PL211888B1 - Związek będący antagonistą NPY Y5 oraz kompozycja farmaceutyczna zawierająca taki związek - Google Patents

Związek będący antagonistą NPY Y5 oraz kompozycja farmaceutyczna zawierająca taki związek

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Publication number
PL211888B1
PL211888B1 PL355382A PL35538200A PL211888B1 PL 211888 B1 PL211888 B1 PL 211888B1 PL 355382 A PL355382 A PL 355382A PL 35538200 A PL35538200 A PL 35538200A PL 211888 B1 PL211888 B1 PL 211888B1
Authority
PL
Poland
Prior art keywords
ppm
nmr
phenyl
cdcl
dmso
Prior art date
Application number
PL355382A
Other languages
English (en)
Other versions
PL355382A1 (pl
Inventor
Yasuyuki Kawanishi
Hideyuki Takenaka
Kohji Hanasaki
Tetsuo Okada
Original Assignee
Shionogi & Co
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Publication date
Application filed by Shionogi & Co filed Critical Shionogi & Co
Publication of PL355382A1 publication Critical patent/PL355382A1/pl
Publication of PL211888B1 publication Critical patent/PL211888B1/pl

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    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
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    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
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    • A61K31/4035—Isoindoles, e.g. phthalimide
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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    • A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
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Description

Dziedzina techniki
Obecny wynalazek dotyczy związku będącego antagonistą NPY Y5, oraz kompozycji farmaceutycznej zawierającej ten związek do stosowania jako antagonista receptora Y5, zwłaszcza jako środek przeciw otyłości.
Podstawa wynalazku
Neuropeptyd Y (określony tu jako NPY) jest peptydem, który zawiera 36 reszt aminokwasowych i był wyodrębniony z mózgu świni w 1982 r. NPY jest szeroko rozprowadzany w centralnym układzie nerwowym i tkankach obwodowych u ludzi i zwierząt.
Zauważono, że NPY ma działanie stymulujące przyjmowanie pożywienia, działanie przeciwpadaczkowe, działanie ułatwiające uczenie się, działanie przeciwlękowe, działanie przeciwstresowe itp. w centralnym układzie nerwowym i może zasadniczo brać udział w chorobach centralnego układu nerwowego takich jak depresja, choroba Alzheimera i Parkinsona. NPY jest prawdopodobnie związany z chorobami sercowo-naczyniowymi, gdyż wywołuje on skurcz mięśni gładkich takich jak naczynia krwionośne lub mięśnie sercowe w tkankach obwodowych. Ponadto NPY jest także znany jako biorący udział w chorobach metabolicznych jak otyłość, cukrzyca i zaburzenia hormonalne (Trends in Pharmacological Sciences, Vol. 15 i 153 (1994)). Dlatego antagonista receptora NPY może okazać się lekiem zapobiegającym lub leczącym różne choroby związane z receptorem NPY.
Obecnie rozpoznano podtypy Y1, Y2, Y3, Y4 , Y5 i Y6 receptora NPY (Trends in Pharmacological Sciences, Vol. 18 i 372 (1997)). Sugeruje się, że receptor Y5 jest co najmniej mający związek z zachowaniami i oczekuje się że jego antagonista będzie środkiem przeciw otyłości (Peptydes, Vol. 18 i 445 (1997)).
Związki chinazolinowe mające podobną strukturę do związków według obecnego wynalazku i wykazują ce działanie antagonisty receptora NPY opisano w WO 97/20820, WO 97/20821, WO 97/20823 itp. Ponadto opisano, że pochodne mocznika mające grupę sulfonamidową i pochodne amidowe mające grupę sulfonylową w WO 99/64349, oraz pochodne benzylosulfonamidu w EP1010691-A, mają działanie antagonisty NPY.
Związki o podobnych strukturach do związków według wynalazku są opisane w JP59-16871-A i WO 97/15567. Ich dział ania są zupeł nie inne od tych wedł ug obecnego wynalazku i dokumenty te nie sugerują rozwiązania według wynalazku.
Ujawnienie wynalazku
Przedmiotem wynalazku jest dostarczenie lepszej kompozycji farmaceutycznej do stosowania jako antagonisty receptora NPY Y5 oraz nowych związków aktywnych.
Przedmiotem obecnego wynalazku są:
1. Związek o wzorze (I):
R1-S—Ν-Χ—Y—Z (I)
II I, (Ο)η R w którym 1
R1 oznacza izopropyl, t-butyl, izobutyl, 1-chloro-1-metyloetyl, 1,1-dimetylopropyl, 2-metylopropyl lub 1-metylopropyl;
R2 oznacza atom wodoru; n oznacza 1 lub 2;
X oznacza butylen, fenylen, cykloheksylen, piperydynodiyl, propylen, metylen, heksylen, bicyklo[2,2,2]heks-1,4-diyl;
Y oznacza -C(O)NH-, -NHC(O)-, -OC(O)NH, -C(S)NH-, -C(O)-N(Me)-;
Z oznacza 4-butylofenyl, 2,6-dimetylomorfolinofenyl, morfolinofenyl, 4-(dietyloamino)fenyl, piperydynofenyl, N-etylokarbazolil, 4-jodofenyl, 4-fluorofenyl, pirolidynofenyl, fenoksyfenyl, 4-fenylopiperazynofenyl, 4-(1,3-diazyn-2-ylo)piperazynofenyl, 4-etoksykarbonylopiperydynofenyl, izochinolinofenyl, pirolilofenyl, 4,5-dichloroimidazolofenyl, 4-bromofenyl, 1,3-benzodioksol-5-il, 4-metylobenzopiran-2-on-7-yl, 3-acetyloaminofenyl, 3-aminofenyl, indolilofenyl, pirazolilofenyl, 1,2,3-tiodiazolilofenyl, fenyloaminofenyl, 1,2,3,4-tetrazolilofenyl, 4-(dihydroksyetylo)aminofenyl, metoksykarbonylopropylofenyl,
PL 211 888 B1
3-hydroksypirolidynylofenyl, 4-butoksyfenyl, 3-difluorometylodifluorometoksyfenyl, acetylofenyl, metylotiofenyl, antryl, 3-chloro-4-fenylometylocyjanofenyl, 4-bromo-2-metylopirazol-5-ilofenyl, 7-metoksydibenzofuran-8-yl, 4-(3-metylobutoksykarbonyloetenylo)fenyl, 3-fenoksyfenyl, fluoren-9-on-7-yl, terfenyl-4-il, 4-(4-cyjanofenylo)fenyl, 2-metylochinolin-6-yl, chinolin-3-yl, 2-fenylotio-6-metoksypirydyl, 5-tri-fluorometylopirydyn-2-yl, 4-naftylo-1,3-tiazol-2-il, 2,3-di(metoksykarbonylo)tien-4-yl, 2,4-difluorofenoksypirydyn-3-yl, 3-furan-2-ylopirazol-5-il, fenyloetyloaminoetyl, 2,6-dichlorofenylometylotioetyl, 2-chloro-6-fluorofenylometylotioetyl, 2-tri-fluorometylochinolin-3-ylo-tioetyl, 2-metylotio-3-hydroksy-4,5,6,7-tetrahydrobenzo[c]-tien-7-yl, naftylometylo, 1-indanon-5-yl, 3-etoksyfenyl, 3-metoksymetyloksyfenyl, 3-hydroksyfenyl, 4-butoksy-3-hydroksyfenyl, 2-butoksypirydyn-5-yl, 2-fenoksypirydyn-5-yl,
4-butoksy-2-nitrofenyl, 2-amino-4-butoksyfenyl, 3-butoksyfenylometyl, 3,4-dietoksyfenyl, 1-hydroksyiminoindan-5-yl, 2,3-dihydrobenzo[1,4]dioksan-6-yl, indan-1-yl, 3-izopropyloaminokarbonylofenyl, 4-pirydynometylofenyl, 1,3-benzotiazol-6-il, benzotien-5-yl, 4-trifluorometylofenyl, 5-(4-fluorofenylo)-1,3,4-tiadiazol-2-il, 4-metylofenyl, 4-etylofenyl, 4-propylofenyl, 4-izopropylofenyl, 4-(1-metylopropylo)fenyl, 4-tertbutylofenyl, 4-chlorofenyl, 3-fluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,3,4-trifluorofenyl, 3-chloro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2-fluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 4-fluoro-2-(2,6-dimetylomorfolin-1-ylo)fenyl, 2-metylo-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,3-difluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,3,5,6-tetrafluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,4-dichlorofenyl, 3,4-dimetoksyfenyl, 4-chloro-2-metoksyfenyl, 3-fluoro-4-metoksyfenyl, 4-(3,5-dimetylopiperydyn-1-ylo)fenyl, 4-(5-metylopiperydyn-1-ylo)fenyl, 3-chloro-4-metoksyfenyl, 2-(2,6-dimetylomorfolin-1-ylo)pirydyn-5-yl, 5-trifluorometylopirydyn-2-yl, 3-chlorofenyl, 4-(2,6-dimetylomorfolin-1-ylosulfonylo)fenyl, 4-(dietoksyetylenoamino)fenyl, 4-(6-metylo-1,3-benzotiazol-2-ilo)fenyl, 4-(piperydyn-4-ono)fenyl, 4-(fenylokarbonylo)fenol, 2-metylo-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 4-(tertbutylosulfonyloamino)fenyl, 4-acetylo-2-okso-2H-chromen-6-yl, 2-metylo-1,3-dioksoizoindol-6-iyl, 2-okso-2H-chromen-6-yl, 4-(metylosulfonyloamino)fenyl, 4-(fenylosulfonyloamino)fenyl, 4-(4-chlorofenylo)-4-hydroksypiperydyn-1-yl, 5-fenylo-1,3,4-tiadiazol-2-il, 1-metylo-1,2,3,4-tetrazol-5-ilofenyl, 6-fenylopirazyn-3-yl, 1-fenylo-1,2,3,4-tetrazol-5-ilofenyl, fluoren-1-yl, 4-(2,5-dihydro-1H-pirol-1-ilo)fenyl, 1,2,3,4-tetrahydronaftalen-1-yl, 3-cykloheksyloaminosulfonylofenyl, 4-cyklopropyloksyfenyl, 3-cykloheksylofenyl,
5-trifluorometylopirydyn-2-yl, 3-(piperydyn-1-ylosulfonylo)fenyl, 4-(cyklopentyloksy)fenyl, 4-(tien-2-ylo)fenyl, lub jego farmaceutycznie dopuszczalną sól.
2. Związek jak określony wyżej, w którym Z oznacza 5-trifluorometylopirydyn-2-yl.
3. Związek jak określony wyżej, w którym R1 oznacza tert-butyl.
1
4. Związek jak określony wyżej, w którym R1 oznacza tert-butyl.
5. Kompozycja farmaceutyczna, która jako substancję czynną zawiera związek jak opisany w jednym z zastrz. 1-4.
6. Związek o wzorze
w którym n oznacza liczbę 21, za ś R oznacza metyl.
8. Związek o wzorze
w którym R oznacza metyl.
Najlepszy sposób prowadzenia wynalazku
Gdy związek (I) według wynalazku ma węgiel asymetryczny, obejmuje on racematy, wszystkie enancjomery i wszystkie stereoizomery takie jak diastereomer, epimer i enancjomer.
Gdy związek (I) według wynalazku mający jedno lub więcej podwójnych wiązań tworzy izomer E lub izomer Z, związek (I) obejmuje oba izomery. Gdy X oznacza cykloalkilen, związek (I) obejmuje izomer cis oraz izomer trans.
PL 211 888 B1
Przykładowo związek (I) według wynalazku może być syntetyzowany następującymi metodami.
gdzie Hal oznacza fluorowiec, Q oznacza grupę zabezpieczającą grupę aminową, a inne symbole są takie same jak wyżej.
Etap A
Związek 1 poddaje się reakcji z aminozwiązkiem 2 mającym żądany podstawnik Z w odpowiednim rozpuszczalniku 0°C do 50°C przez kilka minut do kilku godzin.
Jako rozpuszczalniki mogą być stosowane w razie potrzeby tetrahydrofuran, dimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cyklokehsan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetonitryl, woda i ich mieszaniny. W razie potrzeby można stosować aktywator taki jak chlorek tionylu, chlorek kwasowy, bezwodnik kwasowy i aktywny ester.
Etap B
Związek 3 odbezpiecza się zwykłą metodą i poddaje reakcji z halidkiem sulfonylu 4 mającym pożądany podstawnik R1, w odpowiednim rozpuszczalniku w temperaturze 0°C do 50°C przez kilka minut do kilku godzin uzyskując związek (I-A), gdzie n = 2. Tetrahydrofuran, dimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cyklokeksan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetnitryl, woda i ich mieszanina mogą być stosowane jako rozpuszczalnik.
Etap C
Związek (I-B) w którym n = 1 można syntezować w reakcji związku 3 z halidkiem sulfinylu 5 mającym podstawnik R1. Warunki reakcji są takie same jak w Etapie B.
Etap D
Związek (I-B) otrzymany w Etapie C utlenia się zwykłą metodą uzyskując związek (I-A), w którym n = 2. Kwas m-chloronadbenzoesowy, kwas nadoctowy, nadtlenek wodoru, kwas trifluoronadoctowy, nadjodan sodu, podchloryn sodu, nadmanganian potasu itp. mogą być stosowane jak utleniacze, a reakcję można prowadzić w temperaturze 0°C do 50°C. Przykłady rozpuszczalników to tetrahydrofuran, dimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cykloheksan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetonitryl, woda, metanol, etanol, izopropanol i ich mieszanina.
W przypadku X = heterocyklodiyl zawierający co najmniej jeden atom N i octan N łączy się z CONH-Z w związku (I) moż na prowadzić następujące reakcje dla uzyskania związku (I-A') lub (I-B'). Etap D można prowadzić zaraz po etapie C lub etapie E.
(1-8) (Ι-Α)
PL 211 888 B1 gdzie R oznacza niższy alkil lub aryl, a L jest grupą odchodzącą.
Etap C
Związek 5 poddaje się reakcji ze związkiem 6 w podobny sposób jak w powyższym Etapie C otrzymując związek 7.
Etap E
Tak uzyskany związek 7 traktuje się zasadą w odpowiednim rozpuszczalniku otrzymując związek 8. Przykładowo jako zasady mogą być stosowane wodorotlenek baru, sodu, potasu, hydrazynę lub propanotiolan litu. Jako rozpuszczalnik można stosować tetrahydrofuran, dimetyloformamid, dioksan, aceton, acetonitryl, metanol, etanol, propanol, wodę, oraz ich mieszaninę lub podobne. Reakcję można prowadzić w temperaturze 0-100°C przez kilka minut do kilkudziesięciu godzin.
Etap F
Związek 8 poddaje się reakcji ze związkiem 9 mającym grupę odchodzącą i pożądany podstawnik, w odpowiednim rozpuszczalniku w obecności lub nieobecności zasady w temperaturze 0-100°C przez kilka godzin do kilku dni uzyskując związek (I-B'). Przykłady grup odchodzących to grupy fenoksy, chloro i trichlorometylowa. Przykłady zasady to trietyloamina, pirydyna, diizopropyloetyloamina, wodorotlenek sodu, węglan potasu i kwaśny węglan sodu. Przykłady rozpuszczalnika to tetrahydrofuran, dimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cykloheksan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetonitryl, metanol, etanol i ich mieszanina.
Etap D
Związek (I-B') reaguje w podobny sposób jak w powyższym Etapie D dając związek (I-A').
gdzie każdy z symboli jest taki sam jak wyżej.
Etap G i Etap B.
Związek 10 poddaje się reakcji ze związkiem 11 w takich samych warunkach jak w Etapie B. Tak uzyskany związek 12 reaguje w podobny sposób jak w powyższym Etapie B dając związek (I-C) gdzie n = 2.
Etap C i Etap D.
Dla syntezowania związku (I-D) związek 12 uzyskany w Etapie G może reagować w podobny sposób jak w powyższym Etapie C i Etapie D.
(Związek w którym Y=OCONH)
gdzie każdy z symboli jest taki sam jak wyżej.
PL 211 888 B1
Etap H
Związek 13 poddaje się reakcji ze związkiem izocyjanianowym 14 mającym podstawnik Z w odpowiednim rozpuszczalniku w obecności lub nieobecności odpowiedniego katalizatora w temperaturze 0-100°C przez kilka minut do kilku dni uzyskując związek 15. Przykładami rozpuszczalnika są tetrahydrofuran, dimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cykloheksan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetonitryl i ich mieszanina.
Etap C i Etap D
Tak otrzymany związek 15 poddaje się reakcji w podobny sposób jak w Etapie C i Etapie D uzyskując związek (I-E) według obecnego wynalazku.
(Związek w którym Y=CSNH lub NHCS)
Związek (I) gdzie Y=CSNH lub NHCS można syntetyzować w reakcji związku (I), gdzie Y=CONH lub NHCO syntetyzowany dowolną z powyższych metod, z reagentem Lawessona lub pięcio-siarczkiem fosforu w odpowiednim rozpuszczalniku w temperaturze 30°-100°C przez kilka minut do kilku godzin. Przykłady rozpuszczalnika obejmują tetrahydrofuran, diimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cykloheksan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetonitryl i ich mieszanina.
Grupy aminowe mogą być zabezpieczone odpowiednią grupą zabezpieczającą w zwykły sposób, w odpowiednim etapie. Przykładowo jako grupę zabezpieczającą można stosować ftalimid, niższy alkoksykarbonyl, niższy alkenyloksykarbonyl, fluorowcoalkoksykarbonyl, arylo(niższy)alkoksykarbonyl, trialkilosilil, niższy alkilosulfonyl, fluorowco(niższy)alkilosulfonyl, arylosulfonyl, niższy alkilokarbonyl i arylokarbonyl.
Po zabezpieczeniu grupy aminowej związek poddaje się wyżej wymienionym reakcjom i uzyskany związek odbezpiecza się traktując go kwasem lub zasadą, w odpowiednim rozpuszczalniku na odpowiednim etapie. Przykłady rozpuszczalnika obejmują tetrahydrofuran, dimetyloformamid, dietyloeter, dichlorometan, toluen, benzen, ksylen, cykloheksan, heksan, chloroform, etylooctan, butylooctan, pentan, heptan, dioksan, aceton, acetonitryl i ich mieszanina. Przykładami zasady są hydrazyna, pirydyna, wodorotlenek sodu i potasu, a przykładami kwasu są kwasy chlorowodorowy, trifluorooctowy i fluorowodorowy.
Wszystkie związki według wynalazku mają działanie antagonistyczne NPY Y5, a szczególnie preferowane są niżej podane związki.
We wzorze (I), związek w którym R1 stanowi ewentualnie podstawiony niższy alkil lub ewentualnie podstawiony cykloalkil (tutaj powołany jako „R1 = R1-1), związek w którym R1 = izopropyl lub t-butyl (tutaj powołany jako „R1 = R1-4), związek w którym R2 = wodór (tutaj powołany jako „R2 = R2-1), związek w którym R2 = wodór (tutaj powołany jako „R2 = R2-2), związek w którym X oznacza ewentualnie podstawiony niższy alkilen, ewentualnie podstawiony niższy alkenylen, cykloalkilen lub bicykloalkilen, ewentualnie podstawiony fenylen lub ewentualnie podstawiony heterocyklodiyl (tutaj powołany jako „X = X-1),
-O związek w którym X = C2-C6 alkilen, C3-C6 alkenylen lub grupę v—S którą jest ewentualnie podstawiony cykloalkilen, ewentualnie podstawiony fenylen, ewentualnie podstawiony piperydynylen, ewentualnie podstawiony tiofenodiyl lub ewentualnie podstawiony furandiyl (tutaj powołany jako „X = X-2), związek w którym X = C2-C6 alkilen lub grupę którą jest stanowiącą ewentualnie podstawiony cykloalkilen, ewentualnie podstawiony fenylen, ewentualnie podstawiony piperydynylen, ewentualnie podstawiony tiofenodiyl lub ewentualnie podstawiony furandiyl (tutaj powołany jako „X = X-3), związek w którym X = (i) C2-C6 alkilen albo (ii) cykloalkilen lub fenylen, z których każdy jest ewentualnie podstawiony fluorowcem, hydroksylem, niższym alkilem lub fluorowco(niższym)alkilem (tutaj powołany jako „X = X-4), związek w którym X = C2-C6 alkilen lub C5-C6 cykloalkilen (tutaj powołany jako „X = X-5”), związek w którym X = C3-C6 alkilen lub 1,4-cykloheksylen, (tutaj powołany jako „X = X-6”), związek w którym Y = CONH, CSNH, NHCO lub NHCS, a R7 oznacza wodór lub metyl (tutaj powołany jako „Y = Y-1),
PL 211 888 B1 związek w którym Y = CONH, CSNH lub NHCO (tutaj powołany jako „Y = Y-2), związek w którym Y = CONH (tutaj powołany jako „Y = Y-3), związek w którym Z oznacza ewentualnie podstawiony niższy alkil, ewentualnie podstawiony karbocyklil lub ewentualnie podstawiony heterocyklil (tutaj powołany jako „Z = Z-1), związek w którym Z oznacza ewentualnie podstawiony karbocyklil gdzie podstawnikiem jest fluorowiec; hydroksyl; niższy alkil, gdzie podstawnikami są fluorowiec, hydroksyl, karboksyl, niższy alkoksykarbonyl, cyjano i/lub fenyl; niższy alkenyl ewentualnie podstawiony niższym alkoksykarbonylem;
ewentualnie podstawiony niższy alkoksyl, gdzie podstawnikami są fluorowiec, hydroksy, niższy alkoksyl, karboksyl, niższy alkoksykarbonyl, niższy alkiloamino, cykloalkil, cyjano i/lub heterocyklil;
cykloalkil; cykloalkoksyl, acyl, niższy alkilotio, karbamoil, niższy alkilokarbamoil; cykloalkilokarbamoil; hydroksyimino;
ewentualnie podstawiona amino gdzie podstawnikami są niższy alkil, ewentualnie zabezpieczony hydroksy(niższy)alkil, niższy alkoksy(niższy)alkil, acyl, niższy alkilosulfonyl, arylosulfonyl i/lub fenyl;
fenyl ewentualnie podstawiony fluorowcem, cyjano, fenylem i/lub heterocyklilem;
niższy alkilosulfinyl; niższy alkilosulfaoil; cykloalkilosulfamoil;
nitro; cyjano; alkilenodioksyl; fenylazo ewentualnie podstawiony niższym alkilem; fenoksy; okso;
ewentualnie podstawiony heterocyklil, gdzie podstawnikami są ewentualnie zabezpieczony hydroksyl, merkapto, fluorowiec, niższy alkil cykloalkil, niższy alkoksykarbonyl, acyl, amino, niższy alkoksykarbonyloamino, karbamoil, okso, fenyl, niższy alkoksyfenyl, fluorowcofenyl, heterocyklil i/lub okso; heterocyklilosulfonyl ewentualnie podstawiony niższym alkilem; heterocykliloksyl; heterocyklilokarbonyl ewentualnie podstawiony niższym alkilem, (tutaj powołany jako „Z = Z-5), związek w którym Z oznacza ewentualnie podstawiony fenyl, gdzie podstawnikami są fluorowiec; hydroksyl, niższy alkil ewentualnie podstawiony fluorowcem, hydroksylem, niższym alkoksykarbonylem, cyjano i/lub fenylem; niższy alkoksykarbonylo(niższy)alkenyl; niższy alkoksyl ewentualnie podstawiony fluorowcem, niższym alkoksylem, niższym alkoksykarbonylem, cykloalkilem i/lub heterocyklilem; cykloalkil, cykloalkiloksyl; acyl; niższy alkilotio, karbamoil; niższy alkilkarbamoil; amino ewentualnie podstawiona niższym alkilem, hydroksy(niższym)alkilem; acylem, niższym alkilosulfonylem i/lub fenylem; fenyl ewentualnie podstawiony fluorowcem, cyjano; fenylem i/lub heterocyklilem;
niższy alkilosulfamoil; cykloalkilosulfamoil; nitro; alkilenodioksy; fenylazo ewentualnie podstawiony niższym alkilem; fenoksyl; okso;
heterocyklil ewentualnie podstawiony grupą hydroksylową, fluorowcem, niższym alkilem, niższym alkoksykarbonylem, amino, karbamoilem, fenylem, fluorowcofenylem, heterocyklilem i/lub okso; heterocykliloksyl; i/lub heterocyklilosulfonyl ewentualnie podstawiony niższym alkilem (tutaj powołany jako „Z = Z-6);
związek w którym Z oznacza ewentualnie podstawiony fenyl gdzie podstawnikami jest fluorowiec; niższy alkil ewentualnie podstawiony fluorowcem, hydroksylem, niższy alkoksykarbonylem i/lub fenyl; niższy alkoksyl ewentualnie podstawiony fluorowcem i/lub cykloalkilem; cykloalkil; cykloalkoksyl; acyl; niższy alkilotio; niższy alkilokarbamoil; amino ewentualnie podstawiona niższym alkilem, hydroksy(niższym)alkilem, acylem i/lub fenylem; fenyl ewentualnie podstawiony piperydylem; cykloalkilosulfamoil; alkilenodioksyl; fenoksyl;
morfolinyl lub morfolino, z których każdy jest ewentualnie podstawiony niższym alkilem; piperydyl ewentualnie podstawiony grupą hydroksylową, niższym alkilem, niższym alkoksykarbonylem, fenylem, fluorowcofenylem i/lub okso; pirolidynyl ewentualnie podstawiony grupą hydroksylową, karbamoilową i/lub okso;
piperazynyl ewentualnie podstawiony fenylem lub pirymidynylem; dihydropirydyl; pirolil, pirolinyl; imidazolil ewentualnie podstawiony fluorowcem i/lub niższym alkilem; pirazolil; tienyl; tiadiazolil; furyl; oksazolil; izoksazolil; tetrazolil ewentualnie podstawiony niższym alkilem i/lub fenylem; indolinyl; indolil; tetrahydrochinolil; benzotiazolil ewentualnie podstawiony niższym alkilem; tetrahydroizotiazolil ewentualnie podstawiony grupą okso; benzopiranyl ewentualnie podstawiony grupą okso; tetrahydropiranyloksyl; tetrahydrofuryloksyl; morfolinosulfonyl ewentualnie podstawiony niższym alkilem; i/lub piperydylosulfonyl ewentualnie podstawiony niższym alkilem (tutaj powołany jako „Z = Z-7), związek w którym Z oznacza ewentualnie podstawiony fenyl gdzie podstawnikami są fluorowiec, niższy alkil, fluorowco(niższy)alkil, niższy alkoksyl, cykloalkiloksyl, niższy alkilokarbamoil, fenyl, niższy alkilomorfolino i/lub tetrahydropiranyloksyl (tutaj powołany jako „Z = Z-8), związek w którym Z oznacza ewentualnie podstawiony heterocyklil gdzie podstawnikami są fluorowiec, hydroksyl, niższy alkil, fluorowco(niższy)alkil, niższy alkoksy, merkapto, niższy alkilotio, acyl,
PL 211 888 B1 karboksyl, niższy alkoksykarbonyl, amino, niższa alkiloamino, fenyl, naftyl, fenylotio ewentualnie podstawiony fluorowcem, fenoksy ewentualnie podstawiony fluorowcem, okso, i/lub heterocyklil ewentualnie podstawiony niższym alkilem (tutaj powołany jako „Z = Z-9”), związek, w którym Z oznacza tienyl, pirazolil, tiazolil, tiadiazolil, pirydyl, pirymidynyl, pirazynyl, triazynyl, indolil, izoindolil, indolinyl, izoindolinyl, indazolil, benzopiranyl, benzoksazolil, benzotienyl, benzotiazolil, benzotiazolinyl, benzotiadiazolil, chinolil, izochinolil, dihydrobenzofuryl, karbazolil, akrydynyl lub dibenzofuryl, z których każdy jest ewentualnie podstawiony podstawnikami wybranymi z grupy niższego alkilu; fluorowco(niż szy)alkil; niższy alkoksyl; niższy alkoksykarbonyl; acyl; niższy alkoksykarbonylo(niższy)alkil; merkapto; fenyl, naftyl, fenylotio lub fenoksyl, z których każdy jest ewentualnie podstawiony fluorowcem; furyl; nitro; okso; i morfolino ewentualnie podstawiony niższym alkilem (tutaj powołany jako „Z = Z-10), związek w którym Z oznacza tienyl, tiazolil, tiadiazolil, pirydyl, pirazynyl, indolil, izoindolinyl, benzopiranyl, chinolil, karbazolil, dibenzofuryl, benzopiranyl, benzotienyl lub benzotiazolil, z których każdy jest ewentualnie podstawiony jednym lub większą ilością podstawników wybranych z grupy obejmującej niższy alkil, fluorowco(niższy)alkil, niższy alkoksyl, niższy alkoksykarbonyl, acyl, fenyl, naftyl, fenylotio, niższy alkil, morfolino i okso) (tutaj powołany jako „Z = Z-11”), związek w którym R1 oznacza R1-2, R2 oznacza R2-2, n oznacza 2, a połączenie X, Y i Z tj. (X, Y, Z) jest jednym z poniższych.
(X,Y,Z) = (X-3, Y-2, Z-1), (X-3, Y-2, Z-2), (X-3, Y-2, Z-3), (X-3, Y2, Z-4), (-3, Y-2, Z-5), (X-3 Y-2, Z-6), (X-3, Y-2, Z-7), (X-3, Y-2, Z-8), (X-3, Y2, Z-9), (X-3, Y-2, Z-10), (X-3, Y-2, Z-11), (X-3, Y-3, Z-1), (X-3, Y-3, Z-2), (X-3, Y-3, Z-3), (X-3, Y-3, Z-4), (X-3, Y-3, Z-5), (X-3, Y-3, Z-6), (X-3, Y-3, Z-7), (X-3, Y-3, Z-8), (X-3, Y-3, Z-9), (X-3, Y-3, Z-10), (X-3, Y-3, Z-11), (X-4, Y-2, Z-1), (X-4, Y-2, Z-2), (X-4, Y-2, Z-3), (X-4, Y-2, Z-4), (X-4, Y-2, Z-5), (X-4, Y-2, Z-6), (X-4, Y-2, Z-7), (X-4, Y-2, Z-8), (X-4, Y-2, Z-9), (X-4, Y-2, Z-10), (X-4, Y-2, Z-11), (X-4, Y-3, Z-1), (X-4, Y-3, Z-2), (X-4, Y-3, Z-3), (X-4, Y-3, Z-4), (X-4, Y-3, Z-5), (X-4, Y-3, Z-6), (X-4, Y-3, Z-7), (X-4, Y-3, Z-8), (X-4, Y-3, Z-9), (X-4, Y-3, Z-10), (X-4, Y-3, Z-11), (X-5, Y-2, Z-1), (X-5, Y-2, Z-2), (X-5, Y-2, Z-3), (X-5, Y-2, Z-4), (X-5, Y-2, Z-5), (X-5, Y-2, Z-6), (X-5, Y-2, Z-7), (X-5, Y-2, Z-8), (X-5, Y-2, Z-9), (X-5, Y-2, Z-10), (X-5, Y-2, Z-11), (X-5, Y-3, Z-1), (X-5, Y-3, Z-2), (X-5, Y-3, Z-3), (X-5, Y-3, Z-4), (X-5, Y-3, Z-5), (X-5, Y-3, Z-6), (X-5, Y-3, Z-7), (X-5, Y-3, Z-8), (X-5, Y-3, Z-9), (X-5, Y-3, Z-10), (X-5, Y-3, Z-11), ich farmaceutycznie dopuszczalna sól, solwat lub prolek.
Antagonista receptora NPY Y5 według wynalazku jest skuteczny we wszystkich chorobach, w których NPY Y5 jest zaangażowany i jest szczególnie użyteczny do zapobiegania i/lub leczenia otyłości i stłumienia przyjmowania pokarmu. Ponadto antagonista jest skuteczny w zapobieganiu i/lub leczeniu chorób, w których otyłość jest czynnikiem ryzyka, przykładowo cukrzyca, hipertensja, hiperlipemia, miażdżyca i ostry zespół wieńcowy.
Ponadto antagonista receptora NPY Y5 według wynalazku ma niskie powinowactwo do receptorów NPY Y1 i Y2, zaś ma wysoką selektywność do receptora NPY Y5. NPY powoduje przewlekłe działanie zwężające naczynia obwodowe i to działanie zachodzi głównie poprzez receptor Y1. Ponieważ receptor Y5 nie jest zaangażowany w to działanie w ogóle, antagonista receptora NPY Y5 ma niskie ryzyko wywoływania efektów ubocznych opartych na zwężeniu naczyń obwodowych i oczekuje się, że będzie odpowiednio stosowany jako lek zapobiegawczy. Antagonista receptora NPY Y5 wykazuje działanie przeciw otyłości poprzez hamowanie przyjmowania pokarmu. Dlatego jedną z cech jest to, że ten antagonista nie wywołuje efektów ubocznych takich jak przykładowo niestrawność spowodowaną środkiem przeciw otyłości, który hamuje trawienie i absorpcję, oraz głównego efektu ubocznego takiego jak przeciwdziałanie tłumieniu, spowodowanego przez inhibitor przenoszący serotoninę, wykazując działanie przeciw otyłości.
Związek według obecnego wynalazku można podawać doustnie lub pozajelitowo, jako środek przeciw otyłości lub anoreksji. W przypadku podawania doustnego, może to być zwykła forma, taka jak tabletki, granulki, pudry, kapsułki, roztwory, syropy, tabletki dopoliczkowe i podjęzykowe. Gdy związek podaje się pozajelitowo, każda zwykła forma jest korzystna, przykładowo injekcje np. dożylne, domięśniowe, czopki, środki naskórne i pary. Podawanie doustne jest szczególnie korzystne, gdyż związki według wynalazku wykazują wysoką absorbowalność doustną.
Kompozycja farmaceutyczna może być wytwarzana przez zmieszanie skutecznej ilości związku według wynalazku, z różnymi farmaceutycznymi środkami pomocniczymi, odpowiednimi do postaci podawania, takimi jak zaróbki, lepiszcza, środki nawilżające, dezintegratory, środki smarujące i rozPL 211 888 B1 cieńczalniki. Gdy kompozycja przeznaczona jest do wstrzykiwania, składnik aktywny razem z odpowiednim nośnikiem może być sterylizowany dla uzyskania kompozycji farmaceutycznej.
Przykłady zaróbek obejmują laktozę, sacharozę, glukozę, skrobię, węglan wapnia i celulozę krystaliczną. Przykłady lepiscz obejmują metylocelulozę, karboksymetylocelulozę, hydroksypropylocelulozę, żelatynę i poliwinylopirolidon. Przykłady dezintegratorów obejmują karboksymetylocelulozę, karboksymetylocelulozę sodową, skrobię, alginian sodu, agar i laurylosiarczan sodowy. Przykłady środków smarujących obejmują talk, stearynian magnezu i makrogol. Olej kakaowy, makrogol, metyloceluloza itp. mogą być stosowane jako podłoża do czopków. Gdy kompozycja jest wytwarzana jako roztwór, emulgowane lub zawieszone injekcje, można dodać do nich środki przyspieszające rozpuszczanie, środki zawieszające, emulgatory, stabilizatory, konserwanty, środki izotoniczne itp. Do podawania doustnego można dodać środki słodzące, smakowe itp.
Chociaż dawka związku według wynalazku jako środka przeciw otyłości lub przeciw anoreksji, powinna być określona pod względem wieku pacjenta, jego wagi, typu i stopnia chorób, drogi podawania itp. zwykle dawka doustna dla dorosłych wynosi 0.05 do 100 mg/kg/dzień, a korzystnie 0.1 do 10 mg/kg/dzień. Do podawania pozajelitowego dawka znacznie zmienia się wraz z drogami podawania, zwykle dawka wynosi 0.005 do 10 mg/kg/dzień, korzystnie 0.01 do 1 mg/kg/dzień. Dawka może być podawana jednorazowo lub w kilku porcjach dziennie.
Obecny wynalazek jest dalej objaśniony za pomocą przykładów oraz doświadczeń, które nie są przeznaczone do ograniczenia zakresu wynalazku.
P r z y k ł a d y
P r z y k ł a d 1 Synteza związku (I-7)
Etap 1
C5H11NO2 C13H13NO4
C. cząst.: 117.15 C. cząst.: 247.25
Węglan sodu (995 mg, 9.38 mmoli) rozpuszczono w 30 ml wody i dodano wyjściowy aminokwas (1.0 g, 8.53 mmoli) i N-karbetoksyftalimid (2.49 g, 11.4 mmoli) dodano do mieszaniny. Całość mieszano w temperaturze pokojowej przez noc. pH mieszaniny doprowadzono do 1 dodając stężony kwas chlorowodorowy. Wytrącone kryształy przemyto wodą i suszono uzyskując żądany związek (1.72 g, 82% wydajn.).
1H-NMR (CD3OD) δ ppm: 1.59-1.77 (m, 4H), 2.34 (t, 2H, J=6.3 Hz), 3.69 (t, 2H, J=6.6 Hz), 7.78-7.87 (m, 4H).
C13H13NO4
C. cząst.: 247.25 C23H26N2O3
C. cząst.: 378.46
PL 211 888 B1
Związek otrzymany w Etapie 1 (1.0 g, 4.0 mmoli) rozpuszczono w 5 ml dichlorometanu w temperaturze pokojowej. Chlorek oksalilu (0.459 ml, 5.2 mmoli) i do mieszaniny dodano śladową ilość DMF chłodząc lodem. Reakcja przebiegała w warunkach chłodzenia lodem a następnie w temperaturze pokojowej, w okresach po 30 min. Po usunięciu rozpuszczalnika pod obniżonym ciśnieniem, dodano 5 ml dichlorometanu. W warunkach chłodzenia lodem dodano 4-butyloanilinę (664 mg, 4.4 mmoli) i trietyloaminę (0.564 ml. 4.4 mmoli) i prowadzono reakcję przez 30 minut w temperaturze pokojowej. Reagenty wylano do wody i ekstrahowano chloroformem. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem, a pozostałość oczyszczano na kolumnie chromatograficznej z żelem krzemionkowym uzyskując żądany związek (1.49, 97% wydajn.).
1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.27-1.39 (m, 2H), 1.51-1.62 (m, 2H), 1.72-1.84 (m, 4H), 2.40-2.46 (m, 2H), 2.56 (t, 2H, J=7.5 Hz), 3.76 (t, 1H, J=5.7 Hz), 7.12 (d, 2H, J=7.8 Hz), 7.33 (s, 1H), 7.42 (d, 2H, J=8.1 Hz), 7.71-7.73 (m, 2H), 7.83-7.86 (m, 2H).
C15H24N2O C. cząst.: 248.36 C23H26N2O3
C. cząst.: 378.46
Po rozpuszczeniu związku z etapu 2 (1.49 g, 3.9 mmoli) w 30 ml etanolu dodano monohydrat hydrazyny (0.591 mg, 11.8 mmoli) i prowadzono reakcję mieszaniny w temperaturze 50°C przez 3 h. Rozpuszczalnik usunięto, dodano 1 mol/l wodnego NaOH i roztwór ekstrahowano octanem etylu. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem sodu. Rozpuszczalnik usunięto pod zmniejszonym ciśnieniem uzyskując związek (808 mg, 83% wydajn.) 1H-NMR (CD3OD) δ ppm: 0.93 (t, 3H, J=7.2 Hz), 1.28-1.40 (m, 2H), 1.50-1.62 (m, 4H), 1.67-1.77 (m, 2H), 2.37 (t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 2.68 (t, 2H, J=7.2 Hz), 7.11 (d, 2H, J=8.1 Hz), 7.42 (d, 2H, J=8,4 Hz).
