HRP20110097T1 - Derivati fenilpirazola kao nesteroidni ligandi glukokortikoidnih receptora - Google Patents

Derivati fenilpirazola kao nesteroidni ligandi glukokortikoidnih receptora Download PDF

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HRP20110097T1
HRP20110097T1 HR20110097T HRP20110097T HRP20110097T1 HR P20110097 T1 HRP20110097 T1 HR P20110097T1 HR 20110097 T HR20110097 T HR 20110097T HR P20110097 T HRP20110097 T HR P20110097T HR P20110097 T1 HRP20110097 T1 HR P20110097T1
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amino
compound
fluorophenyl
solvate
methyl
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HR20110097T
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Anne Barnett Heather
Baxter Campbell Ian
Mary Coe Diane
William James Cooper Anthony
George Adam Inglis Graham
Terence Jones Haydn
Philip Keeling Steven
John Fawcett Macdonald Simon
Mcfarlane Mclay Iain
Alan Skone Philip
Gad Weingarten Gordon
Michael Woolven James
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Glaxo Group Limited
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Priority claimed from GB0625457A external-priority patent/GB0625457D0/en
Priority claimed from GB0710217A external-priority patent/GB0710217D0/en
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Publication of HRP20110097T1 publication Critical patent/HRP20110097T1/hr

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Abstract

Spoj formule (I): naznačen time štoR1 se bira između vodika, metila, etila i 2-fluoretila; svakog od R2 i R3 se neovisno bira između broma, klora, fluora, -CHF2, -CF3 i -OCHF2, ili R2 je -SO2CH3, a R3 je vodik; n je cijeli broj, kojeg se bira između 0, 1 i 2, kada n je 1, X se bira između klora i fluora, akada n je 2, svaki X je fluor; ili njegova sol ili solvat. Patent sadrži još 42 patentna zahtjeva.

Claims (43)

