1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl) oxy) napththalen-I-yl) ureas as P38 mapkinase inhibitors

Patent metadata

Field	Value
Publication number	US-9850231-B2
Application number	US-201514795957-A
Country	US
Kind code	B2
Filing date	Jul 10, 2015
Priority date	Oct 3, 2011
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

There is provided a compound of formula (I) which is an inhibitor of the family of p38 mitogen-activated protein kinase enzymes, and to its use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as asthma and COPD.

First claim

The invention claimed is:

1. A method of treatment of a condition selected from COPD chronic bronchitis, emphysema, asthma, pediatric asthma, cystic fibrosis, idiopathic pulmonary fibrosis, allergic rhinitis, rhinitis, sinusitis, allergic conjunctivitis, conjunctivitis, allergic dermatitis, contact dermatitis, psoriasis, ulcerative colitis, inflamed joints secondary to rheumatoid arthritis or osteoarthritis, rheumatoid arthritis, pancreatitis, cachexia, tumors selected from non-small cell lung carcinoma, breast carcinoma, gastric carcinoma, colorectal carcinoma and malignant melanoma which comprises administering to a subject an effective amount of a compound of formula (I)

or a pharmaceutically acceptable salt thereof, including all stereoisomers and tautomers thereof, or a pharmaceutical composition comprising said compound in combination with one or more pharmaceutically acceptable diluents or carriers.

2. A method for sensitizing a subject suffering from COPD or asthma to treatment with a corticosteroid, where the subject has previously become refractory to treatment with a corticosteroid, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I)

or a pharmaceutically acceptable salt thereof, including all stereoisomers and tautomers thereof.

3. The method of claim 2 , wherein the compound of Formula (I) is a free base.

4. The method of claim 2 , wherein the compound of Formula (I) is anhydrous free base in solid crystalline form.

5. The method of claim 2 , wherein the compound of formula (I) as the anhydrous free base is in solid crystalline form having the X-ray powder diffraction pattern substantially as shown in FIG. 1 (Form A).

6. The method of claim 2 , wherein the compound of formula (I) as the anhydrous free base is in solid crystalline form having an X-ray powder diffraction pattern containing one, two, three, four, five, six or seven peaks selected from (±0.2) 10.3, 15.2, 17.5, 23.1, 24.6, 26.7 and 27.4 degrees 2-theta.

7. The method of claim 2 , wherein the compound of formula (I) as the anhydrous free base is in solid crystalline form having the X-ray powder diffraction pattern substantially as shown in FIG. 2 (Form B).

8. The method of claim 2 , wherein the compound of formula (I) as the anhydrous free base is in solid crystalline form having an X-ray powder diffraction pattern containing one, two, three, four, five, six, seven or all eight peaks selected from (±0.2) 3.9, 6.1, 11.8, 14.3, 16.7, 18.3, 18.7 and 28.9 degrees 2-theta.

Assignees

• Respivert Ltd
• Respivert Ltd

Inventors

• Ito Kazuhiro
• Charron Catherine Elisabeth
• King-Underwood John
• Onions Stuart Thomas
• Longshaw Alistair Ian
• Broeckx Rudy
• Filliers Walter
• Copmans Alex

Classifications

• A61P43/00

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

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/04

  specific for metastasis · CPC title