C15H24N2O
C. cząst.: 248.36
Związek otrzymany w Etapie 3 (808 mg, 3.25 mmoli) zawieszono w 5 ml dichlorometanu chłodząc lodem i dodano chlorek izopropylosulfonylu (696 mg, 4.9 mmoli) i trietyloaminę (494 mg, 4.9 mmoli). Po przereagowaniu mieszaniny przy chłodzeniu lodem w ciągu 1 h reagenty wylano do wody i ekstrahowano chloroformem. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod zmniejszonym ciśnieniem, a pozostałość oczyszczano chromatograficznie na żelu krzemionkowym uzyskując żądany związek ilościowo.
1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.27-140 (m, 2H), 1.36 (d, 6H, J=6.6 Hz), 1.51-1.69 (m, 4H), 1.77-1.86 (m, 2H), 2.38 (t, 2H, J=7.2 Hz), 2.56 (t, 2H, J=7.5 Hz), 3.12-3.21 (m, 3H), 4.38 (t, 1H, J=5.7 Hz), 7.11 (d, 2H, J=8.4 Hz), 7.36-7.41 (m, 3H).
PL 211 888 B1
C15H24N2O C19H32N2O2S
C. cząst.: 248.36 C. cząst.: 352.54
Żądany związek syntetyzowano w podobny sposób jak w Etapie 4 Przykładu 1 z wyjątkiem tego, że chlorek tert-butylosulfinowy (689 mg, 4.9 mmoli) i trietyloaminę (494 mg, 4.9 mmoli) dodano do związku otrzymanego w Etapie 3 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.22 (s, 9H), 1.30-1.37 (m, 2H), 1.51-1.68 (m, 4H), 1.76-1.86 (m, 2H), 2.31-2.40 (m, 2H), 2.56 (t, 2H, J=7.5 H), 3.15-3.26 (m, 3H), 7.11 (t, 2H, J=8.7 Hz), 7.42 (d, 2H, J=8.1 Hz), 7.54 (s,1H).
P r z y k ł a d 3 Synteza zwią zku (I-11)
C19H32N2O2S C19H32N2O3S
C. cząst.: 352.54 C. cząst.: 368.54
Związek otrzymany w Przykładzie 2 (352 mg, 1.0 mmoli) rozpuszczono w 5 ml dichlometanu chłodząc lodem i do roztworu dodano mCPBA (259 mg, 1.5 mmoli). Prowadzono reakcję w temperaturze pokojowej przez 1 h, po czym odfiltrowano nierozpuszczalny materiał. Filtrat przemyto kolejno 1 mol/NaOH, Na2S2O5 i wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem, a pozostałość oczyszczono chromatograficznie na żelu krzemionkowym uzyskując żądany związek (338 mg, 92% wydajn.).
1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.29-1.39 (m, 2H), 1.39 (s, 9H), 1.51-1.68 (m, 4H), 1,76-1.84 (m, 2H), 2.37 (t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.19-3.26 (m, 2H), 4.20 (t, 1H, J=5.7 Hz), 7.11 (t, 2H, J=8.1 Hz), 7.42 (d, 2H, J=8.7 Hz), 7.46 (s, 1H).
P r z y k ł a d 4 Synteza zwią zku (I-72)
Etap 1
C7H13NO2 Mol. Wt.: 143.18
CoH, 6CINO2 Mol. Wt.: 193.67
C7H13NO2 C8H16ClNO2
C. cząst.: 143.18 C. cząst.: 193.67
Wyjściowy aminokwas (mieszanka izomeru cis i izomeru trans) (1.0 g, 8.53 mmoli) rozpuszczono w 7.5 ml metanolu. Do mieszaniny dodano chlorek tionylu (1.0 ml, 13.7 mmoli) chłodząc lodem i cał o ść mieszano w temperaturze pokojowej przez noc. Po zatężeniu mieszaniny pod obniż onym ciśnieniem dodano dietyloeter i uzyskano wytrącone kryształy drogą filtracji. Kryształy przemyto dietyloeterem i suszono uzyskując żądany związek (1.25 g, 93% wydajn.)
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.50-2.60 (m, 9H), 3.08-3.36 (m, 1H), 3.67 (s, 3H, O2Me cis izomeru), 3.71, CO2Me trans izomeru), 8.15-8.55 (m, 3H).
Etap 2
Λ·α
HCl
COjMe s
II o
mCPBA
Et3N
C8H16CINO2 Mol. Wt.: 193.67
Ci 2M23NO4S Mol. WL: 277.38
C8H16ClNO2 C12H23NO4S
C. cząst.: 193.67 C. cząst.: 277.38
Żądany sulfonamid (mieszanina izomerów cis i trans) syntetyzowano z wyjściowego estru metylowego w podobny sposób jak w Etapie 3 Przykładu 1 i Przykładu 2.
Izomer cis 1H-NMR (CDCl3) δ ppm: 1.39 (s, 9H), 1.52-1.99 (m, 8H), 2.43-2.53 (m, 1H), 3.42-3.55 (m, 1H), 3.69 (s, 3H), 3.85 (d, 1H, J=9.0 Hz).
Etap 3
C12H23NO4S C12H23NO4S
C. cząst.: 277.38 C. cząst.: 277.38
Wyjściowy sulfonamid (19.4 g, 70,0 mmoli, mieszanina cis izomeru i trans izomeru) rozpuszczono w 30 ml metanolu. Do mieszaniny 28% metanolu sodu dodano (9284 m, 140,0 mmoli) i ogrzewano pod chłodnicą zwrotną chłodząc lodem i mieszając. Po usunięciu rozpuszczalnika pozostałość rozcieńczono chloroformem i dodano 1 mol/HCl mieszając w warunkach chłodzenia lodem aż do osiągnięcia pH = 3 dla warstwy wodnej. Warstwę wodną ekstrahowano chloroformem, fazę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu uzyskane surowe kryształy rekrystalizowano z mieszaniny heksan-etylooctan uzyskując żądany sulfonamid (trans izomer, 7.75 g, 40 wydajn.).
trans izomer 1H-NMR (CD3OD) δ ppm: 1.16-1.32 (m, 2H), 1.39 (s, 9H), 1.44-1.52 (m, 2H), 1.98-2.09 (m, 2H), 2.14-2.29 (m, 3H), 3.18-32.37 (m, 1H), 3.63 (d, 1H, J=9.0 Hz), 3.67 (s, 3H),
Etap 4
C12H23NO4S C11H21NO4S
C. cząst.: 277.38 C. cząst.: 263.35
Wyjściowy ester metylowy (4.77 g, 17.2 mmoli) rozpuszczono w 95 ml metanolu i 1 mol/NaOH (43 ml, 43.0 mmoli) dodano do mieszaniny w warunkach chłodzenia lodem. Całość mieszano w temperaturze pokojowej przez noc i zatężono pod obniżonym ciśnieniem. Po dodaniu 1 mol/HCl z miePL 211 888 B1 szaniem do pH mieszaniny 3 w warunkach chłodzenia lodem, wytrącone kryształy odfiltrowano, przemyto wodą i suszono. Surowe kryształy rekrystalizowano z mieszaniny heksan-octan etylu uzyskując żądany kwas karboksylowy (4.20 g, 93% wydajn.).
1H-NMR (CDCI3) δ ppm: 1.18-1.35 (m, 2H), 1.39 (s, 9H), 1.46-1.63 (n, 2H), 2.01-2.14 (m, 2H), 2.14-2.32 (m, 3H), 3.18-3.35 (m, 1H), 3.80 (d, 1H, J=9.6 Hz).
Etap 5
C11H21NO4S C23H37N3O4S
C. cząst.: 263.35 C. cząst.: 451.62
Wyjściowy kwas karbocykliczny (95.86 g, 22.3 mmoli) rozpuszczono w 88 ml dichlorometanu w temperaturze pokojowej. Do mieszaniny dodano chlorek oksalilu (2.341, 26,7 mmoli) i katalityczną ilość DMF w warunkach chłodzenia lodem i mieszano w temperaturze pokojowej przez 1 h. Po usunięciu rozpuszczalnika pod obniżonym ciśnieniem dodano dichlorometan (115 ml), podstawioną anilinę (5.05 g, 24.5 mmoli) i trietyloaminę (4.65 ml, 33.4 mmoli). Całość mieszano w temperaturze pokojowej przez 2.5 h, dodano lodowatej wody i mieszaninę ekstrahowano chloroformem. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod zmniejszonym ciśnieniem i do pozostałości dodano octan etylu i heksan. Wytrącone kryształy odfiltrowano uzyskując żądany amid (7.00 g, 70% wydajn.).
1H-NMR (CDCI3) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.17-1.42 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.43 (m, 7H), 3.20-3.43 (m, 3H), 3.67 (d, 1H, J=9.6 Hz), 3.74-3.86 (m, 2H), 6.86 (d, 2H, J=9.0 Hz), 7.04 (s, 1H), 7.38 (d, 2H, J=9.0 Hz).
P r z y k ł a d 5 Synteza zwią zku (I-2)
Po zawieszeniu wyjściowej diaminy (461 mg, 2.5 mmoli) w dichlorometanie i podczas chłodzenia lodem dodano chlorek kwasowy (500 mg, 2.5 mmoli) i trietyloaminę (773 mg, 7.5 mmoli) i prowadzono reakcję mieszaniny przez 30 min. Dodano wodę i dichlorometan, po czym odfiltrowano substancje nierozpuszczalne. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem uzyskując żądany związek jako pozostałość (9100 mg, 15% wydajn.).
1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J=7.2 Hz), 1.30-1.42 (m, 2H), 1.57-1.67 (m, 2H), 1.66 (t, 2H, J=7.8 Hz), 3.50 (brs, 1H), 6.57 (s, 1H), 6.68 (d, 2H, J=8.7 Hz), 7.26 (d, 2H, J=8.4 Hz), 7.39 (d, 2H, J=8.7 Hz), 7.68 (s, 1H), 7.75 (d, 2H, J=8.1 Hz).
PL 211 888 B1
C17H20N2O C20H26N2O3S
C. cząst.: 268.35 C. cząst.: 374.50
Żądany związek syntetyzowano w podobny sposób jak w Etapie 4 Przykładu 1.
1H-NMR (CDCl3) δ ppm: 0.94 (t, 3H, J=7.5 Hz), 1.34-1.44 (m, 2H), 1.40 (d, 6H, J=6.6Hz), 1.59-1.68 (m, 2H), 2.69 (t, 2H, J=7.8 Hz), 3.24-3.35 (m, 1H), 6.49 (s, 1H), 7.23-7.32 (m, 4H), 7.6 (d, 2H, J=8.7 Hz), 7.79 (d, 2H, J=8.1 Hz), 7.85 (s, 1H).
P r z y k ł a d 6 Synteza Zwią zku (I-36)
Etap 1
C11H22N2O2 C6H14N2
C. cząst.: 114.19 C. cząst.: 214.30
Wyjściową diaminę (8.37 g, 73.3 mmoli) rozpuszczono w 30 ml dioksanu w temperaturze pokojowej i dodano roztwór Boc2O (2 g, 9.2 mmoli) w dioksanie (30 ml). Prowadzono reakcję mieszaniny w temperaturze pokojowej przez 3 dni i usunię to rozpuszczalnik. Dodano wodę do pozostał o ś ci i mieszaninę ekstrahowano chloroformem. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem uzyskując żądany związek jako pozostałość (1.8 g, 92% wydajn. licząc na Boc2O).
1H-NMR (CDCl3) δ ppm: 1.07-1.26 (m, 6H), 1.44 (s, 9H), 1.84-2.00 (m, 4H), 2.58-2.67 (m, 1H), 3.37 (brs, 1H), 4.43 (brs, 1H).
C11H22N2O2 C22H34N2O3
C. cząst.: 214.30 C. cząst.: 374.52
Żądany związek syntetyzowano w podobny sposób jak w Etapie 1 Przykładu 5.
1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.26-1.42 (m, 6H), 1.45 (s, 9H), 1.54-1.68 (m, 2H), 1.99-2.12 (m, 4H), 2.64 (t, 2H, J=7.8 Hz), 3.43 (brs, 1H), 3.90-4.00 (m, 1H), 4.48 (d, 1H, J=5.7 Hz), 5.95 (d, 1H, J=8.4 Hz), 7.21 (d, 2H, J=8,4 Hz), 7.65 (d, 2H, J=8.4 Hz).
PL 211 888 B1
C22H34N2O3 C17H27ClN2O
C. cząst.: 374.52 C. cząst.: 310.86
Wyjściowy Boc związek (2.08 g, 5.55 mmoli) rozpuszczono w 20 ml octanu etylu chłodząc lodem i dodano 20 ml 4 mol/lHCl/AcOEt. Prowadzono reakcję mieszaniny przez 1 h, po czym usunięto rozpuszczalnik pod obniżonym ciśnieniem uzyskując żądany związek jako pozostałość (1.7 g, 98% wydajn.) 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J=7.2 Hz), 1.29-1.41 (m, 2H), 1.50-1.66 (m, 6H), 2.02-2.18 (m, 4H), 2.66 (t, 2H, J=7.8 Hz), 3.13 (brs, 1H), 3.82-3.94 (m, 1H), 7.26 (d, 2H, J-8.7 Hz), 7.72 (d, 2H, J=8.4 Hz).
Etap 4
C17H27ClN2O C21H34N2O2S
C. cząst.: 31-.86 C. cząst.: 378.57
Żądany związek syntetyzowano w podobny sposób jak w Etapie 4 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 1.21 (s, 9H), 1.28-1.62 (m, 8H), 2.07-2.14 (m, 4H), 2.64 (t, 2H, J=7.8 Hz), 3.11 (d, 1H, J=5.1 Hz), 3.20 (brs, 1H), 3.90-4.04 (m, 1H), 6.06-6.14 (m, 1H), 7.21 (t, 2H, J=8.1 Hz), 7.67 (t, 2H, J=8.4 Hz).
P r z y k ł a d 7 Synteza związku (I-32)
C21H34N2O3S C21H34N2O3S
C. cząst.: 378.57 C. cząst.: 394.57
Żądany związek syntetyzowano ze związku otrzymanego w Przykładzie 6 w podobny sposób jak w Przykładzie 3.
1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.27-1,65 (m, 8H), 1.40 (s, 9H), 2.10-2.23 (m, 4H), 2.65 (t, 2H, J=7.5 Hz), 3.23-3.35 (m, 1H), 3.49 (s, 1H), 3.88-4,02 (m, 1H), 5.84-5.92 (m, 1H), 7.13 (t, 2H, J=8.4 Hz), 7.65 (d, 2H, J=8.1 Hz).
PL 211 888 B1
P r z y k ł a d 8 Synteza zwią zku (I-5) Etap 1
C5H3NO4S C15H16N2O3S
C. cząst.: 173.15 C. cząst.: 304.37
Żądany związek syntetyzowano w podobny sposób jak w Etapie 2 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 0.94 (t, 3H, J=7.5Hz), 1.30-1.42 (m, 2H), 1.50-1.65 (m, 2H), 2.61 (t, 2H, J=78 Hz), 7.20 (d, 2H, J=7.2 Hz), 7.48-7.51 (m, 3H), 7.72 (s, 1H), 7.88-7.90 (m, 1H).
C15H16N2O3S C15H18N2OS
C. cząst.: 304.37 C. cząst.: 274.38
Do mieszaniny wyjściowego związku nitrowego (593 mg, 1.95 mmoli) i cyny (358 mg, 3.0 mmoli) dodano 30 ml 6 ml/l HCI i 6 ml THF i prowadzono reakcję w temperaturze 50°C przez 3 h. Po ochłodzeniu rozpuszczalnik usunięto a pozostałość neutralizowano 10% NaOH i ekstrahowano chloroformem. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem a pozostałość oczyszczano chromatograficznie na żelu krzemionkowym uzyskując żądany związek (110 mg, 21% wydajn.).
1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.26-1.39 (m, 2H), 1.49-1,59 (m, 2H), 2.50 (t, 2H, J=7.8 Hz), 4.37 (s, 1H), 6.65 (d, 2H, J=8.4 Hz), 6.97 (d, 2H, J=8.4 Hz), 7.14 (d, 1H, J=8.4 Hz), 7.43 (d, 1H, J=8.7 Hz).
Etap 3
Żądany związek syntetyzowano w podobny sposób jak w Etapie 4 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.28-1.41 (m, 2H), 1.46 (d, 6H, J=6.9 Hz), 1.53-1.63 (m, 2H), 2.59 (t, 2H, J=7.8 Hz), 3.35-3.44 (m, 1H), 7.15 (d, 2H, J=8.7 Hz), 7.38 (s, 1H), 7.45 (d, 2H, J=8.7 Hz), 7.57 (s, 1H).
PL 211 888 B1
P r z y k ł a d 9 Synteza związku (I-4) Etap 1
H
C6H7NO3 Mol.Wt.: 141.12
C9H13NO5S Mol. Wt.: 247.27
C6H7NO3 C9H13NO5S
C. cząst.: 141.12 C. cząst.: 247.27
Żądany związek syntetyzowano w podobny sposób jak w Etapie 4 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 1.44 (d, 6H, J=6.9 Hz), 3.33-3.43 (m, 1H), 3.88 (s, 9H), 6.24-6.26 (m, 1H), 7.11-7.14 (m, 2H).
Etap 2
H
N.
NaOH
ÓMe
C9H13NOsS
Mol.Wt.: 247.27 \ N_-0 <
c8h71no5s
Mol. Wt.: 233.24 POH
C9H13NO5S C8H11NO5S
C. cząst.: 247.27 C. cząst.: 233.24
Żądany związek syntetyzowano w podobny sposób jak w Etapie 4 Przykładu 4.
1H-NMR (CDCI3) δ ppm: 1.44 (d, 6H, J=6.3 Hz), 3.33-3.45 (m, 1H), 6.25-6.28 (m, 1H), 7.27-7.28 (m, 1H), 7.51 (s, 1H).
Etap 3
C18H24N2O4S
C8H11NO5S
C. cząst.: 233.24 C. cząst.: 364.46
Żądany związek syntetyzowano w podobny sposób jak w Etapie 2 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J=6.9 Hz), 1.28-1.41 (m, 2H), 1.46 (d, 6H, J=6.3 Hz), 1.53-1.63 (m, 2H), 2.58 (t, 2H, J=7.8 Hz), 3.33-3.43 (m, 1H), 6.27-6.29 (m, 1H), 7.14-7.16 (m, 3H), 7.50 (d, 2H, J=8.4 Hz), 7.90 (s, 1H).
P r z y k ł a d 10 Synteza związku (I-28)
Etap 1
C14H15NO3 C. cząst.: 151.63
C. cząst.: 245.27
PL 211 888 B1
Żądany związek syntetyzowano w podobny sposób jak w Etapie 1 Przykładu 1.
1H-NMR (CDCI3) δ ppm: 1.37-1.52 (m, 3H), 1.74-1.79 (m, 2H), 2.07-2.13 (m, 2H), 2.28-2.42 (m, 2H), 3.72-3.81 (m, 1H), 4.09-4.20 (m, 1H), 768-7.73 (m, 2H), 7.81-7.85 (m, 2H).
Etap 2
C14H15NO3 C25H28N2O4
C. cząst.: 245.27 C. cząst.: 420.50
Izocyjanian 4-butylofenylu (2.85 g, 16.3 mmoli) rozpuszczono w 30 ml THF i dodano wyjściowy alkohol (1.0 g, 4.08 mmoli) i tlenek bis(tributylocyny) (972 mg, 1.63 mmoli). Po mieszaniu reagentów w cią gu nocy rozpuszczalnik usunię to, dodano wodę i roztwór ekstrahowano chloroformem. Warstwę organiczną przemyto wodą i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem, a pozostałość oczyszczano chromatograficznie na żelu krzemionkowym uzyskując żądany związek (332 mg, 19% wydajn.).
1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J=6.9 Hz), 1.30-1.40 (m, 2H), 1.48-1.62 (m, 4H), 1.79-1.83 (m, 2H), 2.21-2.25 (m, 2H), 2.37-2.50 (m, 2H), 2.57 (t, 2H, J=7.8 Hz), 4.11-4.22 (m, 1H), 4.77-4.87 (m, 1H), 6.49 (s, 1H), 7.11 (d, 3H, J=8.7 Hz), 7.28 (d, 2H, J=8.7 Hz), 7.69-7.73 (m, 2H), 7.80-7.84 (m, 2H).
C25H28N2O4 C. cząst.: 420.50 C21H34N2O3S C17H26N2O2 C. cząst.: 290.40
C. czą st.: 394.57
Żądany związek syntetyzowano w podobny sposób jak w Etapie 3 Przykład 1 i Przykład 2. 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.21 (s, 9H), 1.30-1.62 (m, 8H), 2.08 (d, 4H,
J=11.1 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.04 (d, 1H, J=4.8Hz), 3.20-3.30 (m, 1H), 4.65-4.76 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.7 Hz), 7.26 (d, 2H, J=8.1 Hz).
PL 211 888 B1
P r z y k ł a d 11 Synteza związku (I-29)
mCPBA
C21H34N2O3S C21H34N2O4S
C. cząst.: 394.57 C. cząst.: 410.57
Żądany związek syntetyzowano w podobny sposób jak w Przykładzie 1.
1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.23-1.62 (m, 8H), 1.40 (s, 9H), 2.12 (d, 4H, J=14.4 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.28-3.40 (m, 1H), 3.90 (s, 1H), 4.60-4.73 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.4 Hz), 7.25 (d, 2H, J=8.4 Hz).
P r z y k ł a d 12 Synteza związku (I-114)
Reagent Lawessona [2,4(bis(4-metoksyfenylo)-1,3-ditia-2,4-difosfetano-2,4-disiarczek] (132 mg) dodano do roztworu 100 mg związku (I-110) syntetyzowanego w podobny sposób w Przykładzie 1 w toluenie (2.7 ml) i całość mieszano w temperaturze 80°C przez 3 h. Reagenty zatężono pod obniżonym ciśnieniem, a pozostałość oczyszczano chromatograficznie na żelu krzemionkowym (etylooctan: n-heksan = 1:1) uzyskując bladożółte kryształy (82.3 mg, 79%), które rekrystalizowano z mieszaniny chlorek metylenu-eter diizopropylowy uzyskując żądany związek jako bezbarwne igły (50.5 mg, 48%).
P r z y k ł a d 13 Synteza związku (I-20)
Etap 1 H2Nr> s . ^·νό ^N'CO2Et θ ^NCO2Ęt
Etylo-4-amino-1-piperydynokarboksylan (300 mg) i trietyloaminę (258 mg) rozpuszczono w 5 ml dichlorometanu. Do mieszaniny dodano 2 ml roztworu chlorku t-butylosulfinylu (222 g) w dichlorometanie i całość mieszano w temperaturze pokojowej przez 4 h. Roztwór rozdzielono na fazę wodną kwaśnego węglanu potasu oraz octan etylu. Warstwę organiczną przemyto solanką i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem i pozostałość oczyszczano chromatograficznie na żelu krzemionkowym uzyskując 378 mg 4-butylosulfiny amino-1-etoksykarbonylo-piperydyny.
Etap 2
W mieszaninie 5 ml 2-propanolu i 5 ml wody zawieszono 378 mg 4-t-butylosulfinyloamino-1-etoksykarbonylopiperydyny i dodano 1.77 g wodorotlenku baru. Mieszaninę ogrzewano pod chłodnicą zwrotną mieszając przez 4 h, po czym rozcieńczono metanolem i odfiltrowano nierozpuszczalne substancje. Rozpuszczalnik usunięto pod obniżonym ciśnieniem uzyskując 4-t-butylosulfinyloaminopiperydynę. Bez oczyszczania uzyskany produkt rozpuszczono w 5 ml THF i dodano 984 mg N-fenoksykarbonylo-4-butyloaniliny i 236 mg diizopropyloetyloaminy, po czym mieszano przez noc
PL 211 888 B1 w temperaturze pokojowej. Dodano wodny roztwór kwaśnego siarczanu potasu i mieszaninę ekstrahowano octanem etylu. Warstwę organiczną przemyto solanką i suszono nad bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem, a pozostałość oczyszczano chromatograficznie na żelu krzemionkowym uzyskując 291 mg (4-t-butylofenylo)amidu kwasu 4-t-butylo-sulfinyloamino-piperydyno-1-karboksylowego.
1H-NMR (CDCI3) δ ppm: 0.89 (t, 3H, J=7.3 Hz), 1.19 (s, 9H), 1.25-1.38 (m, 4H), 1.40-1.60 (m, 4H), 1.89-2.03 (m, 3H), 2.52 (t, 2H, J=7.7 Hz), 2.89-3.04 (m, 2H), 3.14 (d, 1H, J=5.2 Hz), 3.37 (m, 1H), 3.96 (m, 2H), 6.67 (s, 1H), 7.05 (d, 2H, J=8.5 Hz), 7.22 (d, 2H, J=8.5 Hz).
Etap 3
W mieszaninie 2 ml metanolu i 2 ml chlorku metylenu rozpuszczono 291 mg (4-t-butylofenylo)amidu kwasu 4-t-butylosulfinyloaminopiperydyn-1-karboksylowego. Do mieszaniny dodano 570 mg 80% MMPP (sześciohydrat monoperoksyftalanu magnezu) i całość mieszano w temperaturze pokojowej przez 2 h. Warstwę organiczną przemyto solanką i suszono bezwodnym siarczanem magnezu. Rozpuszczalnik usunięto pod obniżonym ciśnieniem a pozostałość oczyszczono chromatograficznie na żelu krzemionkowym uzyskując 130 mg (4-butylofenylo)amidu kwasu 4-t-butylosulfonyloaminopiperydyno-1-karboksylowego.
(I-120)
Inne związki (I) syntetyzowano podobnymi metodami. Struktury i właściwości fizyczne pokazano poniżej.
PL 211 888 B1
PL 211 888 B1
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PL 211 888 B1
I-2 1H-NMR (CDCI3) δ ppm: 0.94 (t, 3H, J = 7.5 Hz), 1.34-1.44 (m, 2H), 1.40 (d, 6H, J = 6.6 Hz), 1.59-1.68 (m, 2H), 2.69 (t, 2H, J = 7.8 Hz), 3.24-3.35 (m, 1H), 6.49 (s, 1H), 7.23-7.32 (m, 4H), 7.6 (d, 2H, J = 8.7 Hz), 7.79 (d, 2H, J = 8.1 Hz), 7.85 (s, 1H).
I-3 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.2 Hz), 1.30-1.39 (m, 2H), 1.37 (d, 6H, J = 6.9 Hz), 1.57 (kwintet, 2H, J = 7.5 Hz), 1.96 (kwintet, 2H, J = 6.6 Hz), 2.49 (t, 2H, J = 6.6 Hz), 2.57 (t, 2H, J = 7.8 Hz), 3.16-3.26 (m, 3H), 4.62 (brs, 1H), 7.12 (d, 2H, J = 8.1 Hz), 7.43 (d, 2H, J = 8.4 Hz), 7.64 (s, 1H).
I-4 1H-NMR (CD3OD) δ ppm: 0.92 (t, 3H, J = 6.9 Hz), 1.28-1.41 (m, 2H), 1.46 (d, 6H, J = 6.3 Hz), 1.53-1.63 (m, 2H), 2.58 (t, 2H, J = 7.8 Hz), 3.33-3.43 (m, 1H), 6.27-6.29 (m, 1H), 7.14-7.16 (m, 3H),
7.50 (d, 2H, J = 8.4 Hz), 7.90 (s, 1H).
I-5 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.2 Hz), 1.28-1.41 (m, 2H), 1.46 (d, 6H, J = 6.9 Hz), 1.53-1.63 (m, 2H), 2.59 (t, 2H, J = 7.8 Hz), 3.35-3.44 (m, 1H), 7.15 (d, 2H, J = 8.7 Hz), 7.38 (s, 1H), 7.45 (d, 2H, J = 8.7 Hz), 7.57(s, 1H).
I-6 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.29-1.39 (m, 2H), 1.37 (d, 6H, J = 6.9 Hz),
1.55 (kwintet, 2H, J = 7.5 Hz), 2.55 (t, 2H, J = 5.1 Hz), 3.18-3.27 (m, 1H), 3.92 (d, 2H, J = 6.0 Hz),
5.51 (t, 1H, J = 5.7 Hz), 7.10 (d, 2H, J = 8.4 Hz), 7.39 (d, 2H, J = 8.4 Hz), 8.23 (s, 1H).
I-7 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.28-1.38 (m, 2H), 1.37 (d, 6H, J = 6.9 Hz),
1.51- 1.67 (m, 4H), 1.78-1.88 (m, 2H), 2.39 (t, 2H, J = 7.2 Hz), 2.57 (t, 2H, J = 7.5 Hz), 3.12-3.22 (m, 3H), 4.30-4.37 (m, 1H), 7.12 (d, 2H, J = 8.4 Hz), 7.36-7.42 (m, 3H).
I-8 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.21-1.47 (m, 4H), 1.35 (d, 6H, J = 6.6 Hz),
1.51- 1.63 (m, 4H), 1.67-1.77 (m, 2H), 2.34 (t, 2H, J = 7.5 Hz), 2.55 (t, 2H, J = 7.8 Hz), 3.08-3.17 (m, 3H), 4.71 (t, 1H, J = 6.0Hz), 7.09 (d, 2H, J = 8.1 Hz), 7.43 (d, 2H, J = 8.4 Hz), 7.74 (s, 1H).
I-9 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7,2 Hz), 1.29-1.39 (m, 2H), 1.35 (d, 6H, J = 6.9 Hz),
1.50- 1.60 (m, 2H), 2.54 (t, 2H, J = 7.8 Hz), 2.64 (t, 2H, J = 5.7 Hz), 3.14-3.23 (m, 1H), 3.41-3.47 (m, 2H), 5.29 (t, 1H, J = 6.3Hz), 7.10 (d, 2H, J = 8.4Hz), 7.39 (d, 2H, J = 8.4Hz), 7.91 (s, 1H).
I-10 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.22 (s, 9H), 1.30- 1.37 (m, 2H), 1.51-1.68 (m, 4H), 1.76-1.86 (m, 2H), 2.31- 2.40 (m, 2H), 2.56 (t, 2H, J = 7.5 Hz), 3.15-3.26 (m, 3H), 7.11 (t, 2H, J = 8.7 Hz), 7.42 (d, 2H, J = 8.1 Hz), 7.54 (s, 1H).
I-11
t.t.: 128-129°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.29-1.39 (m, 2H), 1.39 (s, 9H), 1.51-1.68 (m, 4H), 1.76-1.84 (m, 2H), 2.37 (t, 2H, J = 7.5 Hz), 2.56 (t, 2H, J = 7.8 Hz), 3.19-3.26 (m, 2H), 4.20 (t, 1H, J = 5.7 Hz), 7.11 (d, 2H, J = 8.1 Hz), 7.42 (d, 2H, J = 8.7 Hz), 7.46 (s, 1H).
I-12 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.28-1.37 (m, 2H), 1.47-1.68 (m, 6H), 2.23 (t, 2H, J = 7.2 Hz), 2.56 (t, 2H, J = 7.5 Hz), 2.90-2.97 (m, 2H), 5.10 (brs, 1H), 7.11 (d, 2H, J = 8.4 Hz),
7.36 (d, 2H, J = 8.1 Hz), 7.50-7.68 (m, 3H), 7.93 (d, 1H, J = 8.1 Hz), 8.06 (d, 1H, J = 8.4 Hz), 8.24 (d, 1H, J = 7.5 Hz), 8.66 (d, 1H, J = 8,7 Hz).
I-13 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.28-1.40 (m, 2H), 1.45-1.73 (m, 6H), 2.23 (t, 2H, J = 7.5 Hz, 2.56 (t, 2H, J = 7.8 Hz), 2.88 (s, 6H), 2.88-2.95 (m, 2H), 5.04 (brs, 1H), 7.10 (d, 2H, J = 8.1 Hz), 7.17 (d, 1H, J = 7,2 Hz), 7.37 (d, 2H, J = 8.4 Hz), 7.48-7.54 (m, 2H), 8.23 (d, 1H, J = 7,2 Hz), 8.30 (d, 1H, J = 8.7 Hz), 8.53 (d, 1H, J = 8.4 Hz).
I-14 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.30-1.43 (m, 6H), 1.36 (d, 6H, J = 6.6 Hz),
1.51- 1.62 (m, 4H), 1.67-1.78 (m, 2H), 2.34 (t, 2H, J = 7.5 Hz), 2.56 (t, 2H, J = 7.8 Hz), 3.09-3.20 (m, 3H), 4.34 (brs, 1H), 7.10 (d, 2H, J = 8.4 Hz), 7.41-7.44 (m, 3H).
PL 211 888 B1
I-15 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.23 (s, 9H), 1.27-1.80 (m, 12H), 2.30-2.38 (m, 2H), 2.56 (t, 2H, J = 7.5Hz), 3.15 (brs, 2H), 7.11 (d, 2H, J = 7.8 Hz), 7.43 (d, 2H, J = 7.8 Hz), 7.59 (s, 1H).
I-16 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.29-1.44 (m, 6H), 1.39 {s, 9H), 1.51-1.61 (m, 4H), 1.68-1.78 (m, 2H), 2.35 (t, 2H, J = 7.5 Hz), 2.56 (t, 2H, J = 8.1 Hz), 3.15-3.21 (m, 2H), 4.14-4.23 (m, 1H), 7.11 (d, 2H, J = 7.8 Hz), 7.36-7.44 (m, 3H).
I-19 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.5 Hz), 1.21 (s, 9H), 1.30-1.40 (m, 2H), 1.55-1.72 (m, 6H), 2.64 (t, 2H, J = 7.8 Hz), 3.08-3.33 (m, 3H), 3.42-3.50 (m, 2H), 6.39 (s, 1H), 7.22 (d, 2H, J =
8.4 Hz), 7.69 (d, 2H, J = 8.1 Hz).
I-20 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.2 Hz), 1.31-1.39 (m, 2H), 1.39 (s, 9H), 1.55-1.72 (m, 6H), 2.64 (t, 2H, J = 7.8 Hz), 3.24 (kwartet, 2H, J = 6.6 Hz), 3.48 (kwartet, 2H, J = 6.6 Hz), 4.21 (t, 1H, J = 6.3 Hz), 6.29 (s, 1H), 7.22 (d, 2H, J = 7.8 Hz), 7.67 (d, 2H, J = 8.1 Hz).
I-21 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.23 (s, 9H), 1.30-1.42 (m, 2H), 1.50-2.02 (m, 10H), 2.30-2.42 (m, 1H), 2.57 (t, 2H, J = 8.1 Hz), 3.10 (brs, 1H), 3.57 (brs, 1H), 7.12 (d, 2H, J = 8.4 Hz), 7.41 (d, 2H, J = 7.8 Hz).
I-22
t.t.: 78-79°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.30-1.40 (m, 2H), 1.40 (s, 9H), 1.50-1.65 (m. 4H), 1.70-1.98 (m, 8H), 2.30-2.40 (m, 1H), 2.57 (t, 2H, J = 7.5 Hz), 3.58-3.70 (m, 1H), 4.16 (d, 1H, J = 9,3Hz), 7.11-7.15 (m, 3H), 7.40 (d, 2H, J = 8.1 Hz).
I-23 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.21 (s, 9H), 1.21-1.41 (m, 4H), 1.51-1.64 (m, 4H), 1.86-2.01 (m, 4H), 2.12-2.25 (m, 1H), 2.56 (t, 2H, J = 7.5 Hz), 2.87-2.96 (m, 1H), 3.00-3.12 (m, 1H), 3.23-3.34 (m, 1H), 3.67-3.75 (m, 1H), 7.11 (d, 2H, J = 8.1 Hz), 7.40 (d, 2H, J = 8.4 Hz).
I-24 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.25-1.37 (m, 2H), 1.40 (s, 9H), 1.48-1.65 (m, 6H), 1.90 (d, 2H, J = 11.7 Hz), 2.02 (d, 2H, J = 11.7 Hz), 2.12-2.24 (m, 1H), 2.56 (t, 2H, J = 7,5 Hz), 3.04 (t, 2H, J = 6.3 Hz), 4.31 (t, 1H, J = 5.7 Hz), 7.11 (d, 2H, J = 8.1 Hz), 7.42 (d, 2H, J = 8.4 Hz).
I-25
t.t.: 232-233°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.23-1.40 (m, 4H), 1.40 (s, 9H), 1.51-1.76 (m, 4H), 2.01-2.26 (m, 5H), 2.56 (t, 2H, J = 7.5 Hz), 3.22-3.38 (m, 1H), 3.79 (d, 1H, J = 9.3 Hz), 7.11 (d, 2H, J = 8.7 Hz), 7.17 (s, 1H), 7.40 (d, 2H, J = 8.4 Hz).
I-26 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.22 (s, 9H), 1.28-1.40 (m, 2H), 1.52-1.62 (m, 2H), 1.85-1.96 (m, 1H), 2.00-2.14 (m, 1H), 2.38-2.53 (m, 2H), 2.56 (t, 2H, J = 7.5Hz), 3.22-3.37 (m, 3H), 7.11 (d, 2H, J = 8.4 Hz), 7.45 (d, 2H, J = H 8.4 Hz), 8.19 (s, 1H).
I-27 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.30-1.40 (m, 2H), 1.40 (s, 9H), 1.52-1.61 (m, 2H), 1.95 (kwintet, 2H, J = 6.3 Hz), 2.50 (t, 2H, J = 6.9 Hz), 2.56 (t, 2H, J = 7.8 Hz), 3.31 (kwartet, 2H, J = 6.0 Hz), 4.30-4.36 (m, 1H), 7.12 (d, 2H, J = 8.4 Hz), 7.43 (d, 2H, J = 8.4Hz), 7.65 (s, 1H).
I-28 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.2 Hz), 1.21 (s, 9H), 1.30-1.62 (m, 8H), 2.08 (d, 4H, J = 11.1 Hz), 2.56 (t, 2H, J = 7.8 Hz), 3,04 (d, 1H, J = 4.8 Hz), 3.20-3.30 (m, 1H), 4.65-4.76 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J = 8.7 Hz), 7.26 (d, 2H, J = 8.1Hz).
I-29 1H-NMR (CDCI3) δ ppm; 0.91 (t, 3H, J = 7.2Hz), 1.23-1.62 (m, 8H), 1.40 (s, 9H), 2.12 (d, 4H, J = 14.4 Hz), 2.56 (t, 2H, J = 7.8 Hz), 3.28-3.40 (m, 1H), 3.90 (s, 1H), 4.60-4.73 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J = 8.4 Hz), 7.25 (d, 2H, J = 8.4Hz).
PL 211 888 B1
I-30 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5 Hz), 1.26-1,39 (m, 2H), 1.51-1.64 (m, 4H), 1.721.81 (m, 2H), 2.34 (t, 2H, J = 6.9 Hz), 2.56 (t, 2H, J = 7.8 Hz), 2.95-3.01 (m, 2H), 4.84 (t, 1H, J = 5.7 Hz), 6.99-7.12 (m, 6H), 7.19-7.24 (m, 1H), 7.30 (s, 1H), 7.38-7.43 (m, 4H), 7.79 (d, 2H, J = 8.7Hz).
I-31 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.5 Hz), 1.21(s, 9H), 1.28-1.62 (m, 8H), 2.07-2.14 (m, 4H), 2.64 (t, 2H, J = 7.8Hz), 3.11 (d, 1H, J = 5.1Hz), 3.20 (brs, 1H), 3.90-4.04 (m, 1H), 6.06-6.14 (m, 1H), 7.21 (t, 2H, J = 8.1 Hz), 7.67 (t, 2H, J = 8.4 Hz).
I-32 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.2 Hz), 1.27-1.65 (m, 8H), 1.40 (s, 9H), 2.10-2.23 (m, 4H), 2.65 (t, 2H, J = 7.5 Hz), 3.23-3.35 (m, 1H), 3.49 (s, 1H), 3.88-4.02 (m, 1H), 5.84-5.92 (m, 1H), 7.13 (t, 2H, J = 8.4 Hz), 7.65 (d, 2H, J = 8.1 Hz).