1. Spoj formule (I): [image] naznačen time što R1 se bira između vodika, metila, etila i 2-fluoretila; svakog od R2 i R3 se neovisno bira između broma, klora, fluora, -CHF2, -CF3 i -OCHF2, ili R2 je -SO2CH3, a R3 je vodik; n je cijeli broj, kojeg se bira između 0, 1 i 2, kada n je 1, X se bira između klora i fluora, a kada n je 2, svaki X je fluor; ili njegova sol ili solvat.
2. Spoj, ili njegova sol ili solvat u skladu s patentnim zahtjevom 1, naznačen time što R1 se bira između vodika i etila.
3. Spoj, ili njegova sol ili solvat u skladu s patentnim zahtjevom 1, naznačen time što R1 je vodik.
4. Spoj, ili njegova sol ili solvat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što svakog od R2 i R3 se neovisno bira između fluora, klora, broma, -OCHF2 i -CHF2.
5. Spoj, ili njegova sol ili solvat u skladu s patentnim zahtjevom 4, naznačen time što svaki od R2 i R3 je klor.
6. Spoj, ili njegova sol ili solvat u skladu s patentnim zahtjevom 4, naznačen time što svaki od R2 i R3 je fluor.
7. Spoj, ili njegova sol ili solvat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što n je 1.
8. Spoj, ili njegova sol ili solvat u skladu s patentnim zahtjevom 7, naznačen time što X je fluor.
9. Spoj formule (IA): [image] naznačen time što R1 se bira između vodika, metila i etila; i kada R1 je vodik ili metil, svakog od R2 i R3 se neovisno bira između klora i fluora, ili kada R1 je etil, svakog od R2 i R3 se neovisno bira između klora i fluora, ili R2 je -SO2CH3, a R3 je vodik; ili njegova sol ili solvat.
10. Spoj, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva.
11. Spoj, naznačen time što je: 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); 5-amino-N-(2-{[[(2,6-difluorfenil)karbonil](etil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-(2-{[[(2,6-difluorfenil)karbonil](etil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-(2-{[[(2,6-difluorfenil)karbonil](etil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); 5-amino-N-[2-({[(2-klor-6-fluorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-[2-({[(2-klor-6-fluorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-[2-({[(2-klor-6-fluorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); 5-amino-N-[2-({[(2-bromo-6-fluorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-[2-({[(2-bromo-6-fluorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-[2-({[(2-bromo-6-fluorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); 5-amino-N-(2-{[({2-klor-6-[(difluormetil)oksi]fenil}karbonil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-(2-{[({2-klor-6-[(difluormetil)oksi]fenil}karbonil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-(2-{[({2-klor-6-[(difluormetil)oksi]fenil}karbonil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); 5-amino-N-{2-[({[2,6-bis(difluormetil)fenil]karbonil}amino)metil]-3,3,3-trifluor-2-hidroksipropil}-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-{2-[({[2,6-bis(difluormetil)fenil]karbonil}amino)metil]-3,3,3-trifluor-2-hidroksipropil}-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-{2-[({[2,6-bis(difluormetil)fenil]karbonil}amino)metil]-3,3,3-trifluor-2-hidroksipropil}-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); 5-amino-N-(2-{[({2-[(difluormetil)oksi]-6-fluorfenil}karbonil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid; 5-amino-N-(2-{[({2-[(difluormetil)oksi]-6-fluorfenil}karbonil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 1); 5-amino-N-(2-{[({2-[(difluormetil)oksi]-6-fluorfenil}karbonil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); ili njihove soli ili solvati.
12. Spoj, naznačen time što je spoj u skladu s patentnim zahtjevom 11, ili njegova farmaceutski prihvatljiva sol ili solvat.
13. Spoj, naznačen time što je: 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); ili njegova sol ili solvat.
14. Spoj, naznačen time što je: 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); ili njegova farmaceutski prihvatljiva sol ili solvat.
15. Spoj, naznačen time što je: 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); ili njegova farmaceutski prihvatljiva sol.
16. Spoj, naznačen time što je: 5-amino-N-[2-({[(2,6-diklorfenil)karbonil]amino}metil)-3,3,3-trifluor-2-hidroksipropil]-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2), u obliku slobodne baze.
17. Spoj, naznačen time što je: 5-amino-N-(2-{[[(2,6-difluorfenil)karbonil](etil)amino]metil}-3,3,3-trifluor-2-hidroksipropil)-1-(4-fluorfenil)-1H-pirazol-4-karboksamid (Enantiomer 2); ili njegova sol ili solvat.
18. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u terapiji.
19. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s upalnim i/ili alergijskim stanjem.
20. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s upalnim i/ili autoimunim stanjem.
21. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s reumatoidnim artritisom, astmom, COPD-om, alergijom i/ili rinitisom.
22. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s ekzemom, psorijazom, alergijskim dermatitisom, neurodermatitisom, svrbežom i/ili reakcijama preosjeljivosti.
23. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s upalom u središnjem živčanom sustavu.
24. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s multiplom sklerozom, cerebralnim vaskulitisom, neurosarkoidozom, Sjögrenovim sindromom, sistemnim eritematoznim lupusom, akutnom ili kroničnom upalnoma poliradikulopatijom, Alzheimerovom bolešću, neoplastičnim bolestima živčanog sustava, uključujući meningiom, limfom i zloćudni meningitis, traumom ili zaraznim bolestima živčanog sustava, poput tuberkuloze, ozljede kralježnične moždine ili ozljede mozga, poput postinfarktnog stanja (inzulta).
25. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s neurosarkoidozom.
26. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s upalom oka.
27. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegova farmaceutski prihvatljiva sol ili solvat, naznačen time što je namijenjen upotrebi u liječenju pacijenata s alergijskim konjunktivitisom.
28. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s upalnim i/ili alergijskim stanjem.
29. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s reumatoidnim artritisom, astmom, COPD-om, alergijom i/ili rinitisom.
30. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s ekzemom, psorijazom, alergijskim dermatitisom, neurodermatitisom, svrbežom i/ili reakcijama preosjeljivosti.
31. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s upalnim i/ili autoimunim stanjem.
32. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s upalom u središnjem živčanom sustavu.
33. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s multiplom sklerozom, cerebralnim vaskulitisom, neurosarkoidozom, Sjögrenovim sindromom, sistemnim eritematoznim lupusom, akutnom ili kroničnom upalnoma poliradikulopatijom, Alzheimerovom bolešću, neoplastičnim bolestima živčanog sustava, uključujući meningiom, limfom i zloćudni meningitis, traumom ili zaraznim bolestima živčanog sustava, poput tuberkuloze, ozljede kralježnične moždine ili ozljede mozga, poput postinfarktnog stanja (inzulta).
34. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s neurosarkoidozom.
35. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s upalom oka.
36. Upotreba spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegove farmaceutski prihvatljive soli ili solvata, naznačena time što je navedeni spoj namijenjen proizvodnji medikamenta za liječenje pacijenata s alergijskim konjunktivitisom.
37. Farmaceutski pripravak, naznačen time što sadrži spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 17, ili njegovu farmaceutski prihvatljivu sol ili solvat, u smjesi s jednim ili više farmaceutski prihvatljivih razrjeđivača ili podloga.
38. Farmaceutski pripravak u skladu s patentnim zahtjevom 37, naznačen time što je u obliku kapi za oči, namijenjene za topikalnu primjenu.
39. Spoj formule (II) [image] naznačen time što R1, X i n su definirani kao u patentnom zahtjevu 1.
40. Spoj formule (IV) [image] naznačen time što X i n su definirani kao u patentnom zahtjevu 1.
41. Spoj formule (VII) [image] naznačen time što R1, X i n su definirani kao u patentnom zahtjevu 1.
42. Spoj formule (X) [image] naznačen time što X i n su definirani kao u patentnom zahtjevu 1.
43. Spoj formule (XI) [image] naznačen time što X i n su definirani kao u patentnom zahtjevu 1.
HR20110097T 2006-06-12 2011-02-08 Derivati fenilpirazola kao nesteroidni ligandi glukokortikoidnih receptora HRP20110097T1 (hr)

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