), 6.953 (1.25), 7.157 (1.18), 7.177 (1.96), 7.195 (0.95), 7.381 (1.90), 7.400 (1.94), 7.654 (11.00), 7.658 (5.85),
[M+H]+
7.723 (1.28), 7.741 (1.94), 7.762 (1.68), 7.882 (2.40), 7.898 (1.87), 8.251 (2.03), 8.270 (1.81), 8.917 (0.60), 8.948 (6.71), 9.278
(1.90), 9.298 (1.82).
¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.88), 2.089 (0.52), 2.238 (16.00), 2.669 (1.25), 3.317 (2.60), 3.422 (1.31), 3.438
LC-MS (Method L1): Rt = , 3.460 (1.08), 4.250 (0.72), 4.269 (1.14), 4.278 (1.25), 4.293 , 5.290 (0.69), 5.310 (0.69), 5.754 , 6.792 (1.36),
643 0.91 min; MS (ESIpos): m/z = 6.812 (1.48), 6.900 (0.70), 6.919 (1.32), 6.937 (0.81), 7.158 (0.66), 7.175 (1.10), 7.193 (0.52), 7.366 (1.17), 7.383 (1.06), 7.654
520 [M+H]⁺ (11.60), 7.771 (0.81), 7.789 (1.28), 7.810 (1.17), 7.885 (1.61), 7.900 (1.17), 8.145 (3.08), 8.283 (1.19), 8.302 (1.09), 8.871 (4.70),
9.325 (1.18), 9.345 (1.13).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 2.039 (0.59), 2.046 (0.63), 2.054 (0.65), 2.059 (0.66), 2.067 (0.88), 2.072 (1.06), 2.080
(0.51), 2.186 (0.59), 2.196 (0.76), 2.205 (0.79), 2.212 (0.72), 2.224 (0.47), 2.229 (0.41), 2.335 (10.23), 2.779 (16.00), 4.223 (0.40),
LC-MS d L1): Rt = 4.239 (1.31), 4.246 (1.16), 4.254 (2.05), 4.261 (2.12), 4.274 (1.15), 5.280 (0.52), 5.292 (1.13), 5.307 (1.10), 5.319 (0.50), 6.780
645 1.18 min; MS (ESIpos): m/z = (2.18), 6.795 (2.35), 6.900 , 6.901 (1.08), 6.915 (2.22), 6.929 (1.29), 6.931 (1.20), 7.145 (1.11), 7.147 (1.14), 7.161 (1.96),
443 [M+H]⁺ 7.176 (3.03), 7.178 (3.05), 7.239 , 7.242 (1.36), 7.255 (1.82), 7.258 (1.60), 7.338 (1.91), 7.353 (1.78), 7.411 (2.22), 7.427
(1.81), 7.663 (1.80), 7.666 (1.84), 7.677 (2.62), 7.680 (2.49), 7.731 , 7.746 (1.86), 7.748 (2.32), 7.762 (1.51), 8.260 (2.18),
8.262 (2.20), 8.277 (2.05), 8.279 (1.93), 8.716 (5.69), 9.065 (1.86), 9.082 (1.80).
LC-MS (Method L1): Rt = ¹H-NMR (500 MHz, 6): δ [ppm] = 9.10 (br d, 1H), 8.71 (s, 1H), 8.30 (d, 1H), 7.75 (t, 1H), 7.66 (d, 1H), 7.42 (d, 1H), 7.34 (d,
646 1.24 min; MS (ESIpos): m/z = 1H), 7.25 (dd, 1H), 7.19-7.14 (m, 2H), 6.92 (t, 1H), 6.78 (d, 1H), 5.33-5.28 (m, 1H), 4.29-4.22 (m, 2H), 3.36 (br s, 1H), .20 (m,
457 [M+H]⁺ 2H), 2.33 (s, 3H), 2.27-2.16 (m, 1H), 2.05 (ddd, 1H), 1.33 (t, 3H)
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.160 (0.41), 1.175 (1.01), 1.189 (0.61), 1.235 (0.61), 1.397 (2.84), 1.988 , 2.004
(2.63), 2.085 , 2.155 (2.63), 2.165 (2.63), 2.172 (2.43), 2.362 (1.01), 2.432 (3.04), 2.636 (0.81), 3.375 (0.61), 3.904 (2.23),
4.023 (0.61), 4.037 (0.61), 4.219 (4.46), 4.242 (6.08), 4.249 (6.08), 4.256 (5.47), 4.263 , 4.278 (3.24), 5.233 (3.44), 5.247
LC-MS (Method L1): Rt =
653 (3.44), 5.752 (2.23), 5.856 (5.06), 6.764 (9.32), 6.766 , 6.780 (10.33), 6.782 (10.33), 6.888 (2.84), 6.902 (5.87), 6.918 (3.24),
1.20 min; MS (ESIpos): m/z =
7.138 , 7.141 (4.46), 7.155 , 7.169 (3.65), 7.334 (6.08), 7.349 (6.48), 7.375 , 7.441 (3.85), 7.447 (4.46), 7.457
531 [M+H]⁺
(6.48), 7.463 (6.89), 7.472 (3.24), 7.478 (3.44), 7.708 (11.75), 7.711 (11.75), 7.724 (15.39), 7.728 (16.00), 7.738 (14.38), 7.742
), 7.751 (12.76), 7.767 (12.35), 7.781 (5.67), 8.059 (9.11), 8.062 (9.11), 8.075 (7.90), 8.078 (7.49), 8.819 ), 8.827
(13.57), 8.933 (5.27), 8.949 (4.25).
¹H-NMR (500 MHz, CHLOROFORM-d) δ [ppm]: 0.006 (1.86), 1.222 (0.43), 1.255 (1.78), 1.549 (4.29), 2.005 (0.63), 2.009 (0.62),
2.025 (0.45), 2.034 (0.78), 2.038 (0.71), 2.170 (2.80), 2.175 (0.46), 2.270 (0.45), 2.281 (0.47), 2.285 , 2.292 (0.67), 2.302
(0.60), 3.056 (15.99), 3.423 (4.44), 3.459 (16.00), 3.534 (4.30), 4.074 (0.85), 4.079 (0.78), 4.097 (1.34), 4.101 (1.18), 4.119 (0.75),
4.124 (0.61), 4.294 (0.63), 4.302 (1.10), 4.311 (0.65), 4.317 (0.54), 4.325 (0.84), 4.333 (0.42), 5.348 (0.49), 5.358 (0.84), 5.367
LC-MS (Method L1): Rt =
654 (0.90), 5.375 (0.81), 5.385 (0.43), 6.731 (0.89), 6.733 (0.88), 6.746 (1.75), 6.760 (1.01), 6.762 , 6.823 (2.09), 6.840 (2.28),
1.17 min; MS (ESIpos): m/z =
6.922 (0.50), 7.080 (1.31), 7.092 (1.92), 7.099 (1.43), 7.105 (1.69), 7.178 (1.13), 7.181 (0.97), 7.195 (1.67), 7.209 (1.14), 7.212
587 [M+H]⁺
(1.11), 7.220 (5.56), 7.282 (0.46), 7.376 (1.54), 7.423 , 7.427 (3.79), 7.430 (1.97), 7.526 (2.61), 7.532 (7.59), 7.536 ,
7.590 (1.03), 7.604 (1.42), 7.607 (1.87), 7.621 (2.19), 7.645 (2.30), 7.648 (2.42), 7.656 (0.71), 7.662 (1.26), 7.665 (1.03), 7.736
(2.01), 7.739 (1.84), 7.749 , 7.752 (1.94), 7.764 , 7.766 (0.43), 7.818 (0.54), 7.821 (0.50), 7.835 (0.46), 9.108 (1.57),
9.133 (5.65).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.311 (7.80), 1.327 (16.00), 1.341 (7.58), 2.033 (1.52), 2.041 (1.61), 2.047 (1.74), 2.054
(1.78), 2.061 , 2.067 (1.87), 2.198 (1.93), 2.207 (1.91), 2.215 (1.83), 3.235 (2.53), 3.250 (6.81), 3.265 (6.83), 3.279 (3.01),
LC-MS (Method L1): Rt =
655 4.227 , 4.244 (3.29), 4.258 (5.03), 4.264 , 4.276 (3.07), 4.290 (0.97), 5.288 , 5.300 (2.99), 5.315 (2.94), 5.327
1.18 min; MS (ESIpos): m/z =
(1.35), 6.781 (5.15), 6.797 (5.61), 6.909 (2.60), 6.924 (5.33), 6.939 , 7.151 (2.73), 7.165 (4.53), 7.180 (2.23), 7.228 (2.53),
463 [M+H]⁺
7.236 (2.62), 7.345 (4.77), 7.360 (4.45), 7.601 (2.02), 7.607 (2.10), 7.614 (2.02), 7.782 (2.66), 7.797 , 7.813 (4.47), 7.845
(6.38), 7.857 (3.89), 8.374 (4.77), 8.389 (4.49), 8.789 (13.74), 9.121 (4.49), 9.137 (4.40).
¹H-NMR (500 MHz, 6) δ [ppm]: 1.319 (6.59), 1.334 (14.59), 1.349 (6.59), 1.869 (13.65), 2.031 (1.41), 2.052 (1.88), 2.059
(1.41), 2.200 (1.41), 2.292 (16.00), 2.362 (1.41), 2.636 (1.88), 3.236 (3.29), 3.251 (3.76), 3.375 (0.94), 3.418 , 4.238 (2.35),
LC-MS (Method L1): Rt =
676 4.253 , 4.259 (3.76), 4.271 (2.35), 5.282 (0.94), 5.295 , 5.310 (1.88), 6.778 (4.24), 6.793 (4.71), 6.901 (1.88), 6.916
1.27 min; MS (ESIpos): m/z =
(4.24), 6.931 (2.35), 6.962 (5.18), 7.099 (2.35), 7.114 (4.24), 7.147 (2.35), 7.157 (5.18), 7.171 (3.29), 7.330 (3.29), 7.345 (2.82),
437 [M+H]⁺
7.590 (4.24), 7.592 , 7.604 (5.18), 7.606 (4.71), 7.712 (4.24), 7.726 (3.76), 7.729 (4.24), 7.743 , 8.252 , 8.254
(4.24), 8.269 (3.76), 8.689 (13.65), 9.070 (2.35), 9.088 (1.88).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.120 (0.78), -0.007 (5.46), 0.007 (3.90), 0.117 (0.39), 1.520 (12.10), 1.523 (11.71), 1.534
(12.49), 1.538 (11.71), 1.548 (14.05), 1.563 ), 1.866 (16.00), 1.884 ), 2.036 (1.56), 2.176 (1.56), 2.281 (16.00), 2.294
LC-MS (Method L1): Rt = (16.00), 2.362 (1.95), 2.636 (1.56), 3.363 (1.17), 3.853 (1.95), 4.219 (2.34), 4.245 (2.34), 4.252 (2.73), 4.259 (2.34), 4.266 (2.34),
684 1.28 min; MS (ESIpos): m/z = 5.248 (2.73), 5.264 (2.34), 6.771 , 6.786 (5.85), 6.892 , 6.906 (5.46), 6.924 , 6.948 (3.51), 7.131 (3.51), 7.138
469 [M+H]⁺ (3.12), 7.142 (3.90), 7.147 (5.07), 7.169 (2.34), 7.206 , 7.215 , 7.221 (2.73), 7.230 , 7.318 (3.90), 7.333 (3.51),
7.642 (3.51), 7.660 (5.46), 7.678 (3.51), 8.473 (3.12), 8.484 (3.51), 8.492 (3.51), 8.504 (3.12), 8.640 (11.32), 8.643 (10.54), 9.075
(2.73), 9.082 (2.73), 9.092 (2.73), 9.098 (2.73).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (1.56), 0.006 (1.12), 1.861 (5.14), 2.038 (0.49), 2.044 (0.51), 2.052 (0.51), 2.058
(0.54), 2.066 (0.72), 2.072 (0.58), 2.079 (0.42), 2.185 (0.47), 2.195 (0.63), 2.205 (0.63), 2.212 (0.58), 2.297 , 2.778 (16.00),
LC-MS (Method L1): Rt = 4.237 (0.98), 4.243 (0.79), 4.254 (1.52), 4.261 (1.45), 4.268 (0.93), 4.275 , 5.278 (0.42), 5.290 (0.91), 5.306 (0.89), 5.317
685 1.18 min; MS (ESIpos): m/z = (0.40), 6.779 (1.89), 6.781 (1.96), 6.796 (2.10), 6.798 (2.06), 6.899 (0.84), 6.915 (1.68), 6.929 (0.96), 6.965 , 7.101 (1.03),
423 [M+H]⁺ 7.116 (1.78), 7.145 (1.00), 7.148 (1.10), 7.157 (2.34), 7.172 (1.31), 7.179 , 7.335 (1.31), 7.350 (1.19), 7.599 (1.92), 7.602
(1.92), 7.613 (2.38), 7.616 (2.27), 7.714 (1.96), 7.728 (1.78), 7.731 (2.15), 7.745 (1.64), 8.219 (2.08), 8.222 (2.13), 8.236 (1.96),
8.239 (1.82), 8.701 (6.47), 9.043 (1.66), 9.060 (1.66).
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 , 2.043 (0.47), 2.048 (0.60), 2.053 (0.96), 2.058 (1.04), 2.065 , 2.069
, 2.077 (1.37), 2.081 , 2.087 (2.11), 2.092 , 2.193 (0.58), 2.199 (0.86), 2.202 (0.81), 2.207 (1.32), 2.213 (0.97),
2.216 (1.31), 2.221 , 2.230 (0.99), 2.236 (0.64), 2.239 (0.62), 2.244 (0.46), 2.793 (0.55), 3.345 (8.00), 4.220 (0.71), 4.225
(0.87), 4.234 (0.90), 4.239 (2.32), 4.244 (1.61), 4.253 (1.77), 4.258 (1.47), 4.268 (1.42), 4.273 (1.80), 4.279 (1.58), 4.285 (1.91),
LC-MS (Method L1): Rt =
686 4.292 , 4.298 (0.84), 4.303 (0.65), 5.037 (16.00), 5.287 (0.91), 5.297 (1.95), 5.310 (1.96), 5.320 (0.92), 6.790 (3.66), 6.791
1.14 min; MS (ESIpos): m/z =
(3.76), 6.803 (4.00), 6.804 (3.99), 6.917 (1.85), 6.918 (1.84), 6.929 (3.75), 6.931 (3.68), 6.942 (2.14), 6.943 , 7.159 (1.78),
479 [M+H]⁺
7.161 (1.80), 7.173 (3.01), 7.184 (1.56), 7.187 , 7.259 (1.51), 7.267 (1.49), 7.274 (1.49), 7.376 (3.08), 7.388 , 7.609
(0.49), 7.614 (0.63), 7.619 (0.75), 7.624 (1.18), 7.628 , 7.633 (1.23), 7.638 (1.18), 7.642 (1.18), 7.646 (0.74), 7.651 (0.65),
7.657 (0.56), 7.800 (2.66), 7.812 (3.85), 7.814 (3.18), 7.826 (3.61), 7.873 (4.17), 7.875 (4.29), 7.885 (3.06), 7.887 (2.94), 8.416
(3.61), 8.418 (3.65), 8.430 (3.48), 8.432 (3.27), 8.890 (12.74), 9.184 (3.52), 9.197 (3.43).
¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.306 (6.83), 1.321 (15.00), 1.336 (6.50), 2.030 (0.50), 2.043 (1.17), 2.050 (1.17), 2.058
(1.17), 2.064 (1.33), 2.072 (6.00), 2.078 (1.33), 2.084 , 2.091 (0.67), 2.187 (0.67), 2.194 (1.17), 2.205 (1.33), 2.214 (1.33),
2.222 (1.17), 2.234 (0.83), 2.248 (0.50), 2.363 (0.50), 2.637 (0.50), 3.235 (1.83), 3.250 (5.50), 3.265 (5.67), 3.280 (2.50), 3.352
(3.17), 3.358 , 3.365 (1.17), 3.376 (0.83), 3.429 (0.50), 4.236 (0.83), 4.251 (2.67), 4.261 (2.83), 4.266 (3.50), 4.270 (3.67),
LC-MS (Method L1): Rt =
687 4.274 (3.67), 4.282 (2.33), 4.297 , 5.298 (1.00), 5.310 (2.17), 5.326 (2.17), 5.337 (1.00), 6.786 (4.17), 6.788 (4.33), 6.802
1.24 min; MS (ESIpos): m/z =
(4.67), 6.804 (4.50), 6.916 (2.17), 6.918 (2.17), 6.931 (4.33), 6.933 , 6.945 (2.67), 6.948 (2.50), 7.153 (2.17), 7.156 (2.17),
445 [M+H]⁺
7.170 (3.50), 7.184 (1.83), 7.187 (1.67), 7.257 , 7.261 (1.67), 7.266 (1.33), 7.276 (1.67), 7.280 , 7.285 (2.33), 7.294
(1.00), 7.299 (1.67), 7.304 (1.17), 7.333 (4.67), 7.337 (5.17), 7.350 (8.83), 7.364 (3.83), 7.757 (3.17), 7.771 (4.50), 7.774 (3.83),
7.788 (4.17), 7.868 (5.17), 7.871 (5.17), 7.882 , 7.885 (3.67), 8.316 (4.00), 8.318 (4.00), 8.333 (3.83), 8.335 (3.50), 8.828
(16.00), 9.103 (3.67), 9.120 (3.67).
LC-MS (Method L1): Rt = 1H-NMR (600 MHz, 6): d [ppm] = 9.15 (d, 1H), 8.78 (s, 1H), 8.37 (dd, 1H), 7.83 (d, 1H), 7.80 (d, 1H), 7.47-7.40 (m, 1H),
688 1.21 min; MS (ESIpos): m/z = 7.37-7.31 (m, 2H), 7.17 (t, 1H), 6.93 (t, 1H), 6.79 (d, 1H), 5.33-5.29 (m, 1H), 4.30-4.22 (m, 2H), 3.33-3.20 (m, 2H), 2.24-2.17 (m,
463 [M+H]⁺ 1H), 2.09-2.01 (m, 1H), 1.33 (t, 3H)
¹H-NMR (600 MHz, DMSO-d6) δ [ppm]: 2.063 (0.84), 2.069 , 2.074 (0.95), 2.081 (1.08), 2.086 (1.02), 2.209 (1.01), 2.217
(1.02), 2.223 (0.98), 2.231 (0.76), 2.790 (16.00), 4.237 (0.59), 4.250 (1.61), 4.255 (1.39), 4.269 , 4.275 (1.71), 4.280 (1.46),
LC-MS (Method L1): Rt =
695 4.286 (1.51), 4.299 (0.61), 5.297 (0.70), 5.307 (1.52), 5.319 (1.53), 5.329 , 5.762 (2.23), 6.793 (2.52), 6.807 (2.70), 6.919
1.17 min; MS (ESIpos): m/z =
(1.29), 6.932 (2.60), 6.944 (1.48), 7.162 (1.32), 7.174 (2.26), 7.187 (1.14), 7.280 (0.92), 7.295 (1.78), 7.311 (0.98), 7.349 (3.64),
431 [M+H]⁺
7.358 (5.29), 7.369 , 7.762 (1.45), 7.774 (2.50), 7.788 (1.76), 7.885 (2.83), 7.897 (2.35), 8.285 (2.53), 8.299 , 8.841
(5.87), 9.107 (2.25), 9.120 (2.21).
TABLE 3a-3e: Intermediates
TABLE 3a
1Q-OEt
r e m b R3 R4 R5 R6 Q
1Q-1 H H H H 3,5-dichlorophenyl
1Q-2 H H H H 2,3,5-trichlorophenyl
1Q-3 H H H H 2,3-dichlorophenyl
1Q-4 H H H H 3,5-difluorophenyl
1Q-5 H H H H trifluorophenyl
1Q-6 H H H H 2,3-difluorophenyl
1Q-7 H F H H 3,5-dichlorophenyl
1Q-8 H F H H 2,3,5-trichlorophenyl
1Q-9 H F H H 2,3-dichlorophenyl
1Q-10 H F H H 3,5-difluorophenyl
1Q-11 H F H H 2,3,5-trifluorophenyl
1Q-12 H F H H 2,3-difluorophenyl
1Q-13 H H H H 3,5-dimethylphenyl
TABLE 3b
1U-OEt
r b e
R2 R3 R4 R5 R6 Q
u m N
1U-1 dimethylamino H H H H chlorophenyl
1U-2 dimethylamino H H H H 2,3,5-trichlorophenyl
1U-3 dimethylamino H H H H chlorophenyl
1U-4 dimethylamino H H H H 3,5-difluorophenyl
1U-5 dimethylamino H H H H 2,3,5-trifluorophenyl
1U-6 dimethylamino H H H H 2,3-difluorophenyl
1U-7 dimethylamino H F H H 3,5-dichlorophenyl
1U-8 dimethylamino H F H H 2,3,5-trichlorophenyl
1U-9 dimethylamino H F H H 2,3-dichlorophenyl
1U-10 dimethylamino H F H H 3,5-difluorophenyl
1U-11 dimethylamino H F H H 2,3,5-trifluorophenyl
1U-12 dimethylamino H F H H 2,3-difluorophenyl
1U-13 morpholinyl H H H H 3,5-dichlorophenyl
1U-14 morpholinyl H H H H 2,3,5-trichlorophenyl
1U-15 morpholinyl H H H H 2,3-dichlorophenyl
1U-16 morpholinyl H H H H 3,5-difluorophenyl
1U-17 morpholinyl H H H H trifluorophenyl
1U-18 morpholinyl H H H H 2,3-difluorophenyl
1U-19 morpholinyl H F H H 3,5-dichlorophenyl
1U-20 morpholinyl H F H H 2,3,5-trichlorophenyl
1U-21 morpholinyl H F H H chlorophenyl
1U-22 morpholinyl H F H H 3,5-difluorophenyl
1U-23 morpholinyl H F H H 2,3,5-trifluorophenyl
1U-24 morpholinyl H F H H 2,3-difluorophenyl
TABLE 3c
r b e
R3 R4 R5 R6 Q
u m N
1R-1 H H H H 3,5-dichlorophenyl
1R-2 H H H H 2,3,5-trichlorophenyl
1R-3 H H H H 2,3-dichlorophenyl
1R-4 H H H H 3,5-difluorophenyl
1R-5 H H H H 2,3,5-trifluorophenyl
1R-6 H H H H 2,3-difluorophenyl
1R-7 H F H H 3,5-dichlorophenyl
1R-8 H F H H trichlorophenyl
1R-9 H F H H 2,3-dichlorophenyl
1R-10 H F H H 3,5-difluorophenyl
1R-11 H F H H 2,3,5-trifluorophenyl
1R-12 H F H H 2,3-difluorophenyl
1R-13 H H H H 3,5-dimethylphenyl
TABLE 3d
r e b R2 R3 R4 R5 R6 Q
u m N
1W-1 dimethylamino H H H H 3,5-dichlorophenyl
1W-2 dimethylamino H H H H 2,3,5-trichlorophenyl
1W-3 dimethylamino H H H H chlorophenyl
1W-4 dimethylamino H H H H fluorophenyl
1W-5 dimethylamino H H H H trifluorophenyl
1W-6 dimethylamino H H H H 2,3-difluorophenyl
1W-7 dimethylamino H F H H 3,5-dichlorophenyl
1W-8 dimethylamino H F H H 2,3,5-trichlorophenyl
1W-9 dimethylamino H F H H 2,3-dichlorophenyl
1W-10 dimethylamino H F H H 3,5-difluorophenyl
1W-11 dimethylamino H F H H 2,3,5-trifluorophenyl
1W-12 dimethylamino H F H H 2,3-difluorophenyl
1W-13 morpholinyl H H H H 3,5-dichlorophenyl
1W-14 morpholinyl H H H H 2,3,5-trichlorophenyl
1W-15 morpholinyl H H H H 2,3-dichlorophenyl
1W-16 morpholinyl H H H H 3,5-difluorophenyl
1W-17 morpholinyl H H H H trifluorophenyl
1W-18 morpholinyl H H H H 2,3-difluorophenyl
1W-19 morpholinyl H F H H 3,5-dichlorophenyl
1W-20 morpholinyl H F H H 2,3,5-trichlorophenyl
1W-21 linyl H F H H 2,3-dichlorophenyl
1W-22 morpholinyl H F H H 3,5-difluorophenyl
1W-23 linyl H F H H 2,3,5-trifluorophenyl
1W-24 morpholinyl H F H H 2,3-difluorophenyl
TABLE 3e
1T-Br
R1 R2 R3 R4 R5 R6 A
m b u N
1T-1 H dimethylamino H H H H (4S)-3,4-dihydro-2H-chromenyl
1T-2 H dimethylamino H H H H (1S)-2,3-dihydro-1H-indenyl
1T-3 H dimethylamino H F H H (4S)-3,4-dihydro-2H-chromenyl
1T-4 H dimethylamino H F H H (1S)-2,3-dihydro-1H-indenyl
1T-5 H morpholinyl H H H H (4S)-3,4-dihydro-2H-chromenyl
1T-6 H morpholinyl H H H H (1S)-2,3-dihydro-1H-indenyl
1T-7 H morpholinyl H F H H (4S)-3,4-dihydro-2H-chromenyl
1T-8 H morpholinyl H F H H (1S)-2,3-dihydro-1H-indenyl
Table 4: LC-MS and NMR or NMR Peaklist of ediates
logP LC-MS
Example N° NMR or NMR Peaklist
(Method L0) [a] d L2-L5)
1H-NMR(400.0 MHz, d6-DMSO): δ= 9.100(11.2);8.521(2.9);8.516(3.1);8.501(3.1);8.496(3.3);7.983(1.5);7.965(4.5);7.945(9.0)
1-Q3 5,19 ;7.941(6.3);7.928(1.8);7.756(2.9);7.752(3.4);7.736(3.6);7.732(3.8);7.504(2.2);7.485(5.2);7.465(3.5);7.434(4.1);7.431(4.7);7.4
(2.5);7.412(2.4);4.454(2.4);4.436(7.3);4.418(7.3);4.400(2.5);3.321(80.5);2.891(0.5);2.731(0.5);2.672(1.1);2.502(195.0);2.3
29(1.1);2.075(1.2);1.387(7.9);1.369(16.0);1.351(7.7);0.146(0.4);0.000(90.1);-0.150(0.5)
LC-MS (Method L1): Rt = 1.43
1Q-13 1H-NMR (400MHz, DMSO-d6): δ [ppm] = 9.13 (s, 1H), 8.42 (dd, 1H), 7.87 - 7.96 (m, 2H), 7.20 (s, 2H), 7.07 (s, 1H), 4.44 (q,
min; MS (ESIpos): m/z = 340
2H), 2.35 (s, 6H), 1.38 (t, 3H).
[M+H]+
1U-5 2,40 1H-NMR (400MHz, DMSO-d6): δ [ppm] = 8.73 (s, 1H), 8.35 (d, 1H), 7.83 (d, 1H), 7.72 – 7.69 (t, 1H), 7.61 – 7.58 (m, 1H),
7.24 – 7.22 (m, 1H), 4.41 – 4.35 (q, 2H), 3.09 (s, 6H), 1.36 (t, 3H).
1H-NMR(400.0 MHz, d6-DMSO): δ=8.857(1.9);8.703(3.6);8.425(0.7);8.409(0.8);8.401(0.8);8.386(0.7);8.305(0.4);8.290(0.5);8
.281(0.5);8.266(0.5);7.967(2.0);7.961(2.1);7.687(0.8);7.664(1.2);7.647(0.5);7.641(0.8);7.626(0.5);7.623(0.5);7.603(0.4);7.58
1U-8 4,57 ;7.580(2.0);5.758(5.2);4.420(0.4);4.403(1.3);4.391(0.8);4.385(1.4);4.374(2.3);4.367(0.6);4.356(2.3);4.338(0.7);3.326(1
0.9);3.094(16.0);3.071(9.4);2.514(7.9);2.509(15.9);2.505(21.1);2.500(15.4);2.496(7.6);1.382(1.4);1.364(3.0);1.357(2.6);1.346
(1.6);1.339(5.3);1.321(2.4);1.299(0.5);1.269(0.5);0.008(0.8);0.000(20.5);-0.008(0.9)
1H-NMR(400.0 MHz, d6-DMSO): δ= 8.730(3.6);8.348(1.0);8.345(0.9);8.327(1.1);7.828(0.9);7.813(1.3);7.725(1.0);7.707(1.0);
1U-11 2,40 7.704(1.0);7.686(0.7);7.607(0.4);7.601(0.4);7.594(0.4);7.586(0.4);7.581(0.4);7.243(0.5);7.233(0.4);7.221(0.5);4.407(0.8);4.3
90(2.4);4.372(2.4);4.354(0.8);3.327(5.3);3.089(16.0);2.509(10.6);2.505(13.3);2.501(9.7);1.397(10.3);1.372(2.5);1.355(5.2);1.
