3-Indolyl sultams as selective CRTh2 antagonists

L Nathan Tumey; Michael J Robarge; Elizabeth Gleason; Jianping Song; Steven M Murphy; George Ekema; Chris Doucette; Doug Hanniford; Marc Palmer; Gary Pawlowski; Joel Danzig; Margaret Loftus; Karen Hunady; Bruce Sherf; Robert W Mays; Alain Stricker-Krongrad; Kurt R Brunden; Youssef L Bennani; John J Harrington

doi:10.1016/j.bmcl.2010.04.046

3-Indolyl sultams as selective CRTh2 antagonists

Bioorg Med Chem Lett. 2010 Jun 1;20(11):3287-90. doi: 10.1016/j.bmcl.2010.04.046. Epub 2010 Apr 14.

Affiliation

¹ Athersys, Inc., 3201 Carnegie Ave., Cleveland, OH 44115, USA. [email protected]

PMID: 20457519
DOI: 10.1016/j.bmcl.2010.04.046

Abstract

CRTh2 (DP(2)) is a prostaglandin D(2) receptor implicated in the recruitment of eosinophils and basophils within the asthmatic lung. Here we report the discovery of a novel series of 3-indolyl sultam antagonists with low nM affinity for CRTh2. These compounds proved to be selective over the other primary prostaglandin D(2) receptor (DP1) as well as the thromboxane A(2) receptor (TP).

MeSH terms

Esterification
Humans
Indoles / chemistry*
Indoles / pharmacology*
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Prostaglandin / antagonists & inhibitors*
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Indoles
Receptors, Immunologic
Receptors, Prostaglandin
Sulfonamides
prostaglandin D2 receptor