2,3-Diphenylpropionic acids as potent VLA-4 antagonists.
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.
Hoshina
Yoichiro
Y
Central Research Laboratories, Kaken Pharmaceutical Co. Ltd, 14 Shinomiya-minamikawara, Yamashina, Kyoto 607-8042, Japan.
Ikegami
Satoru
S
Okuyama
Akihiko
A
Fukui
Hideto
H
Inoguchi
Kiyoshi
K
Maruyama
Tatsuya
T
Fujimoto
Kyoko
K
Matsumura
Yuzuru
Y
Aoyama
Akinori
A
Harada
Tatsuhiro
T
Tanaka
Hiroshi
H
Nakamura
Tsutomu
T
D000284:Administration, Oral; D001682:Biological Availability; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D011422:Propionates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D039041:Integrin alpha4beta1; D011422:Propionates; C029658:propionic acid