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

• US 9,745,312 B2
• Filed: 06/28/2016
• Issued: 08/29/2017
• 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:
  US15/195,777
• Publication Number:
  US 20170022205A1
• Time in Patent Office: 427 Days
• Field of Search: None
• 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 method of preparing a compound of Formula A:

2. The method of claim 1, wherein the compound of Formula B is reacted with NaOH and chloromethyl methyl ether to produce the compound of Formula C.

3. The method of claim 1, further comprising reacting a compound of Formula D:

4. The method of claim 3, wherein the reaction is conducted in presence of N,N′

-carbonyldiimidazole.

5. The method of claim 3, further comprising contacting a compound of Formula E:

6. The method of claim 5, further comprising reacting 3-amino-5-methylpicolino-nitrile with 4-chloro-3-trifluoromethyl-benzenesulfonyl chloride in pyridine to form the compound of Formula E.

7. The method of claim 1, wherein the solvent used to produce the Grignard reagent is tetrahydrofuran.

8. The method of claim 1, wherein the solvent used in step (b) is tetrahydrofuran.

9. The method of claim 1, wherein step (c) is conducted with an acid.

10. The method of claim 9, wherein the acid is hydrochloric acid.

11. A compound selected from the group consisting of:

12. The compound of claim 11, wherein the compound is

13. The compound of claim 11, wherein the compound is

14. The compound of claim 11, wherein the compound is

15. The compound of claim 11, wherein the compound is

16. A method of making a compound of Formula A:

17. The method of claim 16, wherein the Grignard reagent is formed by reacting 4-iodo-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine with isopropylmagnesium chloride.

18. The method of claim 16, wherein the acid is hydrochloric acid.

19. The method of claim 16, wherein the intermediate D is reacted with O,N-dimethyl-hydroxylamine hydrochloride in the presence of N,N′

-carbonyldiimidazole.