337(2.4);0.008(0.5);0.000(10.8);-0.009(0.5)
1H-NMR(400.0 MHz, d6-DMSO): δ= 8.829(5.1);8.335(1.1);8.332(1.2);8.314(1.2);8.311(1.2);7.900(1.1);7.897(1.2);7.882(1.5);
1U-13 5,19 LC-MS (Method 1): Rt = 2.36 7.879(1.4);7.759(1.2);7.740(1.3);7.737(1.4);7.719(0.9);7.646(16.0);4.441(0.9);4.423(3.1);4.405(3.1);4.388(1.0);3.896(2.6);3.
min; m/z = 431/433 (M+H)+ 885(3.5);3.874(2.7);3.320(6.3);3.273(2.7);3.262(3.4);3.251(2.4);2.525(0.6);2.511(14.8);2.507(30.3);2.503(39.9);2.498(28.5);
2.494(13.8);1.397(6.5);1.376(7.1);1.359(3.3);0.000(3.3)
1H-NMR(400.0 MHz, d6-DMSO): δ= 8.726(8.4);8.345(1.6);8.337(1.6);8.327(1.7);8.320(1.8);7.768(0.8);7.751(3.0);7.740(3.4);
7.733(6.7);7.723(1.0);7.713(2.2);7.709(2.3);7.693(2.5);7.689(2.5);7.468(1.8);7.448(3.6);7.429(2.2);7.369(2.7);7.366(2.8);7.3
1U-15 3,90 LC-MS (Method 1): Rt = 2.17
50(1.9);7.347(1.7);4.427(1.5);4.409(4.8);4.391(4.9);4.373(1.6);3.899(4.4);3.887(8.0);3.876(4.6);3.321(37.8);3.293(2.5);3.282
min; m/z = 431/433 (M+H)+
3.270(5.3);3.259(2.2);3.239(0.6);2.671(0.4);2.506(61.9);2.502(81.2);2.498(60.0);2.329(0.5);1.397(16.0);1.380(5.5);1.36
2(11.1);1.344(5.2);0.008(2.2);0.000(45.4)
1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.29), 0.008 , 1.760 (0.44), 2.329 (0.64), 2.367 (0.44), 2.524 (2.38),
LC-MS (Method L1): Rt = 1.16
1R-1 2.671 (0.63), 2.711 (0.43), 3.601 (0.50), 7.654 (1.72), 7.660 (4.30), 7.664 , 7.669 (16.00), 7.673 (7.64), 7.804 (1.91),
min; MS (ESIpos): m/z = 352
7.823 (3.49), 7.843 , 7.887 (3.53), 7.890 (3.71), 7.904 (2.79), 8.354 (3.04), 8.357 (3.11), 8.375 (2.85), 8.378 (2.73),
[M+H]+
8.907 (6.32).
1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.175 (0.47), 1.356 (0.45), 1.989 (0.90), 2.074 (8.95), 2.329 (0.81), 2.369 (0.60),
LC-MS (Method L1): Rt = 1.05 2.671 (0.95), 2.711 (0.65), 2.865 (0.47), 3.092 (0.78), 7.362 (0.70), 7.381 (1.05), 7.409 (6.34), 7.427 (11.32), 7.462 (7.73),
1R-3 min; MS (ESIpos): m/z = 352 7.481 (11.58), 7.500 (5.55), 7.530 (1.06), 7.550 (0.60), 7.585 (0.87), 7.693 (1.21), 7.728 (9.06), 7.747 (7.85), 7.895 ,
[M+H]+ 7.911 (13.10), 7.923 (10.39), 7.943 (10.33), 7.961 , 7.992 (0.98), 8.009 (0.69), 8.448 (0.92), 8.485 (8.46), 8.505 (8.03),
9.072 (16.00), 9.141 (1.24), 14.022 (0.91).
LC-MS (Method L1): Rt = 1.15
1R-13 1H-NMR (400 MHz, 6) δ [ppm]: 2.346 (16.00), 7.062 (1.52), 7.189 (3.52), 7.884 (1.52), 7.895 (1.68), 7.902 ,
min; MS (ESIpos): m/z = 312
8.396 (0.99), 8.403 (0.92), 8.414 (0.88), 8.421 (0.87), 9.116 (2.83).
[M+H]+
1H-NMR(400.0 MHz, d6-DMSO): δ= 8.717(3.1);8.422(0.7);8.406(0.8);8.399(0.9);8.383(0.8);7.965(2.0);7.960(2.1);7.823(0.5);
1W-8 2,17 7.815(0.5);7.809(0.5);7.796(0.6);7.783(0.6);7.675(0.9);7.652(1.4);7.630(0.9);7.586(2.0);7.580(2.0);7.502(0.4);7.478(0.7);7.4
66(1.1);7.385(0.6);7.344(0.6);6.579(0.3);3.328(75.7);3.106(16.0);3.077(0.5);2.671(0.7);2.549(1.8);2.503(106.1);2.339(0.8);2.
329(0.8);2.324(0.7);1.271(0.7);1.170(2.7);0.146(0.4);0.000(76.2);-0.150(0.4)
1H-NMR(400.0 MHz, d6-DMSO): δ= 15.5);8.278(3.9);8.275(4.0);8.257(4.4);8.254(4.3);7.688(4.2);7.684(4.3);7.668(5.2)
LC-MS (Method 1): Rt = 1.78
1W-15 1,86 ;7.664(5.0);7.603(3.0);7.586(4.8);7.565(4.2);7.502(5.2);7.499(5.4);7.484(3.9);7.481(3.6);7.447(3.6);7.428(7.2);7.408(4.5);7.3
min; m/z = 403/405 (M+H)+
);7.339(5.5);7.324(4.0);7.320(3.6);3.823(9.2);3.812(16.0);3.801(9.9);3.601(0.4);3.353(665.1);3.325(9.0);3.314(7.9);2.6
[mass of free base]
72(0.7);2.508(106.3);2.503(137.7);2.499(101.0);2.330(0.8);1.759(0.5);0.000(19.5)
1H-NMR (400 MHz, 6) δ [ppm]: 3.050 (16.00), 4.241 (0.59), 4.249 (0.48), 4.262 (0.64), 4.268 (0.76), 4.276 (0.62),
LC-MS (Method L1): Rt = 0.73
1-T1 4.283 (0.49), 4.292 (0.50), 5.245 (0.56), 5.264 (0.55), 6.794 (0.98), 6.814 (1.10), 6.919 (0.49), 6.938 (1.05), 6.956 (0.61),
min; MS (ESIpos): m/z = 426
7.163 (0.52), 7.181 , 7.198 (0.40), 7.362 (0.91), 7.381 (0.84), 7.441 (0.75), 7.461 (1.18), 7.481 , 8.082 (1.07),
[M+H]+
8.099 (1.02), 8.159 (1.09), 8.180 (1.03), 8.680 (3.34), 9.095 (0.82), 9.115 (0.80).
1H-NMR (400 MHz, 6) δ [ppm]: -0.149 (0.41), -0.008 (4.42), 0.008 , 2.041 (0.54), 2.048 (0.76), 2.056 (1.13),
2.063 , 2.076 (1.30), 2.091 (1.80), 2.098 (1.57), 2.106 (1.11), 2.197 (0.74), 2.206 (1.17), 2.218 (1.70), 2.231 (1.59),
2.240 (1.58), 2.253 (1.13), 2.262 (0.74), 2.274 (0.52), 2.327 (0.60), 2.366 (0.49), 2.523 (2.30), 2.669 (0.66), 2.710 (0.48),
LC-MS (Method L1): Rt = 0.92 3.217 , 3.228 (1.18), 3.248 (4.71), 3.258 (11.00), 3.269 (11.28), 3.279 (5.00), 3.842 (8.92), 3.853 ), 3.864 (8.07),
1-T5 min; MS (ESIneg): m/z = 466 4.214 (0.80), 4.221 (1.01), 4.242 (2.68), 4.249 (2.03), 4.263 (2.41), 4.271 (2.08), 4.276 (2.00), 4.286 (2.44), 4.293 (2.07),
[M-H]- 4.302 (2.18), 4.314 (0.86), 4.321 (0.96), 4.329 (0.65), 5.245 (1.10), 5.259 (2.45), 5.279 (2.44), 5.292 (1.06), 6.797 (4.29),
6.815 (4.84), 6.927 (2.26), 6.929 (2.16), 6.946 (4.75), 6.964 (2.87), 7.164 (2.33), 7.167 (2.40), 7.185 (3.85), 7.202 (1.91),
7.206 (1.79), 7.385 (4.05), 7.403 (3.77), 7.499 (3.74), 7.518 (5.40), 7.538 (4.06), 8.123 (4.80), 8.125 (5.04), 8.142 ,
8.144 (4.51), 8.197 (4.92), 8.199 (4.64), 8.218 , 8.753 (16.00), 9.177 (3.99), 9.197 (3.89).
1H-NMR(400.0 MHz, d6-DMSO): δ = 9.220(2.1);9.200(2.1);8.789(9.2);8.283(1.8);8.268(1.9);8.260(2.0);8.244(1.9);
7.671(2.0);7.650(2.6);7.627(1.8);7.402(2.0);7.385(2.2);7.203(1.1);7.186(2.2);7.169(1.3);7.165(1.3);6.964(1.6);6.945(2.6);6.9
29(1.3);6.926(1.2);6.819(2.9);6.798(2.7);5.286(0.6);5.272(1.3);5.252(1.3);5.238(0.6);4.329(0.4);4.320(0.5);4.312(0.5);4.301(
1-T7 2,69 .292(1.1);4.284(1.3);4.276(1.0);4.267(1.1);4.260(1.3);4.246(1.1);4.238(1.4);4.218(0.5);4.211(0.5);3.865(4.4);3.854(7.4)
;3.843(4.7);3.726(3.9);3.715(4.8);3.703(4.1);3.568(16.0);3.487(0.4);3.332(12.7);3.280(4.6);3.270(7.3);3.259(6.7);3.229(1.2);
3.023(3.6);3.011(4.6);2.999(3.4);2.675(0.7);2.671(0.9);2.666(0.7);2.510(61.4);2.506(124.6);2.502(165.2);2.497(119.8);2.329(
1.0);2.272(0.4);2.261(0.5);2.250(0.6);2.237(0.9);2.228(0.9);2.215(1.0);2.202(0.7);2.193(0.4);2.103(0.6);2.095(0.8);2.088(1.0)
;2.071(0.8);2.060(0.7);2.053(0.6);1.470(0.4);0.936(0.4);0.008(1.0);0.000(24.6);-0.008(1.1)
EXPERIMENTAL SECTION – BIOLOGICAL ASSAYS
Examples were tested in selected biological assays one or more times. When tested more
than once, data are reported as either average values or as median values, wherein
• the average value, also referred to as the arithmetic mean value, represents the sum of
the values obtained divided by the number of times tested, and
• the median value represents the middle number of the group of values when ranked in
ascending or descending order. If the number of values in the data set is odd, the
median is the middle value. If the number of values in the data set is even, the median
is the arithmetic mean of the two middle .
Examples were synthesized one or more times. When synthesized more than once, data from
biological assays represent average values or median values calculated utilizing data sets
obtained from g of one or more synthetic batch.
The in vitro activity of the compounds of the present invention can be demonstrated in the
following assays:
In vitro assay 1: C. elegans Slo-1a - Action at a recombinant C. elegans cell line
Generation of a stable C. elegans CHO cell line
A CHO cell line was obtained from ATCC, code ATCC CRL-9096. For transfection with
plasmid DNA to express C. elegans Slo-1a (accession number 02) CHO cells were
passaged to 40% confluence before adding the transfection on to the cell culture. The
transfection solution included 300 μL OptiMEM (Life logies, Nr.: , 2 μL (= 6 µg)
of plasmid DNA containing the C. elegans Slo 1a gene and 9μL FugeneHD ga, Nr.:
E2311), and was added to the cells prior to incubation for 48 hours at 37°C, 5% CO2. The
transfection medium was exchanged for the selection medium which contains additional G418
(2 mg/ml, Invitrogen, Nr.: 10131) and the cells were seeded into 384 well plates (300
cells/well). After a few weeks, the remaining surviving cells were tested with a voltage sensitive
dye (Membrane Potential Assay Kit, Molecular Devices Nr.: R8034) for K+ channel expression.
Positive cell clones were purified by the limited dilution technique. For this the clone with the
highest and most robust signal in the voltage ive dye assay was further subcloned
ated) in 384 well plates (0.7 cells/well) in order to obtain clonal purity. This generated a
final stable CHO cell line expressing the C. elegans Slo-1a.
Cell e conditions
Cells were cultured at 37 °C and 5% CO2 in MEMalpha with Gutamax I (Invitrogen, Nr.:
32571), supplemented with 10% (v/v) heat inactivated fetal bovine serum (Invitrogen, Nr.:
10500), G418 (1 mg/ml, Invitrogen, Nr.: 10131). Cells were detached using Accutase (Sigma,
Nr.: A6964).
Membrane potential measurements
Laboratory compound testing was performed on 384-well iter plates (MTPs, Greiner, Nr.:
). 8000 cells/well were plated onto 384-well MTPs and cultured for 20 to 24 hours at 37
°C and 5% CO2. After removal of the cell culture , the cells were washed once with
tyrode (150 mM NaCl, 0.3 mM KCl, 2 mM CaCl2, 1mM MgCl2, 0.8 mM NaH2PO4, 5mM
Glucose, 28 mM Hepes, pH 7.4) and then loaded with the voltage sensitive dye of the
Membrane Potential Assay Kit diluted in tyrode for 1 h at room temperature.
After starting the measurement of fluorescence using a FLIPR Tetra (Molecular Devices, Exc.
510-545 nm, Emm. 565-625 nm), test compounds were added ed by the addition of KCl
tyrode (final assay concentration: 70 mM KCl, 2 mM CaCl2, 1mM MgCl2, 0.8 mM NaH2PO4,
5mM Glucose, 28 mM Hepes, pH 7.4, including the voltage sensitive dye). The measurement
was completed after 7 minutes.
Statistics
The data were evaluated by using the ActivityBase XLfit software (IDBS) for curve fitting and
calculation of the aximal ive tration (EC50) and are reported as negative
decadic logarithm (pE50).
For the following examples, pE50 >5,3 - 6,5 has been found for: 27, 28, 85, 87, 88, 109, 131,
182, 183, 243, 345, 361, 363, 402, 424, 440, 510, 511, 521, 534, 547, 555, 580, 592, 599, 656.
For the following examples, pE50 ,5 has been found for: 1, 62, 68, 69, 71, 95, 114, 120,
122, 125, 129, 136, 148, 185, 216, 230, 241, 242, 246, 264, 276, 289, 299, 324, 346, 354, 372,
379, 389, 390, 399, 401, 424, 432, 439, 456, 459, 474, 512, 513, 514, 519, 546, 560, 568, 578,
581, 584, 625, 632, 634, 654, 665.
For the following examples, pE50 >7,5-8,5 has been found for: 2, 3, 4, 5, 6, 23, 55, 58, 63, 64,
65, 66, 73, 74, 90, 93, 98, 102, 110, 117, 119, 124, 127, 128, 144, 145, 147, 150, 152, 154,
158, 159, 163, 173, 180, 188, 195, 196, 203, 204, 212, 213, 218, 219, 224, 229, 231, 232, 236,
245, 252, 253, 255, 257, 258, 259, 263, 266, 268, 269, 270, 273, 280, 284, 287, 288, 291, 295,
297, 301, 304, 308, 311, 312, 317, 319, 320, 321, 323, 325, 342, 343, 344, 348, 360, 370, 375,
378, 380, 381, 383, 384, 385, 386, 391, 392, 393, 394, 397, 403, 405, 412, 429, 433, 434, 443,
447, 454, 457, 458, 460, 461, 463, 464, 466, 471, 472, 473, 475, 476, 480, 481, 482, 483, 484,
486, 493, 494, 495, 499, 500, 501, 502, 503, 507, 508, 509, 515, 517, 518, 522, 523, 524, 525,
526, 527, 528, 529, 530, 531, 532, 533, 535, 536, 537, 538, 541, 545, 550, 551, 559, 561, 562,
563, 566, 567, 569, 570, 571, 572, 573, 574, 575, 577, 579, 585, 590, 593, 595, 597, 602, 615,
619, 620, 621, 622, 623, 626, 630, 633, 635, 640, 643, 661.
