Prodrugs of 2,4-pyrimidinediamine compounds and their uses

Patent metadata

Field	Value
Publication number	US-9283238-B2
Application number	US-201414534784-A
Country	US
Kind code	B2
Filing date	Nov 6, 2014
Priority date	Nov 21, 2006
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

The present disclosure provides prodrugs of biologically active 2,4-pyrimidinediamine compounds, salts and hydrates of the prodrugs, compositions comprising the prodrugs, intermediates and methods for synthesizing the prodrugs and methods of using the prodrugs in a variety of applications.

First claim

The invention claimed is:

1. A method of treating an autoimmune disease in a mammal afflicted with the disease, the method comprising administering to the mammal an effective amount of an oral dosage formulation comprising a hydrate of the prodrug salt:

and a pharmaceutically-acceptable carrier, excipient, and/or diluent; wherein:
M is Na;
the prodrug salt hydrate present in the oral dosage formulation comprises crystalline prodrug salt hydrate; and
the powder X-ray diffraction data of the crystalline prodrug salt hydrate comprises a characteristic peak at a two theta value of 9.9±0.1° in response to radiation of wavelength 1.54059 Å,
wherein the autoimmune disease is associated with nonanaphylactic hypersensitivity reactions (Type II, Type III and/or Type IV hypersensitivity reactions) or mediated, at least in part, by activation of the FcγR signaling cascade in monocyte cells.

2. The method according to claim 1 , wherein the autoimmune disease is selected from the group consisting of Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, Goodpasture's disease, autoimmune thrombocytopenia, sympathetic ophthalmia, myasthenia gravis, Graves' disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis and membranous glomerulopathy.

3. The method according to claim 1 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosis, rheumatoid arthritis, Sjogren's syndrome, Reiter's syndrome, polymyositis-dermatomyositis, systemic sclerosis, polyarteritis nodosa, multiple sclerosis and bullous pemphigoid.

4. The method according to claim 1 , wherein the autoimmune disease is selected from the group consisting of autoimmune alopecia, Type I or juvenile onset diabetes, and thyroiditis.

5. The method according to claim 1 , wherein the autoimmune disease is rheumatoid arthritis or systemic lupus erythematosis.

6. The method according to claim 5 , wherein the mammal is a human.

7. The method according to claim 6 , wherein the formulation comprises from about 50 mg to about 400 mg of the crystalline prodrug salt hydrate.

Assignees

• Rigel Pharmaceuticals Inc

Inventors

• Bhamidipati Somasekhar
• Singh Rajinder
• Sun Thomas
• Masuda Esteban

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P5/16

  for decreasing, blocking or antagonising the activity of the thyroid hormones · CPC title

• A61P43/00

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

• A61P7/06

  Antianaemics · CPC title