Claims for Patent: 8,293,923
✉ Email this page to a colleague
Summary for Patent: 8,293,923
Title: | Indazole derivatives as modulators of interleukin-1 receptor-associated kinase |
Abstract: | The present invention relates to modulators of IRAK kinases of formula (I) and provides compositions comprising such modulators, as well as methods therewith for treating IRAK-mediated or IRAK-associated conditions or diseases. |
Inventor(s): | Guckian; Kevin (Marlborough, MA), Jewell; Charles (Sudbury, MA), Conlon; Patrick (Wakefield, MA), Lin; Edward Yin Shiang (Chestnut Hill, MA), Chan; Timothy (Newton, MA) |
Assignee: | Biogen Idec MA Inc. (Cambridge, MA) |
Application Number: | 12/440,163 |
Patent Claims: | 1. A compound of Formula (I) ##STR00007## wherein: R.sup.1 is an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted
heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl; R.sup.2 is H, an optionally substituted aliphatic, an optionally substituted cycloaliphatic, an optionally substituted heterocycloaliphatic, an optionally
substituted aryl, or an optionally substituted heteroaryl; each of a, a', b, and c is independently N or C(R.sup.3); each of R.sup.3, R.sup.5, and R.sup.6 is independently H, an optionally substituted aliphatic, an optionally substituted alkoxy, acyl,
halo, hydroxy, amino, nitro, cyano, guanadino, amidino, carboxy, sulfo, mercapto, sulfanyl, sulfinyl, sulfonyl, sulfonamide, amido, sulfamide, urea, thiourea, carbamoyl, cycloaliphatic, cycloalkyloxy, heterocycloaliphatic, heterocycloalkyloxy, aryl,
aralkyl, aryloxy, aroyl, heteroaryl, heteroaralkyl, heteroaryloxy, or heteroaroyl; R.sup.4 is H; K is --N(R.sup.X')--; J is a bond, --O--, --S(O).sub.i--, --N(R.sup.X')--, alkylene, --C(O)--, --C(O)--O--, --C(O)--N(R.sup.X')--,
--(CH.sub.2).sub.pN(R.sup.X')--, or --N(R.sup.X')--C(O)--; R.sup.X' is independently H or an optionally substituted aliphatic; n is 0, 1, 2, or 3; i is 0, 1, or 2; p is 1, 2, 3, or 4; and provided that when R.sup.1 is an unsubstituted alkyl and J is
--O--, then R.sup.2 is H, an optionally substituted aliphatic, an optionally substituted aryl, or an unsubstituted heteroaryl.
2. The compound of claim 1, wherein R.sup.X' is H. 3. The compound of claim 1, wherein R.sup.1 is an optionally substituted aliphatic, or an optionally substituted cycloaliphatic. 4. The compound of claim 3, wherein R.sup.1 is alkyl optionally substituted with halo, amino, amido, hydroxyl, or alkoxy; or R.sup.1 is a cycloalkyl optionally substituted with: hydroxyl, halo, amido, amino, alkoxy, cyano, carboxy, optionally substituted aliphatic, optionally substituted cycloaliphatic, or optionally substituted heterocycloaliphatic. 5. The compound of claim 4, wherein R.sup.1 is an optionally substituted bicycloaliphatic. 6. The compound of claim 1, wherein R.sup.1 is an optionally substituted heterocycloaliphatic, an optionally substituted aryl, or an optionally substituted heteroaryl. 7. The compound of claim 1, wherein J is a bond, --O--, --N(R.sup.X')--, alkylene, --C(O)--, --C(O)--O--, --C(O)--N(R.sup.X')--, --(CH.sub.2).sub.p--N(R.sup.X')--, or --N(R.sup.X')--C(O)--. 