For the following examples, pE50 >8,5 has been found for: 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,
17, 18, 19, 20, 21, 22, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 39, 40, 41,42, 43, 44, 45,
46, 47, 48, 49, 50, 51, 52, 53, 54, 56, 57, 60, 61, 70, 72, 75, 76, 77, 80, 81, 82, 83, 89, 100,
101, 108, 112, 115, 121, 130, 132, 133, 134, 135, 137, 138, 139, 140, 141, 142, 143, 146, 151,
153, 155, 156, 157, 160, 161, 162, 164, 165, 166, 167, 168, 169, 170, 171, 172, 174, 175, 176,
177, 178, 179, 181, 184, 186, 187, 189, 190, 191, 192, 193, 194, 197, 200, 201, 205, 206, 207,
208, 209, 210, 211, 214, 215, 217, 220, 221, 222, 223, 225, 226, 227, 228, 233, 234, 235, 237,
238, 239, 240, 244, 247, 248, 249, 250, 251, 254, 256, 260, 261, 262, 265, 267, 271, 272, 274,
275, 277, 278, 279, 281, 282, 283, 290, 292, 293, 294, 296, 298, 300, 302, 305, 307, 309, 310,
313,314, 315, 316, 318, 322, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 338, 339, 340,
341, 349, 350, 351, 352, 353, 355, 356, 357, 358, 359, 362, 364, 365, 366, 367, 368, 369, 371,
373, 374, 376, 377, 382, 387, 388, 395, 396, 398, 400, 404, 406, 407, 408, 409, 410, 411, 413,
414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 425, 426, 427, 428, 429, 430, 431, 435, 436,
437, 438, 441, 442, 444, 445, 446, 448, 449, 450, 451, 452, 453, 455, 462, 465, 467, 468, 469,
470, 477, 478, 479, 485, 487, 488, 489, 490, 491, 492, 496, 497, 498, 504, 505, 506, 516, 517,
520, 539, 540, 542, 543, 544, 548, 549, 552, 553, 554, 556, 557, 558, 564, 565, 576, 582, 583,
586, 587, 588, 589, 591, 594, 596, 598, 600, 601, 603, 604, 605, 606, 607, 608, 609, 610, 611,
612, 613, 614, 616, 617, 618, 624, 627, 628, 629, 631, 636, 637, 638, 639, 641, 642, 644, 645,
646, 647, 648, 649, 650, 651, 652, 653, 655, 657, 658, 659, 660, 662, 663, 664, 666.
In vitro assay 2: Nippostrongylus brasiliensis (NIPOBR)
Adult Nippostrongylus iensis were washed with saline buffer containing 100 U/ml
penicillin, 0.1 mg/ml streptomycin and 2.5 µg/ml amphotericin B. Test compounds were
dissolved in DMSO and worms were incubated in medium in a final concentration of 10 µg/ml
(10 ppm) respectively 1µg/ml (1 ppm). An aliquot of the medium was used to determine the
choline esterase activity in comparison to a negative control. The principle of ing
acetylcholine esterase as readout for anthelmintic activity was described in Rapson et al
(1986) and Rapson et al (1987).
For the following examples, activity (reduction of AChE compared to ve control) was
higher than 80% at 10 µg/ml: 8, 9, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29,
31, 32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 57, 58,
59, 60, 61, 62, 64, 65, 66, 67, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 81, 82, 83, 87, 89, 95, 100,
101, 104, 108, 112, 115, 116, 119, 122, 123, 127, 128, 130, 132, 133, 134, 135, 136, 137, 138,
139, 141, 142, 143, 144, 146, 147, 148, 333, 334, 336, 338, 339, 340, 341, 349, 362, 363, 364,
373, 609, 610, 611, 612, 613, 614, 615, 617, 618, 619, 620, 623, 630.
For the ing examples, activity (reduction of AChE compared to negative control) was
higher than 80% at 1 µg/ml: 8, 9, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 29, 31,
32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 57, 58, 60,
61, 65, 67, 69, 70, 73, 74, 75, 76, 77, 80, 81, 82, 83, 84, 89, 92, 93, 95, 100, 101, 108, 112,
114, 115, 116, 117, 118, 119, 122, 124, 125, 126, 127, 128, 129, 130, 132, 133, 134, 135, 136,
137, 138, 139, 142, 143, 144, 146, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 160, 161,
162, 163, 165, 166, 167, 168, 169, 170, 171, 172, 176, 178, 181, 182, 185, 186, 187, 189, 190,
191, 192, 193, 194, 195, 197, 198, 200, 201, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,
214, 215, 217, 218, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 231, 232, 233, 234, 235,
236, 237, 238, 239, 240, 247, 249, 250, 251, 254, 256, 257, 260, 261, 262, 263, 265, 266, 268,
271, 272, 273, 274, 275, 276, 277, 279, 280, 281, 282, 283, 284, 285, 287, 288, 289, 290, 291,
292, 293, 294, 301, 302, 307, 308, 309, 310, 311, 313, 314, 315, 318, 319, 321, 322, 326, 327,
328, 329, 330, 331, 332, 333, 334, 336, 338, 339, 340, 341, 342, 347, 349, 350, 352, 353, 355,
356, 357, 358, 359, 360, 362, 364, 365, 367, 369, 370, 373, 374, 375, 377, 382, 384, 385, 386,
388, 392, 394, 395, 396, 397, 400, 403, 404, 406, 407, 408, 409, 410, 411, 413, 414, 415, 417,
418, 419, 420, 421, 422, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437,
441, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 458, 460, 461, 462, 463,
464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 476, 477, 478, 479, 482, 485, 486, 487, 488,
490, 491, 492, 495, 496, 497, 498, 499, 500, 501, 504, 505, 506, 507, 508, 509, 516, 517, 520,
527, 528, 529, 530, 531, 532, 533, 535, 536, 537, 538, 540, 541, 542, 543, 544, 545, 548, 549,
550, 551, 552, 553, 554, 556, 557, 558, 561, 562, 563, 564, 565, 566, 569, 570, 571, 572, 573,
574, 575, 576, 577, 578, 579, 581, 582, 583, 585, 586, 587, 588, 590, 594, 596, 597, 598, 601,
602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 617, 618, 619, 620, 623,
624, 626, 627, 628, 629, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 645, 646,
647, 648, 649, 650, 651, 652, 653, 655, 657, 658, 660.
In vitro assay 3: Dirofilaria immitis microfilariae (DIROIM L1)
≥ 250 Dirofilaria s microfilariae, which were freshly purified from blood, were added to
wells of a microtitre plate containing a nutrient medium and the test compound in DMSO.
Compounds were tested in concentration-response assay in duplicate. Larvae exposed to
DMSO and no test compounds were used as negative controls. Larvae were evaluated after
72 h of incubation with the compound. Efficacy was ined as the reduction of motility in
comparison to the ve control. Based on the evaluation of a wide concentration range,
concentration-response curves as well as EC50-values were calculated.
For the following examples, the EC50 was < 0.1 ppm: 1, 4, 5, 6, 7, 8, 9, 10, 12, 13, 15, 16, 17,
22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 50,
51, 52, 53, 54, 56, 57, 58, 60, 61, 64, 65, 69, 73, 74, 76, 77, 80, 81, 82, 83, 84, 89, 101, 103,
108, 111, 112, 115, 117, 119, 124, 125, 127, 128, 129, 130, 132, 133, 134, 138, 139, 140, 141,
142, 143, 144, 145, 146, 147, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162,
163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181,
185, 186, 187, 188, 189, 190, 191, 192, 194, 196, 197, 200, 201, 203, 204, 205, 206, 207, 208,
209, 210, 211, 212, 214, 215, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,
231, 232, 233, 234, 235, 236, 237, 238, 239, 240, , 244, 247, 248, 249, 250, 251, 253, 255,
256, 257, 258, 259, 260, 261, 262, , 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275,
276, 277, 278, 279, 280, 281, 283, 290, 292, 293, 296, 300, 303, 304, 305, 306, 307, 308, 309,
310, 311, 312, 313, 314, 315, 317, 319, 322, 326, 327, 329, 330, 331, 332, 333, 334, 338, 339,
340, 340, 341, 342, 344, 350, 351, 352, 353, 355, 356,357, 358, 359, 360, 362, 364, 365, 366,
367, 368, 369, 373, 374, 375, 376, 377, 381, 382, 383, 384, 385, 386, 388, 390, 391, 392, 394,
395, 396, 400, 403, 404, 405, 406, 407, 408, 409, 410, 411, 413, 414, 415, 417, 418, 419, 420,
421, 422, 423, 425, 426, 427, 428, 429, 430, 431, 433, 434, 435, 436, 437, 438, 441, 442, 443,
444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 457, 458, 459, 460, 461, 462, 463,
464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 482, 483,
485, 486, 487, 488, 490, 491, 492, 493, 495, 497, 498, 499, 500, 501, 503, 504, 505, 506, 507
,508, 509, 516, 517, 521, 522, 523, 524, 525, 527, 528, 529, 530, 531, 532, 533, 536, 537,
538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 556, 557,
558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,
577, 578, 579, 581, 582, 583, 584, 586, 587, 588, 589, 590, ,591,594, 596, 597, 598, 600, 601,
602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620,
622, 623 ,624 ,626 ,627, 628, 629, 632, 633, 634, 635, 636, 638, 639, 641, 642, 645, 646, 647,
648, 649, 650, 651, 652, 653, 655, 657, 658, 660.
For the following examples, the EC50 was < 1 ppm: 3, 11, 19, 49, 55, 62, 63, 66, 67, 70, 71, 72,
75, 86, 90, 93, 94, 95, 99-1, 100, 102, 104, 105, 116, 135, 136, 137, 148, 182, 183, 184, 193,
195, 199, 213, 216, 230, 241, 242, 243, 245, 246, 252, 254, 263, 282, 288, 289, 291, 292, 294,
295, 299, 316, 320, 321, 323, 325, 343, 345, 348, 354, 361, 370, 371, 372, 373, 378, 379, 380,
401, 416, 424, 440, 456, 580, 585, 621, 630, 654.
For the ing examples, the EC50 was < 10 ppm: 2, 9, 13, 14, 18, 20, 21, 27, 28, 59, 67, 68,
78, 87, 88, 91, 92, 96, 99-2, 106, 113, 114, 118, 120, 122, 123, 126, 131, 149, 198, 202, 264,
284, 285, 286, 287, 288, 301, 302, 318, 324, 328, 335, 336, 337, 346347, 349, , 363, 387, 389,
393, 397, 398, 399, 402, 412, 432, 439, 481, 484, 485, 489, 491, 492, 494, 510, 511, 512, 513,
514, 515, 518, 519, 520, 526, 534, 535, 555, 595, 599, 625, 631, 637, 640, 643, 644, 656, 659.
In vitro assay 4: Dirofilaria s (DIROIM L4)
Dirofilaria immitis third-stage larvae, which were freshly isolated from their vector
(intermediate host), were added to wells of a itre plate containing a nutrient medium and
the test compound in DMSO. Compounds were tested in concentration-response assay in
duplicate. Larvae exposed to DMSO and no test compounds were used as ve controls.
Larvae were evaluated after 72 h of incubation with the compound. Within these 72 h of
incubation the majority of larvae in negative control moult to fourth-stage larvae. Efficacy was
determined as the reduction of motility in comparison to the negative control. Based on the
evaluation of a wide concentration range, concentration-response curves as well as EC50-
values were calculated.
For the following examples, the EC50 was < 0.1 ppm: 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19,
21, 22, 23, 24, 25, 26, 29, 30, 31, 32, 33, 34, 35, 36, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,
49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 69, 73, 74, 75, 76, 77, 81,
82, 83, 89, 101, 108, 112, 117, 119, 124, 125, 127, 130, 132, 133, 134, 138, 139, 140, 141,
142, 143, 144, 146, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165,
166, 167, 168, 169, 170, 171, 172, 174, 175, 176, 177, 178, 179, 181, 186, 190, 191, 192, 194,
196, 197, 200, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 214, 215, 217, 218, 220, 221,
222, 223, 224, 225, 226, 227, 228, 229, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 247,
248, 249, 250, 251, 253, 256, 257, 258, 259, 260, 261, 262, 265, 267, 268, 271, 272, 275, 277,
278, 279, 280, 281, 283, 290, 300, 304, 309, 310, 313, 314, 315, 319, 322, 326, 327, 330, 331,
332, 333, 334, 336, 338, 339, 340, 341, 350, 351, 352, 353, 355, 356, 357, 358, 359, 360, 362,
365, 366, 367, 374, 376, 377, 382, 384, 385, 386, 388, 390, 392, 394, 395, 396, 400, 403, 404,
405, 406, 407, 408, 409, 410, 411, 413, 414, 415, 417, 418, 419, 420, 421, 422, 423, 425, 426,
427, 429, 430, 431, 433, 434, 436, 437, 438, 441, 442, 443, 444, 446, 447, 448, 449, 450, 451,
452, 453, 454, 455, 457, 462, 463, 465, 466, 467, 468, 469, 470, 476, 477, 478, 479, 480, 482,
485, 486, 487, 488, 490, 491, 492, 493, 495, 496, 497, 498, 499, 504, 505, 506, 507, 516, 517,
523, 525, 527, 528, 529, 530, 531, 532, 533, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545,
548, 549, 550, 551, 552, 553, 554, 556, 557, 558, 559, 561, 562, 563, 564, 565, 566, 567, 568,
570, 571, 572, 573, 575, 576, 577, 578, 579, 582, 583, 584, 587, 589, 590, 591, 596, 597, 600,
602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 617, 618, 619, 628, 629,
635, 638, 660.
For the following examples, the EC50 was < 1 ppm: 1, 2, 3, 14, 20, 54, 80, 115, 150, 201, 244,
266, 364, 373.
For the following examples, the EC50 was < 10 ppm: 133, 187
In vitro assay 5: Litomosoides sigmodontis (LTMOSI L3)
Litomosoides sigmodontis third-stage , which were freshly isolated from the pleural
cavity of an infected rodent, were added to wells of a microtitre plate containing a nutrient
medium and the test compound in DMSO. Compounds were tested in concentration-response
assay in duplicate. Larvae exposed to DMSO and no test compounds were used as negative
controls. Larvae were evaluated after 72 h of incubation with the compound. Efficacy was
determined as the reduction of motility in comparison to the negative control. Based on the
evaluation of a wide concentration range, tration-response curves as well as EC50-
values were calculated.