I-33 1H-NMR (CDCI3) δ ppm: 0.94 (t, 3H, J = 7.2 Hz), 1.30-1.42 (m, 2H), 1.32 (s, 9H), 1.57-1.66 (m, 2H), 2.67 (t, 2H, J = 7.8 Hz), 5.61 (s, 1H), 6.93 (d, 2H, J = 8.7 Hz), 7.25 (d, 2H, J = 8.4 Hz), 7.49 (d, 2H, J = 9.0 Hz), 7.80 (d, 2H, J = 8.1 Hz), 8.22 (s, 1H).
I-34 1H-NMR (CD3OD) δ ppm: 0.95 (t, 3H, J = 7.5 Hz), 1.35 (s, 9H), 1.35-1.44 (m, 2H), 1.57-1.69 (m, 2H), 2.69 (t, 2H, J = 7.5 Hz), 7.28-7.33 (m, 4H), 7.56 (d, 2H, J = 9.0 Hz), 7.83 (d, 2H, J = 8.4Hz).
I-36 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.5 Hz), 1.31-1.70 (m, 11H), 1.39 (s, 9H), 1.75-1.85 (m, 1H), 2.65 (t, 2H, J = 8.1 Hz), 3.13 (t, 2H, J = 6.6 Hz), 3.40 (t, 2H, J = 7.2 Hz), 4.10 (t, 1H, J = 5.7 Hz), 6.21 (t, 1H, J = 5.7 Hz), 7.23 (d, 2H, J = 8.1 Hz), 7.67 (d, 2H, J = 8.4 Hz).
I-37 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.5 Hz), 0.95-1.10 (m, 2H), 1.31-1.40 (m, 2H), 1.39 (s, 9H), 1.55-1.63 (m, 4H), 1.80-1.92 (m, 4H), 2.65 (t, 2H, J = 7.8 Hz), 3.03 (t, 2H, J = 6.6 Hz), 3.31 (t, 2H, J = 6.6 Hz), 4.06 (t, 1H, J = 6.0 Hz), 6.22 (t, 1H, J = 6.0 Hz), 7.23 (d, 2H, J = 8.4 Hz), 7.67 (d, 2H, J = 8.1 Hz).
I-39 1H-NMR (CDCI3) δ ppm; 1.13 (t, 3H, J = 7.2 Hz), 1.39 (s, 9H), 1.69-1.97 (m, 8H), 2.27-2.38 (m, 1H), 3.29-3.35 (m, 4H), 3.60-3.70 (m, 1H), 4.52 (d, 1H, J = 9.3 Hz), 6.64 (d, 2H, J = 8.4 Hz), 7.22 (s, 1H), 7.31 (d, 2H, J = 9.0 Hz).
I-40 1H-NMR (CDCI3) δ ppm: 1.38 (s, 9H), 1.68-1.96 (m, 8H), 2.30-2.40 (m, 1H), 3.11 (t, 4H, J = 4.8 Hz), 3.60-3.72 (m, 1H), 3.86 (t, 4H, J = 4.8 Hz), 4.51 (brs, 1H), 6.89 (d, 2H, J = 9.0 Hz), 7.42 (d, 2H, J = 8.7Hz).
I-41
t.t.: >278°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.18-1.40 (m, 2H), 1.40 (s, 9H), 1.62-1.75 (m, 2H), 2.01-2.27 (m, 5H), 3.10-3.13 (m, 4H), 3.22-3.38 (m, 1H), 3.72 (d, 1H, J = 9.3 Hz), 3.85-3.88 (m, 4H), 6.87 (d, 2H, J = 9.0 Hz), 7.10 (s, 1H), 7.40 (d, 2H, J = 9.0 Hz).
I-42 1H-NMR (CDCI3) δ ppm: 1,40 (s, 9H), 1.61-1.97 (m, 8H), 2.16 (s, 3H), 2.33-2.43 (m, 1H), 3.60-3.70 (m, 1H), 4.66 (brs, 1H), 7.12 (d, 1H, J = 8.7 Hz), 7.46-7.50 (m, 1H), 7.62 (s, H), 7.75-7.78 (m, 1H), 7.86-7.91 (m, 2H).
I-43 1H-NMR (CDCI3) δ ppm: 1.40 (s, 9H), 1.62-2.00 (m, 8H), 1.87 (s, 3H), 2.36-2.47 (m, 1H), 3.24 (s, 3H), 3.64-3.74 (m, 1H), 4.87 (brs, 1H), 7.13 (d, 2H, J = 9.0 Hz), 7.64 (d, 2H, J = 8.4 Hz), 7.81 (s, H).
I-44
t.t.: 235-236°C 1H-NMR (CDCI3) δ ppm: 1,13 (t, 6H, J = 6.9 Hz), 1.18-1.33 (m, 2H), 1.40 (s, 9H), 1.60-1.77 (m, 2H), 2.00-2.26 (m, 5H), 3.28-3.35 (m, 4H), 3.73 (d, 1H, J = 9.3 Hz), 6.60-6.70 (m, 2H), 7.03 (brs, 1H), 7.31 (d, 2H, J = 7.8 Hz).
I-45
t.t.: >268°C (dec.)
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.20-1.34 (m, 2H), 1.40 (s, 9H), 1.56-1.76 (m, 8H), 2.00-2.26 (m, 5H), 3.06-3.14 (m, 4H), 3.24-3.36 (m, 1H), 3.72 (d, 1H, J = 9.3 Hz), 6.90 (d, 2H, J = 8.7 Hz), 7.09 (s, 1H),
7.36 (d, 2H, J = 8.7 Hz).
I-46
t.t.: >272°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.28 (s, 9H), 1.31-1.59 (m, 7H), 1.87-2.00 (m, 4H), 2.23-2.34 (m, 1H), 3.00-3.16 (m, 1H), 4.35-4.45 (m, 2H), 6.81 (d, 1H, J = 9.0 Hz), 7,16 (t, 1H, J = 7.2 Hz), 7,43 (t, 1H, J =
8.4 Hz), 7.52-7.58 (m, 3H), 8.04 (d, 1H, J = 7.8 Hz), 8.43 (s, 1H).
I-47 1H-NMR (CDCI3) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.62-1.77 (m, 2H), 1.98-2.32 (m, 5H), 3.31-3.40 (m, 1H), 3.62 (d, 1H, J = 9.0 Hz), 7.08 (s, 1H), 7.29 (d, 2H, J = 9,0 Hz), 7,61 (d, 2H, J = 9.0 Hz).
I-48 1H-NMR (CDCI3) δ ppm: 1,22-1.36 (m, 2H), 1.40 (s, 9H), 1.62-1.77 (m,2H), 2,00-2.31 (m,5H), 3.24-3.40 (m, 1H), 3.62 (d, 1H, J = 10.2 Hz), 7.01 (t, 2H, J = 8.7 Hz), 7.09 (s, 1H), 7.42-7.50 (m, 2H).
I-49
t.t.: 270°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.61-1.77 (m, 2H), 1.95-2.30 (m, 9H), 3.17-3.38 (m, 5H), 3.67 (d, 1H, J = 9.3 Hz), 6.50 (d, 2H, J = 9.0 Hz), 6.97 (s, 1H), 7.30 (d, 2H, J = 9.0Hz).
I-50
t. t.: 252-253°C 1H-NMR (CDCI3) δ ppm: 1.21-1.37 (m, 2H), 1.40 (s, 9H), 1.62-1.78 (m, 2H), 1.98-2.32 (m, 5H), 3.26-3.40 (m, 1H), 3.68 (d, 1H, J = 9.6 Hz), 6.94-7.02 (m, 4H), 7.08 (t, 1H, J = 7.5 Hz), 7.13 (s, 1H), 7.31 (t, 2H, J = 7.5 Hz), 7.46 (d, 2H, J = 9.0 Hz).
I-51
t.t.: 278-279°C 1H-NMR (CDCI3) δ ppm: 1.02 (d, 6H, J = 6.9 Hz), 1.35 (s, 9H), 1.39-1.71 (m, 6H), 1.90-2.09 (m, 2H), 3.16-3.30 (m, 1H), 3.46 (d, 1H, J = 9.0 Hz), 4.92-5.01 (m, 1H), 6.91-6.95 (m, 2H), 7.00-7.07 (m, 3H), 7.13-7.16 (m, 2H), 7.30-7.36 (m, 2H).
I-52
t.t.: 276-277°C 1H-NMR (CDCI3) δ ppm: 1.20-1,36 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.30 (m, 5H),
2.36 (s, 3H), 2.58 (t, 4H, J = 4.5 Hz), 3.17 (t, 4H, J = 4,5 Hz), 3.21-3.40 (m, 1H), 3.64 (d, 1H, J = 9.0 Hz), 6.88 (d, 2H, J = 9.0 Hz), 7.01 (s, 1H), 7.37 (d, 2H, J = 9.0 Hz).
I-53
t.t.: >300°C 1H-NMR (DMSO-d6) δ ppm: 1,20-1.54 (m, 4H), 1.27 (s, 9H), 1.73-1.88 (m, 2H), 1.89-2.01 (m, 2H), 2.13-2.25 (m, 1H), 2.98-3,12 (m, 1H), 3.15-3.31 (m, 8H), 6.76-6.84 (m, 2H), 6.93 (d, 2H, J = 9.0 Hz), 6.99 (d, 2H, J = 8.1 Hz), 7.24 (d, 2H, J = 8.1 Hz), 7.46 (d, 2H, J = 9.0 Hz), 9.60 (s, 1H).
I-54
t.t.: >215°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1,27-2.00 (m, 18H), 2.14-2.26 (m, 1H), 2.53-2,84 (m, 4H), 2,86-3.30 (m, 2H), 3.46-3.54 (m, 1H), 3.62-3.74 (m, 2H), 6.78 (d, 1H, J = 8.7 Hz), 6.87 (d, 2H, J = 7.8 Hz), 7.42 (d, 2H, J = 8.7 Hz), 9.58 (s, 1H).
I-55
t.t.: >290°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.23-1.40 (m, 2H), 1.40 (s, 9H), 1.60-1.76 (m, 2H), 2.02-2.27 (m, 5H),
3.20 (t, 4H, J = 5.4 Hz), 3.21-3.32 (m, 1H), 3.67 (d, 1H, J = 9.3 Hz), 3.98 (t, 4H, J = 4.8 Hz), 6.52 (t, 1H, J = 4.8 Hz), 6.93 (d, 2H, J = 8.4 Hz), 7.06 (s, 1H), 7.41 (d, 2H, J = 8.7 Hz), 8.33 (d, 2H, J = 4.8 Hz).
I-56
t.t.: >232°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.27-1.48 (m, 4H), 1.80-1.99 (m, 4H), 2.14-2.25 (m, 1H), 3.04-3.24 (m, 8H), 3.68 (s, 3H), 3.76 (s, 3H), 6.44-6.47 (m, 1H), 6.66 (s, 1H), 6.76-6.84 (m, 2H), 6.92 (d, 2H, J = 8.4 Hz), 7.46 (d, 2H, J = 8.4 Hz), 9.61 (s, 1H).
I-57
t.t.: 284-285°C (dec.)
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.27 (t, 3H, J = 7.2 Hz), 1.40 (s, 9H), 1.61-2.24 (m, 9H), 2.35-2.49 (m, 1H), 2.76 (t, 2H, J = 10.2 Hz), 3.04-3.15 (m, 2H), 3.20-3.36 (m, 1H), 3.55-3.59 (m, 2H), 3.87 (d, 1H, J = 9.6 Hz), 4.12-4.19 (m, 2H), 6.90 (d, 2H, J = 8.7 Hz), 2.79 (s, 1H), 7.40 (d, 2H, J = 8.7 Hz).
I-58
t.t.: >299°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.26-1.33 (m, 2H), 1.40 (s, 9H), 1.56-2.42 (m, 19H), 2.73-2.81 (m, 4H), 3.16-3.26 (m, 4H), 3.64 (d, 1H, J = 9.6 Hz), 6.87 (d, 2H, J = 8.7 Hz), 7.04 (s, 1H), 7.37 (d, 2H, J = 9.0 Hz).
I-59
t.t.: >270°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.26-1.47 (m, 2H), 1.47 (s, 9H), 1.60-1.80 (m, 4H), 2.01-2.32 (m, 5H), 3.28-3.40 (m, 3H), 3.62-3.74 (m, 3H), 5.74-5.96 (m, 2H), 6.92 (d, 2H, J = 8.7 Hz), 7.13 (s, 1H), 7.39 (d, 2H, J = 9.0 Hz).
I-60
t.t.: 247-250°C (dec.) 1H-NMR (CDCI3) δ ppm: 1.20-1.37 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.33 (m, 5H), 2.93-3.03 (m, 2H), 3.22-3,40 (m, 1H), 3.52 (t, 2H, J = 6.0 Hz), 3.62 (d, 1H, J = 8.4 Hz), 4.36 (s, 2H), 6.93 (d, 2H, J = 8.7 Hz), 7.00 (s, 1H), 7.11-7.22 (m, 4H), 7.39 (d, 2H, J = 8.7 Hz).
I-61
t.t. : 280-281°C 1H-NMR (CDCI3) δ ppm: 1.21-1.38 (m, 2H), 1.41 (s, 9H), 1.64-1.80 (m, 2H), 2.02-2.33 (m, 5H), 3.24-3.40 (m, 1H), 3.61 (d, 1H, J = 9.0 Hz), 6.33 (t, 2H, J = 2.1Hz), 7.04 (t, 2H, J = 2.1 Hz), 7.14 (s, 1H), 7.34 (d, 2H, J = 9.0 Hz), 7.56 (d, 2H, J = 9.0 Hz).
I-62 t, t.: 260-262°C 1H-NMR (CDCI3) δ ppm: 1.22-1.39 (m, 2H), 1.41 (s, 9H), 1.64-1.82 (m, 2H), 2.02-2.35 (m, 5H), 3.243.40 (m, 1H), 3.62 (d, 1H, J = 9.6 Hz), 7.31 (d, 2H, J = 9.0 Hz), 7.51 (s, 1H), 7.69 (d, 2H, J = 9.0 Hz).
I-63
t.t.: 248°C 1H-NMR (CDCI3) δ ppm 1.20-1.38 (m, 2H), 1.40 (s, 9H), 1.61-1.78 (m, 2H), 1.98-2.32 (m, 5H), 3.22-3.45 (m, 1H), 3.64 (d, 1H, J = 9.3 Hz), 7.11 (s, 1H), 7.37-7.46 (m, 4H).
I-64
t.t.: 272-275°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.20-1.53 (m, 4H), 1.27 (s, 9H), 1.75-H 1.88 (m, 2H), 1.88-2.00 (m, 2H), 2.11-2.24 (m, 1H), 2.96-3.12 (m, 1H), 5.96 (s, 2H), 6.77 (d, 1H, J = 8.7 Hz), 6.82 (d, 1H, J =
8.4 Hz), 6.95 (dd, 1H, J = 1.8, 8.4 Hz), 7.29 (d, 1H, J = 1.8 Hz), 9.70 (s, 1H).
I-65
t.t.: 293-296°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.20-1.70 (m, 10H), 1.27 (s, 9H), 1.79-2.038 (m, 4H), 2.18-2.33 (m, 1H), 2.98-3.30 (m, 5H), 6.79 (d, 1H, J = 9.0 Hz), 6.97 (d, 2H, J = 8.1 Hz), 7.43-7.57 (m, 4H), 7.62 (d, 2H, J = 8.1 Hz), 9.82 (s, 1H).
I-66
t.t.: >300°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.27-1.53 (m, 4H), 1.86-1.99 (m, 4H), 2.22-2.34 (m, 1H), 2.39 (s, 3H), 3.00-3.14 (m, 1H), 6.25 (s, 1H), 6.79 (d, 1H, J = 9.0 Hz), 7.47-7.50 (m, 1H), 7.69-7.76 (m, 1H), 10.27 (s, 1H).
I-67
t.t.: 248-249°C 1H-NMR (DMSO-d6) δ ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H), 1.77-1.90 (m, 2H), 1.90-2.02 (m, 2H), 2.02 (s, 3H), 2.17-2.32 (m, 1H), 2.96-3.13 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 7.12-7.30 (m, 3H), 7.89 (s, 1H), 9.79 (s, 1H), 9.88 (s, 1H).
I-68
t.t.: >300°C 1H-NMR (DMSO-d6) δ ppm: 1,20-1.54 (m, 4H), 1.27 (s, 9H), 1.77-1.89 (m, 2H), 1.89-2.03 (m, 2H), 2.00 (s, 3H), 2.14-2.28 (m, 1H), 2.95-3.13 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 7.40-7.54 (m, 4H), 9.72 (s, 1H), 9.83 (s, 1H).
PL 211 888 B1
I-69
t.t.: 199-201°C 1H-NMR (DMSO-d6) δ ppm: 1.21-1.53 (m, 4H), 1.27 (s, 9H), 1.76-1.89 (m, 2H), 1,89-2.02 (m, 2H), 2.13-2.30 (m, 1H), 2.85 (s, 6H), 2.94-3.14 (m, 1H), 6.40 (dd, 1H, J = 2.4, 8.4 Hz), 6.78 (d, 1H, J = 8.7 Hz), 6.90 (d, 1H, J = 8.4 Hz), 7.05 (t, 2H, J = 8.4 Hz), 9.60 (s, 1H).
I-70
t.t.: 227-230°C 1H-NMR (DMSO-d6) δ ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H), 1.72-1.87 (m, 2H), 1.87-2.01 (m, 2H), 2.12-2.29 (m, 1H), 2.96-3.12 (m, 1H), 5.00 (s, 2H), 6.22 (d, 1H, J = 7.5 Hz), 6.66 (d, 1H, J =
7.5 Hz), 6.78 (d, 1H, J = 9.0 Hz), 6.86 (d, 1H, J = 7.5 Hz), 6.89-6.95 (m, 1H), 9.46 (s, 1H).
I-71
t.t.: 270-272°C 1H-NMR (DMSO-d6) δ ppm: 1.22-1.52 (m, 4H), 1.26 (s, 9H), 1.73-1.86 (m, 2H), 1.88-2,00 (m, 2H), 2.08-2.22 (m, 1H), 2.95-3.11 (m, 1H), 4.80 (s, 2H), 6.47 (d, 2H, J = 8.4 Hz), 6.77 (d, 1H, J = 8.4 Hz), 7.20 (d, 2H, J = 8.4 Hz), 9.35 (s, 1H).
I-72
t.t.: 262-263°C 1H-NMR (CDCI3) δ ppm: 1.25 (d, 6H, J = 6.3 Hz), 1.17-1.42 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.43 (m, 7H), 3.20-3.43 (m, 3H), 3.67 (d, 1H, J = 9.6 Hz), 3.74-3.86 (m, 2H), 6.86 (d, 2H, J = 9.0 Hz), 7.04 (s, 1H), 7.38 (d, 2H, J = 9.0 Hz).
I-73
t.t.: 218-219°C 1H-NMR (CD3OD) δ ppm: 1.36 (s, 9H), 1.36-1.69 (m, 4H), 1.45 (s, 9H), 1.88-2.02 (m, 3H), 2.062.30 (m, 4H), 3.05-3.44 (m, 3H), 3.46-3.56 (m, 1H), 4.16-4.26 (m, 1H), 6.51 (d, 2H, J= 9.0 Hz), 7.30 (d, 2H, J = 8.7 Hz).
I-74
t.t.: 295-296°C (dec.) 1H-NMR (CD3OD) δ ppm: 1.36 (s, 9H), 1.36-1.67 (m, 4H), 1.92-2.13 (m, 4H), 2.26-2.40 (m, 2H), 2.62-2.75 (m, 1H), 3.16-3.25 (m, 1H), 3.58-3.98 (m, 4H), 4.16-4.25 (m, 1H), 7,20-7.30 (m, 2H), 7.62 (d, 2H, J = 9.0 Hz) .
I-75
t.t.: 250-251°C 1H-NMR (DMSO-d6) δ ppm: 1.23-1.55 (m, 4H), 1.27 (s, 9H), 1.78-1.90 (m, 2H), 1.90-2.02 (m, 2H), 2.15-2.28 (m, 1H), 2.98-3.14 (m, 1H), 3.06 (t, 2H, J = 8.4 Hz), 3.87 (t, 2H, J = 8.4 Hz), 6.67 (dd, 1H, J = 1.5, 7.2 Hz), 6.80 (d, 1H, J = 8.4 Hz), 6.94-7.05 (m, 2H), 7.12-7.19 (m, 1H), 7.16 (d, 2H, J = 9.3 Hz), 7.57 (d, 2H, J = 9.3 Hz), 9.73 (s, 1H).
I-76
t.t.: 265-266°C 1H-NMR (DMSO-d6) δ ppm: 1.23-1.58 (m, 4H), 1.28 (s, 9H), 1.83-2.04 (m, 4H), 2.20-2.36 (m, 1H), 2.97-3.16 (m, 1H), 6.67 (d, 1H, J = 3.0 Hz), 6.82 (d, 1H, J = 8.4 Hz), 7.07-7.22 (m, 2H), 7.477.53 (m, 1H), 7.50 (d, 2H, J = 9.0 Hz), 7.58 (d, 1H, J = 3.0 Hz), 7.64 (d, 1H, J = 7.5 Hz), 7.79 (d, 2H, J = 9.0 Hz), 10.02 (s, 1H).
I-77
t.t.: 281°C 1H-NMR (DMSO-d6) δ ppm: 1.21-1.56 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.18-2.31 (m, 1H), 2.97-3.14 (m, 1H), 6.51 (dd, 1H, J = 2.1, 2.7 Hz), 6.81 (d, 1H, J = 9.0 Hz), 7.67-7.78 (m, 5H), 8.41 (d, 1H, J = 2.1 Hz), 9.96 (s, 1H).
I-78
t.t.: >300°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.27-1.52 (m, 4H), 1.74-2.04 (m, 7H), 2.10-2.25 (m, 2H), 2.96-3.20 (m, 2H), 3.48-3.58 (m, 1H), 3.75-3.84 (m, 1H), 6.39 (d, 2H, J = 8.4 Hz), 6.79 (d, 1H, J = 8.4 Hz), 7.02 (s, 1H), 7.30 (s, 1H), 7.36 (d, 2H, J = 8.1 Hz), 9.48 (s, 1H).
I-79
t.t.: 248-250°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.27-1.54 (m, 4H), 1,85-1.99 (m, 4H), 2.24-2.33 (m, 1H), 3.00-3.14 (m, 1H), 6.82 (d, 1H, J = 8.7 Hz), 7.77 (d, 2H, J = 8.4 Hz), 8.07 (d, 2H, J = 8.4 Hz).
PL 211 888 B1
I-80
t.t.: >300°C 1H-NMR (DMSO-d6) δ ppm: 1.22-1.58 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.18-2.32 (m, 1H), 2.98-3.14 (m, 1H), 6.80 (d, 1H, J = 8.7 Hz), 7.35-7.50 (m, 2H), 7.99 (s, 1H), 8.11 (s, 1H), 9.79 (s, 1H), 12.94 (s, 1H).
I-81
t.t.: 261-262°C 1H-NMR (DMSO-d6) δ ppm: 1.21-1.57 (m, 4H), 1.27 (s, 9H), 1.78-2.02 (m, 4H), 2.17-2.30 (m, 1H), 2.96-3.16 (m, 1H), 6.34 (s, 1H), 6.80 (d, 1H, J = 8.7 Hz), 7.14-7.32 (m, 3H), 7.85 (s, 1H), 9.58 (s, 1H), 10.95 (s, 1H).
I-82 1H-NMR (DMSO-d6) δ ppm: 0.86 (s, 18H), 1.24-1.37 (m, 2H), 1.37 (s, 9H), 1.56-1.74 (m, 2H), 1.95-2.19 (m, 5H), 3.18-3.32 (m, 1H), 3.44 (t, 4H, J = 6.3 Hz), 3.70 (t, 4H, J = 6.3 Hz), 4.39 (d, 1H, J = 9.0 Hz), 6.59 (d, 2H, J = 9.0 Hz), 7.31 (d, 2H, J = 8.7 Hz), 7.43 (s, 1H).
I-83
t.t.: 264-265°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.27-1.52 (m, 4H), 1.78-1.88 (m, 2H), 1.90-2.00 (m, 2H), 2.14-2.26 (m, 1H), 2.96-3.14 (m, 1H), 6.72-6.82 (m, 2H), 6.99 (t, 4H, J = 7.8 Hz), 7.18 (t, 2H, J = 7.5 Hz), 7.46 (d, 2H, J = 9.0 Hz), 8.00 (s, 1H), 9.65 (s, 1H).
I-84
t.t.: 257°C (dec.) 1H-NMR (DMSO-d6) δ ppm: 1.23-1.57 (m, 4H), 1.27 (s, 9H), 1.83-2.03 (m, 4H), 2.23-2.35 (m, 1H), 2.98-3.15 (m, 1H), 6.80 (d, 1H, J = 8.1 Hz), 7.87 (d, 2H, J = 9.0 Hz), 8.34 (d, 2H, J = 9.0 Hz),
9.21 (s, 1H), 10.20 (s, 1H).
I-85
t.t.: 256-258°C 1H-NMR (DMSO-d6) δ ppm: 1.22-1,53 (m, 4H), 1.26 (s, 9H), 1.79-2.01 (m, 4H), 2.25 (s, 3H), 2.28-2.42 (m, 1H), 2.97-3.02 (m, 1H), 6.71 (d, 1H, J = 0.9 Hz), 6.80 (d, 1H, J = 8.1 Hz), 11.91 (s, 1H).
I-86
t.t.: 228-230°C 1H-NMR (CD3OD) δ ppm: 1.36 (s, 9H), 1.36-1.48 (m, 2H), 1.55-1.70 (m, 2H), 1.87-1.98 (m, 2H), 2.08-2.17 (m, 2H), 2.20-2.32 (m, 1H), 3.15-3.27 (m, 1H), 3.50 (t, 4H, J = 5.7 Hz), 3.69 (t, 4H, J = 5.7 Hz), 6.72 (d, 2H, J = 9.0 Hz), 7.29-7.33 (m, 2H).
I-87
t.t.: 183-184°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.27-1.48 (m, 4H), 1.73-1.89 (m, 4H), 1.90-2.00 (m, 2H), 2.16-2.28 (m, 1H), 2.28 (t, 2H, J = 7.5 Hz), 2.51-2.54 (m, 2H), 2.97-3.13 (m, 1H), 3.58 (s, 3H), 6.79 (d, 1H, J = 8.7 Hz), 7.08 (d, 2H, J = 8.7 Hz), 7.49 (d, 2H, J = 8.4 Hz), 9.73 (s, 1H).
I-88
t.t.: 217-218°C 1H-NMR (CD3OD) δ ppm: 1.36 (s, 9H), 1.36-1.46 (m, 2H), 1.55-1.69 (m, 2H), 1.83-2.00 (m, 4H), 2.07-2.18 (m, 2H), 2.26-2.36 (m, 3H), 2.61 (t, 2H, J = 7.5 Hz), 3.14-3.26 (m, 1H), 7.13 (d, 2H, J = 8.1Hz), 7.44 (d, 2H, J = 8.1 Hz).
I-89 1H-NMR (DMSO-d6) δ ppm: 0.08 (d, 6H, J = 3.3 Hz), 0.88 (s, 9H), 1.21-1.36 (m, 2H), 1.39 (s, 9H), 1.61-1.74 (m, 2H), 1.88-2.23 (m, 6H), 3.06-3.11 (m, 1H), 3.24-3.74 (m, 4H), 3.92 (d, 1H, J =
9.6 Hz), 4.48-4.56 (m, 1H), 6.47 (d, 2H, J = 9.0 Hz), 7.17 (s, 1H), 7.32 (d, 2H, J = 9.0 Hz).
I-90
t.t.: amorficzny 1H-NMR (CD3OD) δ ppm: 1.36 (s, 9H), 1.36-1.47 (m, 2H), 1.56-1.70 (m, 3H), 1.88-2.30 (m, 6H), 3.05-3.49 (m, 5H), 4.50 (brs, 1H), 6.50 (d, 2H, J = 9.0 Hz), 7.29 (d, 2H, J = 9.0 Hz).
I-91
t.t.: 105-106°C 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.3 Hz), 1.25-1.27 (m, 2H), 1.36 (d, 6H, J = 6.9 Hz),
1.51-1.59 (m, 2H), 2.56 (t, 2H, J = 7.8 Hz), 3.27 (sept, 1H, J = 6.9 Hz), 7.12 (d, 2H, J = 8.6 Hz), 7.32
PL 211 888 B1 (t, 1H, J = 7.8 Hz), 7.45 (brd, 1H, J = 7.8 Hz), 7.53 (d, 2H, J = 8.6 Hz), 7.58 (d, 1H, J = 7.8 Hz), 7.71-7.72 (m, 2H), 8.27 (s, 1H).
I-92
t.t.: 163-164°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3 Hz), 1.32-1.39 (m, 2H), 1.55-1.65 (m, 2H), 1.87 (s, 3H), 1.95 (s, 3H), 2.60 (t, 2H, J = 7.6 Hz), 7.07 (d, 2H, J = 8.4 Hz), 7.18 (d, 2H, J = 8.5 Hz), 7.54 (d, 2H, J = 8.5 Hz), 7.91 (brs, 1H), 8.18 (d, 2H, J = 8.4 Hz), 8.77 (s, 1H).
I-93
t. t.: 173°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3 Hz), 1.32-1.40 (m, 2H), 1.39 (d, 6H, J = 6.9 Hz), 1.55-1.62 (m, 2H), 2.60 (t, 2H, J = 7.8 Hz), 3.13 (sept, 1H, J = 6.9 Hz), 4.39 (d, 2H, J = 6.3 Hz), 4.45 (t, 1H, J = 6.3 Hz), 7.18 (d, 2H, J = 8.7 Hz), 7.46 (d, 2H, J = 8.7 Hz), 7.54 (d, 2H, J = 8.7 Hz), 7.80 (s, 1H), 7.85 (d, 2H, J = 8.7 Hz).
I-94
t.t.:159-160°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3 Hz), 1.32-1.39 (m, 2H), 1.54-1.80 (m, 2H), 1.79 (s, 3H), 1.80 (s, 3H), 2.60 (t, 2H, J = 7.7 Hz), 3.18 (s, 3H), 7.18 (d, 2H, J = 8.5 Hz), 7.30 (d, 2H, J = 8.8 Hz), 7.52 (d, 2H, J = 8.5 Hz), 7.70 (brs, 1H), 7.84 (d, 2H, J = 8.8 Hz), 8.77 (s, 1H).
I-95
t.t.: 177-178°C 1H-NMR (CDCI3) δ ppm: 0.94 (t, 3H, J = 7.2Hz), 1,31-1.48 (m, 8H), 1.54-1.66 (m, 2H), 2.55 (s, 3H), 2.62 (t, 2H, J = 7.6Hz), 3.92 (sept, 1H, J = 6.6Hz), 7.20 (d, 2H, J = 8.45 Hz), 7.74 (d, 2H, J = 8.5Hz), 9.01 (brs, 1H), 9,17 (s, 1H).
I-96
t.t.: 220-223°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.28-1.42 (m, 2H), 1.50 (d, 6H, J = 6.8Hz), 1.54-1.65 (m, 2H), 2.62 (t, 2H, J = 7.6Hz), 4.08 (sept, 1H, J = 7.1Hz), 7.20 (d, 2H, J = 8.5Hz), 7.48 (d, 2H, J = 8.5Hz), 7.71 (brs, 1H), 8.51 (brs, 1H), 8.95 (s, 1H).
I-97
t.t.: 195-197°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.6Hz), 0.94 (t, 3H, J = 7.3Hz), 1.32-1.44 (m, 6H), 1.541.64 (m, 2H), 1.66-1.78 (m, 2H), 2.62 (t, 2H, J = 7.7Hz), 2.86 (brs, 2H), 3.98 (sept, 1H, J = 7.1Hz), 7.19 (d, 2H, J = 8.5Hz), 7.63 (d, 2H, J = 8.4Hz), 8.72 (brs, 1H), 8.81 (brs, 1H).
I-98
t.t.: 216-218°C 1H-NMR (CDCI3+CD3OD) δ ppm: 0.93 (t, 3H, J = 7.4Hz), 1.29-1.40 (m, 2H), 1.43 (d, 2H, J = 6.9Hz), 1.51-1.63 (m, 2H), 2.60 (t, 2H, J = 7.8Hz), 3.65 (sept, 1H, J = 6.9Hz), 7.18 (d, 2H, J = 8.5Hz),
7.22 (d, 1H, J = 8.8Hz), 7.55 (d, 2H, J = 8.5Hz), 8.18 (dd, 1H, J = 8.8, 2.4Hz), 8.63 (d, 1H, J = 2.4Hz).
I-99
t.t.: 201-202°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.22-1.40 (m, 2H), 1.49 (d, 2H, J = 7.1Hz),
1.51-1.63 (m, 2H), 2.59 (t, 2H, J = 7.7Hz), 4.22 (sept, 1H, J = 7.1Hz), 7.16 (d, 2H, J = 8.4 Hz), 7.41 (brs, 1H), 7.52 (d, 2H, J = 8.4Hz), 8.10 (brs, 1H), 8.13 (d, 1H, J = 2.2Hz), 8.61 (brs, 1H).
I-100
t.t.: 160-162°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.22-1.42 (m, 2H), 1.45 (d, 2H, J = 6.9Hz),
1,51-1.63 (m, 2H), 2.61 (t, 2H, J = 7.8Hz), 3.37 (sept, 1H, J = 6.9Hz), 6.89 (brs, 1H), 7.19 (d, 2H, J = 8.4Hz), 7.65 (d, 2H, J = 8.4Hz), 7.80 (dd, 1H, J = 8.4, 2.4Hz), 8.27 (d, 1H, J = 8.4Hz), 8.45 (d, 1H, J = 2.4Hz), 9.75 (brs, 1H).
I-101, I-214 t.t.: 192-194°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.27-1.41 (m, 2H), 1.35 (s, 9H), 1.50-1.66 (m, 2H), 2.60 (t, 2H, J = 7.6Hz), 5.58 (brs, 1H), 7.07 (d, 2H, J = 8.5Hz), 7.17 (d, 2H, J = 8.5Hz), 7.52 (d, 2H, J = 8.5Hz), 7.71 (brs, 1H), 7.79 (d, 2H, J = 8.5Hz).
I-102
t.t.: 216-217°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 0,93 (t, 3H, J = 7.3Hz), 1.26-1.42 (m, 2H), 1.45 (s, 9H), 1.70-1.83 (m, 2H), 2.60 (t, 2H, J = 7.7Hz), 6.42 (brs, 1H), 7.18 (d, 2H, J = 8.5Hz), 7.35 (d, 2H, J = 8.5Hz), 7.51 (d, 2H, J = 8.5Hz), 7.68 (brs, 1H), 7.82 (d, 2H, J = 8.5Hz).
I-103 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.3 Hz), 1.28-1.36 (m, 2H), 1.32 (d, 6H, J = 6.9 Hz), 1.49-1.59 (m, 2H), 2.54 (t, 2H, J = 7.7 Hz), 3.23 (sept, 1H, J = 6.9 Hz), 3.46 (s, 3H), 6.76 (brs, 1H), 6.91 (d, 2H, J = 8.2 Hz), 6.99 (d, 2H, J = 8.8 Hz), 7.03 (d, 2H, J = 8.2 Hz), 7.25 (d, 2H, J = 8.8 Hz).
I-104
t.t.: 182-183°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.28-1.40 (m, 2H), 1.51-1.63 (m, 2H), 1.64-1.88 (m, 4H), 1.90-2.23 (m, 4H), 2.60 (t, 2H, J = 7.6Hz), 3.39 (m, 1H), 6.16 (brs, 1H), 7.07 (d, 2H, J = 8.5Hz), 7.16 (d, 2H, J = 8.5Hz), 7.52 (d, 2H, J = 8.5Hz), 7.74 (brs, 1H), 7.77 (d, 2H, J = 8.5Hz).
I-105
t.t.: 190-191°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.28-1.41 (m, 2H), 1.52-1.69 (m,4H), 1.75-1.90 (m, 2H), 1.92-2.07 (m, 4H), 2.58 (t, 2H, J = 7.6Hz), 3.59 (m, 1H), 6.53 (brs, 1H), 7.18 (d, 2H, J = 8.5Hz), 7.31 (d, 2H, J = 8.5Hz), 7.52 (d, 2H, J = 8.5Hz), 7.67 (brs, 1H), 7.84 (d, 2H, J = 8.5Hz).
I-106
t.t.: 194-197°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.22-1.41 (m, 2H), 1.53-1.65 (m, 2H), 1.90 (s, 6H), 2.60 (t, 2H, J = 7.8Hz), 6.86 (brs, 1H), 7.18 (d, 2H, J = 8.5Hz), 7.43 (d, 2H, J = 8.5Hz), 7.51 (d, 2H, J = 8.5Hz), 7.71 (brs, 1H), 7.84 (d, 2H, J = 8.5Hz).
I-107
t.t.: 211-212°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.24-1.40 (m, 2H), 1.50-1.62 (m, 2H), 2.60 (t, 2H, J = 7.6Hz), 6.19 (brs, 1H), 7.17 (d, 2H, J = 8.5Hz), 7.18 (d, 2H, J = 8.5Hz), 7.51 (d, 2H, J = 8.5Hz), 7.66 (brs, 1H), 7.86 (d, 2H, J = 8.5Hz).
I-108
t.t.: 298-300°C 1H-NMR (DMSO-d6) δ ppm: 0.90 (t, 3H, J = 7.3Hz), 1.22-1.39 (m, 2H), 1.48-1.60 (m, 2H), 2.54 (t, 2H, J = 7.3Hz), 7.04 (d, 2H, J = 8.8Hz), 7.12 (d, 2H, J = 8.5Hz), 7.64 (d, 2H, J = 8.5Hz), 7.69 (d, 2H, J = 8.8Hz), 9.80 (s, 1H).
I-109
t.t.: 122-123°C 1H-NMR (CDCI3) δ ppm: 0.90 (t, 3H, J = 7.4Hz), 0.97 (t, 3H, J = 7.7Hz), 1.26-1.38 (m, 2H), 1.30 (s, 6H), 1,50-1.66 (m, 4H), 1.72-1.83 (m, 4H), 2.34 (t, 2H, J = 7.1Hz), 2.55 (t, 2H, J = 7.6Hz), 3.19 (q, 1H, J = 6.0Hz), 4.60 (brs, 1H), 7.08 (d, 2H, J = 8.5Hz), 7.42 (d, 2H, J = 8.5Hz), 7.85 (s, 1H).
I-110
t.t.: 109-110°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.4Hz), 1.10 (d, 6H, J = 6.7Hz), 1.29-1.38 (m, 2H), 1.55 (s, 9H), 1.60-1.70 (m, 2H), 1.78-1.89 (m, 2H), 2.26 (m, 1H), 2.39 (t, 2H, J = 7.0Hz), 2.57 (t, 2H, J = 7.7Hz), 2.90 (d, 2H, J = 6.6Hz), 3.16 (brs, 1H), 4.24 (brs, 1H), 7.12 (d, 2H, J = 8.5Hz), 7.40 (d, 2H, J = 8.5Hz).
I-111
t.t.: 64-65°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.3Hz), 1.02 (t, 3H, J = 7.5Hz), 1.35 (d, 3H, J = 6.7Hz), 1.26-1.38 (m, 2H), 1.48-1.69 (m, 5H), 1.76-1.87 (m, 2H), 2.04 (m, 1H), 2.38 (t, 2H, J = 7.3Hz), 2.56 (t, 2H, J = 7.6Hz), 2.91 (m, 1H), 3.16 (brs, 2H), 4.42 (brs, 1H), 7.11 (d, 2H, J = 8.5Hz), 7.42 (d, 2H, J = 8.5Hz), 7.47 (brs, 1H).
