Discovery of a Potent, S1P3-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P1)
Year: 2010
Type: article
Abstract: Optimization of a benzofuranyl S1P1 agonist lead compound (3) led to the discovery of 1-(3-fluoro-4-(5-(2-fluorobenzyl)benzo[d]thiazol-2-yl)benzyl)azetidine-3-carboxylic acid (14), a potent S1P1 agonist with minimal activity at S1P3. Dosed orally at 0.3 mg/kg, 14 significantly reduced blood lymphocyte counts 24 h postdose and attenuated a delayed type hypersensitivity (DTH) response to antigen challenge.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml100228m
Authors: Brian A. Lanman, Victor J. Cee, Srinivasa R. Cheruku, Mike Frohn, Jennifer Golden, Jian Lin, Mercedes Lobera, Yael Marantz, Kristine M. Muller, Susana C. Neira, Alexander J. Pickrell, Dalia Rivenzon-Segal, Nili Schutz, Anurag Sharadendu, Xiang Yu, Zhaoda Zhang, Janet Buys, Mike Fiorino, Anu Gore, Michelle Horner, Andrea Itano, Michele McElvain, Scot Middleton, Michael Schrag, Hugo M. Vargas, Han Xu, Yang Xu, Xuxia Zhang, Jerry Siu, Roland W. Bürli
Institutions: Amgen (United States), Epix Pharmaceuticals (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2016856873