1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl) ureas as p38 MAP kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9108950-B2
Application number	US-201214349345-A
Country	US
Kind code	B2
Filing date	Oct 3, 2012
Priority date	Oct 3, 2011
Publication date	Aug 18, 2015
Grant date	Aug 18, 2015

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 compound of formula (I)

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

2. A compound according to claim 1 , as the free base.

3. A compound according to claim 2 , as the anhydrous free base in solid crystalline form.

4. A compound according to claim 3 , 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).

5. A compound according to claim 3 , 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.

6. A compound according to claim 3 , 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).

7. A compound according to claim 3 , 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.

8. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, including all stereoisomers and tautomers thereof, in combination with one or more pharmaceutically acceptable diluents or carriers.

9. A method of treating a disorder selected from the group consisting of: COPD, chronic bronchitis, emphysema, asthma, pediatric asthma, allergic rhinitis, rhinitis, and sinusitis, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 8 .

10. A method of treating respiratory viral infections in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 8 .

11. The method of claim 9 , further comprising administration of a second agent selected from zanamivir and oseltamivir.

12. A combination product comprising:
(A) a compound of claim 1 ; and
(B) another therapeutic agent;
wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable diluent or carrier;
wherein said combination product may be either a single pharmaceutical formulation or a kit-of-parts.

13. The method of claim 10 , further comprising administration of a second agent selected from zanamivir and oseltamivir.

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

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P43/00

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

• A61P37/08

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