NZ793839A - New anthelmintic quinoline-3-carboxamide derivatives - Google Patents

New anthelmintic quinoline-3-carboxamide derivatives

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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
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NZ
New Zealand
Prior art keywords
alkyl
group
halogen atoms
halogenoalkyl
alkoxy
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NZ793839A
Inventor
Claudia Bohm
Kirsten Borngen
Ulrich Gorgens
Nils Griebenow
Maike Hink
Walter Hubsch
Thomas Ilg
Johannes Kobberling
Adeline Kohler
Daniel Kulke
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Bayer Animal Health Gmbh
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Publication of NZ793839A publication Critical patent/NZ793839A/en

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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.
NZ793839A 2016-11-11 2017-11-06 New anthelmintic quinoline-3-carboxamide derivatives NZ793839A (en)

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