(7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists.

Abstract

S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.

• Authors: Daniel J Buzard, Luis Lopez, Jeanne Moody, Andrew Kawasaki, Thomas O Schrader, Michelle Kasem, Ben Johnson, Xiuwen Zhu, Lars Thoresen, Sun Hee Kim, Tawfik Gharbaoui, Dipanjan Sengupta, Lorene Calvano, Ashwin Krishnan, Yinghong Gao, Graeme Semple, Jeff Edwards, Jeremy Barden, Michael Morgan, Khawja Usmani, Chuan Chen, Abu Sadeque, Weichao Chen, Ronald J Christopher, Jayant Thatte, Lixia Fu, Michelle Solomon, Kevin Whelan, Hussien Al-Shamma, Joel Gatlin, Ibragim Gaidarov, Todd Anthony, Minh Le, David J Unett, Scott Stirn, Anthony Blackburn, Dominic P Behan, Robert M Jones
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 5 Issue 12 Pg. 1334-9 (Dec 11 2014) ISSN: 1948-5875 [Print] United States
• PMID: 25516794 (Publication Type: Journal Article)