Benzofuran Derivatives as Potent, Orally Active S1P1 Receptor Agonists: A Preclinical Lead Molecule for MS
ACS Medicinal Chemistry Letters2010Vol. 2(2), pp. 97–101
Citations Over TimeTop 15% of 2010 papers
Ashis Saha, Yu Xiang, 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 L. Salyers, Michael Schrag, Hugo M. Vargas, Yang Xu, Michele McElvain, Han Xu
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.
Related Papers
- → Benzofuran-/Benzothiophene-Incorporated NIR-Absorbing Triphyrins(2.1.1)(2018)31 cited
- → Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening(2018)20 cited
- → Identification of phosphodiesterase-1 and 5 dual inhibitors by a ligand-based virtual screening optimized for lead evolution(2005)16 cited
- → First Cdc7 Kinase Inhibitors: Pyrrolopyridinones as Potent and Orally Active Antitumor Agents. 2. Lead Discovery(2009)1 cited
- → Structure-guided drug discovery for protein kinases using fragment-based lead identification/lead optimization(2005)