N-(arylacetyl)-biphenylalanines as potent VLA-4 antagonists.
A series of potent N-(aralkyl-, arylcycloalkyl-, and heteroaryl-acyl)-4-biphenylalanine VLA-4 antagonists was prepared by rapid analogue methods using solid-phase chemistry. Further optimization led to several highly potent compounds (IC(50) <1 nM). Evaluation of rat pharmacokinetic revealed generally high clearance.
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. bing_li@merck.com
Bing
B
Li
Stephen E
SE
de Laszlo
Theodore M
TM
Kamenecka
Ihor E
IE
Kopka
Philippe L
PL
Durette
Thomas
T
Lanza
Malcolm
M
MacCoss
Sharon
S
Tong
Richard A
RA
Mumford
Ermengilda D
ED
McCauley
Gail
G
Van Riper
John A
JA
Schmidt
William K
WK
Hagmann
D000818:Animals; D001665:Binding Sites; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D039041:Integrin alpha4beta1; D010649:Phenylalanine