FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREATMENT OF INFLAMMATION

• US 20110319433A1
• Filed: 12/22/2010
• Published: 12/29/2011
• Est. Priority Date: 07/12/2007
• Status: Active Grant

• Current Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Original Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Inventors: Krasinski, Antoni, Punna, Sreenivas, Ungashe, Solomon, Wang, Qiang, Zeng, Yibin
• Granted Patent: US 8,546,408 B2
• Time in Patent Office: Days
• US Class Current: 514/263.22
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: C07D 213/79 Acids; Esters
• CPC Class Codes: C07D 213/81 Amides; Imides
• CPC Class Codes: C07D 213/84 Nitriles
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 471/12 in which the condensed system contains three hetero rings
• CPC Class Codes: C07D 473/00 Heterocyclic compounds containing purine ring systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases and as controls in assays for the identification of CCR2 antagonists.

Claims

1. A compound of the formula (I) or a salt thereof:

2. The compound or salt of claim 1, which is of the formula (II):

3. The compound or salt of claim 1, wherein X¹ is N.

4. The compound of claim 3 or salt thereof, wherein X² and X⁴ are N, and X⁶ and X⁷ are CR⁷.

5. The compound or salt of claim 4, where R¹ is Cl.

6. The compound or salt of claim 5, where R² is —

CF₃.

7. The compound or salt of claim 6, where R⁵ is Cl or methyl.

8. The compound or salt of claim 7, where R⁵ is methyl.

9. The compound or salt of claim 4, wherein R¹ is Cl, R² is CF₃, and R⁵ is Cl.

12. A composition comprising a pharmaceutically acceptable carrier and a compound or salt of any of the preceding claims.

13. A method of modulating CCR2 function in a cell, comprising contacting the cell with a CCR2 modulating amount of the compound or salt of any one of claims 1-12.

14. A method of treating a CCR2-mediated condition or disease comprising administering to a subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt of claim 1.

15. The method of claim 14, wherein said CCR2-mediated condition or disease is atherosclerosis.

16. The method of claim 14, wherein said CCR2-mediated condition or disease is restenosis.

17. The method of claim 14, wherein said CCR2-mediated condition or disease is multiple sclerosis.

18. The method of claim 14, wherein said CCR2-mediated condition or disease is selected from the group consisting of inflammatory bowel disease, renal fibrosis, rheumatoid arthritis, obesity and noninsulin-dependent diabetes.

19. The method of claim 14, wherein said CCR2-mediated condition or disease is type 2 diabetes.

20. The method of claim 14, wherein said CCR2-mediated condition or disease is selected from the group consisting of chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and idiopathic pneumonia syndrome.

10. A compound selected from the group consisting of:

11. A compound selected from the group consisting of:

21. A crystalline form of 4-chloro-N-[5-methyl-2-(7H-pyrrolo[2,3-d]pyrimidine-4-carbonyl)-pyridin-3-yl]-3-trifluoromethyl-benzenesulfonamide sodium salt.

22. The crystalline form of claim 21, wherein said crystalline form has an X-ray powder diffraction comprising the following 2-theta values±

0.2 measured using CuK_α

radiation;

6.9, 7.7, 20.0, 24.3, 24.7, and 25.1.

23. The crystalline form of claim 22, wherein said crystalline form has an X-ray powder diffraction comprising the following 2-theta values±

0.2 measured using CuK_α

radiation;

6.9, 7.7, 10.6, 11.3, 11.8, 12.5, 13.7, 15.1, 15.3, 16.1, 16.9, 17.3, 18.2, 18.5, 19.5, 20.0, 21.6, 21.8, 22.6, 24.3, 24.7, 25.1, 25.6, 26.3, 27.5, 28.5, 28.8, 29.3, 31.4, and 32.4.