SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties |
| |
Authors: | Yan Lin Huo Pei Hale Jeffrey J Mills Sander G Hajdu Richard Keohane Carol A Rosenbach Mark J Milligan James A Shei Gan-Ju Chrebet Gary Bergstrom James Card Deborah Mandala Suzanne M |
| |
Affiliation: | Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. lin_yan@merck.com |
| |
Abstract: | Structure-activity relationship (SAR) studies of 3-arylpropionic acids-a class of novel S1P(1) selective agonists-by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|