I-112
t.t.: 79-80°C 1H-NMR (CDCI3) δ ppm: 1.36 (s, 9H), 1.52-1.62 (m, 2H), 1.67-1.76 (m, 2H), 2.22 (t, 2H, J = 7.4Hz), 3.16 (q, 2H, J = 6.3Hz), 3.78 (s, 3H), 4.33 (d, 2H, J = 5.4Hz), 4.62 (brs, 1H), 6.20 (brs, 1H), 6.85 (d, 2H, J = 8.8Hz), 7.19 (d, 2H, J = 8.8Hz).
I-113
t.t.: 125-126°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.38 (s, 9H), 1.62-1.70 (m, 2H), 1.76-1.88 (m, 2H), 2.46 (t, 2H, J = 7.4Hz), 3.22 (q, 2H, J = 6.1Hz), 4.22 (t, 1H, J = 6.1Hz), 7.24 (dd, 1H, J = 8.9, 2.3Hz), 7.36 (d, 1H, J = 2.3Hz), 7.65 (brs, 1H), 8.29 (d, 1H, J = 8.9Hz).
I-114
t.t.: 89-91°C 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.0Hz), 1.06 (d, 6H, J = 7.0Hz), 1.36 (m ,1H), 1.50-1,72 (m ,5H), 1.94-2.06 (m, 2H), 2.26 (m, 1H), 2.60 (t, 2H, J = 7.7Hz), 2.84 (t, 2H, J = 7.7Hz), 2.93 (d, 2H, J = 6.3Hz), 3.20 (t, 2H, J = 6.6Hz), 4.30 (brs, 1H), 7.19 (d, 2H, J = 8.5Hz), 7.63 (d, 2H, J= 8.5Hz), 9.15 (brs, 1H).
I-115
t.t.: 94-95°C 1H-NMR (CDCl3) δ ppm: 0.92 (t, 3H, J = 7.5Hz), 1.03 (t, 3H, J = 7.5Hz), 1.23-1.40 (m ,5H), 1.421.65 (m, 6H), 1.75 (m, 1H), 2.02 (m, 1H), 2.24 (t, 2H, J = 7.0Hz), 2.59 (t, 2H, J = 8.0Hz), 2.90 (m, 1H), 3.14 (q, 2H, J = 6.6Hz), 4.20 (m, 1H), 4.40 (d, 2H, J = 5.4Hz), 5.70 (brs, 1H), 7.14 (d, 2H, J = 8.1Hz), 7.18 (d, 2H, J = 8.1Hz).
I-116
t.t.: 89-91°C 1H-NMR (CDCI3) δ ppm: 0.97 (t, 3H, J = 7.3Hz), 1.02 (t, 3H, J = 7.5Hz), 1.35 (d, 3H, J = 7.0Hz), 1.40-1.90 (m, 9H), 2.04 (m, 1H), 2.37 (t, 2H, J = 7.0Hz), 2.90 (m, 1H), 3.17 (q, 2H, J = 6.6Hz), 3.93 (t, 2H, J = 6.6Hz), 4.32 (m, 1H), 6.84 (d, 2H, J = 9.0Hz), 7.31 (brs, 1H), 7.40 (d, 2H, J = 9.0Hz).
I-117
t.t.:110-111°C 1H-NMR (CDCI3) δ ppm: 1.02 (t, 3H, J = 7.5Hz), 1.34 (d, 3H, J = 6.6Hz), 1.45-1.70 (m, 3H), 1.75-1.85 (m, 2H), 2.05 (m, 1H), 2.36 (t, 2H, J = 7.5Hz), 2.90 (m, 1H), 3.16 (q, 2H, J = 6.6Hz), 3.78 (s, 3H), 4.50 (m, 1H), 6.84 (d, 2H, J = 6.8Hz), 7.42 (d, 2H, J = 6.8Hz), 7.48 (brs, 1H).
I-118
t.t.: 113-115°C 1H-NMR (CDCI3) δ ppm: 0.92 (t, 3H, J = 7.0Hz), 1.20-1.34 (m, 1H), 1.37 (d, 6H, J = 7.0Hz), 1.48-1.70 (m, 3H), 2.43 (q, 2H, J = 6.6Hz), 2.58 (t, 2H, J = 7.7Hz), 3.10-3.31 (m, 3H), 4.75 (m, 1H), 6.04 (d, 1H, J = 15.0Hz), 6.77 (dt, 1H, J = 7.7, 15.0Hz), 7.14 (d, 2H, J = 8.4Hz), 7.55 (d, 2H, J = 8.4Hz), 7.85 (brs, 1H).
I-119
t.t.: 139-140°C 1H-NMR (CDCI3) δ ppm: 1.19 (s, 9H), 1.47 (m, 2H), 1.61 (m, 2H), 2.18 (t, 2H, J = 7.6Hz), 3.03 (q, 2H, J = 6.3Hz), 4.09 (t, 1H, J = 5.9Hz), 6.85 (brd, 1H, J = 8.0Hz), 7.00 (t, 1H, J = 8.0 Hz), 7.16 (brd, 1H, J = 8.0), 7.48 (brs, 1H), 7.57 (brs, 1H).
I-120
t.t.: 183°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.3Hz), 1.20-1.58 (m, 6H), 1.40 (s, 9H), 2.07 (dd, 1H, J = 12.9, 3.1Hz), 2.52 (t, 2H, J = 7.7Hz), 2.95 (dd, 2H, J = 11.5, 2.5Hz), 3.46 (m, 1H), 3.88-4,07 (m, 3H), 6.47 (s, 1H), 7.08 (d, 2H, J = 8.5Hz), 7.22 (d, 2H, J = 8.5Hz).
I-121
t.t.: 163-166°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.3Hz), 1.32 -1.62 (m, 6H), 1.45 (s, 9H), 1.95-2.07 (m, 3H), 2.20 (m, 1H), 2.46 (td, 1H, J = 10.4, 3.7Hz), 2.37 (t, 2H, J = 7.6Hz), 3.43 (brd, 2H, J = 10.4Hz), 4.80 (s, 1H), 7.12 (d, 2H, J = 8.4Hz), 7.14 (s, 1H), 7.39 (d, 2H, J = 8.4Hz).
I-122
t.t.: 188-189°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5Hz), 1.25-1.41 (m, 2H), 1.42 (s, 9H), 1.50-1.62 (m, 2H), 1.78-1.95 (m, 4H), 2.00-2.20 (m, 6H), 2.57 (t, 2H, J = 7.5Hz), 3.99 (brs, 1H), 7.10 (brs, 1H), 7.12 (d, 2H, J = 6.5Hz), 7.41 (d, 2H, J = 6.5Hz).
I-123
t.t.: 197-198°C 1H-NMR (CDCI3) δ ppm: 0.91 (t, 3H, J = 7.5Hz), 1.24-1.40 (m, 2H), 1.39 (s, 9H), 1.50-1.70 (m, 2H), 1.99 (brs, 12H), 2.56 (t, 2H, J = 7.5Hz), 3.47 (brs, 1H), 7.10 (s, 1H), 7.11 (d, 2H, J = 8.5Hz), 7.38 (d, 2H, J = 8.5Hz).
PL 211 888 B1
I-124
t.t.: 258-260°C 1H-NMR (CDCI3) δ ppm: 1.20-1.40 (m, 2H), 1.41 (s, 9H), 1.62-1.81 (m, 2H), 2.03-2.35 (m, 5H), 2.37 (s, 3H), 2.71 (s, 3H), 3.32 (m, 1H), 3..64 (d, 1H, J = 8.4Hz), 7.08 (brs, 1H), 7.24 (m, 1H), 7.33 (m, 2H), 7.60 (d, 1H, J = 8.1Hz), 7.77 (s, 1H), 7.80 (d, 1H, J = 8.4Hz), 8.14 (m, 1H).
I-125
t.t.: 297-299°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.28-1.56 (m, 4H), 1.80-2.01 (m, 4H), 2.47 (m, 1H), 2.76 (brs, 1H), 3.05 (m, 2H), 6.78 (d, 1H, J = 9.0Hz), 7.23 (d, 1H, J = 9.0Hz), 7.46 (dd, 1H, J = 2.0, 9.0Hz), 8.03 (d, 1H, J = 2.0Hz).
I-126
t.t.: 198-199°C 1H-NMR (CDCI3) δ ppm: 1.18-1.39 (m, 2H), 1.40 (s, 9H), 1.60-1.79 (m, 2H), 1.98-2.35 (m, 5H),
3.30 (m, 1H), 3.67 (d, 1H, J = 9.6Hz), 5.89 (tt, 1H, J = 3.0, 50.0Hz), 6.97 (d, 1H, J = 7.8Hz), 7.21 (s, 1H), 7.30-7.40 (m, 2H), 7.55 (s, 1H).
I-127
t.t.: 262-264°C 1H-NMR (CDCI3) δ ppm: 1.20-1.39 (m, 2H), 1.41 (s, 9H), 1.60-1.80 (m, 2H), 2.00-2.36 (m, 5H), 2.57 (s, 3H), 3.33 (m, 1H), 3.62 (d, 1H, J = 8.7Hz), 7.28 (brs, 1H), 7.62 (d, 2H, J = 8.7Hz), 7.94 (d, 2H, J = 8.7Hz).
I-128
t.t.: 252-254°C 1H-NMR (CDCI3) δ ppm: 1.18-1.39 (m, 2H), 1.40 (s, 9H), 1.58-1.79 (m, 2H), 1.99-2.30 (m, 5H), 2.46 (s, 3H), 3.32 (m, 1H), 3.64 (m, 1H), 7.11 (brs, 1H), 7.23 (d, 2H, J = 9.0Hz), 7.44 (d, 2H, J = 9.0Hz).
I-129
t.t.: >300°C 1H-NMR (CDCI3+CD3OD) δ ppm: 1,30-1.45 (m, 2H), 1.42 (s, 9H), 1.70-1.88 (m, 2H), 2.10-2.37 (m, 4H), 2.52 (m, 1H), 3.34 (m, 1H), 7.43-7.54 (m, 3H), 7.82 (d, 1H, J = 6.7Hz), 7.88 (d, 1H, J = 8.5Hz), 7.98-8.07 (m, 2H), 8.44 (s, 1H), 8.46 (s, 1H).
I-130
t.t.: 123-124°C 1H-NMR (CDCI3) δ ppm: 1.18-1.34 (m, 2H), 1.40 (s, 9H), 1.62-1.75 (m, 2H), 2.00-2.28 (m, 5H),
3.31 (m, 1H), 3.61 (d, 1H, J = 9.5Hz), 5.59 (s, 1H), 7.17 (s, 1H), 7.30-7.37 (m, 6H), 7.41 (d, 1H, J = 8.5Hz), 7.84 (d, 1H, J = 2.1Hz).
I-131
t.t.: 202-204°C 1H-NMR (CDCI3) δ ppm: 1.27-1.38 (m, 2H), 1.38 (s, 9H), 1.62-1.75 (m, 2H), 1.97-2.04 (m, 2H), 2.18-2.27 (m, 3H), 3.26 (m, 1H), 3.81 (s, 3H), 4.62 (d, 1H, J = 7.9Hz), 7.12 (d, 1H, J = 7.8Hz), 7.40 (t, 1H, J = 7.8Hz), 7.51 (s, 3H), 7.61 (d, 1H, J = 7.8Hz), 7.71 (s, 1H), 8.21 (brs, 1H).
I-132
t.t.: 236-237°C 1H-NMR (CDCI3) δ ppm: 1.23-1.43 (m, 2H), 1.41 (s, 9H), 1.66-1.80 (m, 2H), 2.08-2.12 (m, 2H), 2.23-2.31 (m, 3H), 3.34 (m, 1H), 3.87 (d, 1H, J = 9.5Hz), 4.02 (s, 3H), 7.30 (td, 1H, J = 7.3, 11Hz), 7.36 (s, 1H), 7.39 (td, 1H, J = 7.3,1.5Hz), 7.53 (brd, 1H, J = 7.3Hz), 7.84 (brd, 1H, J = 7.3Hz), 8.05 (s, 1H), 8.73 (s, 1H).
I-133
t.t.: 198-200°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 0.97 (t, 3H, J = 6.7Hz), 1.18-1.81 (m, 7H), 1.39 (s, 9H), 1.98-2.05 (m, 2H), 2.21-2.24 (m, 3H), 3.29 (m, 1H), 4.00 (dd, 1H, J = 10.7, 6.7Hz), 4.09 (dd, 1H, J = 10.7, 6.1Hz), 4.27 (d, 1H, J = 9.8 Hz), 6.37 (d, 1H, J = 15.9Hz), 7.47 (d, 2H, J = 8.5Hz), 7.59 (d, 2H, J = 8.5Hz), 7.62 (d, 1H, J = 15.9Hz), 7.83 (brs, 1H).
I-134
t.t.: 212-213°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.21-1.32 (m, 2H), 1.39 (s, 9H), 1.59-1.73 (m, 2H), 1.99-2.04 (m, 2H),
2.10-2.26 (m, 3H), 3.26 (m, 1H), 3.72 (d, 1H, J = 9.6Hz), 6.74 (m, 1H), 7.02 (d, 2H, J = 7.4Hz), 7.11 (t, 1H, J = 7.4Hz), 7.13-7.19 (m, 2H), 7.22-7.26 (m, 2H), 7.34 (t, 2H, J = 7.4Hz).
I-135
t.t.: 294-296°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.28-1. 55 (m, 4H), 1.81-2.05 (m, 4H), 2.26 (m, 1H), 2.98-3.20 (m, 2H), 6.78 (d, 1H, J = 9.0Hz), 7.31 (t, 1H, J = 7.5Hz), 7.54-7.72 (m, 5H), 7.94 (brs, 1H).
I-136
t.t.: >300°C 1H-NMR (DMSO-d6) δ ppm: 1.28 (s, 9H), 1.29-1.59 (m, 4H), 1.81-2.02 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.81 (d, 1H, J = 8.7Hz), 7.38 (t, 1H, J = 7.2Hz), 7.48 (t, 2H, J = 7.2Hz), 7.62-7.81 (m, 10H), 9.93 (brs, 1H).
I-137
t.t.: 291-292°C 1H-NMR (CDCI3) δ ppm: 1.25-1.39 (m, 2H), 1.41 (s, 9H), 1.61-1.80 (m, 2H), 2.01-2.36 (m, 5H),
3.32 (m, 1H), 3.63 (d, 1H, J = 9.3Hz), 7.20 (brs, 1H), 7.53-7.74 (m, 8H).
I-138
t.t.: 259-262°C 1H-NMR (CD3OD) δ ppm: 1.40 (s, 9H), 1.40-1.80 (m, 4H), 2.00-2.30 (m, 4H), 2.45 (m, 1H), 3.00 (s, 3H), 3.15-3.30 (m, 2H), 7.90 (d, 1H, J = 8.4Hz), 8.12 (d, 1H, J = 9.0Hz), 8.39 (d, 1H, J = 9.0Hz),
8.72 (s, 1H), 8.92 (d, 1H, J = 8.4Hz), 10.4 (s, 1H).
I-139
t.t.: 265-268°C 1H-NMR (CDCI3) δ ppm: 1.25-1.40 (m, 2H), 1.40 (s, 9H), 168-1.81 (m, 2H), 2.05-2.10 (m, 2H), 2.23-2.37 (m, 3H), 3.32 (m, 1H), 4.27 (d, 1H, J = 9.1Hz), 7.53 (t, 1H, J = 7.9Hz), 7.63 (td, 1H, J = 7.9, 1.4Hz), 7.77 (d, 1H, J = 7.9Hz), 8.03 (d, 1H, J = 7.9Hz), 8.37 (brs, 1H), 8.85-8.86 (m, 2H).
I-140
t.t.: 258-260°C 1H-NMR (CDCI3) δ ppm: 1.20-1.40 (m, 2H), 1.41 (s, 9H), 1.52-1.85 (m, 2H), 2.03-2.35 (m, 5H), 3.34 (m, 1H), 3.75 (m, 1H), 7.35-7.66 (m, 3H), 8.05 (d, 1H, J = 9.0Hz), 8.11 (d, 1H, J = 9.0Hz), 8.40 (brs, 1H), 8.83 (s, 1H).
I-141
t.t.: 205-206°C 1H-NMR (CDCI3) δ ppm: 1.20-1.37 (m, 2H), 1.40 (s, 9H), 1.43-1.62 (m,2H), 1.90-2.01 (m, 2H), 2.02-2.23 (m, 3H), 3.27 (m, 1H), 3.63 (d, 1H, J = 9.6Hz), 3.70 (s, 3H), 6.64 (d, 1H, J = 8.8Hz), 7.287.41 (m, 5H), 7.45 (brs, 1H), 8.26 (d, 1H, J = 8.8Hz).
I-142
t.t.: 277-280°C 1H-NMR (CDCI3) δ ppm: 0.23-0.34 (m, 2H), 1.34 (s, 9H), 1.34-1.55 (m, 5H), 1.76-1.80 (m, 2H), 2.97(m, 1H), 3.31 (d, 1H, J = 9.6Hz), 7.18 (s, 1H), 7.50-7.59 (m, 4H), 7.77 (dd, 1H, J = 7.4, 1.0Hz), 7.91-7.98 (m, 2H), 8.39 (dd, 1H, J = 7.4, 1.9Hz).
I-143
t.t.: 202-203°C 1H-NMR (CDCI3) δ ppm: 1.23-1.40 (m, 2H), 1.40 (s, 9H), 1,57-1.71 (m, 2H), 2.05-2.10 (m, 2H), 2.18-2.28 (m, 3H), 3.3 1 (m, 1H), 3.91 (s, 3H), 3.93 (s, 3H), 4.05 (d, 1H, J = 9.5Hz), 8.15 (s, 1H), 9.56 (s, 1H).
I-144
t.t.: 177-178°C 1H-NMR (CDCI3) δ ppm: 1.27-1.39 (m, 2H), 1.40 (s, 9H), 1.65-1.79 (m, 2H), 2.04-2.07 (m, 2H),
2.12-2.34 (m, 3H), 3.22 (m, 1H), 3.93 (d, 1H, J = 9-1Hz), 6.90-7.03 (m, 3H), 7.25 (m, 1H), 7.77 (dd, 1H, J = 4.9, 1.7Hz), 7.81 (brs, 1H), 8.72 (dd, 1H, J = 7.8, 1.5Hz).
I-145
t.t.: >300°C 1H-NMR (DMSO-d6) δ ppm: 1.30 (s, 9H), 1.44-1.70 (m, 4H), 2,05-2.19 (m, 4H), 2.73 (m, 1H), 3.18 (m, 1H), 6.86 (d, 1H, J = 8.8Hz), 7.62 (t, 2H, J = 8.5Hz), 7.86 (t, 2H, J = 8.5Hz), 7.89 (d, 2H. J = 8.5Hz), 8.16 (d, 2H, J = 8.5Hz).
PL 211 888 B1
I-146
t.t.: 240-242°C 1H-NMR (DMSO-d6) δ ppm: 1.26-1.53 (m, 4H), 1.27 (s, 9H), 1.74-1.83 (m, 2H), 1.90-1.97 (m, 2H), 2.26 (m, 1H), 3.04 (m, 1H), 6,59 (brs, 1H), 6.74-6.79 (m, 3H), 7.74 (s, 1H), 10.32 (s, 1H), 12.80 (s, 1H).
I-147
t.t.: 167-169°C 1H-NMR (CDCI3) δ ppm: 1.05-1.28 (m, 2H), 1.38 (s, 9H), 1.47-1.70 (m, 2H), 1.80-2.00 (m, 3H),
2.13-2.25 (m, 2H), 2.75 (t, 2H, J = 6.9Hz), 3.24 (m, 1H), 3.49 (dt, 2H, J = 6.3, 6.9Hz), 3.58 (d, 1H, J = 8.7Hz), 3.87 (s, 6H), 5.40 (brs, 1H), 6.71 (m, 2H), 6.82 (d, 1H, J = 8.7Hz).
I-148
t.t.: 171-172°C 1H-NMR (CDCI3) δ ppm: 1.16-1.38 (m, 2H), 1.39 (s, 9H), 1.50-1.79 (m, 4H), 1.85-2.02 (m, 3H),
2.15-2.30 (m, 2H), 2.35-2.56 (m, 6H), 3.25 (m, 1H), 3.33 (q, 2H, J = 6.0Hz), 3.63 (d, 1H, J = 9.0Hz),
3.72 (t, 4H, J = 4.6Hz), 6.77 (brs, 1H).
I-149 1H-NMR (CDCI3) δ ppm: 1.20-1.36 (m, 2H), 1.28 (t, 3H, J = 7.2Hz), 1.39 (s, 9H), 1.45-1.70 (m, 2H), 1.85-2.30 (m, 7H), 2.43 (s, 3H), 3.05-3.42 (m, 3H), 3.46-3.80 (m, 3H), 7.31 (d, 1H, J = 7.2Hz), 7.40-7.52 (m, 3H), 8.18 (brs, 1H).
I-150
t.t.: 203-204°C 1H-NMR (CDCI3) δ ppm: 1.15-1.37 (m, 2H), 1.39 (s, 9H), 1.42-1.70 (m, 2H), 1.85-2.29 (m, 5H), 2.76 (t, 2H, J = 6.0Hz), 3.26 (m, 1H), 3.49 (q, 2H, J = 6.0Hz), 3.61 (m, 1H), 4.03 (s, 2H), 5.88 (brs, 1H), 7.15 (dd, 1H, J = 7.0, 8.8Hz), 7.30-7.35 (m, 2H).
I-151
t.t.: 181-183°C 1H-NMR (CDCI3) δ ppm: 1.15-1.30 (m, 2H), 1.39 (s, 9H), 1.45-1.64 (m, 2H), 1.88-2.05 (m, 3H),
2.15-2.25 (m, 2H), 2.69 (t, 2H, J = 6.0Hz), 3.28 (m, 1H), 3.47 (q, 2H, J = 6.0Hz), 3.58 (d, 1H, J = 9.9Hz), 3.87 (s, 2H), 5.83 (brs, 1H), 7.00 (m, 1H), 7.20 (m, 2H).
I-152
t.t.: 222-224°C 1H-NMR (CDCI3) δ ppm: 1.16-1.37 (m, 2H), 1.39 (s, 9H), 1.49-1.70 (m, 2H), 1.90-2.25 (m, 5H), 3.26 (m, 1H), 3.36 (t, 2H, J = 6.4Hz), 3.66 (dt, 3H, J = 6.0, 6.4Hz), 5.87 (t, 1H, J = 6.0Hz), 7.58 (s, 1H), 7.68 (dd, 1H, J = 7.0, 8.5Hz), 7.83 (dd, 1H, J = 7.0, 8.5Hz), 8.19 (t, 2H, J = 8.5Hz).
I-153
t.t.: 207-209°C 1H-NMR (CDCI3) δ ppm: 1.05-1.25 (m, 2H), 1.38 (s, 9H), 1.40-2.03 (m, 10H), 2.05-2.25 (m, 2H), 2.58 (s, 3H), 2.76 (m, 1H), 3.05-3.35 (m, 2H), 3.97 (d, 1H, J = 9.5Hz), 4.94 (t, 1H, J = 4.0Hz), 8.42 (d, 1H, J = 5.5Hz), 8.97 (d, 1H, J = 5.5Hz).
I-154
t.t.: 184-185°C 1H-NMR (CDCI3) δ ppm: 1.05-1.25 (m, 2H), 1.37 (s, 9H), 1.50-1.69 (m, 2H), 1.85-2.05 (m, 3H),
2.10-2.21 (m, 2H), 3.24 (m, 1H), 3.64 (m, 1H), 4.87 (s, 1H), 4.88 (s, 1H), 5.67 (brs, 1H), 7.42 (d, 2H, J = 5.5Hz), 7.52 (m, 2H), 7.78 (m, 1H), 7.82 (m, 1H), 7.95 (d, 1H, J = 7.0Hz).
I-155
t.t.: 208-210°C 1H-NMR (DMSO-d6) δ ppm: 1.26 (s, 9H), 1.27-1.50 (m, 4H), 1.75-2.00 (m, 4H), 2.16 (m, 1H), 2.81 (s, 3H), 3.02 (m, 1H), 6.79 (d, 1H, J = 8.5Hz), 10.00 (s, 1H), 10.66 (s, 1H).
I-156
t.t.: 256-257°C 1H-NMR (CDCI3) δ ppm: 1.20-1.39 (m, 2H), 1.41 (s, 9H), 1.60-1.81 (m, 2H), 2.01-2.35 (m, 5H), 2.69 (t, 2H, J = 6.0Hz), 3.11 (t, 2H, J = 6.0Hz), 3.30 (m, 1H), 3.61 (d, 1H, J = 9.3Hz), 7.21 (d, 1H, J = 8.0Hz), 7.31 (s, 1H), 7.70 (d, 1H, J = 8.0Hz), 7.99 (s, 1H).
I-157
t.t.: 269-271°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.20-1.45 (m, 2H), 1.41 (s, 9H), 1.70-1.90 (m, 2H), 2.10-2.45 (m, 5H), 3.37 (m, 1H), 3.68 (m, 1H), 7.45 (dd, 1H, J = 4.0, 8.0Hz), 7.53 (brs, 1H), 7.72 (t, 1H, J = 8.0Hz), 7.83 (d, 1H, J = 8.0Hz), 8.02 (d, 1H, J = 8.0Hz), 8.18 (d, 1H, J = 8.0Hz), 8.93 (d, 1H, J = 4.0Hz).
I-158
t.t.: 253-255°C 1H-NMR (CDCI3) δ ppm: 1,20-1.40 (m, 2H), 1.42 (s, 9H), 1.60-1.90 (m, 2H), 2.06-2.50 (m, 5H),
2.72 (s, 3H), 3.33 (m, 1H), 3.78 (d, 1H, J = 9.2Hz), 7.52 (t, 1H, J = 7,0Hz), 7,62-7.80 (m, 2H), 7.94 (brs, 1H), 8.05 (d, 1H, J = 8.5Hz), 8.20 (s, 1H).
I-159
t.t.: 253-255°C 1H-NMR (CDCI3) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.60-1.80 (m, 2H), 1.98-2.30 (m, 5H), 2.71 (s, 3H), 3.31 (m, 1H), 3.68 (d, 1H, J = 9.0Hz), 7.41 (brs, 1H), 7.61 (d, 2H, J = 9.0Hz), 7.70 (d, 2H, J = 9.0Hz).
I-160
t.t.: 211-212°C 1H-NMR (CDCI3) δ ppm: 1.20-1.32 (m, 2H), 1.39 (t, 3H, J = 7.0Hz), 1.40 (s, 9H), 1.55-1.79 (m, 2H), 1.98-2.35 (m, 5H), 3.31 (m, 1H), 3,65 (d, 1H, J = 9.5Hz), 4.03 (q, 2H, J = 7.0Hz), 6.64 (d, 1H, J = 8.0Hz), 6.92 (d, 1H, J = 8.0Hz), 7.10 (s, 1H), 7.19 (t, 1H, J = 8.0Hz), 7.30 (brs, 1H).
I-161
t.t.: 202-203°C 1H-NMR (CDCI3) δ ppm: 0.96 (t, 1H, J = 7.3Hz), 1.29-1.39 (m, 2H), 1.40 (s, 9H), 1.41-1.58 (m, 2H),
1.60-1.80 (m, 4H), 1.98-2.31 (m, 5H), 3.31 (m, 1H), 3.66 (d, 1H, J = 8.5Hz), 3.96 (t, 2H, J = 6.4Hz), 6.64 (d, 1H, J = 8.0Hz), 6.90 (d, 1H, J = 8.0Hz), 7.11 (s, 1H), 7.19 (t, 1H, J = 8.0Hz), 7.31 (brs, 1H).
I-162
t.t.: 177-180°C 1H-NMR (CDCI3) δ ppm: 1.18-1.38 (m, 2H), 1.39 (s, 9H), 1.59-H 1.78 (m, 2H), 1.95-2.05 (m, 2H), 2.07-2.25 (m, 3H), 3.26 (m, 1H), 3.46 (s, 3H), 4.17 (d, 1H, J = 9.5Hz), 5.15 (s, 2H), 6.77 (d, 1H, J = 8.0Hz), 7.10-7.23 (m, 2H), 7.34 (s, 1H), 7.58 (s, 1H).
I-163
t.t.:175-178°C 1H-NMR (CDCI3) δ ppm: 1.27 (s, 9H), 1.28-1.50 (m, 4H), 1.78-2.00 (m, 4H), 2.22 (m, 1H), 2.963.15 (m, 2H), 6.67 (m, 1H), 6.79 (d, 1H, J = 8.5Hz), 7.18 (m, 2H), 7.38 (s, 1H), 9.81 (s, 1H).
I-164
t.t.: 232-233°C 1H-NMR (CDCI3) δ ppm: 0.97 (t, 3H, J = 7.3Hz), 1.22-1.30 (m, 2H), 1.40 (s, 9H), 1.44-1.51 (m, 2H), 1.67-1.77 (m, 4H), 2.02-2.24 (m, 5H), 3.22 (m, 1H), 3.62 (d, 1H, J = 9.6Hz), 4.25 (t, 2H, J = 6.8Hz), 6.71 (d, 1H, J = 8.4Hz), 7.01 (brs, 1H), 7.91 (dd, 1H, J = 8.4, 3.3Hz), 8.08 (d, 1H, J = 3.3Hz).
I-165
t.t.: 199-200°C 1H-NMR (CDCI3) δ ppm: 0.96 (t, 3H, J = 7.4Hz), 1.24-1.50 (m, 4H), 1.40 (s, 9H), 1.67-1.76 (m, 3H), 2.03-2.08 (m, 2H), 2.24-2.35 (m, 3H), 3.29 (m, 1H), 3.76 (d, 1H, J = 9,1Hz), 3.91 (t, 2H, J =6.6Hz), 6.41 (dd, 1H, J = 8.8, 2.5Hz), 6.55 (d, 1H, J = 2.5Hz), 6.82 (d, 1H, J = 8.8Hz), 7.43 (s, 1H), 8.95 (s, 1H).
I-166
t.t.: 215-218°C 1H-NMR (CDCI3+CD3OD) δ ppm: 0.97 (t, 3H, J = 7,4Hz), 1.24-1.40 (m, 4H), 1.39 (s, 9H), 1.421.50 (m, 2H), 1.54-1.72 (m, 2H), 1.76-1.82 (m, 2H), 1.91-2.00 (m, 2H), 2.06-2.22 (m, 3H), 3.24 (m, 1H), 4.00 (t, 2H, J = 6.6Hz), 6.78 (d, 1H, J = 8.8Hz), 6.98 (dd, 1H, J = 8.8, 2.5Hz), 7.09 (d, 1H, J = 8.8Hz).
I-167
t.t.: 212-213°C 1H-NMR (CDCI3) δ ppm: 0.96 (t, 3H, J = 7.5Hz), 1.26-1.34 (m, 2H), 1.40 (s, 9H), 1.45-1.50 (m, 2H), 1.68-1.77 (m, 4H), 2.03-2.08 (m, 2H), 2.17 (m, 1H), 2.26-2.29 (m, 2H), 3.29 (m, 1H), 3.60 (d, 1H, J = 9.0Hz), 4.25 (t, 2H, J = 6.8Hz), 6.71 (d, 1H, J = 8.4Hz), 7.01 (brs, 1H), 7.91 (dd, 1H, J = 8.4, 3.3Hz), 8.08 (d, 1H, J = 3.3Hz).
PL 211 888 B1
I-168
t.t.: 230-232°C 1H-NMR (CDCI3) δ ppm: 1.22-1.35 (m, 2H), 1.40 (s, 9H), 1.63-1.77 (m, 2H), 2.03-2.08 (m, 2H),
2.15-2.29 (m, 3H), 3.31 (m, 1H), 3.63 (d, 1H, J = 9.3Hz), 6.89 (d, 1H, J = 9.4Hz), 7.10 (brd, 2H, J = 7.4Hz), 7.12 (brs, 1H), 7.18 (t, 1H, J = 7.4Hz), 7.36 (brt, 2H, J = 7.4Hz), 8.09-8.15 (m, 2H).
I-169
t.t.: 159-160°C 1H-NMR (CDCI3) δ ppm: 0.97 (t, 3H, J = 7.3), 1.20-1.35 (m, 2H), 1.40 (s, 9H), 1.37-1.49 (m, 2H),
1.61-1.78 (m, 4H), 2.05-2.08 (m, 2H), 2.23-2.26 (m, 2H), 2.36 (s, 3H), 2.97 (brs, 1H), 3.32 (m, 1H), 3.86 (brs, 1H), 4.30 (t, 2H, J = 6.5Hz), 6.25 (s, 1H), 7.92 (brs, 1H).
I-170
t.t.: 180-181°C 1H-NMR (CDCI3) δ ppm: 0.88-0.89 (m, 2H), 1.39 (s, 9H), 1.42-1.60 (m, 2H), 1.86-1.90 (m, 2H), 2.04-2.09 (m, 2H), 2.42 (s, 3H), 2.91 (m, 1H), 3.20 (m, 1H), 3.63 (d, 1H, J = 9.2Hz), 6.38 (s, 1H), 7.15 (m, 2H), 7.28 (m, 1H), 7.45 (m, 2H), 7.84 (brs, 1H).
I-171
t.t.:173-174°C 1H-NMR (CDCI3) δ ppm: 0.98 (t, 3H, J = 7.5Hz), 1.29-1.40 (m, 2H), 1.40 (s, 9H), 1.55 (m, 2H), 1.621.83 (m, 4H), 2.09-2.12 (m, 2H), 2.24-2.32 (m, 3H), 3.32 (m, 1H), 3.63 (d, 1H, J = 9.5Hz), 3.99 (t, 2H, J = 6.4Hz), 7.22 (dd, 1H, J = 9.4, 2.7Hz), 7.66 (d, 1H, J = 2.7Hz), 8.63 (d, 1H, J = 9.4Hz), 10.17 (s, 1H).
I-172
t.t.: 238-242°C 1H-NMR (CDCI3) δ ppm: 0.96 (t, 3H, J = 7.3Hz), 1.23-1.52 (m, 4H), 1.40 (s, 9H), 1.61-1,78 (m, 4H), 2.05-2.28 (m, 5H), 3.30 (m, 1H), 3.66 (d, 1H, J = 9.4Hz), 3.84 (brs, 2H), 3.90 (t, 2H, J = 6.4Hz), 6.32-6.35 (m, 2H), 6.96 (brs, 1H), 6.97 (d, 1H, J = 9.4Hz).
I-173
t.t.: 165-166°C 1H-NMR (CDCI3) δ ppm: 1.23-1.26 (m, 2H), 1.40 (s, 9H), 1.67-1.72 (m, 2H), 2.01-2.06 (m, 2H),
2.11-2.28 (m, 3H), 3.31 (m, 1H), 3.60 (s, 2H), 3.69 (s, 3H), 4.02 (brs, 1H), 7.01 (d, 1H, J = 8.0Hz), 7.25 (t, 1H, J = 8.0Hz), 7.43 (d, 1H, J = 8.0Hz), 7.49 (brs, 1H), 7.51 (brs, 1H).
I-174
t.t.: 264-265°C 1H-NMR (CDCI3+CD3OD) δ ppm: 1,26-1.29 (m, 2H), 1.39 (s, 9H), 1.62-1.69 (m, 2H), 1.96-2.00 (m, 2H), 2.18-2.21 (m, 3H), 3.25 (m, 1H), 3.58 (s, 2H), 7.01 (d, 1H, J = 7.5Hz), 7.26 (t, 1H, J = 7.5Hz), 7.42 (brs, 1H), 7.50 (d, 1H, J = 7.5Hz).
I-175
t.t.: 90-94°C 1H-NMR (CDCI3) δ ppm: 1.16-1.23 (m, 2H), 1.37 (s, 9H), 1.44-1.56 (m, 2H), 1.73-1.85 (m, 3H),
2.11-2.15 (m, 2H), 3.57 (t, 2H, J = 6.4Hz), 3.21 (m, 1H), 3.58 (m, 2H), 3.84 (d, 1H, J = 9.3Hz), 5.56 (brs, 1H), 7.01 (s, 1H), 7.11 (t, 1H, 7.5Hz), 7.21 (t, 1H, J = 7.5Hz), 7.38 (d, 1H, J = 7.5Hz), 7.59 (d, 1H, J = 7.5Hz), 8.24 (brs, 1H).
I-176
t.t.:116-118°C 1H-NMR (CDCI3) δ ppm: 1.18-1.38 (m, 2H), 1.40 (s, 9H), 1.60-1.79 (m, 2H), 1.95-2.30 (m, 5H),
3.30 (m, 1H), 3.69 (m, 1H), 3.80 (s, 3H), 4.64 (s, 2H), 6.67 (d, 1H, J = 8.0Hz), 7.00 (d, 1H, J = 8.5Hz),
7.15-7.24 (m, 2H), 7.32 (brs, 1H).
I-177
t.t.:219-220°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.28-1.50 (m, 4H), 1.75-2.01 (m, 4H), 2.18-2.30 (m, 1H), 2.95-3.15 (m, 2H), 4.61 (s, 2H), 6.56 (m, 1H), 6.80 (d, 1H, J = 8.5Hz), 7.16 (m, 2H), 7.28 (brs, 1H), 9.87 (brs, 1H).
I-178
t.t.: 170-173°C 1H-NMR (CDCI3) δ ppm: 1.18-1.39 (m, 2H), 1.40 (s, 9H), 1.50-1.80 (m, 2H), 1.90-2.33 (m, 5H), 2.36 (s, 6H), 2.75 (t, 2H, J = 5.5 Hz), 3.30 (m, 1H), 3.70 (m, 1H), 4.08 (t, 2H, J = 5.5Hz), 6.68 (d, 1H, J = 8.0Hz), 6.94 (d, 1H, J = 7.5Hz), 7.15-7.23 (m, 2H), 7.33 (brs, 1H).
PL 211 888 B1
I-179
t.t.:191-193°C 1H-NMR (CDCI3) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.58-1.80 (m, 2H), 1.98-2.32 (m, 5H),
3.30 (m, 1H), 3.70 (d, 1H, J = 9.5 Hz), 4.77 (s, 2H), 6.73 (d, 1H, J = 8.0Hz), 7.04 (d, 1H, J = 8.0Hz),
7.20-7.31 (m, 2H), 7.48 (brs, 1H).
I-180
t.t.: 174-176°C 1H-NMR (CDCI3) δ ppm: -1.10-1.30 (m, 2H), 1.40 (s, 9H), 1.45-1.65 (m, 2H), 1.81-2.02 (m, 3H),
2.15-2.30 (m, 2H), 2.58 (t, 2H, J = 6.5Hz), 3.25 (m, 1H), 3.37 (dt, 2H, J = 5.5, 6.5Hz), 3.60 (d, 1H, J = 9.5Hz), 3.71 (s, 2H), 5.73 (brs, 1H), 7.20-7.40 (m, 5H).
I-181
t.t.: 176-178°C 1H-NMR (CDCI3) δ ppm: 1.15-1.30 (m, 2H), 1.39 (s, 9H), 1.45-1.70 (m, 6H), 1.85-2.01 (m, 3H),
2.15-2.28 (m, 2H), 2.63 (t, 2H, J = 7.0Hz), 3.25 (dt, 2H, J = 6.0, 7.0Hz), 3.27 (m, 1H), 3.63 (m, 1H), 5.35 (brs, 1H), 7.17 (m, 3H), 7.29 (m, 2H).
I-182
t.t.: 152-154°C 1H-NMR (CDCI3) δ ppm: 1.15-1.30 (m, 2H), 1.39 (s, 9H), 1.45-1.65 (m, 2H), 1.85-2.05 (m, 3H), 2.09-2.25 (m, 2H), 3.25 (m, 1H), 3.45 (dt, 2H, J = 5.0, 5.0Hz), 3.55 (t, 2H, J = 5.0Hz), 3.60 (m, 1H), 4.51 (s, 2H), 5.81 (brs, 1H), 7.29-7.40 (m, 5H).
