Benzofuran Derivatives as Potent, Orally Active S1P1 Receptor Agonists: A Preclinical Lead Molecule for MS
Year: 2010
Type: article
Abstract: We have discovered novel benzofuran-based S1P1 agonists with excellent in vitro potency and selectivity. 1-((4-(5-Benzylbenzofuran-2-yl)-3-fluorophenyl)methyl) azetidine-3-carboxylic acid (18) is a potent S1P1 agonist with >1000× selectivity over S1P3. It demonstrated a good in vitro ADME profile and excellent oral bioavailability across species. Dosed orally at 0.3 mg/kg, 18 significantly reduced blood lymphocyte counts 24 h postdose and demonstrated efficacy in a mouse EAE model of relapsing MS.
Source: ACS Medicinal Chemistry Letters
DOI: 10.1021/ml100227q
Authors: Ashis K. Saha, Xiang Yu, Jian Lin, Mercedes Lobera, Anurag Sharadendu, Srinivas Chereku, Nili Schutz, Dalia Segal, Yael Marantz, Dilara McCauley, Scot Middleton, Jerry Siu, Roland W. Bürli, Janet Buys, Michelle Horner, Kevin Salyers, Michael Schrag, Hugo M. Vargas, Yang Xu, Michele McElvain, Han Xu
Institution: Epix Pharmaceuticals (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Amgen
OpenAlex ID: W1983294393