Central Research Laboratories, Kaken Pharmaceutical Co. Ltd, 14 Shinomiya-minamikawara, Yamashina, Kyoto 607-8042, Japan.
Abstract:
The discovery and SAR of 2,3-diphenylpropionic acid derivatives as highly potent VLA-4 antagonists are described. One representative compound, 9cc has inhibited intercellular adhesion by a VCAM-1/VLA-4 interaction with an IC(50) of 1.7 nM, and has good pharmacokinetics and oral bioavailability.