I-183
t.t.: 208-211°C 1H-NMR (CDCI3) δ ppm: 1.20-1.31 (m, 2H), 1.39 (s, 9H), 1.62-1.68 (m, 2H), 1.98-2.25 (m, 5H),
3.30 (m, 1H), 3,57 (d, 1H, J = 9,2Hz), 4.59 (d, 2H, J = 5.8Hz), 5.76 (brs, 1H), 7.37 (dd, 1H, J = 8.4, 2.0Hz), 7.46-7.52 (m, 2H), 7.69 (brs, 1H), 7.78-7.83 (m, 3H).
I-184
t.t.: 180-182°C 1H-NMR (CDCI3) δ ppm: 1.22-1.37 (m, 2H), 1.40 (s, 9H), 1.60-d 1.69 (m, 2H), 2.05-2.09 (m, 2H),
2.21-2.27 (m, 3H), 3,45 (m, 1H), 3.64 (d, 1H, J = 9.6Hz), 4.77 (d, 2H, J = 4.9Hz), 7.43 (d, 1H, J = 8.6Hz), 7.46 (brs, 1H), 7.61 (t, 1H, J =7.7Hz), 7.73 (t, 1H, J = 7.7Hz), 7.87 (t, 1H, J = 7.7Hz), 8.20 (t, 1H, J = 7.7Hz), 8.24 (d, 1H, J = 8.6Hz).
I-185
t.t.: 260-261°C 1H-NMR (CDCI3) δ ppm: 1.22-1.32 (m, 2H), 1.39 (s, 9H), 1.60-1.70 (m, 2H), 1.97-2.01 (m, 2H), 2.11 (m, 1H), 2.21-2.24 (m, 2H), 3.30 (m, 1H), 3.61 (d, 1H, J = 9. 3Hz), 4.95 (d, 2H, J = 6.0Hz), 5.85 (brs, 1H), 7.33 (d, 1H, J = 4.8Hz), 7.62 (dd, 1H, J = 8.4, 6.9Hz), 7.75 (dd, 1H, J = 8.1, 6.9Hz), 8.00 (d, 1H, J = 8.1Hz), 8.20 (d, 1H, J = 8.4Hz), 8.42 (d, 1H, J = 4.8Hz).
I-186
t.t.: 231-233°C 1H-NMR (CDCI3) δ ppm: 1.23-1.40 (m, 2H), 1.40 (s, 9H), 1.62-1.76 (m, 2H), 2.04-2.10 (m, 2H),
2.22-2.32 (m, 3H), 3.30 (m, 1H), 3.95 (d, 1H, J = 9.3Hz), 5.04 (d, 2H, J = 4.1Hz), 7,61 (d, 1H, J = 5.8Hz), 7.63 (brs, 1H), 7.65 (dd, 1H, J = 8.2, 6.9Hz), 7.73 (dd, 1H, J = 8.5, 6.9Hz), 7.86 (d, 1H, J = 8.2Hz), 8.10 (d, 1H, J = 8.5Hz), 8.42 (d, 1H, J = 5.8Hz).
I-187
t.t.: 184-187°C 1H-NMR (CDCI3) δ ppm: 0.97 (t, 3H, J = 7.3 Hz), 1.18-1.30 (m, 2H), 1.39 (s, 9H), 1.42-1.65 (m, 4H), 1.70-1.80 (m, 2H), 1.94-2.08 (m, 3H), 2.18-2.26 (m, 2H), 3.29 (m, 1H), 3.61 (d, 1H, J = 9.5Hz), 3.93 (t, 2H, J = 6.4Hz), 4.39 (d, 2H, J = 5.5Hz), 5.67 (brs, 1H), 6.79-6.83 (m, 3H), 7,23 (t, 1H, J = 7.6Hz).
I-188
t.t.: 224-226°C 1H-NMR (CDCI3) δ ppm: .16-1.31 (m, 2H), 1.38 (s, 9H), 1.55-1.70 (m, 2H), 1.92-2.07 (m, 3H), 2.17-2.23 (m, 2H), 3.21 (m, 1H), 3.81 (s, 3H), 3.83 (s, 6H), 4.05 (d, 1H, J = 9.8Hz), 4.34 (d, 2H, J = 5.8Hz), 5.96 (brs, 1H), 6.47 (s, 2H).
I-189
t.t.: 217-218°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.15-1.30 (m, 2H), 1.37 (s, 9H), 1.52-1.66 (m, 2H), 1.90-2.06 (m, 3H),
2.13-2.20 (m, 2H), 2.93 (s, 6H), 3.24 (m, 1H), 3.94 (d, 1H, J = 9.5Hz), 4.30 (d, 2H, J = 5.5Hz), 5.73 (brs, 1H), 6.69 (d, 2H, J = 8.9Hz), 7.12 (d, 2H, J = 8.9Hz).
I-190
t.t.: amorficzny stały 1H-NMR (CDCI3) δ ppm: 1.17-1.32 (m, 2H), 1.39 (s, 9H), 1.54-1.72 (m, 2H), 1.96-2.13 (m, 3H), 2.18-2.27 (m, 2H), 3.30 (m, 1H), 3.63 (d, 1H, J = 9.2Hz), 4.51 (d, 2H, J = 5.8Hz), 5.82 (brs, 1H), 7.40 (d, 2H, J = 8.5Hz), 8.02 (d, 2H, J = 8.5Hz), 8,64 (s, 1H).
I-191
t.t.: 126-128°C 1H-NMR (CDCI3) δ ppm: 0.97 (t, 3H, J = 7.4 Hz), 1.10-1.28 (m, 2H), 1.36 (s, 9H), 1.42-1.86 (m, 9H), 2.06-2.18 (m, 2H), 3.22 (m, 1H), 3.95 (t, 2H, J = 4.5Hz), 4.16 (brs, 1H), 4.85 (s, 2H), 6.826.95 (m, 3H), 7.26 (1, 1H, J = 7.8Hz), 8.54 (brs, 1H).
I-192
t.t.: 178-181°C 1H-NMR (CDCI3) δ ppm: 0.96 (t, 3H, J = 7.3 Hz), 1.18-1.52 (m, 4H), 1.39 (s, 9H), 1.58-1.76 (m, 4H), 1.92-2.00 (m, 2H), 2.02-2.29 (m, 3H), 3.28 (m, 1H), 3.78 (d, 1H, J = 9.5Hz), 3.89 (t, 2H, J = 6.6Hz), 6.00 (brs, 1H), 6.78 (s, 4H), 7.35 (brs, 1H).
I-193
t.t.: 187-188°C 1H-NMR (CDCI3+CD3OD) δ ppm: 1,21-1.40 (m, 2H), 1.38 (s, 9H), 1.52-1.69 (m, 2H), 1.90-2.00 (m, 2H), 2.02-2.20 (m, 3H), 3.22 (m, 1H), 3.75 (s, 3H), 6.79 (s, 4H).
I-194
t.t.: 251-253°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.24-1.50 (m, 4H), 1.72-1.83 (m, 2H), 1.91-1.99 (m, 2H), 2.16 (m, 1H), 3.02 (m, 1H), 3.82 (s, 3H), 6.79 (d, 1H, J = 8.2Hz), 7.01 (d, 2H, J = 8.8Hz), 7.85 (d, 2H, J = 8.8Hz), 9.72 (brs, 1H), 8.64 (brs, 1H).
I-195
t.t.: 183-185°C 1H-NMR (CDCI3) δ ppm: 1.22-1.37 (m, 2H), 1.40 (s, 9H), 1.58-1.75 (m, 2H), 2.05-2.10 (m, 2H),
2.20-2.30 (m, 3H), 3.32 (m, 1H), 3.70 (s, 2H), 3.73 (s, 3H), 6.79 (s, 1H), 8.83 (brs, 1H).
I-196
t.t.: 185-187°C 1H-NMR (CDCI3) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.44 (t, 6H, J = 7.0 Hz), 1.60-1.80 (m, 2H), 1.95-2.35 (m, 5H), 3.30 (m, 1H), 3.62 (d, 1H, J = 8.9 Hz), 4.06 (q, 2H, J = 7.0 Hz), 4.09 (q, 2H, J = 7.0 Hz), 6.08 (s, 1H), 7.02 (s, 1H), 7.36 (s, 1H).
I-197
t.t.: 211-213°C 1H-NMR (CDCI3) δ ppm: 1.20-1.40 (m, 2H), 1.41 (s,9H), 1.60-1.80 (m, 2H), 2.00-2.36 (m, 5H), 2.61 (s, 3H), 3.32 (m, 1H), 3.64 (d, 1H, J = 9.2 Hz), 7.28 (s, 1H), 7.43 (t, 1H, J = 7.5 Hz), 7.69 (d, 1H, J = 7.5 Hz), 7.85 (d, 1H, J = 7.5 Hz), 8.02 (s, 1H).
I-198
t.t.: 268-269°C 1H-NMR (CDCI3) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H), 1.42-2.32 (m, 7H), 2.90-3.10 (m, 4H),
3.30 (m, 1H), 3.68 (d, 1H, J = 8.8 Hz), 6.59 (s, 1H), 7.18 (d, 1H, J = 8.7 Hz), 7.59 (d, 1H, J = 8.7 Hz),
7.77 (brs, 1H).
I-199 t.t. 221-224°C
I-200 t.t. 237-240°C
I-201 t.t. 87-90°C
I-202 t.t. 222-223°C
I-203 t.t. 255-257°C
I-204 t.t. 234-236°C
I-205 t.t. 208-210°C
I-206 t.t. 217-218°C
I-207 t.t. 275-279°C
I-208 t.t. 248-250°C
PL 211 888 B1
I-209 t.t.: 256-258°C
I-210 t.t.: 270-271°C
I-211 t.t.: 219-220°C
I-212 t.t.: 260-261°C
I-213 t.t.: >300°C
I-214 t.t.: 206-207°C 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.4 Hz), 1.30-1.42 (m, 2H), 1.49 (d, 6H, J = 6.9 Hz), 1.53-1.65 (m, 2H), 2.61 (t, 2H, J = 7.7 Hz), 4.15 (sept, 1H, J = 6.9 Hz), 7.04 (d, 1H, J = 8.2 Hz), 7.20 (d, 2H, J = 8.2 Hz), 7.51 (d, 2H, J = 8.2 Hz), 7.89 (d, 1H, J = 8.8 Hz), 8.18 (s, 1H), 10.55 (s, 1H).
I-215 1H-NMR (CDCI3) δ ppm: 0.93 (t, 3H, J = 7.3Hz), 1.30-1.41 (m. 2H), 1.52-1.63 (m, 2H), 1.95 (s, 6H), 2.61 (t, 2H, J = 7.8 Hz), 6.99 (brs, 1H), 7.20 (d, 2H, J = 8.5Hz), 7.65 (d, 2H, J = 8.5 Hz), 7.93 (dd, 1H, J = 8.5, 2.5 Hz), 8.28 (d, 1H, J = 8.5 Hz), 8.55 (d, 1H, J = 2.5Hz), 9.76 (brs, 1H).
Ia-1
t.t. 221-224°C 1H-NMR (CDCI3) δ ppm: 1.19-1.38 (m, 2H), 1.40 (s, 9H), 1.62-1.77 (m, 2H), 2.00-2.31 (m, 5H), 3.18 (t, 4H, J = 4.8 Hz), 3.21-3.38 (m, 1H), 3.85 (t, 4H, J = 4.8 Hz), 6.64-6.32 (m,2H), 7.11 (s, 1H), 7.20 (t, 1H, J = 7.8 Hz), 7.45 (s, 1H).
Ia-3
t.t. 87-90°C 1H-NMR (CDCI3) δ ppm: 1.25 (d, 6H, J = 6.3 Hz), 1.37 (d, 6H, J = 6.9 Hz), 1.59-1.70 (m, 2H), 1.76-1.88 (m, 2H), 2.32-2.42 (m, 4H), 3.11-3.23 (m, 3H), 3.39 (d, 2H, J = 10.8 Hz), 3.74-3.86 (m, 2H), 4.34 (t, 1H, J = 9.0 Hz), 6.86 (d, 2H, J = 9.0 Hz), 7.30 (s, 1H), 7.40 (d, 2H, J = 9.0Hz).
Ia-4 1H-NMR (CDCI3) δ ppm: 1.35 (d, 6H, J = 6.3 Hz), 1.40 (s, 9H), 1.26-1.37 (m, 2H), 1.62-1.78 (m, 2H), 2.00-2.22 (m, 5H), 2.42 (t, 2H, J = 11.7 Hz), 3.20-3.40 (m, 1H), 3.46 (d, 2H, J = 10.5 Hz), 3.67 (d, 1H, J = 9.3 Hz), 3.72-3.84 (m, 2H), 6.62-6.76 (m, 2H), 7.10 (s, 1H), 7.18 (t, 1H, J = 7.8 Hz), 7.42 (s, 1H).
Ia-5
t.t. 125-126°C 1H-NMR (CDCI3) δ ppm: 1.25 (d, 6H, J = 6.3Hz), 1.40 (s, 9H), 1.59-1.70 (m, 2H), 1.77-1.84 (m, 2H), 2.30-2.46 (m, 4H), 3.24 (q, 2H, J = 6.6 Hz), 3.38 (d, 2H, J = 11.7Hz), 3.74-3.88 (m, 2H), 4,08 (t, 1H, J = 5,7Hz), 6.87 (d, 2H, J = 8.7Hz), 7.30 (s, 1H), 7.41 (d, 2H, J = 8.7Hz).
Ia-6
t.t. 229-230°C 1H-NMR (CDCI3) δ ppm: 1.25 (d, 6H, J = 6.3 Hz), 1.26-1.34 (m, 2H), 1.39 (d, 6H, J = 6.9 Hz),
1.61-1.77 (m, 2H), 1.98-1.26 (m, 5H), 2.32-2.46 (m, 2H), 3.15 (kwintet, 1H, J = 6.6Hz), 3.22-3.35 (m, 1H), 3.39 (d, 2H, J = 11.4 Hz), 3.74-3.92 (m, 2H), 3.88 (d, 1H, J = 8.4Hz), 6.96-6.71 (m, 2H), 7.05 (brs, 1H), 7.39 (d, 2H, J = 9.3Hz).
Ia-7
t.t. 253-254°C 1H-NMR (DMSO) δ ppm: 1.24-1.60 (m, 4H), 1.27 (s, 9H), 1.77-2.07 (m, 4H), 2.16-2.34 (m, 1H), 2.97-3.15 (m, 1H), 6.78 (d, 1H, J = 7.2 Hz), 7.01 (t, 1H, J = 6.0Hz), 7.27 (t, 2H, J = 6.6 Hz), 7.58 (d, 2H, J = 7.5Hz), 9.78 (s, 1H).
Ia-8
t.t. 257-258°C 1H-NMR (DMSO) δ ppm: 1.22-1.54 (m, 4H), 1.27 (s, 9H), 1.77-1.88 (m, 2H), 1.88-2.00 (m, 2H) ,
2.16-2.34 (m, 1H), 2.23 (s, 3H), 2.92-3.14 (m, 1H), 6.77 (d, 1H, J = 8.4Hz), 7.07 (d, 2H, J = 8.4Hz), 7.46 (d, 2H, J = 8.1 Hz), 9.68 (s, 1H).
Ia-9
t.t. 231-232°C 1H-NMR (CDCI3) δ ppm: 1.21 (t, 3H, J = 7.5 Hz), 1.22-1.38 (m, 2H), 1.40 (s, 9H), 1.62-1.78 (m, 2H), 1.98-2.31 (m, 5H), 2.61 (q, 2H, J = 7.5 Hz), 3.24-3.38 (m, 1H), 3.70 (d, 1H, J = 9.9 Hz), 7.11 (s, 1H), 7.14 (d, 2H, J = 8.7 Hz), 7.40 (d, 2H, J = 8.7 Hz).
Ia-10
t.t. 233-234°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 0.96 (t, 3H, J = 7.2 Hz), 1.20-1.37 (m, 2H), 1.40 (s, 9H), 1.56-1.78 (m, 4H), 1.98-2.32 (m, 5H), 2.54 (t, 2H, J = 7.2 Hz), 3.23-3.39 (m, 1H), 3.66 (d, 1H, J = 9.6 Hz), 7.08 (s, 1H), 7.12 (d, 2H, J = 8.4 Hz), 7.39 (d, 2H, J = 8.4 Hz).
Ia-11
t.t. 243-244°C 1H-NMR (CDCI3) δ ppm: 1,22 (d, 6H, J = 6.9), 1.22-1.77 (m, 4H), 1.40 (s, 9H), 2.01-2.30 (m, 5H), 2.83-2.92 (m, 1H), 3.24-3.40 (m, 1H), 3.66-3.69 (m, 1H), 7.09 (s, 1H), 7.17 (d, 2H, J = 8.4 Hz), 7.41 (d, 2H, J = 8.1 Hz).
Ia-12
t.t. 246-247°C 1H-NMR (CDCI3) δ ppm: 0.80 (t, 3H, J = 7.5), 1.20 (d, 3H, J = 0 7.2), 1.26-1.77 (m, 6H), 1.40 (s, 9H), 2.01-2.27 (m, 5H), 2.51-2.60 (m, 1H), 3.20-3.38 (m, 1H), 3.64-3.69 (m, 1H), 7.08 0 H (s, 1H), 7.12 (d, 2H, J = 8.4 Hz), 7.41 (d, 2H, J = 8.4 Hz).
Ia-13
t.t. 278-279°C 1H-NMR (CDCI3) δ ppm: 1.22-1.52 (m, 4H), 1.29 (s, 9H), 1.40 (s, 9H), 1.61-1.77 (m, 2H), 2.022.30 (m, 5H), 3.20-3.38 (m, 1H), 3.66-3.69 (m, 1H), 7.10 (s, 1H), 7.33 (d, 2H, J = 9.0Hz), 7.42 (d, 2H, J = 8.7Hz).
Ia-14
t.t. 263-264°C 1H-NMR (CDCI3) δ ppm: 1.24-1.51 (m, 4H), 1.27 (s, 9H), 1.82-H 1.99 (m, 4H), 2.19-2.28 (m, 1H), 2.98-3.12 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 7.33 (d, 2H, J = 8.7 Hz), 7.61 (d, 2H, J = 9.0 Hz), 9.94 (s, 1H).
Ia-15
t.t. 209-210°C 1H-NMR (CDCI3) δ ppm: 1.25 (d, 6H, 3 = 6.3 Hz), 1.40 (s, 9H), 1.70-1.98 (m, 8H), 2.19-2.38 (m, 3H), 3.39 (d, 2H, J = 11.7 Hz), 3.58-3.92 (m, 3H), 4.12-4.26 (m, 1H), 6.82-6.96 (m, 2H), 7.10 (br, 1H), 7.41 (d, 2H, J = 8.1 Hz).
Ia-16
t.t. 238-240°C 1H-NMR (DMSO) δ ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H), 1.81-1.84 (m, 2H), 1.93-1.97 (m, 2H),
2.16-2.23 (m, 1H), 2.95-3.12 (m, 1H), 3.70 (s, 3H), 6.77 (d, 1H, J = 8.4 Hz), 6.85 (d, 2H, J = 9.0 Hz), 7.48 (d, 2H, J = 9.3 Hz), 9.64 (s, 1H).
Ia-17
t.t. 245-246°C 1H-NMR (DMSO) δ ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H), 1.83-1.87 (m, 2H), 1.94-1.99 (m, 2H),
2.20-2.28 (m, 1H), 2.98-3.12 (m, 1H), 6.78 (d, 1H, J = 8,7 Hz), 7.28 (d, 2H, J = 8.7 Hz), 7.69 (d, 2H, J = 9.0 Hz), 9.64 (s, 1H).
Ia-18
t.t. 240-241°C 1H-NMR (CDCI3) δ ppm: 1.22-1.78 (m, 4H), 1.40 (s, 9H), 2.05-2.33 (m, 5H), 3.22-3.44 (m, 1H), 3.64-3.67 (m, 1H), 6.61 (s, 1H), 6.69-6.77 (m, 2H).
Ia-19
t.t. 240-241°C 1H-NMR (CDCI3) δ ppm: 1.24-1.77 (m, 4H), 1.40 (s, 9H), 2.05-2.30 (m, 5H), 3.22-3.38 (m, 1H), 3.70-3.74 (m, 1H), 7.00-7.15 (m, 3H), 7.36 (s, 1H), 8.29-8.34 (m, 1H).
Ia-20
t.t. 239-240°C 1H-NMR (CDCI3) δ ppm: 1.24-1.78 (m, 4H), 1.40 (s, 9H), 2.02-2.30 (m, 5H), 3.22-3.40 (m, 1H), 3.63-3.66 (m, 1H), 6.89-6.84 (m, 1H), 7.10-7.17 (m, 2H), 7.22-7.34 (m, 1H), 7.48-7.51 (m, 1H).
Ia-21
t.t. 259-260°C 1H-NMR (CDCI3/DMSO) δ ppm: 1,21 (d, 6H, J = 6.0 Hz), 1.22-1.44 (m, 2H), 1.40 (s, 9H), 1.601.78 (m, 2H), 1.87-2.03 (m, 2H), 2.08-2.29 (m, 3H), 2.39 (t, 2H, J = 10.2 Hz), 3.14-3.32 (m, 1H), 3.19 (d, 2H, J = 11.4 Hz), 3.77-3.93 (m, 2H), 5,33 (d, 1H, J = 9.0 Hz), 6.84 (dd, 1H, JFH, HH = 8.1, 8.1 Hz), 7.20 0 (d, 1H, J = 7.8 Hz), 7.49 (d, 1H, JTH = 14.7 Hz), 8.86 (s, 1H).
PL 211 888 B1
Ia-22
t.t. 234-23°C 1H-NMR (CDCI3) δ ppm: 1,20 (d, 6H, J = 5.7 Hz), 1.22-1.44 (m, 2H), 1.38 (s, 9H), 1.54-1.76 (m, 2H), 1.94-2.32 (m, 5H), 2.27 (s, 3H), 2.39 (t, 2H, J = 10.8 Hz), 2.87 (d, 2H, J = 11.4 Hz), 3.20-3.40 (m, 1H), 3.76-3.92 (m, 2H), 3.91 (d, 1H, J = 9.3 Hz), 6.93 (d, 1H, J = 8.1 Hz), 7.21 (brs, 1H), 7.27 (brs, 1H), 7.36 (brs, 1H).
Ia-23
t.t. 195-196°C 1H-NMR (CDCI3) δ ppm: 1.20-1.44 (m, 4H), 1.41 (s, 9H), 1,59-1.76 (m, 2H), 2.03-2.14 (m, 2H), 2.15-2.33 (m, 3H), 3.20-3.40 (m, 1H), 3.64 (s, 1H, J = 9.0 Hz), 7.19-7.24 (m, 1H), 7.44 (brs, 1H), 7.52-7.63 (m, 2H), 8.17 (d, 1H, J = 8.7 Hz).
Ia-24
t.t. 209-210°C 1H-NMR (CDCI3) δ ppm: 1.22-1.39 (m, 2H), 1.56 (s, 9H), 1.61-1.78 (m, 2H), 2.00-2.12 (m, 2H),
2.17-2.33 (m, 3H), 3.24-3.39 (m, 1H), 3.67 (d, 1H, J = 9.6 Hz), 6.90-7.01 (m, 1H), 7.21 (s, 1H), 7.958.06 (m, 1H).
Ia-25
t.t. 278-281°C 1H-NMR (DMSO-d6) δ ppm: 1.10 (d, 6H, J = 6.3 Hz), 1.27 (s, 9H), 1.28-1.55 (m, 4H), 1.78-2.00 (m, 4H), 2.11-2.26 (m, 1H), 2.31 (t, 2H, J = 11.1 Hz), 3.00-3.10 (m, 1H), 3.08 (d, 1H, J = 10.8 Hz), 3.67-3.80 (m, 2H), 6.78 (d, 1H, J = 8.7 Hz), 7.08 (d, 1H, J = 9.0 Hz), 7.41 (dd, 1H, J = 2.4, 8.7 Hz), 7.78 (d, 1H, J = 8.7 Hz), 9.85 (s, 1H).
Ia-26
t.t. 253-255°C 1H-NMR (DMSO-d6) δ ppm: 1.13 (d, 6H, J = 6.0 Hz), 1.27 (s, 9H), 1.28-1.52 (m, 4H), 1.78-2.00 (m, 4H), 2.21 (t, 2H, J = 11.1 Hz), 2.26-2.36 (m, 1H), 2.96-3.10 (m, 1H), 3.56 (d, 1H, J = 12.3 Hz), 3.60-3.72 (m, 2H), 6.66-6,84 (m, 4H), 7.47 (t, 1H, J = 9.3 Hz), 9.28 (s, 1H).
Ia-27
t.t. 223-226°C 1H-NMR (DMSO-d6) δ ppm: 1.09 (d, 6H, J = 6.3Hz), 1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.77-2.01 (m, 4H), 2.32 (t, 2H, J = 11.1 Hz), 2.32-2.42 (m, 1H), 2.90 (d, 1H, J = 11.4 Hz), 2.96-3.12 (m, 1H), 3.76-3.92 (m, 2H), 6,78-6.98 (m, 3H), 7.68 (dd, 1H, J = 3.3, 8.7 Hz), 8.84 (s, 1H).
Ia-28
t.t. 237-238°C 1H-NMR (CDCI3) δ ppm: 1.22-1.44 (m, 2H), 1,25 (d, 6H, J = 6.3 Hz), 1.40 (s, 9H), 1.61-1.79 (m, 2H), 2.05-2.32 (m, 5H), 2.21 (s, 3H), 2.38 (t, 2H, J = 10.2 Hz), 3.22-3.42 (m, 1H), 3.40 (d, 2H, J = 11.1 Hz), 3.65 (d, 1H, J = 9.3 Hz), 3.72-3.90 (m, 2H), 6.70-6.78 (m, 2H), 6.81 (brs, 1H), 7.50 (d, 1H, J = 9.6 Hz).
Ia-29
t.t. 208-209°C 1H-NMR (CDCI3) δ ppm: 1.22 (d, 6H, J = 6.0 Hz), 1.23-1.40 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 2.00-2.16 (m, 2H), 2.14-2.33 (m, 3H), 2.45 (t, 2H, J = 11.1 Hz), 3.21 (d, 2H, J = 10.8 Hz), 3.24-3.38 (m, 1H), 3.63 (d, 1H, J = 9.3 Hz), 3.80-3.94 (m, 2H), 5.33 (d, 1H, J = 9.0 Hz), 6.66 (dd, 1H, JFH, HH = 6.6, 6.6 Hz), 7.16 (brs, 1H), 7.89 (dd, 1H, JFH, HH = 9.0, 9.0 Hz).
Ia-30
t.t. 284-287°C 1H-NMR (DMSO-d6) δ ppm: 1.08 (d, 6H, J = 6.0 Hz), 1.26 (s, 9H), 1.28-1.53 (m, 4H), 1.82-2.22 (m, 4H), 2.25-2.39 (m, 1H), 2.78 (t, 2H, J = 10.5 Hz), 2.97-3.14 (m, 1H), 3.18 (d, 2H, J = 11.4 Hz), 3.65-3.76 (m, 2H), 6.79 (d, 1H, J = 8.7 Hz), 9.75 (s, 1H).
Ia-31
t.t. 200-201°C 1H-NMR (CDCI3) δ ppm: 1.22-1.40 (m, 2H), 1.40 (s, 9H), 1.62-1,76 (m, 2H), 2.04-2.32 (m, 5H), 3.223.40 (m, 1H), 3.62-3.66 (m, 1H), 7.22-7.24 (m, 1H), 7.38-7.38 (m, 1H), 7.60 (s, 1H), 8.33-8.36 (m, 1H).
Ia-32
t.t. 260-261°C
PL 211 888 B1 1H-NMR (CDCI3/DMSO) δ ppm: 1.25-1.42 (m, 2H), 1.38 (s, 9H), 1.64 (q, 2H, J = 13.5 Hz), 1.95 (d, 2H, J = 12.3 Hz), 2.16 (d, 2H, J = 10.5 Hz), 2.18-2.32 (m, 1H), 3.14-3.30 (m, 1H), 5.53 (d, 1H, J = 9.0 Hz), 7.31 (d, 1H, J = 8.7 Hz), 7.46 (dd, 1H, J = 2.4, 8.7 Hz), 7.90 (d, 1H, J = 2.1Hz), 9.35 (s, 1H).
Ia-33
t.t.: 227°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.30-1.56 (m, 4H), 1.78-2.01 (m, 2H), 2.12-2.36 (m, 2H), 2.96-3.13 (m, 1H), 3.70 (s, 3H), 3.71 (s, 3H), 6.77 (d, 1H, J = 8.7 Hz), 6.85 (d, 1H, J = 8.7 Hz), 7.06 (dd, 1H, J = 2.4, 8.7 Hz), 7.33 (d, 1H, J = 2.4 Hz), 9.65 (s, 1H).
Ia-35
t.t. 214-216°C 1H-NMR (CDCI3) δ ppm: 1.23-1.38 (m, 2H), 1.40 (s,9H), 1.60-1.76 (m, 2H), 2.00-2.12 (m, 2H),
2.20-2.32 (m, 3H), 3.24-3.39 (m, 1H), 3.68 (d, 1H, J = 9.0 Hz), 6.77 (d, 1H, J = 8.7 Hz), 7.00 (dd, 1H, J = 2.4, 8.7 Hz), 7.77 (s, 1H), 8.45 (d, 1H, J = 2.4 Hz).
Ia-36
t.t. 241-242°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.25-1.42 (m, 2H), 1.37 (s, 9H), 1.62 (q, 2H, J = 11.7 Hz), 1.93 (d, 2H, J = 12.0 Hz), 2.12 (d, 2H, J = 10.8 Hz), 2.16-2.30 (m, 1H), 3.12-3.28 (m, 1H), 3.84 (s, 3H), 6.07 (d, 1H, J = 8.4 Hz), 6.89 (dd, 1H, JFH, HH = 9-3, 9.3 Hz), 7.24 (d, 1H, J = 8.7 Hz), 7.55 (d, 1H, JFH = 13.5 Hz), 9.32 (s, 1H).
Ia-37
t.t. 248-249°C 1H-NMR (CDCI3) δ ppm: 0.60-0.73 (m, 1H), 0.91 (d, 6H, J = 6.6), 1.12-1.40 (m, 2H), 1.40 (s, 9H), 1.54-1.88 (m, 5H), 1.98-2.29 (m, 7H), 3.22-3.37 (m, 1H), 3.51-3.54 (m, 2H), 3.72 (d, 1H, J = 9.6), 6.88 (d, 1H, J = 8.7), 7.06 (s. 1H), 7.35 (d, 1H, J = 9.0).
Ia-38
t.t.: 237-238°C 1H-NMR (CDCI3) δ ppm: 1.01 (d, 6H, J = 6.6), 1.20-1,40 (m, 2H), 1.40 (s, 9H), 1.60-1.74 (m, 4H), 1.99-2.28 (m, 7H), 2.69-2.82 (m, 2H), 3.02-3.14 (m, 2H), 3.20-3.38 (m, 1H), 3.80-3.90 (m, 1H), 6.83-6.86 (m, 2H), 7.14 (s, 1H), 7.34 (d, 1H, J = 8.4).
Ia-39
t.t. 234-235°C 1H-NMR (CDCI3) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.60-1.77 (m, 2H), 1.90-2.32 (m, 5H),
3.21-3.39 (m, 1H), 3.65 (d, 1H, J = 9.6 Hz), 6.87 (d, 1H, J = 8.7 Hz), 7.04 (s, 1H), 7.37 (dd, 1H, J = 2.7, 8.7 Hz), 7.56 (d, 1H, J = 2.7 Hz).
Ia-40
t.t. 257-258°C 1H-NMR (DMSO-d6) δ ppm: 1.14 (d, 6H, J = 6.0 Hz), 1.27 (s, 9H), 1.28-1.53 (m, 4H), 1.78-2.00 (m, 4H), 2.13-2.256 (m, 1H), 2.30 (t, 2H, J = 11.7 Hz), 2.97-3.12 (m, 1H), 3.53-3.67 (m, 2H), 4.01 (d, 1H, J = 12.3 Hz), 6.80 (dd, 1H, J = 3.0, 9.0 Hz), 7.79 (d, 1H, J = 9.0 Hz), 8.27 (s, 1H), 9.66 (s, 1H).
Ia-41
t.t. 245-246°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.25-1.42 (m, 2H), 1.37 (s, 9H), 1.62 (q, 2H, J = 12.6 Hz), 1.94 (d, 2H, J = 11.1 Hz), 2.13 (d, 2H, J = 11.1 Hz), 2.18-2.35 (m, 1H), 3.11-3.29 (m, 1H), 6.07 (d, 1H, J = 8.1 Hz), 6.95-7.06 (m, 1H), 7.14-7.27 (m, 1H), 7.44 (d, 1H, J = 7.2 Hz), 7.79 (s, 1H), 9.48 (s, 1H).
Ia-43
t.t. 294-295°C 1H-NMR (DMSO-d6) δ ppm: 1,26 (s, 9H), 1.28-1.53 (m, 4H), 1.76-1.87 (m, 2H), 1.89-2.00 (m, 2H), 2.13-2.25 (m, 1H), 2.96-3.10 (m, 5H), 3.52-3.60 (m, 4H), 6.78 (d, 1H, J = 9.0 Hz), 6.88 (d, 2H, J = 9.0 Hz), 7.44 (d, 2H, J = 9,0 Hz), 9.59 (s, 1H).
Ia-44
t.t. 250-252°C 1H-NMR (CDCI3) δ ppm: 1.13 (d, 6H, J = 6.3 Hz), 1.21-1.38 (m, 2H), 1.41 (s, 9H), 1.63-1.80 (m, 2H), 1.93 (t, 2H, J = 10.8 Hz), 2.00-2.10 (m, 2H), 2.16-2.32 (m, 3H), 3.24-3.39 (m, 1H), 3.54 (d, 2H, J = 10.2 Hz), 3.64-3.78 (m, 3H), 7.47 (s, 1H), 7.69 (d, 2H, J = 9.0 Hz), 7.73 (d, 2H, J = 9.0 Hz).
Ia-45
t.t. 193°C
PL 211 888 B1 1H-NMR (DMSO-d6) δ ppm: 1.10 (t, 6H, J = 7.2 Hz), 1.26 (s, 9H), 1.28-1.52 (m, 4H), 1.75-1.86 (m, 2H), 1.89-2.01 (m, 2H), 2.10-2.22 (m, 1H), 2.96-3.10 (m, 1H), 3.30-3.52 (m, 12H), 6.60 (d, 2H, J = 9.0 Hz), 6.80 (d, 1H, J = 9.0 Hz), 7,33 (d, 2H, J = 9.0 Hz), 9.46 (s, 1H).
Ia-46
t.t. >300°C 1H-NMR (DMSO-d6) δ ppm: 1.28 (s, 9H), 1.28-1.58 (m, 4H), 1.83-2.04 (m, 4H), 2.23-2.36 (m, 1H), 2.46 (s, 3H), 3.00-3.14 (m, 1H), 6.79 (d, 1H, J = 8.7 Hz), 7.34 (d, 1H, J = 8.7 Hz), 7.78 (d, 2H, J = 8.7 Hz), 7.89 (d, 1H, J = 8.4 Hz), 7.91 (s, 1H), 8.00 (d, 2H, J = 8.7 Hz), 10.13 (s, 1H).
Ia-47
t.t. 236-237°C 1H-NMR (CDCI3) δ ppm: 0.97 (d, 6H, J = 6.6 Hz), 1.01 (d, 6H, J = 6.6 Hz), 1.20-1.37 (m, 2H), 1.40 (s, 9H), 1.60-1.84 (m, 3H), 1.97-2.31 (m, 5H), 2.50 (t, 1H, J = 10.8 Hz), 2.78 (dt, 1H, J = 3,3, 11.4 Hz), 3.25-3.38 (m, 1H), 3.45 (d, 1H, J = 4 Hz), 3.75 (dt, 1H, J = 2.4, II.4 Hz), 4.02 (dt, 1H, J = 2.4, 11.4 Hz), 6.88 (d, 2H, J = 9.0 Hz), 7.05 (s, 1H), 7.39 (d, 2H, J = 9.0 Hz).
Ia-48
t.t. 228-229°C 1H-NMR (CDCI3) δ ppm: 0.88 (t, 6H, J = 7.2 Hz), 1.19-1.45 (m, 4H), 1.40 (s, 9H), 1.45-1.76 (m, 4H), 1.76-1.92 (m, 1H), 1.96-2.30 (m, 5H), 2.66-3.20 (m, 3H), 3.20-3.40 (m, 1H), 3.78 (d, 1H, J = 9.3 Hz), 3.82 (s, 1H), 6.62-6.98 (m, 2H), 7.09 (brs, 1H), 7.37 (d, 2H, J = 7,8 Hz).
Ia-49
t.t. 262-263°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.21 (d, 6H, J = 5.7 Hz), 1.26-1.34 (m, 2H), 1.37 (d, 6H, J = 5.4 Hz), 1.52-1.76 (m, 2H), 1.85-2.03 (m, 2H), 2.03-2.30 (m, 3H), 2.30-2.53 (m, 2H), 3.02-3.33 (m, 4H), 3.75-3.98 (m, 2H), 5.70 (brs, 1H), 6.73-6.98 (m, 1H), 7.14-7.25 (m, 1H), 7.52 (d, 1H, JFH = 13.5 Hz),
8.86 m (brs, 1H).
Ia-50
t.t. 232-233°C 1H-NMR (CDCI3) δ ppm: 1.21 (d, 6H, J = 6.3 Hz), 1.22-1.37 (m, 2H), 1.38 (d, 6H, J = 6.9 Hz), 1.68 (q, 2H, J = 12.6 Hz), 1.98-2.26 (m, 5H), 2.29 (s, 3H), 2.41 (t, 2H, J = 10.2 Hz), 2.88 (d, 2H, J = 11.1 Hz), 3.15 (septet, 1H, J = 6.6 Hz), 3.21-3.37 (m, 1H), 3.77-3.92 (m, 2H), 3.87 (d, 1H, J = 7.8 Hz), 6.88-7.06 (m, 3H), 7.35 (s, 1H).
la-51
t.t. 211-212°C 1H-NMR (CDCI3) δ ppm: 1.20-1.42 (m, 2H), 1.26 (d, 6H, J = 6.3 Hz), 1.38 (d, 6H, J = 6.9 Hz),
1.62-1.78 (m, 2H), 1.99-2.28 (m, 5H), 2.49 (dd, 2H, J = 10.5, 10.5 Hz), 3.17 (kwintet, 1H, J = 6.9 Hz), 3.20-3.38 (m, 1H), 3.66-3.99 (m, 2H), 3.90-4.01 (m, 3H), 6.62 (d, 1H, J = 9.0 Hz), 7.06 (s, 1H), 7.90 (dd, 1H, J = 2.4, 9.0 Hz), 8.09 (d, 1H, J = 2.4 Hz).
Ia-52
t.t. 247-249°C 1H-NMR (CDCI3) δ ppm: 1.21-1.36 (m, 2H), 1.40 (s, 9H) 1.62-1.78 (m, 2H), 1.98-2.32 (m, 5H), 2.55 (t, 4H, J = 6.0 Hz), 3.23-3.38 (m, 1H), 3.55 (t, 4H, J = 6.0 Hz), 3.72 (d, 1H, J = 9,6 Hz), 6.94 (d, 2H, J = 9.0 Hz), 7.10 (s, 1H), 7.42 (d, 1H, J = 9.0 Hz).
Ia-53
t.t. 234-235°C 1H-NMR (CDCI3) δ ppm: 1,22-1.38 (m, 2H), 1.41 (s, 9H) 1.64-1.80 (m, 2H), 2.00-2.32 (m, 5H), 3.25-3.40 (m, 1H), 3.73 (d, 1H, J = 9.3 Hz), 7.43 (s, 1H), 7.48 (t, 2H, J = 7.5 Hz), 7.55-7.66 (m, 3H), 7.68-7.89 (m, 4H).