For the following es, the EC50 was < 0.1 ppm: 8, 9, 10, 12, 13, 16, 17, 18, 19, 20, 21,
22, 23, 24, 25, 29, 32, 33, 34, 35, 36, 37, 45, 46, 48, 52, 53, 54, 74, 76, 77, 112, 133, 134, 141,
143, 339, 341, 350, 376, 382, 384, 385, 386, 394, 395, 396.
For the following examples, the EC50 was < 1 ppm: 3, 15, 44, 73, 373.
In vitro assay 6: Cooperia ei (COOPCU L3)
Solvent: dimethyl sulfoxide
To produce a suitable ation of active compound, 10 mg of active compound are
dissolved in 0.5 ml t, and the concentrate is diluted with “Ringer’s solution” to the
desired concentration.
Approximately 40 nematode larvae (Cooperia ei) are transferred into a test tube
containing the compound solution.
After 5 days percentage of larval mortality is recorded. 100 % efficacy means all larvae are
killed; 0% efficacy means no larvae are killed.
In this test for example, the following compounds from the preparation examples showed good
activity of 100% at an application rate of 20 ppm: 8, 9, 10,13, 17, 22, 23, 24, 29, 32, 33, 34, 36,
37, 45, 46, 52, 53, 57, 76, 77, 81, 83, 132, 133, 134, 139, 143, 150, 153, 155, 156, 157, 166,
167, 169, 170, 172, 191, 192, 193, 194, 195, 196, 197, 200, 204, 205, 206, 207, 208, 209, 210,
214, 215, 217, 218, 221, 222, 224, 226, 235, 236, 237, 247, 265, 266, 274, 280, 300, 309, 326,
327, 329, 332, 341, 350, 353, 356, 357, 359, 373, 377, 384, 385, 386, 395, 396, 407, 408, 410,
411, 415, 419, 420, 421, 426, 431, 438, 445, 449, 450, 451, 453, 454, 455, 464, 477, 479, 486,
487, 488, 496, 497, 504, 505, 506, 507, 516, 528, 529, 530, 531, 532, 533, 536, 537, 538, 539,
541, 542, 545, 551, 554, 557, 558, 562, 563, 564, 565, 569, 572, 573, 575, 576, 596, 600, 603,
604, 605, 607, 608, 624, 628, 631, 637, 638, 639, 642, 647, 651, 652, 655, 657, 658, 659, 660.
In this test for example, the following nds from the preparation examples showed good
activity of 90% at an application rate of 20 ppm: 16, 31, 40, 48, 50, 54, 60, 80, 108, 125, 142,
152, 176, 178, 179, 191, 201, 203, 220, 223, 229, 240, 251, 257, 259, 260, 271, 275, 276, 281,
292, 314, 330, 331, 333, 338, 339, 358, 382, 400, 406, 435, 444, 446, 462, 465, 467, 469, 473,
476, 491, 500, 509, 540, 543, 548, 552, 553, 601, 602, 615, 640, 648.
In this test for example, the following compounds from the preparation es showed good
activity of 80% at an application rate of 20 ppm: 15, 21, 30, 41, 42, 44, 47, 49, 51, 58, 65, 70,
75, 89, 135, 146, 154, 162, 163, 181, 211, 212, 228, 238, 239, 250, 272, 294, 298, 307, 310,
315, 318, 322, 328, 367, 394, 404, 409, 418, 424, 432, 460, 471, 482, 485, 490, 492, 495, 508,
556, 583, 587, 614, 650.
In this test for example, the following compounds from the preparation examples showed good
activity of 100% at an application rate of 4 ppm: 8, 13, 17, 22, 23, 24, 32, 33, 34, 36, 37, 45,
46, 52, 53, 57, 76, 77, 81, 83, 132, 133, 134, 143, 151, 153, 155, 167, 169, 170, 172, 192, 194,
195, 197, 200, 205, 207, 209, 210, 214, 215, 217, 222, 226, 237, 265, 266, 273,274, 300, 309,
327, 329, 332, 350, 353, 359, 373, 384, 385, 386, 395, 395, 396, 407, 408, 410, 411, 415, 420,
421, 426, 431, 438, 445, 449, 450, 451, 453, 455, 477, 479, 487, 488, 496, 497, 499, 504, 505,
529, 530, 531, 532, 533, 536, 539, 541, 542, 545, 554, 557, 558, 562, 563, 564, 565, 569, 572,
573, 575, 576, 596, 600, 604, 607, 608, 628, 631, 637, 638, 639, 642, 647, 651, 652, 655, 657,
658, 659, 660.
In this test for example, the following compounds from the ation examples showed good
activity of 90% at an application rate of 4 ppm: 9, 29, 31, 40, 54, 60, 125, 139, 142, 152, 156,
157, 166, 191, 193, 196, 208, 218, 221, 223, 229, 235, 236, 247, 271, 275, 292, 326, 330, 338,
341, 356, 357, 358, 419, 435, 446, 462, 464, 469, 476, 500, 506, 507, 540, 551, 552, 601, 603,
605, 648.
In this test for example, the ing compounds from the preparation examples showed good
activity of 80% at an application rate of 4 ppm: 10, 16, 39, 42, 44, 47, 48, 50, 51, 58, 80, 108,
146, 163, 171, 178, 201, 203, 206, 211, 212, 224, 240, 258, 260, 280, 281, 286, 318, 333, 339,
400, 406, 409, 430, 437, 444, 465, 467, 486, 491, 508, 509, 516, 528, 537, 548, 583, 602, 614,
624, 640.
In this test for example, the following compounds from the preparation examples showed good
activity of 80% at an application rate of 0.8 ppm: 190, 549.
In vitro assay 7: Haemonchus contortus (HAEMCO L3)
Solvent: dimethyl ide
To produce a suitable preparation of active compound, 10 mg of active nd are
dissolved in 0.5 ml solvent, and the concentrate is diluted with “Ringer’s solution” to the
desired concentration.
Approximately 40 larvae of the red stomach worm (Haemonchus contortus) are transferred into
a test tube containing compound on.
After 5 days the percentage of larval ity is recorded. 100 % efficacy means all larvae are
killed, 0% efficacy means no larvae are killed.
In this test for example, the following compounds from the preparation examples showed good
activity of 100% at an application rate of 20 ppm: 8, 13, 15, 17, 22, 23, 24, 29, 32, 33, 34, 36,
37, 46, 47, 48, 50, 52, 53, 57, 60, 76, 77, 81, 83, 132, 133, 134, 135, 139, 142, 143, 153, 155,
166, 167, 169, 170, 172, 192, 194, 197, 200, 205, 206, 207, 214, 215, 218, 221, 222, 224, 226,
235, 237, 247, 265, 266, 274, 275, 280, 300, 309, 312, 326, 329, 330, 331, 332, 350, 353, 359,
373, 377, 384, 385, 386, 395, 396, 407, 410, 411, 415, 450, 455, 477, 486, 487, 488, 496, 497,
504, 505, 506, 509, 528, 529, 530, 531, 533, 537, 538, 539, 541, 542, 545, 551, 552, 554, 558,
562, 563, 564, 565, 569, 572, 573, 575, 576, 596, 604, 605, 608, 628, 631, 637, 638, 647, 651,
652, 655, 658, 659, 660.
In this test for example, the following compounds from the preparation examples showed good
ty of 90% at an application rate of 20 ppm: 10, 31, 44, 45, 51, 74, 75, 136, 146, 150, 156,
179, 191, 203, 204, 209, 210, 217, 220, 223, 229, 236, 249, 250, 251, 258, 260, 271, 272, 327,
356, 357, 358, 400, 408, 421, 435, 438, 444, 445, 449, 451, 453, 460, 469, 476, 508, 532, 540,
548, 553, 557, 600, 602, 603, 615, 640, 642, 648, 657.
In this test for example, the following compounds from the preparation examples showed good
ty of 80% at an application rate of 20 ppm: 12, 16, 39, 40, 42, 70, 125, 137, 138, 152,
157, 176, 178, 180, 208, 257, 259, 273, 276, 281, 292, 307, 310, 333, 341, 388, 392, 394, 419,
420, 432, 434, 446, 464, 473, 479, 491, 499, 500, 507, 516, 535, 543, 619, 624, 645, 646, 650.
In this test for example, the following compounds from the ation examples showed good
activity of 100% at an application rate of 4 ppm: 8, 9, 13, 17, 22, 23, 24, 29, 32, 34, 36, 37, 40,
46, 52, 57, 60, 76, 77, 81, 132, 133, 134, 139, 142, 143, 153, 155, 170, 192, 197, 200, 205,
214, 222, 237, 247, 265, 266, 274, 309, 330, 332, 339, 350, 359, 373, 384, 385, 386, 395, 410,
411, 455, 477, 488, 496, 497, 504, 509, 530, 531, 539, 541, 542, 545, 554, 558, 562, 563, 564,
565, 569, 572, 573, 575, 576, 596, 605, 608, 628, 631, 637, 639, 647, 651, 652, 655, 658, 659,
In this test for example, the following compounds from the preparation examples showed good
activity of 90% at an application rate of 4 ppm: 10, 15, 31, 33, 45, 47, 50, 83, 135, 146, 151,
166, 167, 169, 191, 194, 207, 209, 221, 226, 229, 235, 236, 271, 272, 275, 300, 326, 329, 353,
357, 358, 396, 400 ,407, 408, 415, 421, 435, 436, 438, 445, 450, 451, 476, 487, 505, 508, 528,
529, 533, 536, 537, 540, 552, 600, 603, 604, 638, 640, 648.
In this test for example, the following compounds from the preparation examples showed good
activity of 80% at an application rate of 4 ppm: 42, 44, 48, 51, 53, 74, 75, 150, 156, 172, 195,
206, 210, 215, 217, 218, 223, 232, 260, 281, 307, 327, 341, 356, 377, 392, 394, 403, 419, 42,
426, 444, 449, 453, 469, 470, 471, 479, 486, 500, 506, 507, 551, 557, 642, 645, 650, 657.
Formulation Example
Exemplary formulations consisted of the active substance in 10% Transcutol, 10% hor
EL and 80% isotonic saline solution. First the active substance was dissolved in Transcutol.
After solution in Transcutol, Cremophor and isotonic saline solution were added. These
ations were used as service ations in the following in vivo assay.
An example for a formulation according to the present invention is the following formulation
Example F1. Therein, the active substance was dissolved in utol to form a stock
on A. Then 0.100 mL of this stock solution A were taken and 0.100 mL Cremophor EL
and 0.800 mL isotonic saline solution were added. The resulting liquid formulation (formulation
example F1) had a volume of 1 mL.
Stock solution A:
4.0 mg compound of example 8,
0.100 mL Transcutol.
Formulation e F1:
0.100 mL stock solution A,
0.100 mL Cremophor EL, and
0.800 mL isotonic saline solution.
In vivo assay
chus contortus / Trichostrongylus colubriformis / gerbil
s, experimentally infected with Haemonchus and / or Trichostrongylus, were treated
once during late prepatency. Test compounds were formulated as solutions or suspensions
and applied orally or intraperitoneally. For both applications the same service formulation was
used. The volume of the application amounted to normally 20 ml/kg at a maximum. By way of
example, a gerbil with 40 g body weight was treated with 0.200 mL of the formulation of
formulation example F1. This corresponded to a treatment with 20 mg/kg body weight.
cy was determined per group as reduction of worm count in stomach and small intestine,
respectively, after necropsy compared to worm count in an infected and placebo-treated
control group.
