Heteroaryl sulfonamides and CCR2

• US 20070037794A1
• Filed: 07/14/2006
• Published: 02/15/2007
• Est. Priority Date: 01/14/2005
• Status: Active Grant

• Current Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Original Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Inventors: Zeng, Yibin, Wei, Zheng, Punna, Sreenivas, Chen, Wei, Ungashe, Solomon, Jin, Jeff, Pennell, Andrew, Basak, Arindrajit, Hansen, Derek, Dairaghi, Daniel, Moore, Jimmie, Wright, John, Charvat, Trevor
• Granted Patent: US 7,622,583 B2
• Time in Patent Office: Days
• US Class Current: 514/217.40
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07C 311/21 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 241/22 Benzenesulfonamido pyrazines
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 407/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 498/04 Ortho-condensed systems

Abstract

Compounds are provided that act as potent antagonists of the CCR2 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2. 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 of claim 1, which is represented by formula (II) or a salt thereof:

3. The compound of claim 1, which is represented by formula (CLI) or a salt thereof:

4. The compound of claim 1, which is represented by formula (CLII) or a salt thereof:

5. The compound of claim 1, which is represented by formula (CLIII) or a salt thereof:

6. A composition comprising a pharmaceutically acceptable carrier and a compound of claim 1.

18. A method of modulating CCR2 function in a cell, comprising contacting the cell with a CCR2 modulating amount of the compound of claim 1.

19. A method of modulating CCR9 function in a cell, comprising contacting the cell with a CCR9 modulating amount of the compound of claim 1.

20. A method for treating a CCR9-mediated condition or disease comprising administering to a subject an effective amount of the compound of claim 1.

7. A method for treating a CCR2-mediated condition or disease comprising administering to a subject an effective amount of a compound of formula (I), or a salt thereof:

8. The method of claim 7, where the CCR2-mediated disease or condition is atherosclerosis.

9. The method of claim 7, where the CCR2-mediated disease or condition is restenosis.

10. The method of claim 7, where the CCR2-mediated condition or disease is multiple sclerosis.

11. The method of claim 7, where the CCR2-mediated condition or disease is selected from the group consisting of inflammatory bowel disease, renal fibrosis, rheumatoid arthritis, obesity and diabetes.

12. The method of claim 7, where the CCR2-mediated condition or disease is selected from the group consisting of chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and idiopathic pneumonia syndrome.

13. The method of claim 7, where the CCR2-mediated condition or disease is selected from the group consisting of pulmonary fibrosis, transplantation rejection, graft-versus-host disease and cancer.

14. The method of claim 7, where the CCR2-mediated condition or disease is neuropathic pain.

15. The method of claim 7, where the administering is oral, parenteral, rectal, transdermal, sublingual, nasal or topical.

16. The method of claim 7, where the compound is administered in combination with an anti-inflammatory or analgesic agent.

17. The method of claim 7, further comprising administering an anti-inflammatory or analgesic agent.