3-Indolyl sultams as selective CRTh2 antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 11; pp. 3287 - 3290
• Main Authors: Tumey, L. Nathan, Robarge, Michael J., Gleason, Elizabeth, Song, Jianping, Murphy, Steven M., Ekema, George, Doucette, Chris, Hanniford, Doug, Palmer, Marc, Pawlowski, Gary, Danzig, Joel, Loftus, Margaret, Hunady, Karen, Sherf, Bruce, Mays, Robert W., Stricker-Krongrad, Alain, Brunden, Kurt R., Bennani, Youssef L., Harrington, John J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2010
• Subjects: Antagonist; CRTh2; Esterification; Humans; Indole; Indoles - chemistry; Indoles - pharmacology; Prostaglandin D2; Ramatroban; Receptors, Immunologic - antagonists & inhibitors; Receptors, Prostaglandin - antagonists & inhibitors; Sulfonamides - chemistry; Sulfonamides - pharmacology; Sultam; Sultam; Indole; CRTh2; Antagonist; Prostaglandin D2; DP; Ramatroban
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.04.046

CRTh2 (DP2) is a prostaglandin D2 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 sultams that are low nM antagonists of CRTh2. These compounds proved to be selective over the other primary prostaglandin D2 receptor (DP1) as well as the thromboxane A2 receptor (TP). CRTh2 (DP2) is a prostaglandin D2 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 D2 receptor (DP1) as well as the thromboxane A2 receptor (TP).