Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation

• US 8,546,408 B2
• Filed: 12/22/2010
• Issued: 10/01/2013
• 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
• Primary Examiner(s): MURRAY, JEFFREY H
• Application Number:
  US12/976,768
• Publication Number:
  US 20110319433A1
• Time in Patent Office: 1,014 Days
• Field of Search: None
• US Class Current: 514/265.1
• 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

Fused heteroaryl pyridyl benzenesulfonamides 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 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.

2. The crystalline form of claim 1, wherein said crystalline form has an X-ray powder diffraction comprising the following 2-theta values ±

0.2 measured using CuKα

radiation;

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

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

0.2 measured using CuKα

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.

4. A method of modulating CCR2 function in a cell, comprising contacting the cell with a CCR2 modulating amount of the compound or salt of anyone of claims 1-3.

5. 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 claims 1-3.

6. The method of claim 5, wherein said CCR2-mediated condition or disease is atherosclerosis.

7. The method of claim 5, wherein said CCR2-mediated condition or disease is restenosis.

8. The method of claim 5, wherein said CCR2-mediated condition or disease is multiple sclerosis.

9. The method of claim 5, 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.

10. The method of claim 5, wherein said CCR2-mediated condition or disease is type 2 diabetes.

11. The method of claim 5, 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.