8. The compound of claim 7, wherein J is --C(O)--, --CH.sub.2--, a bond, or an alkylene. 9. The compound of claim 1, wherein R.sup.2-J- is H, HO--CH.sub.2--, ((((pyridin-4-yl)ethyl)piperazin-1-yl)methyl)-, CH.sub.3CH.sub.2O--C(O)--, morpholinomethyl, cyclopentylaminocarbonyl, isopentylaminocarbonyl, piperidinylmethyl, or pyrolidinecarbonyl. 10. The compound of claim 1, wherein R.sup.5 is an optionally substituted aryl or an optionally substituted heteroaryl. 11. The compound of claim 10, wherein R.sup.5 is a heteroaryl optionally substituted with 1 to 3 alkyl, alkoxy, amino, carboxy, amido, halo or cyano; or R.sup.5 is an aryl optionally substituted with alkyl, alkoxy, amino, halo, or cyano. 12. The compound of claim 11, wherein R.sup.5 is pyridyl optionally substituted with alkyl, alkoxy, amino, amido, halo, or cyano; or R.sup.5 is phenyl optionally substituted with alkyl, alkoxy, amino, halo, or cyano. 13. The compound of claim 12, wherein R.sup.5 is (4-methoxy)pyridin-3-yl, 3-methoxymethylphenyl, 2-methoxyphenyl, or 2-trifluoromethoxyphenyl. 14. The compound of claim 1, wherein R.sup.5 is bromo, H, or phenyl substituted with --N(R.sup.X')( R.sup.Y'), --N(R.sup.X')--C(O)--R.sup.Y', or --N(R.sup.X')--S(O).sub.2--R.sup.Y', wherein R.sup.Y' is independently H or an optionally substituted aliphatic. 15. The compound of claim 14, wherein R.sup.5 is 3-aminophenyl. 16. The compound of claim 1, wherein n is 0 or n is 1. 17. The compound of claim 1, wherein each of a, a', b, and c is independently CR.sup.3. 18. The compound of claim 17, wherein R.sup.3 is H. 19. The compound of claim 1, wherein one or two of a, a', b, and c are N. 20. The compound of claim 1, wherein R.sup.1 is a cycloaliphatic optionally substituted with hydroxy; J is --CH.sub.2--, --C(O)--, or --CH.sub.2--N(R.sup.X')--; R.sup.5 is optionally substituted phenyl or pyridyl; each of a, a', b, and c is independently CH; and n is 0. 21. The compound of claim 20, wherein J is --CH.sub.2--; and R.sup.2 is an optionally substituted heterocycle containing at least one N attached to J. 22. The compound of claim 1, wherein R.sup.1 is aliphatic optionally substituted with hydroxy; R.sup.2J- is H; R.sup.5 is H or halo; each of a, a', b, and c is independently CH; and n is 0. 23. The compound of claim 1, wherein K is --NH--; R.sup.1 is an alkyl or cyclohexyl, optionally substituted with hydroxy; J is a bond or --CH.sub.2--; R.sup.2 is alkyl, cycloalkyl, or heterocycloalkyl; R.sup.5 is heteroaryl or amino phenyl; and n is 0. 24. The compound of claim 1, wherein the compound is: (2-(5-(3-aminophenyl)-1H-indazol-3-ylamino)-1-cyclohexyl-1H-benzo[d]imida- zol-6-yl)methanol; (1-cyclohexyl-2-(5-(3-(methoxymethyl)phenyl)-1H-indazol-3-ylamino)-1H-ben- zo[d]imidazol-5-yl)methanol; 4-(2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino)-5((4-(2-(pyridin-4-- yl)ethyl)piperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)cyclohexanol; ethyl 1-((2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino)-1-(4-hydroxy- cyclohexyl)-1H-benzo[d]imidazol-5-yl)methyl)piperidine-4-carboxylate; (2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino)-1-phenyl-1H-benzo[d]i- midazol-5-yl)methanol; N-(1-cyclohexyl-5-(morpholinomethyl)-1H-benzo[d]imidazol-2-yl)-5-(4-metho- xypyridin-3-yl)-1H-indazol-3-amine; 