Compositions and methods for inhibition of the JAK pathway

Patent metadata

Field	Value
Publication number	US-9566283-B2
Application number	US-201514793506-A
Country	US
Kind code	B2
Filing date	Jul 7, 2015
Priority date	Jan 23, 2009
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful.

First claim

We claim:

1. A method, comprising administering to a subject an amount of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or a salt thereof, or a composition compromising 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one or salt thereof, effective to contact a JAK kinase and inhibit a property thereof.

2. The method according to claim 1 , comprising administering 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one in an amount effective for treating a disease selected from allergies, autoimmune diseases, transplant rejection, T-cell mediated autoimmune diseases, Type II inflammatory diseases, delayed Type IV hypersensitivity reactions, or hematologic malignancies.

3. The method according to claim 1 comprising administering 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or a salt thereof, in combination with or adjunctively to a second therapeutic.

4. The method according to claim 3 , wherein the second therapeutic is a corticosteroid, an alkylating agent, a calcineurin inhibitor, an inhibitor of inosine monophosphate dehydrogenase (IMPDH), an agent designed to suppress cellular immunity while leaving the recipient's humoral immunologic response intact, a Syk kinase inhibitor, or a combination thereof.

5. The method according to claim 3 , wherein the second therapeutic is mercaptopurine, prednisone, methylprednisolone, prednisolone, cyclophosphamide, cyclosporine, sirolimus, tacrolimus, mycophenolate, mycophenolate mofetil, azathioprine, antilymphocyte globulin (ALG), antithymocyte globulin (ATG), monoclonal anti-T-cell antibodies (OKT3)), irradiation, or a combination thereof.

6. The method according to claim 1 comprising administering to the subject a hydrochloride salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or administering to the subject a composition compromising the hydrochloride salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one.

7. The method according to claim 1 comprising administering to the subject a benzene sulfonic acid salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or administering to the subject a composition compromising the benzene sulfonic acid salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one.

8. A method, comprising contacting a JAK kinase with 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or a salt thereof, or a composition compromising 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one or salt thereof, in an amount effective to inhibit an activity of the JAK kinase.

9. The method according to claim 8 , comprising contacting the JAK kinase ex vivo.

10. The method according to claim 8 , comprising contacting the JAK kinase in vivo.

11. The method according to claim 8 comprising contacting the JAK kinase with a hydrochloride salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or contacting the JAK kinase with a composition compromising the hydrochloride salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one.

12. The method according to claim 8 comprising contacting the JAK kinase with a benzene sulfonic acid salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one, or contacting the JAK kinase with a composition compromising the benzene sulfonic acid salt of 5-(2-(4-fluoro-3-methoxy-5-methylphenylamino)-5-methylpyrimidin-4-ylamino)benzo[d]oxazol-2(3H)-one.

Assignees

• Rigel Pharmaceuticals Inc

Inventors

• Chen Yan
• Taylor Vanessa
• Li Hui
• Singh Rajinder

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title