Ia-54
t.t. 235-236°C 1H-NMR (CDCI3) δ ppm: 1.24-1.39 (m, 2H), 1.25 (d, 6H, J = 6.3 Hz), 1.39 (d, 6H, J = 6.9 Hz), 1.60-1.80 (m, 2H), 2.00-2.28 (m, 5H), 2.21 (s, 3H), 2.38 (t, 2H, J = 10,8 Hz), 3.15 (septet, 1H, J = 6.3 Hz), 3.23-3.38 (m, 1H), 3.40 (d, 2H, J = 11.7 Hz), 3.72-3.88 (m, 2H), 3.87 (d, 1H, J = 9.3 Hz), 6.786.86 (m, 3H), 7.50 (d, 1H, J = 9.6 Hz).
Ia-55
t.t. 185-186°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.14 (d, 6H, J = 6.3 Hz), 1.22-1.38 (m, 2H), 1.41 (s, 9H), 1.62-1.78 (m, 2H), 2.02 (t, 2H, J = 10.5 Hz), 2.02-2.10 (m, 2H), 2.16-2.31 (m, 3H), 3.24-3.39 (m, 1H), 3.56 (d, 2H, J = 9.3 Hz), 3.63-3.80 (m, 3H), 7.46 (dd, 1H, J = 1.5, 8.1 Hz), 7.51 (t, 1H, J = 8.1 Hz), 7.63 (s, 1H), 7.81 (t, 1H, J = 1.8 Hz), 7.98 (dt, 1H, J = 1.8, 8.1 Hz).
Ia-56
t.t. 229-230°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.28-1,54 (m, 4H), 1.38 (s, 6H), 1.78-1,84 (m, 2H), 1.902.00 (m, 2H), 2.15-2.30 (m, 1H), 2.97-3.13 (m, 1H), 4.90 (s, 1H), 6.79 (d, 1H, J = 9.0 Hz), 7.34 (d, 2H, J = 8.7 Hz), 7.48 (d, 2H, J = 8.4 Hz), 9.72 (s, 1H).
Ia-57
t.t. 211-212°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.24-1.40 (m, 2H), 1.38 (s, 9H), 1.57-1.74 (m, 2H), 1.91 (s, 3H), 1.92-2.01 (m, 2H), 2.12-2.24 (m, 2H), 2.51 (brs, 1H), 3.18-3.33 (m, 1H), 4.96 (d, 1H, J = 9.3 Hz), 7.167.53 (m, 9H), 7.41 (s, 1H).
Ia-58
t.t. 298-299°C 1H-NMR (CDCI3) δ ppm: 1.24 (s, 9H), 1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.75-2.02 (m, 4H), 2.142.28 (m, 1H), 2.97-3.11 (m, 1H), 6.78 (d, 1H, J = 8.4 Hz), 7.18 (d, 2H, J = 9.0 Hz), 7.48 (d, 2H, J = 9.0 Hz), 9.46 (s, 1H), 9.76 (s, 1H).
Ia-59
t.t. 253-254°C 1H-NMR (CDCI3) δ ppm: 1.22-1.40 (m, 2H), 1.41 (s, 9H), 1.65-1.81 (m, 2H), 2.04-2.16 (m, 2H),
2.22-2.36 (m, 2H), 3.24-3.41 (m, 1H), 3.74 (d, 1H, J = 9.6 Hz), 7.40-7.54 (m, 3H), 7.88-8.01 (m, 3H), 8.66 (d, 1H, J = 1.5 Hz), 9.57 (d, 1H, J = 1.2 Hz).
Ia-60
t.t. 213-214°C 1H-NMR (DMSO) δ ppm: 1.32-1.50 (m, 2H), 1.35 (s, 9H), 1.52-1.70 (m, 2H), 1.88-2.00 (m, 2H), 2.04-2.16 (m, 2H), 2.22-2.38 (m, 1H), 2.65 (s, 3H), 2.99-3.15 (m, 1H), 6.46 (d, 1H, J = 9.3 Hz), 7.28 (d, 1H, J = 9.0 Hz), 7.81 (s, 1H), 8.20 (s, 1H), 8.47 (s, 1H), 9.89 (s, 1H).
Ia-61
t.t. 274-275°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 1H), 1.28-1.58 (m, 4H), 1.84-2.08 (m, 4H), 2.22-2.40 (m, 1H), 2.99-3.15 (m, 1H), 3.01 (s, 3H), 6.81 (d, 1H, J = 8.1 Hz), 7.78 (d, 2H, J = 7.8 Hz), 7.84 (d, 2H, J = 8.4 Hz), 8.18 (s, 1H), 10.43 (s, 1H).
Ia-62
t.t. 235-236°C 1H-NMR (CDCI3) δ ppm: 1.22-1.39 (m, 2H), 1.41 (s, 3H), 1.66-1.80 (m, 2H), 2.01-2.12 (m, 2H), 2.14-2.22 (m, 1H), 2.23-2.34 (m, 2H), 3.24-3.42 (m, 1H), 3.69 (d, 1H, J = 9.5 Hz), 6.44 (d, 1H, J = 9.3 Hz), 7.27 (brs, 1H), 7.28 (d, 1H, J = 9.3 Hz), 7,37 (dd, 1H, J = 2.4, 9.0 Hz), 7.68 (d, 1H, J = 9.6 Hz), 8.04 (d, 1H, J = 2.4 Hz).
Ia-63
t.t. 277-279°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.77-2.02 (m, 4H), 2.15-2.29 (m, 1H), 2.90 (s, 3H), 2.96-3.13 (m, 1H), 6.79 (d, 1H, J = 8.7 Hz), 7.12 (d, 2H, J = 9.0 Hz), 7.54 (d, 2H, J =9.0 Hz), 9.50 (s, 1H), 9.81 (s, 1H).
Ia-64
t.t. 259-260°C 1H-NMR (DMSO-d6) δ ppm: 1.26 (s, 9H), 1.26-1.50 (m, 4H), 1.74-1.99 (m, 4H), 2.10-2.25 (m, 1H), 2.95-3.10 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 6.97 (d, 2H, J = 9.0 Hz), 7.42 (d, 2H, J = 9.0 Hz), 7.50-7.71 (m, 5H), 9.73 (s, 1H), 10.05 (s, 1H).
Ia-65
t.t. 292-293°C 1H-NMR (DMSO-d63) δ ppm: 1.27 (s, 9H), 1.28-1.54 (m, 4H), 1.62-1.72 (m, 2H), 1.77-1.87 (m, 2H), 1.91-2.10 (m, 4H), 2.13-2.25 (m, 1H), 2.98-3.12 (m, 1H), 3.41-3.52 (m, 2H), 5.09 (s, 1H), 6.79 (d, 1H, J = 9.0 Hz), 6.91 (d, 2H, J = 9.0 Hz), 7.37 (d, 2H, J = 9.0 Hz), 7.42 (d, 2H, J = 9.0 Hz), 7.51 (d, 2H, J = 9.0 Hz), 9.56 (s, 1H).
PL 211 888 B1
Ia-66
t.t. >300°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.28-1.58 (m, 4H), 1.85-2.02 (m, 4H), 2.40-2.52 (m, 1H), 3.00-3.16 (m, 1H), 6.81 (d, 1H, J = 9.0Hz), 7.50-7.58 (m, 3H), 7.90-7.97 (m, 2H), 12.58 (s, 1H).
Ia-67
t.t. 199-200°C 1H-NMR (DMSO-d6) δ ppm: 1.14 (d, 6H, J = 6.3 Hz), 1.28 (s, 9H), 1.31-1.48 (m, 4H), 1.76-1.88 (m, 2H), 2.17 (t, 2H, J = 11.1 Hz), 2.82 (t, 2H, J = 11.7 Hz), 3.46 (d, 2H, J = 11.4 Hz), 3.20-3.36 (m, 1H), 3.62-3.74 (m, 2H), 4.02 (d, 2H, J = 12.9 Hz), 6.83 (d, 2H, J = 9.0 Hz), 6.89 (d, 1H, J = 8.7 Hz),
7.28 (d, 2H, J = 9.0 Hz), 8.27 (s, 1H).
Ia-68
t.t. 237-239°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.40 (s, 9H), 1.49-1.65 (m, 2H), 1.99-2.10 (m, 2H), 2.95 (t, 2H, J = 11.1 Hz), 3.36-3.52 (m, 1H), 4.17 (d, 1H, J = 12.9 Hz), 5.84 (d, 1H, J = 8.7 Hz), 6.39 (d, 1H, J = 9.6 Hz), 7.21 (d, 1H, J = 9.3 Hz), 7.51 (dd, 1H, J = 2.4, 9.3 Hz), 7.72 (d, 1H, J = 9.9 Hz), 7.85 (d, 1H, J = 2.7 Hz), 8.04 (s, 1H).
Ia-69
t.t. 259-260°C 1H-NMR (DMSO) δ ppm: 1.25-1.55 (m, 4H), 1.27 (s, 9H), 1.82-2.05 (m, 4H), 2.22-2.36 (m, 1H), 2.98-3.17 (m, 1H), 4.16 (s, 3H), 6.80 (d, 1H, J = 8.4 Hz), 7.77-7.87 (m, 4H), 10.16 (s, 1H).
Ia-70
t.t. 259-260°C 1H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.36-1.56 (m, 2H), 1.80-1.92 (m, 2H), 2.86-3.02 (m, 2H), 3.36-3.52 (m, 1H), 4.04-4.20 (m, 2H), 6.92 (d, 1H, J = 7.5 Hz), 7.38-7.58 (m, 3H), 8.00-8.14 (m, 2H), 8.90 (s, 1H), 9.08 (s, 1H), 9.63 (s, 1H).
Ia-71
t.t. 228-229°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.27-1.42 (m, 2H), 1.38 (s, 9H), 1.57-1.75 (m, 2H), 1.90-2.02 (m, 2H), 2.12-2.34 (m, 3H), 3.14-3.32 (m, 1H), 5.37 (d, 1H, J = 9.3 Hz), 7.38-7.43 (m, 3H), 7.46 (d, 2H, J = 8.7 Hz), 7.51-7.60 (m, 2H), 7.68 (d, 2H, J = 9.0 Hz), 9.33 (s, 1H).
Ia-75
t.t. 169-170°C 1H-NMR (CDCI3) δ ppm: 0.58-0.72 (m, 1H), 0.80 (d, 3H, J = 6.6 Hz), 0.94 (d, 3H, J = 6.0 Hz), 1.14-1.35 (m, 3H), 1.39 (s, 9H), 1.48-1.66 (m, 2H), 1.74-2.06 (m, 5H), 2.06-2.44 (m, 6H), 3.18-3.35 (m, 1H), 3.64-3.74 (m, 1H), 4.46-4.60 (m, 1H), 6.98-7.38 (m, 5H).
Ia-76
t.t. 236-237°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.27-1.42 (m, 2H), 1.38 (d, 6H, J = 6.6 Hz), 1.60-1.78 (m, 2H), 1.94-2.06 (m, 2H), 2.12-2.30 (m, 3H), 3.06-3.34 (m, 2H), 5.10 (brs, 1H), 6.41 (d, 1H, J = 9.9 Hz), 7.25 (d, 1H, J = 8.4 Hz), 7.48 (dd, 1H, J = 2.4, 8.7 Hz), 7.68 (d, 1H, J = 9.9 Hz), 8.12 (d, 1H, J = 2.4 Hz), 8.88 (brs, 1H).
Ia-77
t.t. 117-118°C 1H-NMR (CDCI3) δ ppm: 1.38 (d, 6H, J = 6.9 Hz), 1.65 (kwintet, 2H, J = 5.4 Hz), 1.75-1.91 (m, 2H), 2.42 (t, 2H, J = 7.4 Hz), 3.10-3.24 (m, 3H), 4.77 (brs, 1H), 6.41 (d, 1H, J = 9.6 Hz), 7.18-7.26 (m, 1H), 7.48 (dd, 1H, J = 1.8, 8.7 Hz), 7.67 (d, 1H, J = 9.9 Hz), 8.01 (s, 1H), 8.23 (brs, 1H).
Ia-78
t.t. 138-139°C 1H-NMR (CDCI3) δ ppm: 1.41 (s, 9H), 1.64 (kwintet, 2H, J = 6.6 Hz), 1.84 (kwintet, 2H, J = 7.3 Hz), 2.42 (t, 2H, J = 7.5 Hz), 3.26 (q, 2H, J = 6.5 Hz), 4.59 (brs, 1H), 6.41 (d, 1H, J = 9.3 Hz), 7.23 (d, 1H, J = 8.7 Hz), 7.49 (dd, 1H, J = 2.4, 9.0 Hz), 7.67 (d, 1H, J = 9.9 Hz), 8.03 (d, 1H, J = 2.4 Hz),
8.28 (brs, 1H).
Ia-79
t.t. 289-290°C
PL 211 888 B1 1H-NMR (DMSO) δ ppm: 1.24-1.63 (m, 4H), 1.28 (s, 9H), 1.84-2.08 (m, 4H), 2.24-2.41 (m, 1H), 3.00-3.16 (m, 1H), 6.82 (d, 1H, J = 8.1 Hz), 7.36-7.60 (m, 5H), 7.86-7.99 (m, 2H), 8.28 (s, 1H), 10.50 (s, 1H).
Ia-80
t.t. 239-240°C 1H-NMR (DMSO) δ ppm: 1.22 (d, 1H, J = 6.6 Hz), 1.23-1.40 (m, 2H), 1.40-1.59 (m, 2H), 1.832.04 (m, 4H), 2.23-2.39 (m, 1H), 2.98-3.23 (m, 2H), 7.00 (d, 1H, J = 7.8 Hz), 7.36-7.59 (m, 5H), 7.857.97 (m, 2H), 8.29 (s, 1H), 10.50 (s, 1H).
Ia-81
t.t. 205-206°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.40 (s, 9H), 1.66 (kwintet, 2H, J = 7.0 Hz), 1.85 (kwintet, 2H, J = 7.2 Hz), 2.45 (t, 2H, J = 7.5 Hz), 3.24 (t, 2H, J = 6.5 Hz), 5.17 (brs, 1H), 7.36-7.54 (m, 5H), 7.85 (d, 1H, J = 8.4 Hz), 8.07 (dd, 1H, J = 1.8, 8.1 Hz), 8.23 (d, 1H, J = 1.8 Hz), 9.61 (s, 1H).
Ia-82
t.t. 216-217°C 1H-NMR (DMSO-d6) δ ppm: 1.14 (d, 6H, J = 6.3 Hz), 1.22 (d, 6H, J = 6.9 Hz), 1.22-1.53 (m, 4H), 1.76-1.98 (m, 2H), 2.21 (t, 2H, J = 10.8 Hz), 2.22-2.36 (m, 1H), 2.96-3.20 (m, 2H), 3.57 (d, 2H, J = 12.0 Hz), 3.60-3.74 (m, 1H), 6.66-6.85 (m, 2H), 6.98 (d, 1H, J = 7.8 Hz), 7.47 (d, 1H, J = 8.7 Hz), 9.30 (s, 1H).
Ia-83
t.t. 118-119°C 1H-NMR (DMSO-d6) δ ppm: 1.41 (d, 6H, J = 6.3 Hz), 1.26 (s, 9H), 1.40-1.67 (m, 4H), 2.17-2.36 (m, 3H), 2.97-3.10 (m, 2H), 3.57 (d, 2H, J = 12.0 Hz), 3.61-3.74 (m, 1H), 6.67-6.92 (m, 3H), 7.48 (t, 1H, J = 9.0 Hz), 9.37 (s, 1H).
Ia-84
t.t. 265-267°C 1H-NMR (DMSO-d6) δ ppm: 1.21 (d, 6H, J = 6.6 Hz), 1.20-1.57 (m, 4H), 1.60-2.30 (m, 9H), 2.993.20 (m, 4H), 3.40-3.52 (m, 2H), 5.09 (s, 1H), 6.91 (d, 2H, J = 8.7 Hz), 6.98 (d, 1H, J = 7.5 Hz), 7.37 (d, 2H, J = 8.7 Hz), 7.42 (d, 2H, J = 8.7 Hz), 7.51 (d, 2H, J = 8.7 Hz), 9.56 (s, 1H).
Ia-85
t.t. 185-186°C 1H-NMR (DMSO-d6) δ ppm: 1.26 (s, 9H), 1.42-1.72 (m, 6H), 1.96-2.10 (m, 2H), 2.26 (t, 2H, J = 6.9 Hz), 2.96-3.12 (m, 4H), 3.41-3.52 (m, 2H), 5.09 (s, 1H), 6.88 (d, 1H, J = 8.7 Hz), 6.92 (d, 2H, J = 9.0 Hz), 7.37 (d, 2H, J = 8.7 Hz), 7.43 (d, 2H, J = 9.0 Hz), 7.52 (d, 2H, J = 8.7 Hz), 9.63 (s, 1H).
Ia-86
t.t. 162-164°C 1H-NMR (DMSO-d6) δ ppm: 1.21 (d, 6H, J = 6.6 Hz), 1.41-1.73 (m, 6H), 1.96-2.10 (m, 2H), 2.26 (t, 2H, J = 7.2 Hz), 2,91-3.20 (m, 5H), 3.42-3.52 (m, 2H), 5.09 (s, 1H), 6.92 (d, 2H, J = 9.3 Hz), 6.99 (t, 1H, J = 6.0 Hz), 7.37 (d, 2H, J = 8.7 Hz), 7.43 (d, 2H, J = 9.3 Hz), 7.52 (d, 2H, J = 8.7 Hz), 9.64 (s, 1H).
Ia-87
t.t. 245-247°C 1H-NMR (DMSO-d6) δ ppm: 1.22 (d, 6H, J = 6.6 Hz), 1.22-1.58 (m, 4H), 1.81-2.02 (m, 4H), 2.222.36 (m, 1H), 3.00-3.20 (m, 2H), 3.01 (s, 3H), 6.99 (d, 1H, J = 8.4 Hz), 7.75-7.88 (m, 2H), 8.19 (d, 1H, J = 1.2 Hz), 10.43 (s, 1H).
Ia-88
t.t. 208-209°C 1H-NMR (DMSO-d6) δ ppm: 1.22 (d, 6H, J = 6.9 Hz), 1.22-1.55 (m, 4H), 1.75-1.98 (m, 4H), 2.112.24 (m, 1H), 2.98-3.20 (m, 2H), 5.96 (s, 2H), 6.82 (d, 1H, J = 8.4 Hz), 6.91-7.03 (m, 2H), 7.30 (d, 1H, J = 1.8 Hz), 9.72 (s, 1H).
Ia-89
t.t. 142-143°C 1H-NMR (DMSO-d6) δ ppm: 1.27 (s, 9H), 1.40-1.66 (m, 4H), 2.26 (t, 2H, J = 7.5 Hz), 3.02 (q, 2H, J = 6.6 Hz), 5.96 (s, 2H), 6.82 (d, 1H, J = 8.4 Hz), 6.88 (t, 1H, J = 8.4 Hz), 6.94 (dd, 1H, J = 1.8, 8.4 Hz), 7.30 (d, 1H, J = 1.8 Hz), 9.78 (s, 1H).
PL 211 888 B1
Ia-90
t.t. 100°C 1H-NMR (DMSO-d6) δ ppm: 1.20 (d, 6H, J = 6.9 Hz), 1.40-1.66 (m, 4H), 2.26 (t, 2H, J = 7,5 Hz), 2.89-2.99 (m, 2H), 3.13 (kwintet, 1H, J = 6.6 Hz), 5.96 (s, 2H), 6.83 (d, 1H, J = 8.1 Hz), 6.91-7.02 (m, 2H), 7.30 (d, 1H, J = 1.8 Hz), 9.78 (s, 1H).
Ia-91
t.t. 189-190°C 1H-NMR (DMSO-d6) δ ppm: 1.26 (s, 9H), 1.43-1.71 (m, 4H), 2.40 (t, 2H, J = 7.5 Hz), 2.97-3.09 (m, 2H), 3.01 (s, 3H), 6.85-6.93 (m, 1H), 7.76-7.88 (m, 2H), 8.20 (d, 1H, J = 1.2 Hz), 10.49 (s, 1H).
Ia-104
t.t. 238-241°C 1H-NMR (DMSO) δ ppm: 1.27 (s. 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.50 (m, 1H), 3.05 (m, 1H), 6.55 (br s, 1H), 6.79 (d, 1H, J = 8.2), 7.15 (t, 1H, J = 4.8), 8.64 (d, 2H, J = 4.8).
Ia-105
t.t. 232-234°C 1H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.55 (m, 1H), 3.05 (m, 1H), 6.77 (d, 1H, J = 8.7), 9.92 (s, 2H), 10.93 (s, 1H).
Ia-106
t.t. 226-228°C 1H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.22-1.58 (m, 4H), 1.82-2.04 (m, 4H), 2.29 (m, 1H), 3.07 (m, 1H), 6.79 (d, 1H, J = 8.7 Hz), 7.61 (d-d, 1H, J = 1.8 Hz, 8.7 Hz), 8.04 (d, 1H, J = 8.7 Hz), 8.48 (d, 1H, 2.1 Hz), 9.35 (s, 1H), 10.05 (s, 1H).
Ia-107
t.t. 282-283°C 1H-NMR (DMSO) δ ppm: 1.22-1.57 (m, 4H), 1.27 (s, 9H), 1.80-2.04 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.81 (d, 1H, J = 8.7 Hz), 7.32 (m, 1H), 7.44 (t, 2H, J = 7.5 Hz), 7.57-7.72 (m, 6H), 9,91 (s, 1H).
Ia-108
t.t. 191-192°C 1H-NMR (DMSO) δ ppm: 1.24-1.58 (m, 4H), 1.28 (s, 9H), 1.86-2.04 (m, 4H), 2.70 (m, 1H), 3.08 (m, 1H), 6.83 (d, 1H, J = 8.7 Hz), 7.63-7.79 (m, 2H), 8.31 (d, 1H, J = 7.2 Hz). 10,27 (s, 1H).
Ia-109
t.t. 283-285°C 1H-NMR (DMSO) δ ppm: 1.24-1.60 (m, 4H), 1.28 (s, 9H), 1.87-2.04 (m, 4H), 2.42 (m, 1H), 3.09 (m, 1H), 3.87 (s, 2H), 6.82 (d, 1H, J = 8.7 Hz), 7.28-7.43 (m, 3H), 7.60 (d, 2H, J = 7.8Hz), 7.68 (d, 1H, J = 7.2 Hz), 7.89 (d, 1H, J = 7.5 Hz), 9.48 (s, 1H).
Ia-110
t.t. 263-265°C 1H-NMR (DMSO) δ ppm: 1.24-1.54 (m, 4H), 1.27 (s, 9H), 1.76-1.87 (m, 2H), 1.89-2.01 (m, 2H), 2.17 (m, 1H), 3.04 (m, 1H), 4.01 (s, 4H), 6.01 (s, 2H), 6.44 (d, 2H, J = 8.7 Hz), 6.77(d, 1H, J = 8.7 Hz), 7.39 (d, 2H, J = 9,0 Hz), 9.44 (s, 1H).
Ia-111
t.t. 239-241°C 1H-NMR (DMSO) δ ppm: 1.24-1.54 (m, 4H), 1.27 (s, 9H), 1.62-1.76 (m, 4H), 1.80-2.02 (m, 4H),
2.30 (m, 1H), 2.47-2.59 (m, 2H), 2.66-2.76 (m, 2H), 6.08 (m, 1H), 6.79 (d, 1H, J = 9.0 Hz), 6.88 (d, 1H, J = 6.9 Hz), 7.02 (t, 1H, J = 7.5 Hz), 7.13 (d, 1H, J = 7.5 Hz), 8.98 (s, 1H).
Ia-124
t.t. 247-249°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J= 6.3 Hz), 1.30 (s, 9H), 2.15-2.26 (m, 2H), 3.48-3.57 (m, 2H), 3.63-3.76 (m, 2H), 6.92 (d, 2H, J = 8.7 Hz), 7.59 (d, 2H, J = 9,0 Hz), 7.38 (d, 2H, J = 9.0 Hz),
7.87 (d, 2H, J = 8.7 Hz), 9.92 (brs, 1H), 9.98 (brs, 1H).
Ia-125
t.t. 228.-232°C 1H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 1.95-2.08 (m, 2H), 2.77-2.89 (m, 4H), 7.17 (d, 1H, J = 8.4 Hz), 7.39 (d, 2H, J = 9.0 Hz), 7.42-7.48 (m, 1H), 7.64 (brs, 1H), 7.87 (d, 2H, J = 9.0 Hz), 9.99 (brs, 2H).
Ia-126
t.t. 244-246°C
PL 211 888 B1 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.42 (d, 2H, J = 8.4 Hz), 7.81 (d-d, 1H, J = 2.1 Hz, 8.7 Hz), 7.93 (d, 2H, J = 9.0 Hz), 8.05 (d, 1H, J = 9.0 Hz), 8.66 (d, 1H, J = 2.1 Hz), 9.29 (s, 1H), 10.05 (brs, 1H), 10.39 (brs, 1H).
Ia-127
t.t. 238-239°C 1H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 4.18-4.27 (m, 4H), 6.81 (d, 1H, J = 8.4 Hz), 7.16 (d-d, 1H, J = 2.7 Hz, 9.0 Hz), 7,34-7.42 (m, 3H), 7.85 (d, 2H, J = 8.4 Hz), 9.94 (brs, 1H), 9.99 (brs, 1H).
Ia-128
t.t. 286-287°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.41 (d, 2H, J = 8.7 Hz), 7.71 (d, 2H, J = 8.4 Hz), 7.91 (d, 2H, J = 8.7 Hz), 7.99 (d, 2H, J = 8.7 Hz), 10.05 (brs, 1H), 10.44 (brs, 1H).
Ia-129
t.t. 232-234°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.25 (1H, m), 3.07 (m, 1H), 6.80 (d, 1H, J = 9.0), 7.37 (d, 1H, J = 8.1), 7.53 (t, 1H, J = 8.1), 7.75 (t, 1H, J = 8.1), 8.12 (s, 1H), 10.16 (s, 1H).
Ia-130
t.t. 274-277°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.23-1.58 (m, 4H), 1.81-2.03 (m, 4H), 2.28 (m, 1H), 3.07 (m, 1H), 6.80 (d, 1H, J = 8.4 Hz), 7.36 (d-d, 1H, J = 0.9 Hz, 5.7 Hz), 7.43 (d-d, 1H, J = 2.1 Hz, 8.7 Hz), 7.60 (d, 1H, J = 5.4 Hz), 7.78 (d, 1H, J = 8.7 Hz), 8.40 (d, 1H, 1.8 Hz), 9.97 (brs, 1H).
Ia-131
t.t. 259-260°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.40 (d, 1H, J = 4.8 Hz), 7.41 (d, 2H, J = 8.7 Hz), 7.66 (d, 1H, J = 5.1 Hz), 7.67 (d-d, 1H, J = 1.8 Hz, 8.7 Hz), 7.84 (d, 1H, J = 9.0 Hz), 7.92 (d, 2H, J = 8.7 Hz), 8.50 (s, 1H), 10,03 (brs, 1H), 10,27 (brs, 1H).
Ia-132
t.t. 265-266°C 1H-NMR (DMSO) δ ppm: 1.17 (d, 6H, J = 6.6Hz), 1.31 (s, 9H), 4.10 (m, 1H), 7.35-7.46 (m, 3H), 7.54 (d, 1H, J = 7.5 Hz), 7.87-7.97 (m, 3H), 8.15 (brs, 1H), 8.20 (d, 1H, J = 7.5 Hz), 10.03 (brs, 1H), 10.25 (brs, 1H).
Ia-133
t.t. 249-250°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.41 (d, 2H, J = 8.7 Hz), 7.45 (d, 1H, J = 5.4 Hz), 7.67 (d-d, 1H, J = 1.8 Hz, 8.7 Hz), 7.76 (d, 1H, J = 5.4 Hz), 7.92 (d, 2H, J = 8.7 Hz), 7.95 (d, 1H, J = 8.1 Hz), 8.39 (d, 1H, J = 1.8 Hz), 10.02 (brs, 1H), 10 23 (brs, 1H).
Ia-134
t.t. 305-306°C 1H-NMR (DMSO) δ ppm: 1.25 (m, 2H), 1.25 (s, 9H), 1.52 (m, 2H), 1.82 (m, 2H), 1.94 (m, 2H), 2.13 (m, 1H), 3.04 (m, 1H), 6.00 (d, 1H, J = 8.1), 6.74 (d, 1H, J = 8.4), 7.3-7.5 (m, 6H), 7.85 (d, 2H, J = 7.5), 8.31 (d, 1H, J = 8.4).
Ia-135
t.t. 220-222°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.37 (m, 1H), 3.03 (m, 1H), 6.80 (d, 1H, J = 8.7), 7.04 (m, 1H), 7.29 (m, 1H), 7.79 (m, 1H), 9.60 (s, 1H).
Ia-136
t.t. 263-264°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.20 (m, 1H), 3.03 (m, 1H), 6.80 (d, 1H, J = 8.4), 6.87 (m, 1H), 7.31 (m, 2H), 10.21 (s, 1H).
Ia-137
t.t. 260-262°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1,8-2.0 (m, 4H), 2.30 (m, 1H), 3.05 (m, 1H), 6.80 (d, 1H, J = 8.4), 7.13 (t, 2H, J = 8.1), 7.31 (m, 1H), 9.52 (s, 1H).
Ia-138
t.t. 270-273°C
PL 211 888 B1 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.12 (m, 1H), 3.05 (m, 1H), 6.79 (d, 1H, J = 9.0), 7.31 (m, 2H), 7.80 (m, 1H), 10.05 (s, 1H).
Ia-139
t.t. 267-270°C 1H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 4.05 (s, 4H), 6.04 (s, 2H), 6.51 (d, 2H, J = 8.7 Hz), 7.34 (d, 2H, J = 8.4 Hz), 7.54 (d, 2H, J = 8.4 Hz), 7.87 (d, 2H, J = 8.4 Hz), 9.82 (brs, 1H), 9.97 (brs, 1H).
Ia-140
t.t. 227-229°C 1H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J = 6.6 Hz), 1.20-1.57 (m, 4H), 1.80-2.01 (m, 4H), 2.27 (m, 1H), 2.95-3.22 (m, 2H), 6.99 (d, 1H, J = 7.8 Hz), 7.65 (d, 2H, J = 8.7 Hz), 7.80 (d, 2H, J = 8.4 Hz), 10.18 (brs, 1H).
Ia-141
t.t. 205-207°C 1H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J = 6.9 Hz), 1.20-1.55 (m, 4H), 1.75-2.05 (m, 6H), 2.21 (m, 1H), 2.72-2.85 (m, 4H), 2.93-3.20 (m, 2H), 6.98 (d, 1H, J = 8,1 Hz), 7.10 (d, 1H, J = 8.1 Hz), 7.26 (d-d, 1H, J = 2.1 Hz, 8.1 Hz), 7.51 (s, 1H), 9.67 (brs, 1H).
Ia-142
t.t. 295-296°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J = 6.6), 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H),
2.27 (m, 1H), 3.05 (m, 1H) , 4.07 (m, 1H), 6.80 (d, 1H, J = 8.7), 7.64 (d, 2H, J = 8.7), 7.79 (d, 2H, J = 8.7), 8.06 (d, 1H, J = 7.5), 10.01 (s, 1H).
Ia-143
t.t. 146-147°C 1H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.5-1.7 (m, 4H), 2.36 (t, 2H, J = 7.8), 3.03 (q, 2H, J =
6.3), 6.89 (t, 1H, J = 6.3), 7.66 (d, 2H, J = 8.4), 7.80 (d, 2H, J = 8.4), 10.25 (s, 1H).
Ia-144
t.t. 138-140°C 1H-NMR (DMSO) δ ppm: 1.21 (d, 6H, J = 6.0), 1.4-1.7 (m, 4H), 2.37 (t, 2H, J = 7.5), 2.96 (q, 2H, J = 6.3), 3.14 (m, 1H), 6.99 (t, 1H, J = 5.4), 7.66 (d, 2H, J = 7.8), 7.81 (d, 2H, J = 7.8), 10.26 (s, 1H).
Ia-145
t.t. 134-136°C 1H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.39 (m, 2H), 1.4-1.7 (m, 4H), 2.28 (t, 2H, J = 7.2), 2.79 (m, 4H), 3.02 (q, 2H, J = 7.2), 6.88 (t, 1H, J = 6.0), 7.10 (t, 1H, J = 6.0), 7.51 (s, 1H), 9.73 (s, 1H).
Ia-146
t.t. 135-137°C 1H-NMR (DMSO) δ ppm: 1.20 (d, 6H, J = 6.6), 1.4-1.7 (m, 4H), 1.99 (m, 2H), 2.28 (t, 2H, J = 7.2), 2.79 (m, 4H), 2.94 (q, 2H, J = 6.3), 3.13 (m, 1H), 6.98 (t, 1H, J = 6.9), 7.10 (d, 2H, J = 8.1), 7.26 (d, 2H, J = 8.1), 7.51 (s, 1H), 9.73 (s, 1H).
Ia-147
t.t. 206-207°C 1H-NMR (DMSO) δ ppm: 1.29 (s, 9H), 4.54 (d, 2H, J = 5.7 Hz), 7.35 (d, 2H, J = 9.0 Hz), 7.52 (d, 2H, J = 7.8 Hz), 7.69 (d, 2H, J = 8.1 Hz), 7.83 (d, 2H, J = 8.7Hz), 9.02 (t, 1H, J = 5.7 Hz), 9,97 (brs, 1H).
Ia-148
t.t. 250-251°C 1H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 7.18 (t, 2H, J = 9.3 Hz), 7.40 (d, 2H, J = 8.7 Hz), 7.76 (d-d, 2H, J = 5.1 Hz, 9.3 Hz), 7.88 (d, 2H, J = 9.0 Hz), 10.02 (brs, 1H), 10.17 (brs, 1H).
Ia-149
t.t. 220-222°C 1H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 3.74 (s, 3H), 6.92 (d, 2H, J = 9.0 Hz), 7.38 (d, 2H, J = 9.0 Hz), 7.64 (d, 2H, J = 9.0 Hz), 7.87 (d, 2H, J = 9.0 Hz), 9.99 (s, 2H).
Ia-150
t.t. 264-266°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 1.66-1.76 (m, 4H), 2.57-2.66 (m, 2H), 2,71-2.80 (m, 2H), 6.98 (m, 1H), 7.06-7.16 (m, 2H), 7.38 (d, 2H, J = 9.0 Hz), 7.90 (d, 2H, J = 8.7 Hz), 9.60 (s, 1H), 9.99 (s, 1H).
PL 211 888 B1
Ia-151
t.t. 235-236°C 1H-NMR (DMSO) δ ppm: 1.03-1.39 (m, 5H), 1.27 (s, 9H), 1.55-1.87 (m, 5H), 3.73 (m, 1H), 7.31 (d, 2H, J = 8.7 Hz), 7.76 (d, 2H, J = 8.4 Hz), 8.01 (d, 1H, J = 7.8 Hz), 9.90 (s, 1H).
Ia-152
t.t. 244-246°C 1H-NMR (DMSO) δ ppm: 0.50-0.72 (m, 4H), 1.27 (s, 9H), 2.81 (m, 1H), 7.31 (d, 2H, J = 8.7 Hz),
7.73 (d, 2H, J = 8.7 Hz), 8.30 (d, 1H, J = 4.2 Hz), 9.91 (brs, 1H).
Ia-153
t.t. >300°C 1H-NMR (DMSO) δ ppm: 1.06 (m, 6H), 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.25 (m, 1H), 2.7 (m, 1H), 3.05 (m, 1H), 3.51 (m, 4H), 4.30 (m, 1H), 6.80 (d, 1H, J = 8.4), 7.34 (d, 2H, J =
8.4), 7.65 (d, 2H, J = 8.4), 10.01 (s, 1H).
Ia-154
t.t. 247-249°C 1H-NMR (DMSO) δ ppm: 1.05 (m, 6H), 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.23 (m, 1H), 2.77 (m, 1H), 3.05 (m, 1H), 3.52 (m, 4H), 4.33 (m, 1H), 6.80 (d, 1H, J = 9.0), 7.03 (d, 1H, J = 7,8), 7.35 (t, 1H, J = 7.8), 7,59 (d, 1H, J = 7.8), 7.68 (s, 1H), 9.96 (s, 1H).
Ia-155
t.t. 258-259°C 1H-NMR (DMSO) δ ppm: 1.25 (m, 2H), 1.50 (m, 2H), 1.86 (m, 2H), 1.99 (m, 2H), 2.28 (m, 1H), 2.93 (s, 3H), 3.10 (m, 1H), 7.02 (d, 1H, J = 7.5), 7.65 (d, 2H, J = 8.4), 7.80 (d, 2H, J = 8.4). 10.20 (s, 1H).
Ia-156
t.t. 250-253°C 1H-NMR (DMSO) δ ppm: 1.28 (m, 2H), 1.50 (m, 2H), 1.82 (m, 2H), 2.00 (m, 4H), 2.22 (m, 1H), 2.79 (m, 4H), 2.92 (s, 3H), 3.11 (m, 1H), 7.01 (d, 1H, J = (.1), 7.26 (d, 1H, J = 8.1), 7.51 (s, 1H), 9.68 (s, 1H).
Ia-157
t.t. 259-262°C 1H-NMR (DMSO) δ ppm: 1.13 (d, 6H, J = 6.0), 1.25 (m, 2H), 1.50 (m, 2H), 1.80 (m, 2H), 1.95 (m, 2H), 2.17 (m, 3H), 2.92 (s, 3H), 3.10 (m, 1H), 3.70 (m, 2H), 3.68 (m, 2H), 6.86 (d, 2H J = 9.3), 7.00 (d, 1H, J = 7,2), 7.43 (d, 2H, J = 9.3), 9.58 (s, 1H).
Ia-158
t.t. 298-300°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7,30-7.50 (m, 5H), 7.63-7,71 (m, 4H), 7.87 (d, 2H, J = 8.7 Hz), 7.91 (d, 2H, J = 9.0 Hz), 10.03 (brs, 1H), 10.22 (brs, 1H).
Ia-159
t.t. 278-281°C 1H-NMR (DMSO) δ ppm: 0.74-1.87 (m, 20H), 1.29 (s, 9H), 3.76 (m, 1H), 7.32 (d, 2H, J = 8.4 Hz), 7.75 (d, 2H, J = 8.7 Hz), 7.75 (d, 1H, J = 8.7 Hz), 7.90 (brs, 1H).
Ia-160
t.t. 227-228°C 1H-NMR (DMSO) δ ppm: 1.22-1.55 (m, 4H), 1.27 (s, 9H), 1.80-2.02 (m, 4H) , 2.23 (m, 1H), 3.06 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 7.45 (t, 1H, J = 9.9 Hz), 7.82 (m, 1H), 8.12 (d-d, 1H, J = 2.4 Hz, 6.3 Hz), 10.17 (brs, 1H).
Ia-161
t.t. 259-260°C 1H-NMR (DMSO) δ ppm: 1.22-1.54 (m, 4H), 1.27(s, 9H), 1.78-2.01 (m, 4H), 2.16 (s, 3H), 2.21 (m, 1H), 3.05 (m, 1H), 6.77 (d, 1H, J = 8.4 Hz), 7.12-7.21 (m, 2H), 7.53 (m, 1H), 9.90 (brs, 1H).
Ia-162
t.t. 222-226°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J = 6.3 Hz), 1.26 (d, 6H, J = 6.9 Hz), 2.16-2.26 (m, 2H),
3.31 (m, 1H), 3.48-3.58 (m, 2H), 3.63-3.76 (m, 2H), 6.92 (d, 2H, J = 9.0 H), 7.32 (d, 2H, J = 8.7 Hz), 7.59 (d, 2H, 9.0 Hz), 7.89 (d, 2H, J = 9.0 Hz), 9.92 (s, 1H), 10.13 (brs, 1H).
