HRP20230833T1 - Spojevi indolinona i njihova uporaba u liječenju fibroznih bolesti - Google Patents

Spojevi indolinona i njihova uporaba u liječenju fibroznih bolesti Download PDF

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HRP20230833T1
HRP20230833T1 HRP20230833TT HRP20230833T HRP20230833T1 HR P20230833 T1 HRP20230833 T1 HR P20230833T1 HR P20230833T T HRP20230833T T HR P20230833TT HR P20230833 T HRP20230833 T HR P20230833T HR P20230833 T1 HRP20230833 T1 HR P20230833T1
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cycloalkyl
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Iain Walters
Louise BIRCH
Joseph HILL-COUSINS
Stephen Paul Collingwood
Christopher Scott Stevenson
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Respivert Limited
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Claims (15)

1. Spoj, naznačen time, da je predstavljen formulom (Ib) [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; R8 i R9 neovisno predstavljaju H, ili C1-C4alkil opcionalno supstituiran s OH, okso, NR14R15 ili C1-C4alkoksi ili NR8R9 predstavlja alifatski 4-8-člani heterocikl koji sadrži jedan ili više heteroatoma odabranih od O, N i S; i R14 i R15neovisno predstavljaju H ili C1-C4alkil; ili njegova farmaceutski prihvatljiva sol.
2. Spoj, naznačen time, da je predstavljen formulom (Ic) [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; R8 i R9 neovisno predstavljaju H, ili C1-C4alkil opcionalno supstituiran s OH, okso, NR14R15 ili -C1-C4alkoksi ili NR8R9 predstavlja alifatski 4-8-člani heterocikl koji sadrži jedan ili više heteroatoma odabranih od O, N i S; i R14 i R15neovisno predstavljaju H ili C1-C4alkil; Z predstavlja CO ili SO2; ili njegova farmaceutski prihvatljiva sol.
3. Postupak za proizvodnju spoja formule (Ib), ili njegove farmaceutski prihvatljive soli, prema patentnom zahtjevu 1, naznačen time, da on obuhvaća: reakciju spoja formule (XIII): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli; sa spojem formule (XIV): [image] gdje R8 i R9 neovisno predstavljaju H, ili C1-C4alkil opcionalno supstituiran s OH, okso, NR14R15 ili -C1-C4alkoksi ili NR8R9 predstavlja alifatski 4-8-člani heterocikl koji sadrži jedan ili više heteroatoma odabranih od O, N i S; R14 i R15neovisno predstavljaju H ili C1-C4alkil; ili njegovom soli.
4. Postupak prema patentnom zahtjevu 3, naznačen time, da nadalje obuhvaća uklanjanje zaštite spoja formule (Ib) za odstranjivanje acetil skupine.
5. Postupak za proizvodnju spoja formule (XIII): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli; naznačen time, da on obuhvaća: reakciju spoja formule (IX): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli; sa spojem formule (XV): [image] ili njegovom soli.
6. Postupak prema patentnom zahtjevu 5, naznačen time, da postupak za proizvodnju spoja formule (IX): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli; obuhvaća uklanjanje zaštite spoja formule (XI): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli.
7. Postupak prema patentnom zahtjevu 6, naznačen time, da postupak za proizvodnju spoja formule (XI): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli; obuhvaća reakciju spoja formule (II): [image] gdje R1 predstavlja Me, Et, CH=CH2, C≡C-H ili C≡C-Me; L predstavlja -OC1-C4 alkil; ili njegove soli; sa spojem formule (XII): [image] gdje R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegovom soli.
8. Postupak prema patentnom zahtjevu 7, naznačen time, da postupak za proizvodnju spoja formule (II): [image] gdje R1 predstavlja Me, Et, CH=CH2, C≡C-H ili C≡C-Me; L predstavlja -Oetil; ili njegove soli, obuhvaća: (a) reakciju spoja formule (IV): [image] gdje R1 predstavlja Me, Et, CH=CH2, C≡C-H ili C≡C-Me; ili njegove soli; sa spojem formule (V): [image] ili njegovom soli; ili (b) reakciju spoja formule (VI): [image] gdje R1 predstavlja Et, CH=CH2, C≡C-H ili C≡C-Me; ili njegove soli; sa spojem formule (V): [image] ili njegovom soli.
9. Postupak za proizvodnju spoja formule (XVI): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; Z predstavlja CO ili SO2; ili njegove soli; naznačen time, da on obuhvaća: reakciju spoja formule (XVII): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; Z predstavlja CO ili SO2; ili njegove soli; sa CBr4 i PPh3.