The following examples were tested and had an ty of >70% or higher at the given
treatment:
ent Haemonchus contortus Trichostrongylus colubriformis
≤2.5 mg/kg Expl N° 8, 9, 13, 15, 17, 18, 21, Expl N° 8, 13, 17, 22, 37, 51, 52,
intraperitoneally 22, 23, 24, 25, 33, 34, 36, 37, 44, 132, 133, 134, 142, 143, 168, 169,
46, 52, 54, 130, 153, 156, 166, 170, 200 206, 222, 235, 251, 359,
167, 168, 181, 192, 200, 201, 203, 395, 660
205, 206, 209, 214, 220, 221, 222,
232, 233, 234, 235, 237, 238, 239,
250, 251, 300, 301, 309, 310, 322,
326, 327, 330, 331, 355, 357, 358,
359, 360, 374, 385, 386, 392, 395,
409, 410, 411, 413, 415, 419, 427,
430, 431, 438, 444, 450, 455
462, 465, 467, 468, 477, 485, 487,
491, 492, 496, 516, 530, 533, 538,
540, 543, 548, 553, 557, 558, 564,
565, 660
Claims (15)
1. A compound of general formula (I): 5 in which : A is A1 or A2, A1 A2 o is 0, 1, 2, 3 or 4, R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -OH, C1-C4- 10 alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- noalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl, –S(O)-C1-C4-halogenoalkyl and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, 15 Rp is selected from the group consisting of hydrogen, C1-C4-alkyl, X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9, wherein at least one of X and Y is CR7R8, or X, Y form together a ring member selected from the group consisting of -C(O)-O-, -C(O)- NR9-, -S(O)-NR9-, -SO2-NR9- and -SO2-O-, 20 R1 is selected from the group consisting of hydrogen, cyano, -CHO, -OH, C1-C4-alkyl, C1- C4-halogenoalkyl having 1 to 5 n atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5 halogen atoms, C3-C4-alkenyl, alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6- cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, -NH-C1-C4-alkyl, -N(C1-C4-alkyl)2, NH2-C1-C4- 25 alkyl-, C1-C4-alkyl-NH-C1-C4-alkyl-, (C1-C4-alkyl)2N-C1-C4-alkyl-, C1-C4-alkyl-C(O)-, C1- ogenoalkyl-C(O)- having 1 to 5 halogen atoms, C1-C4-alkoxy-C(O)-, benzyloxy- C(O)-, alkoxy-C1-C4-alkyl-C(O)-, -SO2-C1-C4-alkyl, and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl-C1-C4-alkyl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4-halogenoalkyl 5 having 1 to 5 halogen atoms, C1-C4-alkoxy, halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4- alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1- C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; 10 heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 tuents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 15 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)- C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, -S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, R2 is selected from the group consisting of 20 hydrogen, halogen, cyano, -COOH, C1-C4-alkoxy-C(O)-, NH2, -C(O)-NH(C1-C4- alkyl), -C(O)-N(C1-C4-alkyl)2; –NR12R13; –OR14; -SR15, 15, -SO2R15; 25 C1-C6-alkyl, C3-C6-cycloalkyl, alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or -C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4- alkyl-C(O)-, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, - 30 NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1- C4-alkyl), -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group 35 consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4- halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)- 5 alkyl, -SO2-C1-C4-alkyl, C4-halogenoalkyl having 1 to 5 halogen atoms, – S(O)-C1-C4-halogenoalkyl having 1 to 5 n atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl which is optionally tuted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4- 10 halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1- C4-alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1- C4-halogenoalkyl having 1 to 5 halogen atoms; and 15 a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10- membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of n, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), 20 -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)--, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, y-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4- halogenoalkoxy having 1 to 5 n atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 25 halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, and 4- to 10- membered heterocycloalkyl, R3 is hydrogen or C1-C4-alkyl, R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, C3-C6-cycloalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy-C1- 30 C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-alkyl- C(O)-, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2- C1-C4-alkyl, R5 is selected from the group consisting of hydrogen, halogen, -OH, cyano, alkyl, C3-C6-cycloalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy-C1- 35 C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-alkyl- C(O)-, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, C1-C4-alkyl, -SO2- C1-C4-alkyl, R6 is ed from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, C3-C6-cycloalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy-C1- yl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-alkyl- C(O)-, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2- 5 alkyl, R7 is selected from the group consisting of hydrogen, -OH, fluorine, C1-C4-alkyl and C1-C4- alkoxy, R8 is selected from the group consisting of hydrogen, -OH, fluorine, C1-C4-alkyl and C1-C4- alkoxy, 10 or R7 and R8 together form an oxo group (=O), or R7 and R8 form, together with the carbon atom to which they are attached, a 3- to 6- membered ring selected from the group consisting of C3-C6-cycloalkyl and 3- to 6- membered heterocycloalkyl, R9 is selected from the group ting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl 15 having 1 to 5 halogen atoms and C1-C4-alkoxy, R10 is selected from the group consisting of hydrogen, -OH, C1-C4-alkyl and C1-C4-alkoxy, R11 is selected from the group consisting of hydrogen, C1-C4-alkyl and C1-C4-alkoxy, or R10 and R11 form, er with the carbon atom to which they are ed, a 3- to 6- membered ring selected from the group consisting of C3-C6-cycloalkyl and 3- to 6- 20 membered heterocycloalkyl, R12 and R13 are independently selected from the group consisting of hydrogen, -OH, -NH2, -NH(C1-C4-alkyl), C4-alkyl)2, -NH(-C(O)-C1-C4-alkyl), -N(C1- C4-alkyl)(-C(O)-C1-C4-alkyl), C1-C4-alkoxy, C1-C4-alkoxy-C(O)-; C1-C4-alkyl, C3-C6-cycloalkyl, -C1-C4-alkyl, each of which is optionally substituted 25 by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)(-C(O)-C1-C4-alkyl), C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, cycloalkyl, -NH2, -NH(C1-C4-alkyl), 30 -N(C1-C4-alkyl)2, C4-alkyl, C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4- alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to bered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, 5 , -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- 2, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, halogenoalkoxy having 1 to 5 halogen atoms, C3-C6- cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, - SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4- 10 halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl, benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, 15 C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4- alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, C4- noalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 1-C4-halogenoalkyl having 1 to 5 halogen atoms; a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered 20 heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, - C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4- noalkyl having 1 to 5 halogen atoms, alkoxy, hydroxy-C1-C4-alkyl, C1-C4- 25 halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R14 is selected from the group consisting of 30 -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1- 35 C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, cycloalkyl, -NH2, - NH(C1-C4-alkyl), C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, – S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 1-C4-halogenoalkyl having 1 to 5 halogen atoms; heterocyclyl-C1-C4-alkyl, n the heterocyclyl subsitutent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- 5 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents ndently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, , -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6- 10 cycloalkyl, -NH2, -C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, - SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4- halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 n atoms; phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected 15 from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4- noalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms, cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1- C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1- 20 C4-halogenoalkyl having 1 to 5 halogen atoms; and a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10- membered heterocycloalkyl, 5-membered heteroaryl and ered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy- 25 C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 30 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R15 is selected from the group consisting of hydrogen; alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of 35 n, -OH, cyano, -COOH, alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1- C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, - NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, – S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; 5 heterocyclyl-C1-C4-alkyl, wherein the cyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently ed from the group consisting of halogen, cyano, nitro, -OH, oxo, , -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- 10 alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 n atoms, C3-C6- cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, - SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4- halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 15 5 halogen atoms; phenyl, which is optionally substituted by 1, 2 or 3 substituents independently ed from the group ting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1- 20 C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1- C4-halogenoalkyl having 1 to 5 halogen atoms; and a clic or a ic heterocycle selected from the group consisting of 4- to 10- ed heterocycloalkyl, 5-membered heteroaryl and 6-membered aryl, each 25 of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy- C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), 30 -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 1-C4-halogenoalkyl having 1 to 5 halogen atoms, Q is selected from the group consisting of 6- or bered aryl and 5- to 10-membered heteroaryl, each of which is optionally substituted by 1, 2, 3, 4 or 5 35 substituents selected from the group consisting of halogen, SF5, cyano, -CHO, nitro, oxo, C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), C4-alkyl)2, -NHSO2- (C1-C4-alkyl), -[C1-C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to ered cyclyl, which is optionally substituted with 1 or 2 substituents selected from the group consisting of fluorine, ne, bromine, methyl and cyano, - 5 CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, methyl substituted with a 4- to 6-membered heterocyclyl which itself is optionally substituted with 1 or 2 substituents selected from the group ting of fluorine, chlorine, bromine, methyl and cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S- (C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1 10 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2- (C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6- lkyl), -NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4- halogenoalkyl) having 1 to 5 halogen atoms, wherein when Y is O, S or N-R9, none of R7, R8, R10 and R11 is -OH, and wherein when X is O, 15 S or N-R9, none of R7 and R8 is -OH, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.
2. The compound according to claim 1, wherein: 20 A is A1 or A2, A1 A2 o is 0, 1, 2, 3 or 4, R is selected from the group consisting of hydrogen, halogen, cyano, nitro, -OH, C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- 25 halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- noalkyl, C1-C4-halogenoalkyl and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, Rp is selected from the group consisting of hydrogen, C1-C4-alkyl, 30 X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9, wherein at least one of X and Y is CR7R8, or X, Y form together a ring member selected from the group consisting of -C(O)-O-, -C(O)- NR9-, -S(O)-NR9-, -SO2-NR9- and -SO2-O-, R1 is selected from the group consisting of en, cyano, -CHO, -OH, C1-C4-alkyl, C1- C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy 5 having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5 halogen atoms, C3-C4-alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6- cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, -NH-C1-C4-alkyl, -N(C1-C4-alkyl)2, NH2-C1-C4- , C1-C4-alkyl-NH-C1-C4-alkyl-, (C1-C4-alkyl)2N-C1-C4-alkyl-, C1-C4-alkyl-C(O)-, C1- C4-halogenoalkyl-C(O)- having 1 to 5 halogen atoms, C1-C4-alkoxy-C(O)-, benzyloxy- 10 C(O)-, alkoxy-C1-C4-alkyl-C(O)-, -SO2-C1-C4-alkyl, and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl-C1-C4-alkyl, optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of n, -OH, -NO2, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 15 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4- alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1- C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 n atoms; cyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is ed from the group 20 consisting of 4- to 10-membered heterocycloalkyl, ered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)- 25 C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, – S(O)-C1-C4-halogenoalkyl having 1 to 5 n atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R2 is selected from the group ting of hydrogen, n, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4- 30 alkyl), -C(O)-N(C1-C4-alkyl)2; –NR12R13; –OR14; -SR15, -S(O)R15, 5; C1-C6-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or 35 phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4- alkyl-C(O)-, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- 2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, - NH2, -NH(C1-C4-alkyl), C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1- 5 C4-alkyl), -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- 10 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, -NO2, cyano, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)- C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, – 15 S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl which is optionally substituted by 1, 2 or 3 tuents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 20 1 to 5 halogen atoms, cycloalkyl, -NH2, -C4-alkyl), -N(C1-C4-alkyl)2, -S-C1- C4-alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1- ogenoalkyl having 1 to 5 halogen atoms; and a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10- 25 membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl having 1 to 5 30 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen –SO2-C1-C4-halogenoalkyl having 1 to 5 n atoms and 4- to 10- 35 membered heterocycloalkyl, R3 is hydrogen, or C1-C4-alkyl, R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, R5 is selected from the group ting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, 5 C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, R6 is ed from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, 10 R7 is selected from the group consisting of hydrogen, -OH, fluorine, C1-C4-alkyl and C1-C4- alkoxy, R8 is selected from the group consisting of hydrogen, -OH, fluorine, C1-C4-alkyl and C1-C4- alkoxy, or R7 and R8 er form an oxo group (=O), 15 R9 is selected from the group consisting of hydrogen, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy, R10 is selected from the group ting of hydrogen, -OH, C1-C4-alkyl and C1-C4-alkoxy, R11 is selected from the group consisting of hydrogen, C1-C4-alkyl and C1-C4-alkoxy, R12 and R13 are independently selected from the group consisting of 20 hydrogen, -OH, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH(-C(O)-C1-C4-alkyl), C1- C4-alkoxy; C1-C4-alkyl, C3-C6-cycloalkyl, -C1-C4-alkyl, each of which is ally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - 25 C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 30 n atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 n atoms and (C1-C4- alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is ed from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, NH(C1-C4-alkyl), -C(O)-N(C1-C4- alkyl)2, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, halogenoalkoxy having 1 to 5 n atoms, C3-C6- 5 cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, - SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4- noalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl, benzo-C5-C6-cycloalkyl, each of which is ally substituted by 1, 2 or 3 10 tuents independently selected from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4- alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 15 halogen atoms and 1-C4-halogenoalkyl having 1 to 5 halogen atoms; and a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, - 20 C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 25 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R14 is selected from the group consisting of -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of 30 halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - C(O)-N(C1-C4-alkyl)2, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1- C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms, C3-C6-cycloalkyl, -NH2, - NH(C1-C4-alkyl), C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, – S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 35 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; cyclyl-C1-C4-alkyl, wherein the heterocyclyl subsitutent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, 5 thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6- cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, - SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4- 10 halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; , which is optionally substituted by 1, 2 or 3 substituents ndently selected from the group consisting of halogen, cyano, nitro, -OH, alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 15 1 to 5 n atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1- C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 n atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1- C4-halogenoalkyl having 1 to 5 halogen atoms; and a clic or a bicyclic heterocycle selected from the group ting of 4- to 10- 20 membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of n, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy- C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4- 25 halogenoalkoxy having 1 to 5 n atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, R15 is selected from the group consisting of 30 hydrogen; C1-C4-alkyl, C3-C6-cycloalkyl, -C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1- 35 C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, cycloalkyl, -NH2, - NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, – S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, ered heteroaryl and 6- 5 membered aryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4- alkyl)2, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6- 10 cycloalkyl, -NH2, -NH(C1-C4-alkyl), C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, - SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4- halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms; phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected 15 from the group consisting of halogen, cyano, nitro, -OH, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1- C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and –SO2-C1- 20 C4-halogenoalkyl having 1 to 5 halogen atoms; and a monocyclic or a bicyclic heterocycle ed from the group consisting of 4- to 10- membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group ting of n, cyano, nitro, -OH, oxo, thiono, -COOH, C1-C4-alkoxy- 25 C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 30 halogen atoms and –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, Q is a substituted phenyl ring of the formula (Q1) in which: Z1, Z2, Z3, Z4, and Z5 are independently selected from the group consisting of en, n, SF5, cyano, -CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4- 5 alkoxy, cyano-C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-C4- alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to ered heterocyclyl, which is optionally tuted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -CH2- 10 O-(C1-C4-alkyl), H(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, methyl substituted with a 4- to 6-membered heterocyclyl which itself is optionally substituted with 1 or 2 substituents selected from the group consisting of fluorine, chlorine, bromine, methyl and cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2- SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S- 15 (C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 n atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-cycloalkyl), -NHCO(C1-C4-alkyl), - NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or 20 Z1 and Z2 form, er with the carbon atoms that they are connected to, a 5- or 6-membered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which may be optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine and oxo, and 25 Z3, Z4, and Z5 are independently selected from the group consisting of hydrogen, halogen, SF5, cyano, CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1- C4-alkoxy, C1-C4-alkoxy-C(O)-, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1- 30 C4-alkyl])(C1-C4-alkyl), (C1-C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered cycloalkyl which is optionally substituted with 1 or 2 substituents selected from the group consisting of fluorine, methyl or cyano, -CH2-O-(C1-C4- alkyl), -CH2-NH(C1-C4-alkyl), -CH2-N(C1-C4-alkyl)2, methyl substituted with a 4- to 6-membered cycloalkyl which itself is optionally substituted with 1 or 2 35 substituents selected from the group consisting of fluorine, methyl or cyano, -CH2-S-(C1-C4-alkyl), -CH2-S(O)-(C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), - S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4- alkyl), -CONH(C3-C6-cycloalkyl), -NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or 5 Z2 and Z3 form, together with the carbon atoms that they are connected to, a 5- or ered saturated or partially saturated heterocyclic ring, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which may be optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine and oxo, and 10 Z1, Z4, and Z5 are ndently selected from the group consisting of en, halogen, SF5, cyano, CHO, nitro, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, hydroxy, C1-C4-alkoxy, C3-C6-cycloalkyl-C1-C4-alkoxy, cyano-C1- C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), C4-alkyl)2, -NH-SO2-(C1-C4-alkyl), -N(SO2-[C1-C4-alkyl])(C1-C4-alkyl), (C1- 15 C4-alkoxyimino)-C1-C4-alkyl, 4- to 6-membered heterocycloalkyl which is optionally substituted with 1 or 2 substituents selected from the group consisting of fluorine, methyl or cyano, -CH2-O-(C1-C4-alkyl), -CH2-NH(C1-C4-alkyl), -CH2- N(C1-C4-alkyl)2, methyl substituted with a 4- to 6-membered heterocycloalkyl which itself is ally substituted with 1 or 2 tuents selected from the 20 group consisting of fluorine, methyl or cyano, -(C1-C4-alkyl), -CH2-S(O)- (C1-C4-alkyl), -CH2-SO2-(C1-C4-alkyl), -S-(C1-C4-alkyl), -S(O)-(C1-C4-alkyl), -SO2- (C1-C4-alkyl), -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1- C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -CONH(C1-C4-alkyl), -CONH(C3-C6-cycloalkyl), - 25 NHCO(C1-C4-alkyl), -NHCO(C3-C6-cycloalkyl), -NHCO(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or Q is a pyridine ring of the formula (Q2) in which: 30 Z6, Z7, Z8 and Z9 are independently selected from the group consisting of en, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or Q is a pyrimidine ring of the formula (Q3) 5 in which: Z10, Z11 and Z12 are ndently selected from the group consisting of en, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or 10 Q is a pyridine ring of the formula (Q4) in which: Z13, Z14, Z15 and Z16 are independently selected from the group consisting of hydrogen halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, 15 C1-C4-alkoxy, halogenoalkoxy having 1 to 5 n atoms, C1-C4- hydroxyalkyl, NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1-C4-alkyl, and monocyclic cycles selected from the group of 4- to 7-membered heterocycloalkyl or 5-membered heteroaryls having at least one nitrogen atom via which the heteroaryl ring is connected to the pyridine ring, each of which is 20 optionally substituted with 1, 2 or 3 tuents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4- alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4- 25 halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, Q is a pyridine ring of the formula (Q5) in which: Z17, Z18, Z19 and Z20 are independently selected from the group consisting of 5 hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -C4-alkyl), -N(C1-C4-alkyl)2, or Q is a ered aromatic cycle of the formula (Q6) 10 (Q6) in which: T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and NZ22 , wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is S, not more than one of T1 – T4 is N-Z22, and n 15 each Z21 is independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, and each Z22 is independently selected from the group consisting of hydrogen, C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6- 20 cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or Q is a 5-membered aromatic heterocycle of the formula (Q7) in which: U1 – U4 are independently selected from the group consisting of N and C-Z23, wherein not more than three of U1 – U4 are N, and wherein each Z23 is independently selected from the group consisting of hydrogen, 5 halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms, wherein when Y is O, S or N-R9, none of R7, R8, R10 and R11 is -OH, and wherein when X is O, S or N-R9, none of R7 and R8 is -OH, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture 10 of same.