PL 211 888 B1
Ia-163
t.t. 197-200°C 1H-NMR (DMSO) δ ppm: 1.26 (d, 6H, J = 6.3 Hz), 1.95-2.09 (m, 2H) , 2.77-2.90 (m, 4H), 3.32 (m, 1H), 7.17 (d, 1H, J = 8.1 Hz), 7.32 (d, 2H, J = 8.7 Hz), 7.45 (d-d, 1H, J = 1.8 Hz, 8.1 Hz), 7.64 (brs, 1H), 7.90 (d, 2H, J = 8.7 Hz), 9.99 (brs, 1H), 10.13 (brs, 1H).
Ia-164
t.t. 145-247°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-2.0 (m, 16H), 2.19 (m, 1H), 3.05 (m, 1H), 4.74 (m, 1H), 6.79 (d, 1H, J = 9.0), 6.80 (d, 2H, J = 9.0), 7.47 (d, 2H, J = 9.0), 9.63 (s, 1H).
Ia-165
t.t. >300°C 1H-NMR (DMSO) δ ppm: 1.03-2.02 (m, 18H), 1.27 (s, 9H), 2.26 (m, 1H), 3.06 (m, 1H), 3.73 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 7.63 (d, 2H, J = 9.0 Hz), 7,78 (d, 2H, J = 8.7 Hz), 8.02 (d, 1H, J = 8.1Hz), 10.00 (brs, 1H).
Ia-166
t.t. 200-201°C 1H-NMR (DMSO) δ ppm: 1,03-2.02 (m, 18H), 1.27 (s, 9H), 2.25 (m, 1H), 3.06 (m, 1H), 3.73 (m, 1H), 6.78 (d, 1H, J = 8.7Hz), 7.33 (t, 1H, J = 8.1Hz), 7.46 (d, 1H, J = 8.1Hz), 7.76 (m, 1H), 7.94 (m, 1H), 8.14 (d, 1H, J = 8.1 Hz), 9.92 (brs, 1H).
Ia-167
t.t. 282-285°C 1H-NMR (DMSO) δ ppm: 1.22-1.57 (m, 4H), 1.27 (s, 9H), 1.87-2.03 (m, 4H), 2.49 (m, 1H), 3.07 (m, 1H), 6.83 (d, 1H, J = 8.7 Hz), 13.20 (brs, 1H).
Ia-168
t.t. 120-124°C 1H-NMR (DMSO) δ ppm: 0.94-1.66 (m, 14H), 1.27 (s, 9H), 1.80-2.04 (m, 4H), 2.25 (m, 1H), 2.92 (m, 1H), 3.06 (m, 1H), 6.78 (d, 1H, J = 8.7 Hz), 7.42-7.53 (m, 2H), 7.63 (d, 1H, J = 7.2 Hz), 7.73 (m, 1H), 8.17 (m, 1H), 10.11 (brs, 1H).
Ia-169
t.t. 256-257°C 1H-NMR (DMSO) δ ppm: 0.93-1.20 (m, 5H), 1.24-1.64 (m, 9H), 1.27 (s, 9H), 1.80-2.02 (m, 4H),
2.27 (m, 1H), 2.87 (m, 1H), 3.06 (m, 1H), 6.79 (d, 1H, J = 9.0 Hz), 7.48 (d, 1H, J = 7.2 Hz), 7.68-7.79 (m, 4H), 10.17 (brs, 1H).
Ia-171
t.t. 242-244°C 1H-NMR (DMSO) δ ppm: 1.27 (m, 12H), 1.45 (m, 4H), 1.90 (m, 4H), 2.25 (m, 1H), 3.07 (m, 1H), 3.67 (m, 2H), 6.77(d, 1H, J = 8.7), 6.90 (d, 1H, J = 7.8), 7.31 (t, 1H, J = 7.5), 7.53 (d, 1H, J = 7.8), 7.59 (s, 1H), 9.89 (s, 1H).
Ia-172
t.t. >310°C 1H-NMR (DMSO) δ ppm: 1.27 (m, 12H), 1.38 (m, 4H), 1.84 (m, 2H), 1.97 (m, 2H), 2.25 (m, 1H), 3.07 (m, 1H), 3.66 (m, 2H), 6.81 (d, 1H, J = 8.7), 7,20 (d, 2H, J = 6.7), 7.61 (d, 2H, J = 8.7), 9.94 (s, 1H).
Ia-173
t.t. 279-281°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.83 (m, 6H), 1.93 (m, 2H), 2.21 (m, 1H), 2.36 (m, 2H), 3.05 (m, 1H), 3.54 (m, 2H), 6.79 (d, 1H, J = 8.7), 7.16 (d, 2H, J = 9.0), 7.56 (d, 2H, J = 9.0), 9.83 (s, 1H).
Ia-174
t.t. 258-262°C 1H-NMR (DMSO) δ ppm: 0.29 (m, 2H), 0.53 (m, 2H), 1.20 (m, 1H), 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.7-2.0 (m, 4H), 2.20 (m, 1H), 3.05 (m, 1H), 3.75 (d, 2H, J = 6.9), 6.79 (d, 1H, J = 9.0), 6.83 (d, 2H, J = 9.0), 7.46 (d, 2H, J = 9.0), 9.64 (s, 1H).
Ia-175
t.t. 246-248°C
PL 211 888 B1 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-2.0 (m, 18H), 2.19 (m, 1H), 3.04 (m, 1H), 4.23 (m, 1H), 6.79 (d, 1H, J = 8.7), 6.84 (d, 2H, J = 9.0), 7.45 (d, 2H, J = 9.0), 9.64 (s, 1H).
Ia-176
t.t. 200-202°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-2.0 (m, 18H), 2.21 (m, 1H), 3.05 (m, 1H), 4.23 (m, 1H), 6.57 (d, 1H, J = 6.9), 6.80 (d, 1H, J = 9.0), 7.0-7.2 (m, 2H), 7.28 (s, 1H), 9.74 (s, 1H).
Ia-177
t.t. 266-268°C 1H-NMR (DMSO) δ ppm: 1.22-1.56 (m, 4H), 1.27 (s, 9H), 1.79-2.02 (m, 4H), 2.25 (m, 1H), 3.05 (m, 1H), 6.56 (m, 1H), 6.77-6.84 (m, 2H), 7.58-7.71 (m, 5H), 9.92 (brs, 1H) .
Ia-178
t.t. 223-224°C 1H-NMR (DMSO) δ ppm: 1.26-1.54 (m, 4H), 1.27 (s, 9H), 1.81-2.02 (m, 4H), 2.45 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J = 8.7 Hz), 8,15 (d-d, 1H, J = 2.4 Hz, 9.0 Hz), 8.27 (d, 1H, J = 9.0 Hz), 8.70 (m, 1H), 10.85 (brs, 1H).
Ia-179
t.t. 224-227°C 1H-NMR (DMSO) δ ppm: 1.24-1.56 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J = 8.7 Hz), 6.90 (d, 1H, J = 1.8 Hz), 7.72-7.84 (m, 4H), 8.60 (d, 1H, J = 1.8 Hz), 10.09 (brs, 1H).
Ia-180
t.t. 226-227°C 1H-NMR (DMSO) δ ppm: 0,92 (d, 6H, J = 6.6 Hz), 1.26-1.55 (m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.27 (m, 1H), 3.05 (m, 1H), 3.20 (m, 1H), 6.80 (d, 1H, J = 8.7 Hz), 7.42 (d, 1H, J = 7.2 Hz), 7.67-7.79 (m, 4H), 10.19 (brs, 1H).
Ia-181
t.t. 191-192°C 1H-NMR (DMSO) δ ppm: 0.95 (d, 6H, J = 6.6 Hz), 1.26-1.55 (m, 4H), 1.27(s, 9H), 1.80-2.03 (m,4H), 2.25(m, 1H), 3.06 (m, 1H), 3.23 (m, 1H), 6.80 (d, 1H, J=8.4 Hz), 7.41-7.53 (m, 2H), 7.58 (d, 1H, J = 7.2 Hz), 7.73 (m, 1H), 8.18(m, 1H), 10.13 (brs, 1H).
Ia-182
t.t. 192-193°C 1H-NMR (DMSO) δ ppm: 0.30 (m, 2H), 0.55 (m, 2H), 1.2-1.5 (m, 5H), 1.27 (s, 1H), 1.8-2.0 (m, 4H), 2.20 (m, 1H), 3.04 (m, 1H), 3.75 (d, 2H, J = 6.9), 6.58 (m, 1H), 6.79 (d, 1H, J = 8.7), 7.0-7.2 (m, 2H), 7.31 (s, 1H), 9.76 (s, 1H).
Ia-183
t.t. >310°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.82 (m, 2H), 1.97 (m, 2H), 2.04 (m, 2H), 2.39 (m, 1H), 2.46 (t, 2H, J = 7.8), 3.07 (m, 1H), 3.79 (t, 2H, J = 7.5), 6.79 (d, 1H, J = 8.7), 7.56 (m, 4H), 9.80 (s, 1H).
Ia-184
t.t. 281-283°C 1H-NMR (DMSO) δ ppm: 1.24-1.57 (m, 4H), 1.27 (s, 9H), 1.80-2.04 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J = 9,0 Hz), 7.33 (s, 1H), 7.75 (d, 2H, J = 9.3 Hz), 7.91 (d, 2H, J = 8.7 Hz), 8.16 (s, 1H), 10.09 (brs, 1H).
Ia-185
t.t. 226-227°C 1H-NMR (DMSO) δ ppm: 1.24-1.58 (m, 10H), 1.27 (s, 9H), 1.81-2.02 (m, 4H), 2.28 (m, 1H), 2.78-2.88 (m, 4H), 3.06 (m, 1H), 6.80 (d, 1H, J = 8.7 Hz), 7.64 (d, 2H, J = 8.7 Hz), 7.82 (d, 2H, J = 8.7 Hz), 10.25 (brs, 1H).
Ia-186
t.t. 148-150°C 1H-NMR (DMSO) δ ppm: 1.25-1.60 (m, 10H), 1.27 (s, 9H), 1.82-2.03 (m, 4H), 2.24 (m, 1H), 2.82-2.92 (m, 4H), 3.06 (m, 1H), 6.79 (d, 1H, J = 8.4 Hz), 7.36 (m, 1H), 7.55 (t, 1H, J = 7.8 Hz), 7.84 (m, 1H), 8.06 (m, 1H), 10.18 (brs, 1H).
PL 211 888 B1
Ia-187
t.t. >310°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.36 (s, 9H), 1.43 (m, 4H), 1.85 (m, 2H), 1.93 (m, 2H),
2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J = 8.7), 7.58 (s, 1H), 7.62 (d, 2H), 7.75 (d, 2H, J = 9.0), 10.00 (s, 1H).
Ia-188
t.t. 285-292°C 1H-NMR (DMSO) δ ppm: 0.85 (t, 3H, J = 7.5), 1.11 (d, 3H, J = 6.3), 1.26 (s, 9H), 1.3-1.6 (m, 6H), 1.85 (m, 2H), 1.95 (m, 2H), 2.27 (m, 1H), 3.06 (m, 1H), 3.90 (m, 1H), 6.80 (d, 1H, J = 8.4), 7.64 (d, 2H, J = 8.7), 7.79 (d, 2H, J = 8.7), 7.99 (d, 1H, J = 8.1), 10.02 (s, 1H).
Ia-189
t.t. 278-281°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-2.0 (m, 17H), 2.03 (m, 2H), 3.03 (m, 1H), 6.79 (d, 1H, J = 8.4), 7.1-7.3 (m, 3H), 7.94 (s, 1H), 9.78 (m, 2H).
Ia-190
t.t. >310°C 1H-NMR (DMSO) δ ppm: 1.1-2.0 (m, 17H), 1.27 (s, 9H), 2.25 (m, 2H), 3.03 (m, 1H), 6.79 (d, 1H, J = 8.7), 7.48 (m, 4H), 9.71 (m, 2H).
Ia-191
t.t. 275-277°C 1H-NMR (DMSO) δ ppm: 1.16 (d, 6H, J = 6.6 Hz), 1.31 (s, 9H), 4.09 (m, 1H), 7.41 (d, 2H, J = 8.7 Hz), 7.84 (s, 4H), 7.90 (d, 2H, J = 9.0 Hz), 8.11 (d, 1H, J = 7,5 Hz), 10.04 (brs, 1H), 10.30 (brs, 1H).
Ia-192
t.t. 204-205°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J = 6.6 Hz), 1.20-1.56 (m, 4H), 1.22 (d, 6H, J = 6.6Hz), 1.782.00 (m, 4H), 2.25 (m, 1H), 2.98-3.22 (m, 2H), 4.06 (m, 1H), 6.99 (d, 1H, J = 8.1Hz), 7.34 (t, 1H, J = 8.1 Hz), 7.46 (d, 1H, J = 7.8 Hz), 7.75 (m, 1H), 7.96 (m, 1H), 8.17(d, 1H, J = 8.7 Hz), 9.94 (brs, 1H).
Ia-193
t.t. 285-286°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J = 6.6 Hz), 1.20-1.56 (m, 4H), 1.22 (d, 6H, J = 6.9Hz), 1,79-2.00 (m, 4H), 2.26 (m, 1H), 2.97-3.20 (m, 2H), 4.07 (m, 1H), 6.99 (d, 1H, J = 7.8Hz), 7,64 (d, 2H, J = 8.7 Hz), 7.79 (d, 2H, J = 8.7 Hz), 8.06 (d, 1H, J = 7.5 Hz), 10,02 (brs, 1H).
Ia-194
t.t. 248-250°C 1H-NMR (DMSO) δ ppm: 1.22-1.57 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.78-2.00 (m, 4H), 2.25 (m, 1H), 2.98-3.22 (m, 2H), 6.56 (m, 1H), 6.82 (d, 1H, J = 3.3 Hz), 6.99 (d, 1H, J = 7.8Hz), 7.58- 7.71 (m, 5H), 9.92 (brs, 1H).
Ia-195
t.t. 271-275°C 1H-NMR (DMSO) δ ppm: 1.27(s, 9H), 1.28-1.56 (m, 4H), 1.80-2.02 (m, 4H), 2.25 (m, 1H), 3.06(m, 1H), 6.80 (d. 1H, J = 9.0 Hz), 7.57(s, 1H), 7.62-7.74 (m, 4H), 8.39 (s, 1H), 9,99 (brs, 1H).
Ia-196
t.t. 226-228°C 1H-NMR (CDCI3) δ ppm: 0.30 (m, 2H), 1.23 (d, 6H, J = 6.9), 1.2-2.0 (m, 4H), 2.20 (m, 1H), 3.10 (m, 2H), 3.76 (d, 2H, J = 6.9), 6.83 (d, 2H, J = 8.7), 6.99 (d, 1H, J = 8.1), 7.46 (d, 2H, J = 8.7), 9.65 (s, 1H).
Ia-197
t.t. 173-175°C 1H-NMR (DMSO) δ ppm: 0.31 (m, 2H), 0.56 (m, 2H), 1.22 (d, 6H, J = 6.6), 1.2-1.5 (m, 4H), 1.82.0 (m, 4H), 2.22 (m, 1H), 3.10 (m, 1H), 3.76 (d, 1H, J = 7.2), 6.58 (d, 1H, J = 8.1), 7,0-7.2 (m, 2H),
7.32 (s, 1H), 9.78 (s, 1H).
Ia-198
t.t. 233-235°C 1H-NMR (DMSO) δ ppm: 1.25 (d, 6H, J = 6.9), 1.2-2.0 (m, 16H), 2.19 (m, 1H), 3.10 (m, 2H),
4,73 (m, 1H), 6.80 (d, 2H, J = 8.7), 6.98 (d, 1H, J = 7.8), 7.45 (d, 2H, 3 = 8.7, 9.63 (s, 1H).
PL 211 888 B1
Ia-199
t.t. 185-186°C 1H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J = 6.9), 1.2-2.0 (m, 16H), 2.22 (m, 1H), 3.10 (m, 2H),
4.73 (m, 1H), 6.54 (m, 1H), 7.0-7.2 (m, 2H), 7.3 (s, 1H), 9.75 (s, 1H).
Ia-200
t.t. 235-237°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.6 (m, 6H), 1.8-2.0 (m, 6H), 2.20 (m, 1H), 3,05 (m, 1H), 3.45 (m, 2H), 3.82 (m, 2H), 4.47 (m, 1H), 6.79 (d, 1H, J = 9.0), 6.89 (d, 2H, J = 9.0), 7.47 (d, 2H, J = 9.0), 9.66 (s, 1H).
Ia-201
t.t. 300-301°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J = 6.6 Hz), 1.26-1.56 (m, 4H), 1.27 (s, 9H), 1.82-2.03 (m, 4H), 2.23 (s, 3H), 2.37 (m, 1H), 3.06 (m, 1H), 4.07 (m, 1H), 6,81 (d, 1H, J = 8.7 Hz), 7.52 (d, 1H, J = 8.4 Hz), 7.62 (d, 1H, J = 8.4 Hz), 7.68 (s, 1H), 8.09 (d, 1H, J = 7.5 Hz), 9.22 (brs, 1H).
Ia-202
t.t. 269-270°C 1H-NMR (DMSO) δ ppm: 1.25-1.26 (m, 4H), 1.27(s, 9H), 1.80-2.03 (m, 4H), 2.25 (m, 1H), 3.07(m, 1H), 6.80 (d, 1H, J = 8.4 Hz), 7.11 (m, 1H), 7.42 (d, 1H, =3.6 Hz), 7.48 (m, 1H), 7.58 (d, 2H, J = 8.7 Hz), 7.64 (d, 2H, J = 8.4 Hz), 9.92 (brs, 1H).
Ia-203
t.t. 271-273°C 1H-NMR (DMSO) δ ppm: 1.14-1.54 (m, 9H), 1.26 (s, 9H), 1.63-1.88 (m, 7H), 1.89-2.01 (m, 2H) , 2.21 (m, 1H), 2.42 (m, 1H), 3.04 (m, 1H), 6.79 (d, 1H, J = 9.0 Hz), 7.11 (d, 2H, J = 8.4 Hz), 7.47 (d, 2H, J = 8.1 Hz), 9.70 (brs, 1H).
Ia-204
t.t. 250-251°C 1H-NMR (DMSO) δ ppm: 1.22-1.39 (m, 2H), 1.22 (d, 6H, J = 6.6 Hz), 1.40-1.57 (m 2H), 1.802.01 (m, 4H), 2.28 (m, 1H), 2.98-3.21 (m, 2H), 7.00 (d, 1H, J = 7.8 Hz), 7.34 (s, 1H), 7.75 (d, 2H, J = 9.0 Hz), 7.91 (d, 2H, J = 8.7 Hz), 8.17 (s, 1H), 10.10 (brs, 1H).
Ia-205
t.t. 239-240°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 5H), 2.08 (m, 2H), 3.05 (m, 1H), 3.80 (m, 4H), 4.95 (m, 1H), 6.79 (d, 1H, J = 8.7), 6.8.3 (d, 2H, J = 8.7), 7.48 (d, 2H, J = 8.7), 9.66 (s, 1H).
Ia-206
t.t. 236-238°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.7 (m, 8H), 1.8-2.0 (m, 6H), 2.18 (m, 1H), 3.04 (m, 1H), 3.3-3.6 (m, 2H), 3.85 (m, 3H), 6.80 (d, 1H, J = 9.0), 6.84 (d, 2H, J = 9.0), 7.47 (d, 2H, J = 9.0), 9.65 (s, 1H).
Ia-207
t.t. 224-226°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.24 (m, 1H), 2.39 (m, 2H), 3.06 (m, 1H), 3.50 (t, 2H, J = 7.5), 3.70 (t, 2H, J = 6.3), 6.78 (d, 1H, J = 6.6), 6.83 (m, 1H), 7.25 (m, 1H), 7.27 (m, 1H), 7.54 (s, 1H), 9.61 (s, 1H).
Ia-208
t.t. 275-277°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.22 (m, 1H), 2.38 (m, 2H), 3.07 (m, 1H), 3.47 (t, 2H, J = 6.9), 3.69 (t, 2H, J = 6.6), 6.80 (d, 1H, J = 8.7), 7.14 (d, 2H, J =
8.4), 7.58 (d, 2H, J = 8.4), 9.83 (s, 1H).
Ia-209
t.t. 214-215°C 1H-NMR (DMSO) δ ppm: 1.26-1.56 (m, 4H), 1.27 (s, 9H), 1.80-2,03 9 (m, 4H), 2.25 (m, 1H), 3.06 (m, 1H), 6.59 (m, 1H), 6.81 (d, 1H, J = 8.4 Hz), 6.86 (d, 1H, J2.7 Hz), 7.28-7.40 (m, 2H), 7.47 (m, 1H), 7.75 (s, 1H), 8.01 (s, 1H), 9.91 (brs, 1H).
Ia-210
t.t. 272-275°C
PL 211 888 B1 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 6.59 (m, 1H), 6.87 (d, 1H, J = 3.3 Hz), 7.41 (d, 2H, J =
8.7 Hz), 7.68 (d, 2H, J = 8.7 Hz), 7.72 (m, 1H), 7,83 (d, 2H, J = 8.7 Hz), 7.90 (d, 2H, J = 8.7 Hz), 10.03 (brs, 1H), 10.22 (brs, 1H).
Ia-211
t.t. 251-255°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.36 (s, 1H), 7.41 (d, 2H, J = 8.4 Hz), 7.91 (d, 2H, J = 8.4 Hz), 7,92-8.00 (m, 4H), 8.19 (s, 1H), 10.06 (brs, 1H), 10.38 (brs, 1H).
Ia-212
t.t. 241-244°C 1H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 1.50-1.78 (m, 6H), 1.81-1.97 (m, 2H), 4.78 (m, 1H), 6.87 (d, 2H, J = 9.0 Hz), 7.38 (d, 2H, J = 8.7 Hz), 7.61 (d, 2H, J = 9.0 Hz), 7.87 (d, 2H, J = 8.7 Hz), 9.97 (brs, 1H), 9.99 (brs, 1H).
Ia-213
t.t. 283-286°C 1H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.12 (d-d, 1H, J = 3.6 Hz, 5.1 Hz), 7.41 (d, 2H, J = 9.0 Hz), 7.46 (m, 1H), 7.50 (d-d, 1H, J = 1.2 Hz, 5.1 Hz), 7.64 (d, 2H, J = 8.7 Hz), 7.82 (d, 2H, J = 8.7 Hz),
7.90 (d, 2H, J = 9.3 Hz), 10.03 (brs, 1H), 10.22 (brs, 1H).
Ia-216
t.t. 224-225°C 1H-NMR (CDCI3) δ ppm: 1.22 (d, 6H, J = 6.9), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.45 (m, 1H), 3.12 (m,2H), 6.99 (d, 1H, J = 8.1), 8.15 (m, 1H), 8.27 (d, 1H, J = 9.0), 8.69 (s, 1H), 10.86 (s, 1H).
Ia-219
t.t. 270-272°C 1H-NMR (DMSO) δ ppm: 1,28 (s, 9H), 1.34-1.51 (m, 2H), 1.80-1.92 (m, 2H), 2.83- 2.97 (m, 2H),
3.32 (m, 1H), 3.99-4.12 (m, 2H), 6.92 (d, 1H, J = 8.7 Hz), 7.57 (d, 2H, J = 8.7 Hz), 7.68 (d, 2H, J = 9.0 Hz), 8.90 (brs, 1H).
Ia-220
t.t. 187-189°C 1H-NMR (DMSO) δ ppm: 1,28 (s, 9H), 1.31-1.51 (m, 2H), 1.78-1.90 (m, 2H), 2.78-2.93 (m, 2H), 3.30 (m, 1H), 3.97-4.09 (m, 2H), 6.90 (d, 1H, J = 8.7 Hz), 7.06 (t, 2H, J = 9.0 Hz), 7.44 (d-d, 2H, J = 4.8 Hz, 9.0 Hz), 8.53 (brs, 1H).
Ia-221
t.t. 260-262°C 1H-NNR (DMSO) δ ppm: 1.12-1.50 (m, 7H), 1.28 (s, 9H), 1.63-1.90 (m, 7H), 2.40 (m, 1H), 2.762.91 (m, 2H), 3.28 (m, 1H), 3.96-4.09 (m, 2H), 6.90 (d, 1H, J = 8.7 Hz), 7.06 (d, 2H, J = 8.4 Hz), 7.32 (d, 2H, J = 8.4 Hz), 8.40 (brs, 1H).
Ia-222
t.t. 265-267°C 1H-NMR (DMSO) δ ppm: 1.23 (d, 6H, J = 6.6 Hz), 1.31-1.48 (m, 2H), 1.77-1.90 (m, 2H), 2.842.98(m, 2H), 3.16 (m, 1H), 3.33 (m, 1H), 3.96-4.10 (m, 2H), 7.11 (d, 1H, J = 7.8 Hz), 7.57 (d, 2H, J =
8.7 Hz), 7.67 (d, 2H, J = 8.4 Hz), 8.90 (brs, 1H).
Ia-223
t.t. 183-186°C 1H-NMR (DMSO) δ ppm: 1.23 (d, 6H, J = 6.9 Hz), 1.28-1.47 (m, 2H), 1.76-1.88 (m, 2H), 2.803.16 (m, 2H), 3.16 (m, 1H), 3.32 (m, 1H), 3.94-4.07 (m, 2H), 7.00-7.14 (m, 3H), 7.44 (d-d, 2H, J = 4.8 Hz, 9.0 Hz), 8.53 (brs, 1H).
Ia-224
t.t. 232-234°C 1H-NMR (DMSO) δ ppm: 1.12-1.46 (m, 7H), 1.23 (d, 6H, J = 6.6 Hz), 1.63-1.87 (m, 7H), 2.40 (m, 1H), 2.78-2.93 (m, 2H), 3.15 (m, 1H), 3.31 (m, 1H), 3.94-4.07 (m, 2H), 7,06 (d, 2H, J = 8.4 Hz), 7.09 (d, 1H, J = 8.1 Hz), 7.32 (d, 2H, J = 8.4 Hz), 8.39 (brs, 1H).
Ia-225
t.t. 222-224°C 1H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.30-1.61 (m, 4H), 1.77-1.98 (m, 4H), 2.66-2.90 (m, 2H),
3.28 (m, 1H), 3.40-3,50 (m, 2H), 3.79-3.88 (m, 2H), 3.96-4.08 (m, 2H), 4.44 (m, 1H), 6.85 (d, 2H, J = 9.0 Hz), 6.91 (d, 1H, J = 9.0 Hz), 7.31 (d, 2H, J = 9.3 Hz), 8.34 (brs, 1H).
PL 211 888 B1
Ia-226
t.t. 194-195°C 1H-NMR (CDCI3/DMSO) δ ppm: 1.39 (d, 6H, J = 7.2 Hz), 1.66 (kwintet, 2H, J = 6.8Hz), 1.87 (kwintet, 2H, J = 7.7 Hz), 2,47 (t, 2H, J = 7.5 Hz), 3.11-3.22 (m, 1H), 3.21 (t, 2H, J = 6.2 Hz), 5.00 (brs, 1H), 7.35-7.56 (m, 5H), 7.86 (d, 1H, J = 8.4 Hz), 8.05 (dd, 1H, J = 1.8, 8.1Hz), 8.20 (d, 1H, J = 1.8 Hz), 9.24 (s, 1H).
Ia-227
t.t. >300°C 1H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J = 6.3 Hz), 1.20-1.40 (m, 4H), 1.74-2.10 (m, 4H), 2.202.40 (m, 1H), 2.39 (s, 3H), 3.00-3.30 (m, 2H), 6.25 (s, 1H), 6.99 (brs, 1H), 7.43-7.57 (m, 1H), 7.71 (d, 1H, J = 8.1Hz), 7.76 (s, 1H), 10.27 (s, 1H).
Ia-228
t.t. 168-169°C 1H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.49 (kwintet, 2H, J = 7.5 Hz), 1.64 (kwintet, 2H, J = 7.4 Hz), 2.38 (t, 2H, J = 7.2 Hz), 2.40 (s, 3H), 3.04 (q, 2H, J = 6.5 Hz), 6.25 (s, 1H), 6.89 (t, 1H, J = 6.0 Hz), 7.48 (dd, 1H, J = 1.8, 8.4 Hz), 7.71 (d, 1H, J = 8.4 Hz), 7.77 (d, 1H, J = 1.8Hz), 10.33 (s, 1H).
Ia-229
t.t. 174-175°C 1H-NMR (DMSO) δ ppm: 1.21 (d, 6H, J = 6.6 Hz), 1.42-1.56 (m, 2H), 1.56-1.70 (m, 2H), 2.332.42 (m, 2H), 2.40 (s, 3H), 2.90-3.02 (m, 2H), 3.14 (septet, 1H, J = 6.5 Hz), 6.26 (s, 1H), 6.99 (brs, 1H), 7.48 (d, 1H, J = 8.4 Hz), 7.71 (d, 1H, J = 8.7 Hz), 7.77 (s, 1H), 10.33 (s, 1H).
Ia-230
t.t. 194-195°C 1H-NMR (DMSO) δ ppm: 0,86 (d, 6H, J = 6.9 Hz), 1.25-1.65 (m, 4H), 1.27 (s, 9H), 1.81-2.05 (m, 5H), 2.23-2.35 (m, 1H), 2.99-3.15 (m, 1H), 3.36 (d, 2H, J = 7.2 Hz), 6.80 (d, 1H, J = 8.4 Hz), 7.80 (d, 1H, J = 8.4 Hz), 7.87 (d, 1H, J = 8.4 Hz), 8.19 (s, 1H), 10.44 (s, 1H).
Ia-231
t.t. 221-222°C 1H-NMR (DMSO) δ ppm: 0.86 (d, 6H, J = 6.9 Hz), 1.22-1.40 (m, 2H), 1.23 (d, 6H, J = 6.9 Hz), 1.40-1.58 (m, 2H), 1.82-2.04 (m, 5H), 2.22-2.37 (m, 1H), 3.00-3.16 (m, 1H), 3.15 (septet, 1H, J = 6.6 Hz), 3.36 (d, 2H, J = 7.5 Hz), 6.99 (d, 1H, J = 7.5 Hz), 7.80 (d, 1H, J = 8.4 Hz), 7.86 (d, 1H, J = 8.4 Hz), 8.19 (s, 1H), 10.45 (s, 1H).
Ia-232
t.t. 196-197°C 1H-NMR (CDCI3) δ ppm: 0.93 (d, 6H, J = 6.6 Hz), 1.42 (s, 1H), 1.60-1.70 (m, 2H), 1.88 (kwintet, 2H, J = 7.4 Hz), 2.02-2.20 (m, 1H), 2.46 (t, 2H, J = 7.7 Hz), 3.29 (q, 2H, J = 6.1 Hz), 3.48 (d, 2H, J =
7.8 Hz), 4.26 (t, 1H, J = 6.0 Hz), 7.76 (d, 1H, J = 8.1 Hz), 7.90 (dd, 1H, J = 1.8, 8.1 Hz), 8.07 (d, 1H, J = 1.5 Hz), 8.39 (s, 1H).
Ia-233
t.t. 151-152°C 1H-NMR (CDCI3) δ ppm: 0.93 (d, 6H, J = 6.6 Hz), 1.40 (d, 6H, J = 6.6 H Hz), 1.62-1.69 (m, 2H), 1.88 (kwintet, 2H, J = 7.3 Hz), 2.03-2.16 (m, 1H), 2.47 (t, 2H, J = 7.5 Hz), 3.21 (septet, 1H, J = 6.8 Hz), 3.23 (q, 2H, J = 6.3 Hz), 3.48 (d, 2H, J = 7.5 Hz), 4.43 (t, 1H, J = 6.0 Hz), 7.76 (d, 1H, J = 8.4 Hz), 7.91 (dd, 1H, J = 1.8, 8.4 Hz), 8,06 (d, 1H, J = 1.8 Hz), 8.36 (s, 1H).
Ia-234
t.t. 219-220°C 1H-NMR (DMSO-d6) δ ppm: 1.28 (s, 9H), 1.30-1.50 (m, 2H), 1.74-1.88 (m, 2H), 2.83 (t, 2H, J = 11.1 Hz), 3.20-3.32 (m, 1H), 3.94-4.07 (m, 2H), 5.94 (s, 2H), 6.77 (d, 1H, J = 8.8 Hz), 6.82 (dd, 1H, J = 1.8, 8.7 Hz), 6.89 (d, 1H, J = 8.7 Hz), 7.11 (d, 1H, J = 1.8 Hz), 8.38 (s, 1H).
Ia-235
t.t. 280-282°C 1H-NMR (DMS-d6) δ ppm: 1.27 (s, 9H), 1.26-1.57 (m, 4H), 1.86-2.03 (m, 4H), 2.38-2.50 (m, 1H), 3.00-3.14 (m, 1H), 6.81 (d, 1H, J = 8.4 Hz), 7.29 (t, 1H, J = 8.4 Hz), 7.43 (t, 1H, J = 7.5 Hz),
7.73 (d, 1H, J = 8.4 Hz), 7.96 (d, 1H, J = 7.5 Hz), 12.27 (s, 1H).
Ia-237
t.t. 204-205°C
PL 211 888 B1 1H-NMR (DMSO) δ ppm: 1.23 (d, 6H, J = 6.6Hz), 1.29-1.61 (m, 4H), 1.75- 1.98 (m, 4H), 2.782.92 (m, 2H), 3.15 (m, 1H), 3.29 (m, 1H), 3.38-3.51 (m, 2H), 3.78-3.89 (m, 2H), 3.94-4.06 (m, 2H), 4.44 (m, 1H), 6.85 (d, 2H, J = 9.0 Hz), 7.10 (d, 1H, J = 7.8 Hz), 7.31 (d, 2H, J = 9.3 Hz), 8.34 (brs, 1H).
Ia-238
t.t. 128-130°C 1H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.41-1.53 (m, 2H), 1.55-1.68 (m, 2H), 2.44 (t, 2H, J = 7.2 Hz), 2.98-3.07 (m, 2H), 6.90 (t, 1H, J = 6.0 Hz), 8.16 (d-d, 1H, J = 2.1 Hz, 8.7 Hz), 8.29 (d, 1H, J = 8.7 Hz), 8.70 (m, 1H), 10.91 (brs, 1H).
Ia-239
t.t. 256-258°C 1H-NMR (DMSO) δ ppm: 1.26-1.53 (m, 4H), 1.26 (s, 9H), 1.76-2.00 (m, 4H), 2.23 (s, 3H), 2.39 (m, 1H), 3.04 (m, 1H), 6.80 (d, 1H, J = 8.7 Hz), 7.57 (d-d, 1H, J = 2.4 Hz, 8.4 Hz), 7.97 (d, 1H, J = 8.4 Hz), 8.12 (m, 1H), 10.26 (brs, 1H).
Ia-240
t.t. 288-290°C 1H-NMR (DMSO) δ ppm: 1.26-1.53 (m, 4H), 1.27 (s, 9H), 1.78-1.90 (m, 4H), 2.40 (m, 1H), 3.04 (m, 1H), 6.81 (d, 1H, J = 8.7 Hz), 7.07 (m, 1H), 7.75 (m, 1H), 8.07 (d, 1H, J = 8.4 Hz), 8.29 (m, 1H), 10.36 (brs, 1H).
Ia-241
t.t. 249-250°C 1H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.34-1.50 (m, 2H), 1.79-1.90 (m, 2H), 2.74-2.98 (m, 2H),
3.32 (m, 1H), 4.02-4.14 (m, 2H), 6.91 (d, 1H, J = 8.4 Hz), 7.94 (d, 1H, J = 9.0 Hz), 8.04 (d-d, 1H, J = 2.1 Hz, 9.0 Hz), 8.60 (s, 1H), 9.76 (brs, 1H).
Ia-242
t.t. 250-252°C 1H-NMR (DMSO) δ ppm: 1.24 (s, 9H), 1.27 (s, 9H), 1.24-1.54 (m, 4H), 1.76-1.88 (m, 2H), 1.902.01 (m, 2H), 2.21 (m, 1H), 3.05 (m, 1H), 6.79 (d, 1H, J = 8.7 Hz), 6.88 (d, 2H, J = 9.0 Hz), 7.48 (d, 2H, J = 9.0 Hz), 9.72 (brs, 1H).
Ia-243
t.t. 250-252°C 1H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J = 6.6 Hz), 1.28 (s, 9H), 1.35-1.52 (m, 2H), 1.78-1.92 (m, 2H), 2.20 (s, 3H), 2.81-2.96 (m, 2H), 3.33 (m, 1H), 3.96-4.16 (m, 3H), 6.92 (d, 1H, J = 8.7 Hz), 7.27 (d, 1H, J = 8.1 Hz), 7.60 (m, 1H), 7.66 (m, 1H), 8.06 (d, 1H, J = 7.8 Hz), 8.14 (brs, 1H).
Ia-244
t.t. 211-213°C
1H-NMR (DMSO) δ ppm: 1.29 (s, 9H), 1.35-1.52 (m, 2H), 1.81-1.93 (m, 2H), 2.83-2.97 (m, 2H),
3.32 (m, 1H), 4.03-4.14 (m, 2H), 6.93 (d, 1H, J = 8.7 Hz), 7.55 (d-d, 1H, J = 2.1 Hz, 9.0 Hz), 7.94 (d, 1H, J = 9.0 Hz), 8.29 (d, 1H, J = 1.8 Hz), 8.78 (brs, 1H), 9.19 (s, 1H).
Ia-245
t.t. 196-197°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.6 (m, 6H), 1.8-2.0 (m, 6H), 2.23 (m, 1H), 3.05 (m, 1H), 3.73 (m, 4H), 4.99 (s, 1H), 6.79 (d, 1H, J = 8.7), 7.13 (d, 1H, J = 6.8), 7.22 (t, 1H, J = 6.8), 7.49 (d, 1H, J = 6.8), 7.72 (s, 1H), 9.78 (s, 1H).
Ia-246
t.t. 242-244°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.65 (m, 4H), 1.8-2.0 (m, 4H), 2.23 (m, 1H), 2.71 (m, 1H), 3.06 (m, 1H), 3.43 (m, 2H), 3.93 (m, 2H), 6.79 (d, 1H, J = 8.7), 6.91 (d, 1H, J = 8.7), 7.20 (t, 1H, J = 7.5), 7.40 (d, 1H, J = 7.5), 7.53 (s, 1H), 9.76 (s, 1H).
Ia-247
t.t. 242-245°C 1H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.6 (m, 6H), 1.8-2.0 (m, 6H), 2.23 (m, 1H), 3.05 (m, 1H), 3.74 (m, 4H), 4.94 (brs, 1H), 6.79 (d, 1H, J = 8.7), 7.38 (d, 1H, 3 = 8.7), 7.52 (d, 1H, J = 8.7), 9.76 (s, 1H).
Ia-248
t.t. 272-274°C
PL 211 888 B1 1H-NMR (CDCI3) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.62 (m, 4H), 1.8-2.0 (m, 4H), 2.22 (m, 1H), 2.68 (m, 1H), 3.05 (m, 1H), 3.41 (m, 2H), 3.92 (m, 2H), 6.79 (d, 1H, J = 9.0), 7.15 (d, 2H, J = 8.7), 7.50 (d, 2H, J = 8.7), 9.73 (s, 1H).
Ia-249 t.t. 174-176°C
Ia-250 t.t. 255-257°C
Ia-252 t.t. 249-251°C
Ia-253 t.t. 120-121°C
Ia-254 t.t. 236-237°C
Ia-255 t.t. 172-174°C
Ia-256 t.t. 257-259°C
Ia-257 t.t. 179-180°C
Ia-258 t.t. 227-229°C
Ia-259 t.t. 135-136°C
Doświadczenie 1. Powinowactwo do receptora NPY Y5
Sekwencję cDNA kodującą ludzki receptor NPY Y5 (WO96/16542) 9 klonowano w wektorze ekspresji pME18S (Takebe i in. Mol. Cell. Biol. 8,8957). Uzyskany wektor ekspresji transfekowano do komórek gospodarza CHO stosując reagent Lipotect AMINE (Trademark, Gico BRL Co., Ltd) zgodnie z protokołem instrukcji dla uzyskania komórek, które trwale umożliwiaję ekspresję receptora NPY Y5.