10. Postupak za proizvodnju spoja formule (XVII): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; Z predstavlja CO; ili njegove soli; naznačen time, da on obuhvaća: reakciju spoja formule (IX): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; ili njegove soli; sa spojem formule (XVIII): [image] ili njegovom soli.
11. Postupak za proizvodnju spoja formule (XVII): [image] gdje R1 predstavlja H, Me, Et, CH=CH2, C≡C-H ili C≡C-Me; R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; Z predstavlja SO2; ili njegove soli; naznačen time, da on obuhvaća: reakciju spoja formule (II): [image] gdje R1 predstavlja Me, Et, CH=CH2, C≡C-H ili C≡C-Me; L predstavlja -OC1-C4 alkil; ili njegove soli; sa spojem formule (III): [image] gdje R2 predstavlja H, C1-C6alkil, C1-C6alkoksi, C3-C8cikloalkil, -CH2-(C3-C8cikloalkil), halogen ili cijano; R3 predstavlja formulu (i): [image] gdje X1-R4 predstavlja Me i Y1-R5 predstavlja CH2CH2OH; Z predstavlja SO2; ili njegovom soli.
12. Farmaceutski pripravak, naznačen time, da sadrži spoj formule (Ib) prema patentnom zahtjevu 1 ili formule (Ic) prema patentnom zahtjevu 2, u kombinaciji s jednim ili više farmaceutski prihvatljivih razrjeđivača ili nosača.
13. Spoj formule (Ib) prema patentnom zahtjevu 1 ili formule (Ic) prema patentnom zahtjevu 2, naznačen time, da je za uporabu kao lijek.
14. Spoj formule (Ib) prema patentnom zahtjevu 1 ili formule (Ic) prema patentnom zahtjevu 2, ili pripravak prema patentnom zahtjevu 12, naznačen time, da je za uporabu u liječenju fibroznih bolesti ili intersticijskih plućnih bolesti prvenstveno odabranih od IPF, intersticijske pneumonije divovskih stanica, sarkoidoze, cistične fibroze, respiratornog distresnog sindroma, supstancom inducirane plućne fibroze, granulomatoze, silikoze, azbestoze, sustavne skleroderme, virusno inducirane ciroze jetre odabrane od ciroze jetre koja je inducirana hepatitisom C, ili kožnih bolesti s fibroznom komponentom prvenstveno odabranih od skleroderme, sarkoidoze i sustavnog eritemskog lupusa, ili za uporabu u liječenju bolesti koje su naznačene hiperproliferacijom stanica, primjerice, rak, posebice rak pluća, ili za uporabu u liječenju respiratornih poremećaja uključujući KOPB, prvenstveno uključujući kronični bronhitis i emfizem, astmu, pedijatrijsku astmu, alergijski rinitis, rinitis i sinusitis.
15. Spoj formule (Ib) prema patentnom zahtjevu 1 ili formule (Ic) prema patentnom zahtjevu 2, ili pripravak prema patentnom zahtjevu 12, u kombinaciji s nintedanibom ili pirfenidonom, naznačen time, da je za uporabu u liječenju fibroznih bolesti ili intersticijskih plućnih bolesti prvenstveno odabranih od IPF, intersticijske pneumonije divovskih stanica, sarkoidoze, cistične fibroze, respiratornog distresnog sindroma, supstancom inducirane plućne fibroze, granulomatoze, silikoze, azbestoze, sustavne skleroderme, virusno inducirane ciroze jetre odabrane od ciroze jetre koja je inducirana hepatitisom C, ili kožnih bolesti s fibroznom komponentom prvenstveno odabranih od skleroderme, sarkoidoze i sustavnog eritemskog lupusa, ili za uporabu u liječenju bolesti koje su naznačene hiperproliferacijom stanica, primjerice, rak, posebice rak pluća, ili za uporabu u liječenju respiratornih poremećaja uključujući KOPB, prvenstveno uključujući kronični bronhitis i emfizem, astmu, pedijatrijsku astmu, alergijski rinitis, rinitis i sinusitis.
HRP20230833TT 2015-12-24 2016-12-23 Spojevi indolinona i njihova uporaba u liječenju fibroznih bolesti HRP20230833T1 (hr)

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DE10117204A1 (de) * 2001-04-06 2002-10-10 Boehringer Ingelheim Pharma In 6-Stellung substituierte Indolinone, ihre Herstellung und ihre Verwendung als Arzneimittel
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US20060154939A1 (en) 2004-12-24 2006-07-13 Boehringer Ingelheim International Gmbh Medicaments for the Treatment or Prevention of Fibrotic Diseases
PE20060777A1 (es) 2004-12-24 2006-10-06 Boehringer Ingelheim Int Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas
WO2007008895A1 (en) 2005-07-13 2007-01-18 Allergan, Inc. Kinase inhibitors
WO2010009166A1 (en) 2008-07-14 2010-01-21 Gilead Colorado, Inc. Oxindolyl inhibitor compounds
CN109153666B (zh) 2016-03-08 2021-07-16 莱斯彼维特有限公司 吲哚衍生物及其作为蛋白激酶抑制剂的用途

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