3. The compound according to claim 1 or 2, n: A is A1 or A2, A1 A2 15 o is 0, 1 or 2, R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, cyano, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, Rp is selected from the group consisting of hydrogen, C1-C4-alkyl, X, Y are independently selected from the group consisting of CR7R8, O, S, and N-R9, 20 wherein at least one of X and Y is CR7R8, R1 is selected from the group consisting of hydrogen, C1-C4-alkyl, C3-C6-cycloalkyl, C3-C4- alkenyl, C3-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl, cyano-C1- C4-alkyl, R2 is selected from the group consisting of 25 hydrogen, n, cyano, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, NH(C1-C4- alkyl), N(C1-C4-alkyl)2; –OR14; -SR15, -S(O)R15, -SO2R15; C1-C4-alkyl, cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, alkynyl or phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of halogen, -OH, cyano, C1-C4- alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), -C(O)-N(C1-C4-alkyl)2, C1-C4-alkyl, C1- 5 ogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, -NH2, -NH(C1-C4-alkyl), - N(C1-C4-alkyl)2, -NH(C(O)-C1-C4-alkyl), -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl), -S-C1-C4- alkyl, -S(O)-C1-C4-alkyl, 1-C4-alkyl, –S-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and 1- C4-halogenoalkyl having 1 to 5 halogen atoms; and 10 a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10- membered heterocycloalkyl, spirocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently ed from the group consisting of halogen, cyano, -OH, oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), N(C1-C4- 15 alkyl)2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, hydroxy-C1-C4-alkyl, C1-C4-alkoxy-C1-C4-alkyl-, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, and 4- to bered heterocycloalkyl, R3 is hydrogen or C1-C4-alkyl, 20 R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, R5 is selected from the group consisting of hydrogen, n, cyano, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 25 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, R6 is selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, R7 is selected from the group consisting of hydrogen and C1-C4-alkyl, 30 R8 is selected from the group consisting of hydrogen and C1-C4-alkyl, or R7 and R8 together form an oxo group (=O), R9 is C1-C4-alkyl, R10 is selected from the group ting of hydrogen, -OH, C1-C4-alkyl and C1-C4-alkoxy, R11 is hydrogen, R12 and R13 are independently selected from the group consisting of hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy; C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is ally tuted by 1, 2 or 3 substituents independently selected from the group consisting of 5 halogen, -OH, cyano, -COOH, alkoxy-C(O)-, -C(O)-NH2, -C(O)-NH(C1-C4-alkyl), - C(O)-N(C1-C4-alkyl)2, -NH-C(O)-C1-C4-alkyl, -N(C1-C4-alkyl)-(-C(O)-C1-C4-alkyl), C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, –S-C1-C4- 10 halogenoalkyl having 1 to 5 halogen atoms, –S(O)-C1-C4-halogenoalkyl having 1 to 5 halogen atoms, –SO2-C1-C4-halogenoalkyl having 1 to 5 halogen atoms and (C1-C4- alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the cyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- 15 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of n, cyano, -OH, oxo, C1-C4- alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms; phenyl, benzo-C5-C6-cycloalkyl, each of which is optionally substituted by 1, 2 or 3 20 substituents independently ed from the group consisting of halogen, cyano, C1- C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms; and a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, ered heteroaryl and ered heteroaryl, each of which is 25 optionally substituted by 1, 2 or 3 substituents independently selected from the group ting of n, cyano, -OH, oxo, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, R14 is selected from the group consisting of alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted 30 by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl; and cyclyl-C1-C4-alkyl, wherein the heterocyclyl subsitutent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- 35 membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, -OH, oxo, C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms; R15 is selected from the group ting of hydrogen; 5 C1-C4-alkyl, -C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms; heterocyclyl-C1-C4-alkyl, n the heterocyclyl substituent is selected from the group 10 consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C1-C4-alkyl, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms; 15 Q is a tuted phenyl ring of the formula (Q1) in which: Z1, Z2, Z3, Z4, and Z5 are independently selected from the group ting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 20 halogen atoms, hydroxy, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, 4- to 6-membered heterocyclyl, which is optionally tuted with 1 or 2 substituents selected from the group consisting of ne, chlorine, bromine, methyl and cyano, -S- -alkyl), -S(O)-(C1-C4-alkyl), -SO2-(C1-C4-alkyl), or 25 Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5- or 6-membered heterocycloalkyl, a 5-membered heteroaryl, or a 6-membered heteroaryl, each of which may be optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine and oxo, and Z3, Z4, and Z5 are independently selected from the group consisting of hydrogen, 30 n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-alkoxy-C(O)-, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, or Z2 and Z3 form, together with the carbon atoms that they are connected to, a 5- or 6-membered ted or partially saturated heterocyclic ring, a 5-membered 5 heteroaryl, or a 6-membered heteroaryl, each of which may be optionally substituted with one or two substituents selected from the group consisting of methyl, fluorine and oxo, and Z1, Z4, and Z5 are independently selected from the group consisting of hydrogen, n, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, 10 C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, or Q is a pyridine ring of the formula (Q2) in which: Z6, Z7, Z8 and Z9 are independently selected from the group ting of hydrogen 15 n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4- alkyl), -N(C1-C4-alkyl)2, or Q is a pyrimidine ring of the formula (Q3) 20 in which: Z10, Z11 and Z12 are independently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or 25 Q is a pyridine ring of the formula (Q4) in which: Z13, Z14, Z15 and Z16 are independently selected from the group ting of en, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 5 halogen atoms, alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -NH-CO-C1- C4-alkyl, and monocyclic heterocycles selected from the group of 4- to 7- membered heterocycloalkyl or 5-membered heteroaryls having at least one nitrogen atom via which the heteroaryl ring is connected to the pyridine ring, 10 each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1- C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, - C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4- 15 alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4- halogenoalkyl) having 1 to 5 halogen atoms, -SO2-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or Q is a ne ring of the formula (Q5) 20 in which: Z17, Z18, Z19 and Z20 are independently selected from the group consisting of hydrogen, n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, or 25 Q is a 5-membered ic heterocycle of the formula (Q6) in which: T1 – T4 are independently ed from the group consisting of N, O, S, C-Z21 and NZ22 , wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is 5 S, not more than one of T1 – T4 is N-Z22, and wherein each Z21 is independently selected from the group consisting of hydrogen, halogen, cyano, alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, and each Z22 is ndently selected from the group consisting of hydrogen, C1-C4- 10 alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6- cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or Q is a 5-membered aromatic heterocycle of the formula (Q7) in which: 15 U1 – U4 are independently selected from the group consisting of N and C-Z23, wherein not more than three of U1 – U4 are N, and wherein each Z23 is independently selected from the group consisting of hydrogen, n, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, alkoxy, 20 wherein when Y is O, S or N-R9, R10 is not -OH, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.
4. The compound according to claim 1, 2 or 3, wherein: 25 A is A1 or A2, A1 A2 o is 0, 1 or 2, R is selected from the group consisting of halogen, C1-C4-alkyl and C1-C4-alkoxy, Rp is selected from the group consisting of hydrogen, C1-C4-alkyl, 5 X is selected from the group consisting of CR7R8, O, S, and N-R9, Y is CR7R8 or O, R1 is hydrogen or C1-C4-alkyl, R2 is selected from the group consisting of hydrogen, n, -C(O)-N(C1-C4-alkyl)2; 10 –NR12R13; –OR14; -SR15, -S(O)R15, -SO2R15; alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl or C3-C6-cycloalkenyl, each of which is ally substituted by 1, 2, 3, 4 or 5 tuents independently selected from the 15 group consisting of halogen, -OH, cyano, C1-C4-alkoxy-C(O)- and -C(O)-NH2 C1-C4- , -NH2, -N(C1-C4-alkyl)2, -N(C1-C4-alkyl)(C(O)-C1-C4-alkyl); and a monocyclic or a bicyclic heterocycle selected from the group consisting of 4- to 10- membered heterocycloalkyl, heterospirocycloalkyl, 5-membered heteroaryl, and 6- membered heteroaryl, each of which is optionally substituted by 1, 2, 3 or 4 20 substituents independently selected from the group consisting of halogen, -OH, oxo, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, C1-C4-alkyl, C1-C4-alkyl-C(O)-, C1-C4- halogenoalkyl having 1 to 5 halogen atoms, hydroxy-C1-C4-alkyl-, C1-C4-alkoxy-C1-C4- alkyl-, -NH2, -N(C1-C4-alkyl)2, and 4- to 10-membered heterocycloalkyl, R3 is en or C1-C4-alkyl, 25 R4 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 n atoms, R5 is selected from the group consisting of hydrogen, n, -OH, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, R6 is selected from the group consisting of hydrogen, halogen, -OH, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, R7 is selected from the group consisting of hydrogen and C1-C4-alkyl, R8 is selected from the group consisting of hydrogen and C1-C4-alkyl, 5 or R7 and R8 together form an oxo group (=O), R9 is C1-C4-alkyl, R10 is selected from the group consisting of hydrogen, -OH and C1-C4-alkyl, R11 is en, R12 and R13 are independently selected from the group consisting of 10 hydrogen, -NH(-C(O)-C1-C4-alkyl), C1-C4-alkoxy; C1-C4-alkyl, cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently ed from the group consisting of halogen, -OH, -COOH, C1-C4-alkoxy-C(O)-, -C(O)-NH2, -C(O)-N(C1-C4-alkyl)2, -NHC -C4-alkyl, C1-C4-alkyl, C1-C4-alkoxy, C3-C6-cycloalkyl, -NH2, -N(C1-C4-alkyl)2, -S- 15 C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, and (C1-C4-alkoxy)2P(=O)-; heterocyclyl-C1-C4-alkyl, wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6- membered heteroaryl, each of which is ally tuted by 1, 2 or 3 substituents independently selected from the group ting of halogen, cyano, -OH, oxo, C1-C4- 20 alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms and C1-C4-alkoxy; phenyl and benzo-C5-C6-cycloalkyl, each of which is optionally tuted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, cyano, C1- C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4- halogenoalkoxy having 1 to 5 halogen atoms; and 25 a monocyclic or a bicyclic heterocycle selected from the group of 4- to 10-membered heterocycloalkyl, 5-membered heteroaryl and 6-membered heteroaryl each of which is optionally tuted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, oxo, cyano, C1-C4-alkyl, halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, 30 R14 is selected from the group consisting of C1-C4-alkyl, C3-C6-cycloalkyl, phenyl-C1-C4-alkyl, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, -OH, C1-C4-alkyl, alkoxy and C3-C6-cycloalkyl; and 4- to 10-membered cycloalkyl, R15 is selected from the group consisting of hydrogen; C1-C4-alkyl, which is optionally substituted by 1, 2 or 3 substituents independently 5 selected from the group consisting of -OH and -COOH; and a 6-membered heteroaryl, Q is a substituted phenyl ring of the formula (Q1) in which: 10 Z1 and Z5 are independently selected from the group consisting of hydrogen, halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, Z2 and Z4 are independently selected from the group consisting of hydrogen, halogen, cyano, -OH, C1-C4-alkyl, C1-C4-alkoxy, -NH(C1-C4-alkyl), -N(C1-C4- 15 2, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-halogenoalkoxy having 1 to 5 n atoms, -S-(C1-C4-alkyl) and a 4- to 6-membered heterocycloalkyl, and Z3 is selected from the group consisting of hydrogen, n, C1-C4-alkyl, C1-C4- alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, and -N(C1-C4- 20 alkyl)2, or Z1 and Z2 form, together with the carbon atoms that they are connected to, a 5- membered heterocycloalkyl or a 5-membered heteroaryl, each of which may be optionally substituted with one or two tuents ed from the group consisting of methyl, fluorine and oxo, 25 Z3 and Z5 are hydrogen, and Z4 is ed from the group consisting of hydrogen and C1-C4-alkoxy-C(O)-, or Q is a pyridine ring of the formula (Q4) in which: Z13, Z14, Z15 and Z16 are ndently selected from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-hydroxyalkyl, NH2, -NH(C1-C4- 5 alkyl), -N(C1-C4-alkyl)2, -C1-C4-alkyl, and monocyclic heterocycles selected from the group of 4- to 7-membered heterocycloalkyl or 5-membered heteroaryls having at least one nitrogen atom via which the heteroaryl ring is connected to the pyridine ring, each of which is ally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, 10 cyano, nitro, -OH, oxo, thiono, C1-C4-alkyl, halogenoalkyl having 1 to 5 n atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, -NH2, -NH(C1-C4-alkyl), -N(C1-C4-alkyl)2, -S-C1-C4-alkyl, -S(O)-C1-C4-alkyl, -SO2-C1-C4-alkyl, -S-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -S(O)-(C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, -SO2- 15 (C1-C4-halogenoalkyl) having 1 to 5 halogen atoms, or Q is a pyridine ring of the formula (Q5) in which: Z17, Z18, and Z19 are hydrogen, and 20 Z20 is halogen, or Q is a 5-membered aromatic heterocycle of the formula (Q6) in which: T1 – T4 are independently selected from the group consisting of N, O, S, C-Z21 and NZ22 , wherein not more than one of T1 – T4 is O, not more than one of T1 – T4 is S, not more than one of T1 – T4 is N-Z22, and n each Z21 is independently selected from the group consisting of hydrogen, 5 halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, and each Z22 is independently selected from the group consisting of hydrogen, C1-C4- alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkyl-C3-C6- cycloalkyl, C1-C4-alkoxy-C1-C4-alkyl, or 10 Q is a ered aromatic heterocycle of the formula (Q7) in which: U1 – U4 are independently selected from the group consisting of N and C-Z23, wherein not more than three of U1 – U4 are N, and wherein 15 each Z23 is independently ed from the group consisting of hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-halogenoalkyl having 1 to 5 halogen atoms, alkoxy, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt f, or a mixture of same.
