Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization |
| |
| Authors: | Elworthy Todd R Kertesz Denis J Kim Woongki Roepel Michael G Quattrocchio-Setti Lina Smith David B Tracy Jahari Laurant Chow Audrey Li Fujun Brill Emma R Lach Leang K McGee Daren Yang Diana S Chiou San-San |
| |
| Affiliation: | Roche Palo Alto, Department of Medicinal Chemistry, 3431Hillview Avenue, Palo Alto, CA 94304-1397, USA. todd.elworthy@roche.com |
| |
| Abstract: | A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP(4) receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP(4) versus the other EP prostanoid receptors. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
