N-acyl phenylalanine analogues as potent small molecule VLA-4 antagonists.
We have identified a series of low molecular weight (Mr < 500) N-acylphenylalanines that are effective inhibitors of the VCAM-VLA-4 interaction. Investigation of the SAR of the N-acyl moiety led to the identification of N-benzylpyroglutamyl derivatives as being particularly potent.
Chen
L
L
Roche Research Center, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110, USA.
Tilley
J W
JW
Huang
T N
TN
Miklowski
D
D
Trilles
R
R
Guthrie
R W
RW
Luk
K
K
Hanglow
A
A
Rowan
K
K
Schwinge
V
V
Wolitzky
B
B
D000215:Acylation; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D010649:Phenylalanine