5. The compound according to claim 1, 2, 3 or 4, wherein:
6. A is selected from the group consisting of 5 , R1 is hydrogen or methyl, R2 is ed from the group consisting of hydrogen, chlorine, iodine, -C(O)-N(CH3)2, –NR12R13; 10 –OR14; -SR15, -S(O)R15, -SO2R15; methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethenyl, yl, cyclopentenyl, cyclohexenyl, each of which is optionally substituted by 1 or 2 substituents independently selected from the group ting of -OH, cyano, ethoxy- C(O)-, -C(O)-NH2, methoxy, NH2, N(CH3)2, (C(O)CH3); and a monocyclic or a bicyclic heterocycle selected from the group ting of azetidine, oxetane, idine, tetrahydrofurane, pyrazolidine, imidazolidine, 1,2,4-triazolidine, 5 piperidine, piperazine, tetrahydropyrane, tetrahydropyridine, o-2H-pyrane, 1,2- oxazolidine, 1,2-oxazine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3- dihydro-indole, 1,3-dihydro-isoindoel, 3,9-dioxaazabicyclo[3.3.1]nonane, 6-oxa azabicyclo[3.1.1]heptane, 8-oxaazabicyclo[3.2.1]octane, thiophene, ole, pyrazole, 1,2,4-triazole, triazole, 1,2,3,4-tetrazole, pyridine, dihydropyridine, 10 pyrimidine, tetrahydropyrimidine, 4-oxaazaspiro[2.5]octane, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of fluorine, chlorine, cyano, -OH, oxo, -COOH, methoxy-C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH2, methyl, methyl-C(O)-, difluoromethyl, trifluoromethyl, hydroxymethyl-, methoxymethyl-, -NH2, -NMe2, pyrrolidine, 15 R3 is hydrogen or methyl, R4 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl, methoxy, trifluoromethyl, trifluoromethoxy and NH2, R5 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl, methoxy and trifluoromethyl, 20 R6 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl and methoxy, R12 and R13 are independently selected from the group consisting of hydrogen, -NH(-C(O)-methyl), methoxy; methyl, ethyl, , isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, benzyl, 1- 25 phenylethyl, each of which is optionally substituted by 1, 2 or 3 substituents independently ed from the group ting of fluorine, -OH, -COOH, y- C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, -C(O)-NH2, -C(O)-NMe2, -NH-C(O)-methyl, methyl, methoxy, cyclopropyl, -NH2, NMe2, S-methyl, S(O)-methyl, SO2-methyl, and (EtO)2P(=O)-; 30 heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocyclyl substituent is selected from the group consisting of oxetane, tetrahydrofurane, tetrahydropyrane idine, morpholine, pyrazole, ole, 1, 2, 4-oxadiazole, pyridine, each of which is ally substituted by 1 substituent ndently selected from the group consisting of fluorine, chlorine, -OH, oxo and methyl; 35 phenyl; 2,3-dihydro-1H-indene, and a monocyclic or a bicyclic heterocycle selected from the group of oxetane, thietane, pyrrolidine, morpholine, tetrahydropyrane, pyridine and pyrazole, each of which is optionally substituted by 1 or 2 substituents ndently selected from the group 5 consisting of fluorine, chlorine, -OH, oxo, methyl; R14 is selected from the group consisting of methyl, ethyl, isopropyl, butyl, entyl, benzyl, each of which is optionally substituted by 1 or 2 tuents independently selected from the group ting of ne, -OH, methyl, methoxy and cyclopentyl; and 10 a monocyclic or a bicyclic heterocycle selected from the group ting of pyrrolidin and tetrahydropyran, R15 is selected from the group consisting of methyl and ethyl, each of which is optionally substituted by 1 substituent independently selected from the group consisting of -OH and -COOH; and 15 ne, Q is a substituted phenyl ring of the formula (Q1) in which: Z1 and Z5 are independently selected from the group consisting of hydrogen, 20 fluorine, chlorine, methyl, trifluoromethyl and methoxy, Z2 and Z4 are independently selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2, trifluoromethyl, methoxy, trifluoromethoxy, -SMe and morpholinyl, and Z3 is independently selected from the group ting of hydrogen, fluorine, 25 chlorine, methyl, methoxy, difluoromethoxy and –NMe2, or Q is a pyridine ring of the formula (Q4) in which: Z13, Z14, Z15 and Z16 are independently ed from the group consisting of hydrogen, fluorine, chlorine, cyano, methyl, methoxy, ethoxy, poxy, hydroxymethyl, 5 NH2, -NHMe -NMe2, -NH-C(O)-Me, morpholinyl, or Q is a pyridine ring of the formula (Q5) in which: Z17, Z18, and Z19 are hydrogen, and 10 Z20 is fluorine, chlorine, or Q is selected from the group consisting of (Q6-1) (Q6-2) (Q6-3) (Q6-4) (Q6-5) (Q6-6) (Q6-7) (Q6-8) (Q6-9) (Q6-10) (Q6-11) (Q6-12) (Q6-13) (Q6-14) (Q6-15) (Q6-16) (Q6-17) (Q6-18) (Q6-19) (Q6-20) (Q6-21) (Q6-22) (Q6-23) (Q6-24) (Q6-25) (Q6-26) (Q6-27) (Q6-28) (Q6-29) (Q6-30) (Q6-31) (Q6-32) (Q6-33) (Q6-34) (Q6-35) (Q6-36) (Q6-37) (Q6-38) or (Q6-39) in which: 5 each Z21 is ndently selected from the group consisting of hydrogen, fluorine, ne, cyano, methyl, trifluoromethyl, y and Z22 is hydrogen, , or Q is selected from the group consisting of (Q7-1) (Q7-2) (Q7-3) (Q7-4) (Q7-5) (Q7-6) (Q7-7) (Q7-8) (Q7-9) in which: each Z23 is independently selected from the group consisting of hydrogen, ne, chlorine, cyano, methyl, trifluoromethyl, methoxy, or 5 Q is selected from the group consisting of or a stereoisomer, a er, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same. 10 6. The compound according to claim 1, 2, 3, 4 or 5, wherein:
7. A is selected from the group consisting of 5 R1 is hydrogen or methyl, R2 is selected from the group consisting of chlorine, , -C(O)-N(CH3)2, –NR12R13; –OR14; 10 -SR15, -S(O)R15, -SO2R15; methyl, ethyl, propyl, isopropyl, cyclopropyl, cyclobutyl, entyl, ethenyl, propenyl, each of which is optionally substituted by 1 or 2 substituents ndently selected from the group consisting of -OH, cyano, ethoxy-C(O)-, NH2, y, NH2, N(CH3)2, (C(O)CH3); and 15 a monocyclic or a bicyclic heterocycle selected from the group consisting of azetidine, oxetane, pyrrolidine, tetrahydrofurane, pyrazolidine, imidazolidine, 1,2,4-triazolidine, piperidine, piperazine, tetrahydropyrane, dihydro-2H-pyrane, 1,2-oxazolidine, morpholine, thiomorpholine, 3,4-dihydroisoquinoline, 2,3-dihydro-indoel, 1,3-dihydroisoindole , 3,9-dioxaazabicyclo[3.3.1]nonane, 6-oxaazabicyclo[3.1.1]heptane, 8- 20 oxaazabicyclo[3.2.1]octane, thiophene, imidazole, pyrazole, 1,2,3-triazole, 1,2,3,4- tetrazole, pyridine, dihydropyridine, pyrimidine, tetrahydropyrimidine, each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of fluorine, -OH, oxo, -COOH, methoxy-C(O)-, -C(O)-, tert-butoxy- C(O)-, NH2, methyl, methyl-C(O)-, difluoromethyl, trifluoromethyl, hydroxymethyl-, methoxymethyl-, -NH2, -NMe2, pyrrolidine, R3 is hydrogen or methyl, R4 is selected from the group consisting of hydrogen, chlorine, fluorine, methyl, methoxy 5 and trifluoromethyl, R5 is selected from the group consisting of hydrogen, chlorine, fluorine, -OH, cyano, methyl, trifluoromethoxy and NH2, R6 is selected from the group consisting of hydrogen, fluorine, chlorine, -OH, cyano, methyl and methoxy, 10 R12 and R13 are independently selected from the group consisting of hydrogen, -NH(-C(O)-methyl), methoxy; methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, , 1- ethyl, each of which is optionally tuted by 1, 2 or 3 substituents independently selected from the group consisting of fluorine, -OH, -COOH, methoxy- 15 C(O)-, ethoxy-C(O)-, tert-butoxy-C(O)-, NH2, NMe2, -NH-C(O)-methyl, methyl, methoxy, cyclopropyl, -NH2, -NMe2, , SO2-methyl and (EtO)2P(=O)-; heterocyclyl-methyl, heterocyclyl-ethyl, wherein the heterocycyl substituent is selected from the group consisting of oxetane, tetrahydrofurane, tetrahydropyrane, idine, pyrazole, imidazole 1, 2, 4-oxadiazole, morpholine, pyridine, each of which is optionally 20 substituted by 1 substituent independently selected from the group consisting of oxo and ; phenyl; 2,3-dihydro-1H-indene, and a monocyclic or a ic cycle selected from the group of oxetane, morpholine, 25 tetrahydropyrane, pyridine and pyrazole; R14 is selected from the group consisting of methyl, ethyl, isopropyl, butyl, cyclopentyl, benzyl, each of which is ally substituted by 1 or 2 substituents independently ed from the group consisting of fluorine, -OH, methyl, methoxy and cyclopentyl; and 30 a monocyclic or a bicyclic heterocycle selected from the group consisting of pyrrolidin and tetrahydropyran, R15 is selected from the group consisting of methyl and ethyl, each of which is optionally substituted by 1 substituent independently selected from the group consisting of -OH and -COOH; and pyridine, Q is a substituted phenyl ring of the a (Q1) 5 (Q1) in which: Z1 and Z5 are independently selected from the group consisting of hydrogen, fluorine, ne, methyl, methoxy and trifluoromethyl, Z2 and Z4 are independently selected from the group consisting of hydrogen, 10 fluorine, chlorine, -OH, cyano, methyl, ethyl, tert-butyl, -NHMe, -NMe2, trifluoromethyl, y, trifluoromethoxy, -SMe and morpholinyl, and Z3 is independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, methoxy, difluoromethoxy and –NMe2, or Q is a pyridine ring of the formula (Q4) 15 (Q4) in which: Z14 and Z15 are independently selected from the group consisting of hydrogen, fluorine, ne, cyano, methyl, methoxy, ethoxy, isopropoxy, hydroxymethyl, NH2, morpholinyl and 20 Z13 and Z16 are independently selected from the group ting of hydrogen, ne, chlorine, methyl, methoxy, or Q is a pyridine ring of the formula (Q5) in which: Z17, Z18, and Z19 are hydrogen, and Z20 is fluorine, or 5 Q is selected from the group consisting of or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same. 10 7. A method of preparing a compound of l a (I) according to any one of claims 1 to 6, said method comprising the step of allowing an intermediate compound of general formula 1N : 15 in which A, R1, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) ing to any one of claims 1 to 6, to react with a compound of general formula 1F : in which R2 is NR12R13, OR14, or SR15, each as defined for the compound of general formula (I) according to any one of claims 1 to 6, thereby giving a compound of l formula (I) : in which A, R1, R2, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) according to any one of claims 1 to 6, or the step of allowing an intermediate compound of general formula 1T : in which A, R1, R2, R3, R4, R5 and R6 are as defined for the compound of general a (I) according to any one of claims 1 to 6, and in which Hal is halogen, particularly chlorine, bromine or iodine, 15 to react with a compound of general formula 1H : Q-B(OR)2 in which Q is as defined for the compound of l formula (I) according to any one of claims 1 to 6, and each R may be individually H or Me or both R are pinacolate, 20 thereby giving a compound of general formula (I) : in which A, R1, R2, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) according to any one of claims 1 to 6, or the step of allowing an intermediate compound of general formula 1W : 5 1W, in which Q, R2, R3, R4, R5 and R6 are as defined for the compound of general formula (I) according to any one of claims 1 to 6, to react with a compound of general formula 1M : 10 1M, in which R1 and A are as defined for the compound of general formula (I) according to any one of claims 1 to 6, thereby giving a compound of l formula (I) : 15 (I), in which A, R1, R2, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) ing to any one of claims 1 to 6, or the step of allowing an intermediate nd of general formula 1X : 20 1X, in which Q, A, R1, R3, R4, R5 and R6 are as defined for the compound of general formula (I) according to any one of claims 1 to 6, to react with a compound of general formula 1Y : 5 1Y, in which R2 is OR14 as defined for the compound of general formula (I) according to any one of claims 1 to 6, thereby giving a compound of general formula (I) : 10 (I), in which A, R1, R3, R4, R5, R6, and Q are as defined for the compound of l formula (I) ing to any one of claims 1 to 6 and R2 is C1-C4-alkoxy which is optionally substituted as d for the compound of general formula (I) according to any one of claims 1 to 6, or the step of allowing an intermediate compound of general formula 1N : in which Q, A, R1, R3, R4, R5 and R6 are as defined for the compound of l formula (I) according to any one of claims 1 to 6, to react with a compound of general formula 2A : 20 R2Met-X in which R2 is C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3-C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of which is optionally substituted as defined for the compound of general a (I) ing to any one of claims 1 to 6, Met is magnesium or zinc, and X is 25 chlorine, bromine or iodine, y giving a compound of general formula (I) : in which A, R1, R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) 5 according to any one of claims 1 to 6 and R2 is C1-C4-alkyl, C3-C6-cycloalkyl, C2-C4-alkenyl, C3- C6-cycloalkenyl, C2-C4-alkynyl or phenyl-C1-C4-alkyl, each of which is optionally substituted as defined for the compound of general formula (I) according to any one of claims 1 to 6.
8. A compound of general formula (II): (II), in which : R2 is -OH or as defined for the compound of l formula (I) ing to any one of claims 1 to 6, 15 R3, R4, R5, R6, and Q are as defined for the compound of general formula (I) according to any one of claims 1 to 6, and RA is H or alkyl, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.
9. A compound of general formula (III): (III), in which : R2 is -OH or as defined for the compound of general formula (I) according to any one of claims 1 to 6, 5 A, R1, R3, R4, R5, and R6 are as defined for the compound of general formula (I) according to any one of claims 1 to 6, and Hal is halogen, or a isomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.
10. A compound of general formula (I) according to any one of claims 1 to 6 for use in the control, treatment and/or prevention of a disease.
11. A pharmaceutical composition comprising a compound of general a (I) according to 15 any one of claims 1 to 6 and one or more pharmaceutically able ents.
12. Use of a compound of general formula (I) according to any one of claims 1 to 6 for the control, treatment and/or prevention of a disease. 20
13. Use of a compound of general formula (I) according to any one of claims 1 to 6 for the preparation of a medicament for the control, treatment and/or prevention of a disease.
14. Use ing to claim 10, 12 or 13, wherein the disease is a helminthic ion. 25
15. Method for controlling helminth infections in humans and/or s by administering an anthelminthically effective amount of at least one compound of general formula (I) according to any one of claims 1 to 6 to a human or an animal in need thereof.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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EP16198550.2 | 2016-11-11 |
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NZ793839A true NZ793839A (en) | 2022-10-28 |
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