Heteroaryl sulfonamides and CCR2/CCR9

• US 10,532,044 B2
• Filed: 02/11/2019
• Issued: 01/14/2020
• Est. Priority Date: 07/14/2006
• Status: Active Grant

• Current Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Original Assignee: ChemoCentryx, Inc. (Amgen Inc.)
• Inventors: Ungashe, Solomon, Wei, Zheng, Basak, Arindrajit, Charvat, Trevor T., Chen, Wei, Jin, Jeff, Moore, Jimmie, Zeng, Yibin, Punna, Sreenivas, Dairaghi, Daniel, Hansen, Derek, Pennell, Andrew M. K., Wright, John J., Krasinski, Antoni, Wang, Qiang
• Primary Examiner(s): Reese, Heidi
• Application Number:
  US16/272,401
• Publication Number:
  US 20190167651A1
• Time in Patent Office: 337 Days
• Field of Search: None
• 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 method of preparing a compound of Formula A, comprising:

2. The method of claim 1, wherein Y⁶ is unsubstituted C_1-8 alkyl.

3. The method of claim 1, wherein R⁶⁷ is hydrogen.

4. The method of claim 1, wherein R¹⁰⁰ is hydrogen.

5. The method of claim 1, wherein Ar is substituted or unsubstituted C_6-10 aryl.

6. The method of claim 1, wherein the compound of Formula A is

7. The method of claim 1, wherein the Grignard reagent is formed by reacting an iodoheterocycle with an alkyl- or aryl-magnesium chloride in a solvent.

8. The method of claim 7, wherein the alkyl-magnesium chloride is isopropylmagnesium chloride.

9. The method of claim 7, wherein the iodoheterocycle is a protected or unprotected 4-iodo-1H-pyrrolo[2,3-b]pyridine.

10. The method of claim 7, wherein iodoheterocycle is 1-(tert-butyl-dimethyl-silanyl)-4-iodo-1H-pyrrolo[2,3-b]pyridine.

11. The method of claim 7, wherein the solvent is tetrahydrofuran.

12. The method of claim 1, wherein the compound of Formula C is deprotected in the presence of an acid.

13. The method of claim 12, wherein the acid is hydrochloric acid.

14. A method of preparing a compound of Formula A, comprising:

15. The method of claim 14, wherein Y⁶ is unsubstituted C_1-8 alkyl.

16. The method of claim 14, wherein R⁶⁷ is hydrogen.

17. The method of claim 14, wherein R¹⁰⁰ is hydrogen.

18. The method of claim 14, wherein Ar is substituted or unsubstituted C_6-10 aryl.

19. The method of claim 14, wherein the compound of Formula A is

20. The method of claim 14, wherein the Grignard reagent is formed by reacting an iodoheterocycle with an alkyl- or aryl-magnesium chloride in a solvent.