Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease

Jing Zhang; Jan Romero; Audrey Chan; Jennifer Goss; Sabrina Stucka; Jason Cross; Brian Chamberlain; Mustafa Varoglu; Haoqun Chandonnet; Dominic Ryan; Blaise Lippa

doi:10.1016/j.bmcl.2015.06.046

Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3661-4. doi: 10.1016/j.bmcl.2015.06.046. Epub 2015 Jun 18.

Authors

Affiliations

¹ Cubist Pharmaceuticals, 65 Hayden Avenue, Lexington, MA 02421, United States. Electronic address: [email protected].
² Cubist Pharmaceuticals, 65 Hayden Avenue, Lexington, MA 02421, United States.

PMID: 26117562
DOI: 10.1016/j.bmcl.2015.06.046

Abstract

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, affects millions of people worldwide. CCR9 has been shown to be a key chemokine receptor mediating the local inflammatory responses in the GI tract. The CCR9 inhibitor Vercirnon advanced to phase 3 clinical trials, but carries several liabilities which we sought to improve.

Keywords: CCR9; Crohn’s disease; IBD; Sulfonamide; Ulcerative colitis.

MeSH terms

Animals
Chemistry Techniques, Synthetic
Drug Evaluation, Preclinical / methods
Humans
Inflammatory Bowel Diseases / drug therapy*
Inhibitory Concentration 50
Mice
Receptors, CCR / antagonists & inhibitors*
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / pharmacology*

Substances

CC chemokine receptor 9
CCX282-B
Receptors, CCR
Sulfonamides