2-(5-(2-methoxyphenyl)-1H-indazol-3-ylamino)-N-cyclopentyl-1-(4-hydroxycy- clohexyl)-1H-benzo[d]imidazole-5-carboxamide; 1-(4-hydroxycyclohexyl)-N-isopentyl-2-(5-(2-methoxyphenyl)-1H-indazol-3-y- lamino)-1H-benzo[d]imidazole-5-carboxamide; (1-(4-hydroxycyclohexyl)-2-(5-(2-methoxyphenyl)-1H-indazol-3-ylamino)-1H-- benzo[d]imidazol-5-yl)(pyrrolidin-1-yl)methanone; N-cyclopentyl-1-(4-hydroxycyclohexyl)-2-(5-(2-(trifluoromethoxy)phenyl)-1- H-indazol-3-ylamino)-1H-benzo[d]imidazole-5-carboxamide; 2-(5-(2-(trifluoromethoxy)phenyl)-1H-indazol-3-ylamino)-1-(4-hydroxycyclo- hexyl)-N-isopentyl-1H-benzo[d]imidazole-5-carboxamide; ethyl 1-(4-hydroxycyclohexyl)-2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino- )-1H-benzo[d]imidazole-5-carboxylate; 4-(5-(hydroxymethyl)-2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino)-1- H-benzo[d]imidazol-1-yl)cyclohexanol; (1-cyclohexyl-2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino)-1H-benzo- [d]imidazol-5-yl)methanol; N-(1-cyclohexyl-5-(piperidin-1-ylmethyl)-1H-benzo[d]imidazol-2-yl)-5-(4-m- ethoxypyridin-3-yl)-1H-indazol-3-amine; 3-(2-(5-(4-methoxypyridin-3-yl)-1H-indazol-3-ylamino)-1H-benzo[d]imidazol- -1-yl)propan-1-ol; or 3-(2-(5-bromo-1H-indazol-3-ylamino)-1H-benzo[d]imidazol-1-yl)propan-1-ol. 25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a compound of claim 1. 26. A method of treating rheumatoid arthritis or osteoarthritis in a subject, comprising administering to the subject in need of such treatment a therapeutically effective amount of a compound of claim 1. 27. The method of claim 26, wherein said compound is administered in combination with a therapeutic agent selected from the group consisting of methotrexate, sulfasalazine, a COX-2 inhibitor, hydroxychloroquine, cyclosporine A, D-penicillamine, infliximab, etanercept, auranofin, aurothioglucose, sulfasalazine, sulfasalazine analogs, mesalamine, corticosteroids, corticosteroid analogs, 6-mercaptopurine, cyclosporine A, methotrextate and infliximab, interferon beta-1 beta, interferon beta-1 alpha, azathioprine, glatiramer acetate, a glucocorticoid, and cyclophosphamide. |
Details for Patent 8,293,923
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Janssen Biotech, Inc. | REMICADE | infliximab | For Injection | 103772 | 08/24/1998 | ⤷ Try a Trial | 2026-09-07 |
Immunex Corporation | ENBREL | etanercept | For Injection | 103795 | 11/02/1998 | ⤷ Try a Trial | 2026-09-07 |
Immunex Corporation | ENBREL | etanercept | For Injection | 103795 | 05/27/1999 | ⤷ Try a Trial | 2026-09-07 |
Immunex Corporation | ENBREL | etanercept | Injection | 103795 | 09/27/2004 | ⤷ Try a Trial | 2026-09-07 |
Immunex Corporation | ENBREL | etanercept | Injection | 103795 | 02/01/2007 | ⤷ Try a Trial | 2026-09-07 |
Immunex Corporation | ENBREL MINI | etanercept | Injection | 103795 | 09/14/2017 | ⤷ Try a Trial | 2026-09-07 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
Make Better Decisions: Try a trial or see plans & pricing
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.