Błony preparowano z powyższych komórek CHO wyrażających receptor NPY Y5, związek według wynalazku i 30, 000 cpm [125J] peptydu YY (60 pM końcowe stężenie: Amersham) inkubowano w buforze (20 mM HEPES-Hanks bufor zawierający 0.1% albuminę surowicy bydlęcej, pH 7.4) przy 25°C przez 2 h, po czym mieszaninę filtrowano przez filtr szklany GF/C potraktowany polietylenoiminą. Po przemyciu filtra szklanego za pomocą 50 mM buforu Tris-HCl (pH 7.4) radioaktywność na filtrze mierzono stosując licznik Gamma. Niespecyficzne wiązanie określano w obcności 200 nM peptydu YY. Obliczono 50% stężenie inhibitujące badany związek przeciw wiązaniu specyficznego peptydu YY (IC50) (Inui, A. i in. Endocrinology 131, 2090-2096 (1992)). Wyniki pokazano w Tabelach 1 i 2.
Związki według obecnego wynalazku hamowały wiązanie peptydu YY (NPY homolog) do NPY Y5 receptorów. Innymi słowy związki według wynalazku wykazywały powinowactwo do NPY Y5 receptora.
Doświadczenie 2. Aktywność inhibitująca produkcję cAMP w komórkach CHO
Po ekspresj i komórek CHO ludzki NPY Y5 receptor inkubowano w obecności 2.5 mM izobutylometyloksantyny (SIGMA) w temperaturze 37°C przez 20 min. dodano związek według obecnego wynalazku i inkubowano przez 5 min. Następnie do komórek dodano 50 nM NPY i 10 μΜ forskolin (SIGMA) i inkubowano przez 30 min. Po zakończeniu reakcji przez dodanie 1N HCI, ilość cAMP w supernatancie mierzono za pomocą zestawu EIA (Amersham LIFE SCIENCE). Oszacowano działanie hamujące NPY przeciw cAMP stymulowanego forskolin jako 100%, a jako 50% stężenie hamowania (IC50) związku według wynalazku przeciwko aktywności NPY. Wyniki pokazano w tabelach 1 do 4.
PL 211 888 B1
TABELA 1
związek wiązanie ICńn(nM) cAMP IC^n(nM)
1-2 7.5 72
1-7 3 <10
I-11 1.3 5
[-18 4,4 29
1-20 7 21
1-22 8.6 51
1-24 9.6 71
1-25 0.6 2.6
1-41 5.3 38.2
1-44 1.0 13.4
1-45 1.2 27.9
I -46 0.8 10.5
1-47 0.6 14.9
1-49 0.4 8.1
1-50 0.3 8.4
1-53 4.1 21
1-55 9.0 40
1-57 4.8 47
1-59 0.8 35
1-60 0.69 18
1-61 0.26 5.3
PL 211 888 B1
TABELA 2
| 1-109 1.2 3.2
l· I-110 4.3 13.6
1-111 1.8 6.1
1-114 7 30
1-116 1.2 11
1-120 1.4 4.8
1-123 1.8 168
1-126 0.6 13.2
1-127 1.4 30.4
1-128 1.3 10.2
1-129 2.1 174
1-130 1.1 42.5
1-131 1.1 34.8
1-132 2.2 30.4
1-133 0.9 21.1
1-134 0.5 10.0
1-135 0.7 22.0
1-136 2.8 -
1-137 1.4 68.2
1-138 1.0 18.6
1-139 0.41 7.6
1-140 0.48 8.9
1-141 0.42 7.4
1-142 0.49 28
1-143 3.5 44
1-144 3.4 52
1-146 2.3 20
1-147 7.1 63
1-149 0.83 15
1-150 0.17 5.2
1-151 0.17 2.6
1-152 0.88 46
1-153 1.7 29
1-154 1.1 11
1-156 0.81 17
1-160 0.61 8.8
1-161 0.49 3.1
1-162 1.7 32
1-163 2.3 83
1-164 0.71 5.9
1-165 0.44 47
1-166 0.37 9.7
1-167 0.72 39
1-168 2.1 32
1-171 2.4 71
1-172 0.91 36
1-187 0.58 13
1-191 1.1 11
1-196 1.4 6.8
1-197 6.7 38
1-198 7.2 33
1-199 4.8 31
1-202 6.7 67
1-204 1.0 6.3
1-205 2.9 17
1-206 5.9 54
1-207 4.6 23
1-210 1.1 13
1-212 0.67 7.5
1-213 0.44 4.0
Ia-1 4.8 31
Ia-3 9.2 150
Ia-4 1.4 15
Ia-5 1.6 43
Ia-6 2.4 23
Ia-8 2.9 34
Ia-9 0.94 11
Ia-10 0.47 2.7
Ia-11 0.64 7.2
Ia-12 0,94 5.5
Ia-13 1.5 3.3
la-14 4.8 28
Ia-16 0.1 -
Ia-17 0.1 1.9
Ia-20 4.9 100
PL 211 888 B1
TABELA 3
Ia-21 3.4 35
Ia-22 3.1 38
Ia-24 5.2 74
Ia-25 1.1 18
Ia-26 1.9 27
Ia-28 5.2 130
Ia-29 1 7.3
la-30 2.6 25
Ia-31 3.8 11
Ia-32 0.52 6.7
Ia-33 1.8 64
la-35 1.8 -
la-36 1.6 86
la-37 0.73 3.8
la-38 1 2.2
la-39 1.5 3.5
Ia-40 2.2 9.3
Ia-41 2.5 9
Ia-42 3.6 20
Ia-44 4.8 27
Ia-45 4.8 42
Ia-46 0.87 8.3
Ia-47 0.82 3.8
Ia-48 1.2 6.1
Ia-49 2.6 83
Ia-50 1.7 24
Ia-51 1.3 3.4
la-52 1.9 22
Ia-53 0.22 8.1
Ia-54 0.44 9
Ia-55 1.1 27
Ia-56 2.3 96
Ia-57 0.93 31
la-58 2.5 110
la-59 0.71 16
Ia-60 0.95 10
Ia-61 0.68 19
Ia-62 1.1 29
Ia-63 3.9 370
Ia-64 7.1 96
la-65 1.1 11
Ia-66 0.59 3.2
Ia-67 6.3 7 5
Ia-68 9.5 180
Ia-69 2.7 33
Ia-70 1.5 31
Ia-71 1.3 12
Ia-76 2.2 -
Ia-78 2 150
Ia-79 0.82 -
Ia-80 0.44 O co
Ia-81 2.7 4.5
Ia-83 1.2 53
Ia-84 0.25 13
Ia-85 0.22 14
Ia-86 0.73 11
Ia-87 0.49 61
Ia-88 0.62 48
Ia-91 4 150
Ia-106 1.9 24
la-107 0.14 1.3
Ia-109 0.6 3.9
Ia-110 0.3 1.1
Ia-111 5.1 28
Ia-124 1.1 22
I a -12 5 4.1 46
Ia-126 2.3 58
Ia-127 6.1 160
Ia-129 1.3 26
Ia-130 0.21 3
Ia-131 1.3 17
Ia-132 2.8 76
la-133 1.7 8.8
la-135 8.2 49
Ia-136 1.6 13
Ia-138 2.2 28
Ia-139 1.9 25
Ia-140 1 24
Ia-141 1 5.7
la-142 0.67 5.5
PL 211 888 B1
TABELA 4
Ia-143 7.8 39
Ia-144 6.1 57
Ia-145 7 86 ..
Ia-146 9.9 79
Ia-158 0.71 1.7
ia-ieo 0.76 140
Ia-161 1.9 18
Ia-163 7 400
Ia-164 0.38 4.7
Ia-168 0.95 13
Ia-169 1.9 88
Ia-173 6.9 140
Ia-174 0.35 5.4
Ia-175 0.49 9.2
Ia-176 0.63 5.1
Ia-177 0.49 7.5
Ia-178 4.6 16
Ia-179 0.89 19
Ia-180 1.9 11
Ia-181 7.7 25
Ia-182 0.24 - 2.1
Ia-183 1.9 7.8
Ia-184 0.38 -
Ia-185 0.94 4.4
la-186 0.93 12
la-187 1.9 60
Ia-188 0.75 28
Ia-189 3.5 95
Ia-190 0.34 1000
Ia-191 0.49 220
Ia-192 5.9 200
la-193 1.4 43
Ia-194 0.22 - 8.1
Ia-195 1.4 31
Ia-196 0.39 1.3
Ia-197 0.44 2.5
Ia-198 0.23 2.6
Ia-199 0.11 1.6
la-200 1.4 18
Ia-201 3.1 74
Ia-202 0.37 3.4
Ia-203 0.2 2.6
Ia-204 1 6.3
Ia-205 2.4 99
Ia-206 1.9 460
Ia-207 0.55 5.9
Ia-208 1.2 9.7
Ia-209 0.55 -
Ia-210 2.8 99
Ia-211 4.8 240
Ia-212 0.52 2.6
Ia-213 0.91 28
Ia-219 2.5 28
Ia-221 0.47 1.5
Ia-222 3.7 18
Ia-224 0.1 1.2
Ia-225 3.4 20
Ia-226 0.37 21
Ia-227 0.59 -
Ia-228 0.96 -
Ia-229 1.9 -
Ia-230 0.32 -
Ia-231 0.29 -
Ia-232 0.7 -
la-233 0.63 -
Ia-235 5.5 -
Ia-237 1.1 15
Ia-241 1.9 -
Ia-243 1.3 -
Ia-246 0.26 20
Ia-247 0.79 31
Ia-248 0.27 17
Ia-250 1.9 -
Ia-2-52 1.2 -
Ia-253 0.53 -
la-254 2.0 -
Ia-255 3.2 -
Ia-256 5.7
Ia-257 8.6 -
Ia-258 1.8 | -
PL 211 888 B1
Doświadczenie 3
Stosując błony wytworzone z komórek ekspresyjnych Y1 (ludzki nerwiak niedojrzały SK-N-MC) i błony preparowane z komórek ekspresyjnych Y2 (ludzki nerwiak niedojrzały SMS-KAN), doświadczenie prowadzono w podobny sposób jak doświadczenie 1 dla określenia powinowactwa do receptora NPY Y1 i NPY Y2.
Wartość wiązania IC50 do receptorów NPY Y1 i NPY Y2 I-27, I-32, I-41, I-45, I-46, I-47, I-48, I-49, I-59, I-61, I-63, I-64, I-66, I-69, I-72, I-152, I-154, I-204, I-205, I-212, la-3, Ia-5, Ia-6, Ia-12, Ia-16, Ia-17, Ia-20, Ia-21, la-22, Ia-26, Ia-28, Ia-29, Ia-30, Ia-31, Ia-32, Ia-33, Ia-37, Ia-39, Ia-40, Ia-50, Ia-51, Ia-54, Ia-62, Ia-67, Ia-124, la-126, Ia-139, Ia-140, Ia-142, Ia-178, Ia-199 i Ia-200 wynosiły 100,000 nM lub więcej, a każdy związek był selektywny w stosunku do receptora NPY Y5.
Przykład preparatu 1 Tabletki
Związek (I-1) 15 mg
Skrobia 15 mg
Laktoza 15 mg
Celuloza krystaliczna 19 mg
alkohol poliwinylowy 3 mg
woda destylowana 30 ml
stearynian sodu 3 mg
Po dokładnym zmieszaniu wszystkich składników poza stearynianem wapnia
zmiażdżono i granulowano, po czym suszono uzyskując odpowiednią wielkość granulek. Po dodaniu stearynianu wapnia do granulek, uformowano tabletki na drodze prasowania.
Przykład preparatu 2 Kapsułki
Związek (I-2) 10 mg
Stearynian magnezu 10 mg
Laktoza 80 mg
Po zmieszaniu powyższych składników wytworzono proszki lub granulki którymi napełniono kapsułki.
Przykład preparatu 3 Granulki
Związek (I-3) 30 g
Laktoza 265 g
Stearynian 5 g
Po zmieszaniu powyższych składników i utworzeniu przez prasowanie uzyskany produkt zmiażdżono, granulowano i przesiano uzyskując odpowiednią objętość granulek.
Zastosowanie przemysłowe
Jak pokazano wyżej związki według wynalazku mają aktywność antagonistyczną NPY Y5. Dlatego związki według wynalazku są użyteczne jako środek przeciw otyłości i przeciw anoreksji.

Claims (7)

1. Związek o wzorze (I)
R1-S—Ν-Χ—Y—Z (I)
II I, (Ο)η R 1
R1 oznacza izopropyl, t-butyl, izobutyl, 1-chloro-1-metyloetyl, 1,1-dimetylopropyl, 2-metylopropyl lub 1-metylopropyl;
R2 oznacza atom wodoru; n oznacza 1 lub 2;
X oznacza butylen, fenylen, cykloheksylen, piperydynodiyl, propylen, metylen, heksylen, bicyklo[2,2,2]heks-1,4-diyl;
Y oznacza -C(O)NH-, -NHC(O)-, -OC(O)NH, -C(S)NH-, -C(O)-N(Me)-;
Z oznacza 4-butylofenyl, 2,6-dimetylomorfolinofenyl, morfolinofenyl, 4-(dietyloamino)fenyl, piperydynofenyl, N-etylokarbazolil, 4-jodofenyl, 4-fluorofenyl, pirolidynofenyl, fenoksyfenyl, 4-fenylopiperaPL 211 888 B1 zynofenyl, 4-(1,3-diazyn-2-ylo)piperazynofenyl, 4-etoksykarbonylopiperydynofenyl, izochinolinofenyl, pirolilofenyl, 4,5-dichloroimidazolofenyl, 4-bromofenyl, 1,3-benzodioksol-5-il, 4-metylobenzopiran-2-on-7-yl, 3-acetyloaminofenyl, 3-aminofenyl, indolilofenyl, pirazolilofenyl, 1,2,3-tiodiazolilofenyl, fenyloaminofenyl, 1,2,3,4-tetrazolilofenyl, 4-(dihydroksyetylo)aminofenyl, metoksykarbonylopropylofenyl, 3-hydroksypirolidynylofenyl, 4-butoksyfenyl, 3-difluorometylodifluorometoksyfenyl, acetylofenyl, metylotiofenyl, antryl, 3-chloro-4-fenylometylocyjanofenyl, 4-bromo-2-metylopirazol-5-ilofenyl, 7-metoksydibenzofuran-8-yl, 4-(3-metylobutoksykarbonyloetenylo)fenyl, 3-fenoksyfenyl, fluoren-9-on-7-yl, terfenyl-4-il, 4-(4-cyjanofenylo)fenyl, 2-metylochinolin-6-yl, chinolin-3-yl, 2-fenylotio-6-metoksypirydyl, 5-tri-fluorometylopirydyn-2-yl, 4-naftylo-1,3-tiazol-2-il, 2,3-di(metoksykarbonylo)tien-4-yl, 2,4-difluorofenoksypirydyn-3-yl, 3-furan-2-ylopirazol-5-il, fenyloetyloaminoetyl, 2,6-dichlorofenylometylotioetyl, 2-chloro-6-fluorofenylometylotioetyl, 2-tri-fluorometylochinolin-3-ylo-tioetyl, 2-metylotio-3-hydroksy-4,5,6,7-tetrahydrobenzo[c]-tien-7-yl, naftylometylo, 1-indanon-5-yl, 3-etoksyfenyl, 3-metoksymetyloksyfenyl, 3-hydroksyfenyl, 4-butoksy-3-hydroksyfenyl, 2-butoksypirydyn-5-yl, 2-fenoksypirydyn-5-yl, 4-butoksy-2-nitrofenyl, 2-amino-4-butoksyfenyl, 3-butoksyfenylometyl, 3,4-dietoksyfenyl, 1-hydroksyiminoindan-5-yl, 2,3-dihydrobenzo-[1,4]-dioksan-6-yl, indan-1-yl, 3-izopropyloaminokarbonylofenyl, 4-pirydynometylofenyl, 1,3-benzotiazol-6-il, benzotien-5-yl, 4-trifluorometylofenyl, 5-(4-fluorofenylo)-1,3,4-tiadiazol-2-il, 4-metylofenyl, 4-etylofenyl, 4-propylofenyl, 4-izopropylofenyl, 4-(1-metylopropylo)fenyl, 4-tertbutylofenyl, 4-chlorofenyl, 3-fluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,3,4-trifluorofenyl, 3-chloro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2-fluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 4-fluoro-2-(2,6-dimetylomorfolin-1-ylo)fenyl, 2-metylo-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,3-difluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,3,5,6-tetrafluoro-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 2,4-dichlorofenyl, 3,4-dimetoksyfenyl, 4-chloro-2-metoksyfenyl, 3-fluoro-4-metoksyfenyl, 4-(3,5-dimetylopiperydyn-1-ylo)fenyl, 4-(5-metylopiperydyn-1-ylo)fenyl, 3-chloro-4-metoksyfenyl, 2-(2,6-dimetylomorfolin-1-ylo)pirydyn-5-yl, 5-trifluorometylopirydyn-2-yl, 3-chlorofenyl, 4-(2,6-dimetylomorfolin-1-ylosulfonylo)fenyl, 4-(dietoksyetylenoamino)fenyl, 4-(6-metylo-1,3-benzotiazol-2-ilo)fenyl, 4-(piperydyn-4-ono)fenyl, 4-(fenylokarbonylo)fenol, 2-metylo-4-(2,6-dimetylomorfolin-1-ylo)fenyl, 4-(tertbutylosulfonyloamino)fenyl, 4-acetylo-2-okso-2H-chromen-6-yl, 2-metylo-1,3-dioksoizoindol-6-iyl, 2-okso-2H-chromen-6-yl, 4-(metylosulfonyloamino)fenyl, 4-(fenylosulfonyloamino)fenyl, 4-(4-chlorofenylo)-4-hydroksypiperydyn-1-yl, 5-fenylo-1,3,4-tiadiazol-2-il, 1-metylo-1,2,3,4-tetrazol-5-ilofenyl, 6-fenylopirazyn-3-yl, 1-fenylo-1,2,3,4-tetrazol-5-ilofenyl, fluoren-1-yl, 4-(2,5-dihydro-1H-pirol-1-ilo)fenyl, 1,2,3,4-tetrahydronaftalen-1-yl, 3-cykloheksyloaminosulfonylofenyl, 4-cyklopropyloksyfenyl, 3-cykloheksylofenyl,
5-trifluorometylopirydyn-2-yl, 3-(piperydyn-1-ylosulfonylo)fenyl, 4-(cyklopentyloksy)fenyl, 4-(tien-2-ylo)fenyl, lub jego farmaceutycznie dopuszczalną sól
2. Związek jak określony w zastrz. 1, w którym Z oznacza 5-trifluorometylopirydyn-2-yl.
3. Związek jak określony w zastrz. 1 albo 2, w którym R1 oznacza tert-butyl.
4. Związek jak określony w zastrz. 2, w którym R1 oznacza tert-butyl.
5. Kompozycja farmaceutyczna, znamienna tym, że jako substancję czynną zawiera związek jak opisany w jednym z zastrz. 1-4.
6. Związek o wzorze w którym n oznacza liczbę 2, zaś R oznacza metyl.
7. Związek o wzorze
PL355382A 1999-11-26 2000-11-21 Związek będący antagonistą NPY Y5 oraz kompozycja farmaceutyczna zawierająca taki związek PL211888B1 (pl)

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Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1249233B9 (en) * 1999-11-26 2009-08-05 Shionogi & Co., Ltd. Npyy5 antagonists
US6894063B2 (en) 2000-09-14 2005-05-17 Schering Corporation Substituted urea neuropeptide Y Y5 Receptor antagonists
US6946476B2 (en) 2000-12-21 2005-09-20 Schering Corporation Heteroaryl urea neuropeptide Y Y5 receptor antagonists
WO2002049648A1 (en) 2000-12-21 2002-06-27 Schering Corporation Heteroaryl urea neuropeptide y y5 receptor antagonists
US7507767B2 (en) 2001-02-08 2009-03-24 Schering Corporation Cannabinoid receptor ligands
US7067539B2 (en) 2001-02-08 2006-06-27 Schering Corporation Cannabinoid receptor ligands
GB0121709D0 (en) * 2001-09-07 2001-10-31 Imp College Innovations Ltd Food inhibition agent
CN100350968C (zh) * 2001-09-24 2007-11-28 皇家创新有限公司 饮食行为的改进
JP2005509032A (ja) 2001-11-14 2005-04-07 シェーリング　コーポレイション カンナビノイドレセプターリガンド
US8058233B2 (en) * 2002-01-10 2011-11-15 Oregon Health And Science University Modification of feeding behavior using PYY and GLP-1
CN101104598B (zh) 2002-03-12 2011-06-15 盐野义制药株式会社 反式-4-氨基-1-环己烷羧酸衍生物的制备方法
EP1539693B9 (en) 2002-06-19 2008-10-08 Schering Corporation Cannabinoid receptor agonists
AR040335A1 (es) * 2002-06-26 2005-03-30 Glaxo Group Ltd Compuesto de ciclohexano o ciclohexeno, uso del mismo para preparar un medicamento, composicion farmaceutica que lo comprende, procedimiento y compuestos intermediarios de utilidad para preparar dicho compuesto
AR040336A1 (es) * 2002-06-26 2005-03-30 Glaxo Group Ltd Compuesto de piperidina, uso del mismo para la fabricacion de un medicamento, composicion farmaceutica que lo comprende y procedimiento para preparar dicho compuesto
US7166575B2 (en) * 2002-12-17 2007-01-23 Nastech Pharmaceutical Company Inc. Compositions and methods for enhanced mucosal delivery of peptide YY and methods for treating and preventing obesity
GB0300571D0 (en) * 2003-01-10 2003-02-12 Imp College Innovations Ltd Modification of feeding behaviour
TW200505902A (en) 2003-03-20 2005-02-16 Schering Corp Cannabinoid receptor ligands
GB0312609D0 (en) * 2003-06-02 2003-07-09 Astrazeneca Ab Novel compounds
CN100567270C (zh) * 2004-02-19 2009-12-09 万有制药株式会社 磺酰胺衍生物
JPWO2006001318A1 (ja) * 2004-06-24 2008-07-31 塩野義製薬株式会社 スルホンアミド化合物
EP1797034B1 (en) * 2004-08-06 2010-06-30 Merck Sharp & Dohme Corp. Sulfonyl compounds as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1
DE102004039789A1 (de) * 2004-08-16 2006-03-02 Sanofi-Aventis Deutschland Gmbh Arylsubstituierte polycyclische Amine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
TW200630337A (en) * 2004-10-14 2006-09-01 Euro Celtique Sa Piperidinyl compounds and the use thereof
AU2006208045B2 (en) 2005-01-25 2012-08-30 Synta Pharmaceuticals Corp. Compounds for inflammation and immune-related uses
CN101146768B (zh) * 2005-03-31 2012-01-25 盐野义制药株式会社 氨磺酰羧酸衍生物的制备方法
GB0511986D0 (en) * 2005-06-13 2005-07-20 Imp College Innovations Ltd Novel compounds and their effects on feeding behaviour
US20060293341A1 (en) * 2005-06-23 2006-12-28 Vrej Jubian Alkyl sulfonamide derivatives
CA2637530A1 (en) * 2006-01-18 2007-09-07 Siena Biotech S.P.A. Modulators of alpha7 nicotinic acetylcholine receptors and therapeutic uses thereof
TW200800979A (en) * 2006-03-07 2008-01-01 Lundbeck & Co As H Halogenated sulfonamide derivatives
US8247442B2 (en) 2006-03-29 2012-08-21 Purdue Pharma L.P. Benzenesulfonamide compounds and their use
TW200812963A (en) 2006-04-13 2008-03-16 Euro Celtique Sa Benzenesulfonamide compounds and the use thereof
US8791264B2 (en) * 2006-04-13 2014-07-29 Purdue Pharma L.P. Benzenesulfonamide compounds and their use as blockers of calcium channels
NZ572381A (en) * 2006-04-28 2011-01-28 Shionogi & Co Amine derivative having npy y5 receptor antagonist activity
DE102006039003A1 (de) 2006-08-19 2008-02-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Verbindungen
WO2008026563A1 (fr) 2006-08-30 2008-03-06 Shionogi & Co., Ltd. Dérivé d'hydrazine amide
EP2058305A4 (en) 2006-08-30 2010-09-22 Shionogi & Co UREA DERIVATIVE
EP2526948A1 (en) 2006-09-20 2012-11-28 Aerie Pharmaceuticals, Inc. RHO kinase inhibitors
WO2008047769A1 (fr) 2006-10-18 2008-04-24 Shionogi & Co., Ltd. Agent améliorant le métabolisme du glucose
TWI428346B (zh) * 2006-12-13 2014-03-01 Imp Innovations Ltd 新穎化合物及其等對進食行為影響
US8455513B2 (en) 2007-01-10 2013-06-04 Aerie Pharmaceuticals, Inc. 6-aminoisoquinoline compounds
JP2010522227A (ja) 2007-03-22 2010-07-01 アストラゼネカ・アクチエボラーグ 炎症性疾患の処置のためのキノリン誘導体
US8399486B2 (en) 2007-04-09 2013-03-19 Purdue Pharma L.P. Benzenesulfonyl compounds and the use thereof
EP2025675A1 (de) 2007-08-14 2009-02-18 Boehringer Ingelheim International GmbH Arylsulfonamide mit analgetischer Wirkung
US8394805B2 (en) 2007-08-14 2013-03-12 Boehringer Ingelheim International Gmbh Compounds
JPWO2009038112A1 (ja) * 2007-09-21 2011-01-06 塩野義製薬株式会社 Ｎｐｙｙ５受容体拮抗剤を含有する固形製剤
WO2009040659A2 (en) 2007-09-28 2009-04-02 Purdue Pharma L.P. Benzenesulfonamide compounds and the use thereof
SA08290668B1 (ar) 2007-10-25 2012-02-12 شيونوجي آند كو.، ليمتد مشتقات أمين لها نشاط مضاد لمستقبل npy y5 واستخداماتها
US8106073B2 (en) 2007-11-30 2012-01-31 Astrazeneca Ab Quinoline derivatives 057
US8455514B2 (en) * 2008-01-17 2013-06-04 Aerie Pharmaceuticals, Inc. 6-and 7-amino isoquinoline compounds and methods for making and using the same
CL2009000904A1 (es) * 2008-04-21 2010-04-30 Shionogi & Co Compuestos derivados de ciclohexil sulfonamidas que tienen actividad antagonista en el receptor npy y5, composicion farmaceutica y formulacion farmaceutica que los comprende.
CL2009001088A1 (es) * 2008-05-08 2011-06-17 Shionogi & Co Forma cristalina (ii) de (1r,4r)-4-(1,1-dimetiletilsulfonamido)-n-(5-(trifluorometil) piridin-2-il) ciclohexancarboxamida; procesos de preparacion; utiles como antagonistas del receptor npyy5.
US8450344B2 (en) 2008-07-25 2013-05-28 Aerie Pharmaceuticals, Inc. Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
WO2010053861A2 (en) * 2008-11-07 2010-05-14 H. Lundbeck A/S Biologically active amides
WO2010098298A1 (ja) * 2009-02-27 2010-09-02 塩野義製薬株式会社 栄養素の消化吸収抑制作用を有する化合物とシクロヘキサンカルボキサミド誘導体を組み合わせてなる医薬組成物
WO2010101246A1 (ja) * 2009-03-05 2010-09-10 塩野義製薬株式会社 Ｎｐｙ ｙ５受容体拮抗作用を有するピペリジンおよびピロリジン誘導体
EP2404896A1 (en) 2009-03-05 2012-01-11 Shionogi&Co., Ltd. Cyclohexane derivative having npy y5 receptor antagonism
JPWO2010107040A1 (ja) * 2009-03-19 2012-09-20 塩野義製薬株式会社 Ｎｐｙｙ５受容体拮抗剤を含有する固形製剤
US8227618B2 (en) 2009-04-23 2012-07-24 Shionogi & Co., Ltd. Amine-derivatives having NPY Y5 receptor antagonistic activity and the uses thereof
EP3053913B1 (en) 2009-05-01 2018-03-07 Aerie Pharmaceuticals, Inc. Dual mechanism inhibitors for the treatment of disease
WO2011058943A1 (ja) * 2009-11-11 2011-05-19 塩野義製薬株式会社 Ｍｃｈ ｒ１アンタゴニスト活性を有する化合物とｎｐｙ ｙ５受容体アンタゴニスト活性を有する化合物を組み合わせてなる医薬組成物
WO2011060321A1 (en) 2009-11-16 2011-05-19 Chdi, Inc. Transglutaminase tg2 inhibitors, pharmaceutical compositions, and methods of use thereof
US8394858B2 (en) 2009-12-03 2013-03-12 Novartis Ag Cyclohexane derivatives and uses thereof
MX358421B (es) * 2011-04-27 2018-08-20 Shionogi & Co Derivados heteroaromaticos de anillo de 5 miembros que tienen actividad antagonista del receptor y5 de neuropeptido (npy).
US8889716B2 (en) 2011-05-10 2014-11-18 Chdi Foundation, Inc. Transglutaminase TG2 inhibitors, pharmaceutical compositions, and methods of use thereof
WO2013002313A1 (ja) * 2011-06-29 2013-01-03 塩野義製薬株式会社 体重管理薬
US10092574B2 (en) 2012-09-26 2018-10-09 Valorisation-Recherche, Limited Partnership Inhibitors of polynucleotide repeat-associated RNA foci and uses thereof
ES2664782T3 (es) * 2012-11-05 2018-04-23 Nantbio, Inc Derivados que contienen sulfonamida cíclica como inhibidores de la ruta de señalización de hedgehog
US20140275160A1 (en) 2013-03-15 2014-09-18 Aerie Pharmaceuticals, Inc. Combination therapy
WO2015187673A1 (en) 2014-06-02 2015-12-10 Afshari Thomas Linear actuator assembly and system
US9765050B2 (en) * 2014-12-30 2017-09-19 Novira Therapeutics, Inc. Pyridyl reverse sulfonamides for HBV treatment
US9643927B1 (en) 2015-11-17 2017-05-09 Aerie Pharmaceuticals, Inc. Process for the preparation of kinase inhibitors and intermediates thereof
AU2015414743B2 (en) 2015-11-17 2019-07-18 Alcon Inc. Process for the preparation of kinase inhibitors and intermediates thereof
WO2017134212A1 (en) 2016-02-05 2017-08-10 Siegfried Ag Process for the preparation of trans-4-amino-1-cyclohexanecarboxilic acid and its derivatives
JP6907319B2 (ja) 2016-08-31 2021-07-21 アエリエ ファーマシューティカルズ インコーポレイテッド 眼科用組成物
HUE049979T2 (hu) 2017-03-20 2020-11-30 Forma Therapeutics Inc Pirrolopirrol készítmények piruvát-kináz (PKR) aktivátorokként
EP3609871A4 (en) 2017-03-31 2021-01-06 Aerie Pharmaceuticals, Inc. ARYL CYCLOPROPYL-AMINO-ISOQUINOLINYL AMIDE COMPOUNDS
CA3112391A1 (en) 2018-09-14 2020-03-19 Aerie Pharmaceuticals, Inc. Aryl cyclopropyl-amino-isoquinolinyl amide compounds
BR112021005188A2 (pt) 2018-09-19 2021-06-08 Forma Therapeutics, Inc. tratamento de anemia falciforme com um composto de ativação de piruvato cinase r
CN113226356A (zh) 2018-09-19 2021-08-06 福马治疗股份有限公司 活化丙酮酸激酶r

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3704290A (en) * 1970-12-09 1972-11-28 American Home Prod 6-(1 - substituted aminocycloalkane-carboxamido)-penicillanic acid and salts
JPS5916871A (ja) * 1982-07-20 1984-01-28 Shionogi & Co Ltd スルホンアミド系ベンズアミド類
AU567140B2 (en) * 1984-01-06 1987-11-12 Shionogi & Co., Ltd. Sulphonamido-benzamide derivatives
DE3535167A1 (de) 1985-10-02 1987-04-09 Boehringer Mannheim Gmbh Neue sulfonyl-phenyl(alkyl)amine, verfahren zu ihrer herstellung sowie arzneimittel
CA1278577C (en) 1985-11-18 1991-01-02 Tatsuo Tsuri Bicyclic sulfonamide derivatives
JP2565746B2 (ja) 1987-10-23 1996-12-18 小野薬品工業株式会社 新規な炭素環系スルホンアミド誘導体
US5378691A (en) * 1988-04-14 1995-01-03 Merck Patent Gesellschaft Mit Beschrankter Haftung Amino acid derivatives
DE3821540A1 (de) 1988-06-25 1989-12-28 Boehringer Mannheim Gmbh Neue sulfonamide, verfahren zu ihrer herstellung sowie solche sulfonamide enthaltende arzneimittel
US5189211A (en) 1990-08-01 1993-02-23 Taisho Pharmaceutical Co., Ltd. Sulfonamide derivatives
JP3052010B2 (ja) 1991-07-18 2000-06-12 本田技研工業株式会社 摺動部材
JPH05194370A (ja) 1992-01-22 1993-08-03 Taisho Pharmaceut Co Ltd スルホンアミド誘導体
JPH05262643A (ja) 1992-01-23 1993-10-12 Taisho Pharmaceut Co Ltd トロンボキサンａ２拮抗剤
US5506242A (en) 1993-01-06 1996-04-09 Ciba-Geigy Corporation Arylsufonamido-substituted hydroxamic acids
CA2193691A1 (en) 1994-06-22 1995-12-28 Andrew Miller Metalloproteinase inhibitors
FI97148C (fi) 1994-07-14 1996-10-25 Lahden Polttimo Ab Oy Menetelmä kasvien käsittelemiseksi siementen laatuominaisuuksien parantamiseksi
JPH0892249A (ja) 1994-07-20 1996-04-09 Sankyo Co Ltd スルホンアミド誘導体
MX9710256A (es) 1995-06-21 1998-03-31 Shionogi & Co Derivados de amino biciclicos y antagonistas pgd2 que contienen los mismos.
KR980009238A (ko) 1995-07-28 1998-04-30 우에노 도시오 설포닐아미노산 유도체
WO1997015567A1 (de) 1995-10-20 1997-05-01 Dr. Karl Thomae Gmbh 5-gliedrige heterocyclen, diese verbindungen enthaltende arzneimittel und deren verwendung sowie verfahren zu ihrer herstellung
WO1997020821A1 (en) * 1995-12-01 1997-06-12 Novartis Ag Heteroaryl derivatives
WO1997019682A1 (en) 1995-12-01 1997-06-05 Synaptic Pharmaceutical Corporation Aryl sulfonamide and sulfamide derivatives and uses thereof
WO1997020823A2 (en) 1995-12-01 1997-06-12 Novartis Ag 2-amino quinazoline derivatives as npy receptor antagonists
WO1997020820A1 (en) * 1995-12-01 1997-06-12 Novartis Ag Heteroaryl compounds
ES2284180T3 (es) 1996-01-23 2007-11-01 SHIONOGI &amp; CO., LTD. Derivados de aminoacidos sulfonados e inhibidores de metaloproteinasas que contienen los mismos.
ATE236137T1 (de) 1996-02-02 2003-04-15 Merck & Co Inc Heterocyclische verbindungen als antidiabetische mittel und für die behandlung von fettleibigkeit
DE69707865T2 (de) 1996-05-17 2002-05-02 Warner-Lambert Co., Morris Plains Biphenylsulfonamid matrix metalloproteinase inhibitoren
AU2792097A (en) 1996-05-24 1998-01-05 Ono Pharmaceutical Co. Ltd. Phenylsulfonamide derivatives
PE20000127A1 (es) * 1997-12-22 2000-03-14 Novartis Ag Derivado de bencenosulfonamida
CN1289475C (zh) * 1998-04-29 2006-12-13 奥索-麦克尼尔药品公司 在肥胖症和其它病症的治疗中用作神经肽yy5受体配体的n－取代的氨基1,2,3,4－四氢化萘
IL139913A0 (en) 1998-06-08 2002-02-10 Schering Corp Neuropeptide y5 receptor antagonists
DE19830431A1 (de) * 1998-07-08 2000-01-13 Hoechst Marion Roussel De Gmbh Sulfonylamino-carbonsäure-N-arylamide als Guanylatcyclase-Aktivatoren
HU228111B1 (en) * 1998-07-08 2012-11-28 Sanofi Aventis Deutschland Sulfur substituted sulfonylaminocarboxylic acid n-arylamides, their preparation, their use and pharmaceutical preparations comprising them
ES2161594B1 (es) 1998-12-17 2003-04-01 Servier Lab Nuevos derivados de la hidrazida, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen.
WO2000063171A1 (fr) 1999-04-20 2000-10-26 Meiji Seika Kaisha, Ltd. Composes tricycliques
JP2002543067A (ja) 1999-04-22 2002-12-17 シナプティック・ファーマスーティカル・コーポレーション 選択的なｎｐｙ（ｙ５）のアンタゴニスト
US6124331A (en) * 1999-06-30 2000-09-26 Synaptic Pharmaceutical Corporation Selective NPY (Y5) antagonists (tricyclics)
EP1177172A1 (en) 1999-05-05 2002-02-06 Ortho-McNeil Pharmaceutical, Inc. 3a,4,5,9b-TETRAHYDRO-1H-BENZ e]INDOL-2-YL AMINE-DERIVED NEUROPEPTIDE Y RECEPTORS LIGANDS USEFUL IN THE TREATMENT OF OBESITY AND OTHER DISORDERS
JP2003503486A (ja) * 1999-06-30 2003-01-28 シナプティック・ファーマスーティカル・コーポレーション 選択的ｎｐｙ（ｙ５）アンタゴニスト
AU6000900A (en) 1999-07-23 2001-02-13 Astrazeneca Uk Limited Carbazole derivatives and their use as neuropeptide y5 receptor ligands
US6380224B1 (en) 1999-07-28 2002-04-30 Ortho-Mcneil Pharmaceutical, Inc. Amine and amide derivatives as ligands for the neuropeptide Y Y5 receptor useful in the treatment of obesity and other disorders
JP2001172257A (ja) 1999-10-05 2001-06-26 Fujisawa Pharmaceut Co Ltd 有機スルホンアミド化合物
EP1218377A1 (en) 1999-10-08 2002-07-03 Bristol-Myers Squibb Pharma Company AMINO LACTAM SULFONAMIDES AS INHIBITORS OF A$g(b) PROTEIN PRODUCTION
JP2001122865A (ja) 1999-10-27 2001-05-08 Meiji Seika Kaisha Ltd ベンゾチアゾロン誘導体
EP1249233B9 (en) * 1999-11-26 2009-08-05 Shionogi & Co., Ltd. Npyy5 antagonists
CN101104598B (zh) * 2002-03-12 2011-06-15 盐野义制药株式会社 反式-4-氨基-1-环己烷羧酸衍生物的制备方法
WO2004052832A1 (ja) * 2002-12-11 2004-06-24 Asahi Glass Company, Limited フッ素化されたアダマンタン誘導体
GB0514203D0 (en) * 2005-07-11 2005-08-17 Novartis Ag Organic compounds
NZ572381A (en) 2006-04-28 2011-01-28 Shionogi & Co Amine derivative having npy y5 receptor antagonist activity
WO2008026563A1 (fr) 2006-08-30 2008-03-06 Shionogi & Co., Ltd. Dérivé d'hydrazine amide
EP2058305A4 (en) 2006-08-30 2010-09-22 Shionogi & Co UREA DERIVATIVE
WO2008047769A1 (fr) 2006-10-18 2008-04-24 Shionogi & Co., Ltd. Agent améliorant le métabolisme du glucose

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