N-aryl 2,6-dimethoxybiphenylalanine analogues as VLA-4 antagonists.
A series of N-arylated phenylalanine derivatives has been synthesized and has been shown to be potent inhibitors of the integrin VLA-4. N-phenyl and N-heteroaryl derivatives with hydrogen bond acceptors in the meta position demonstrated low nanomolar activity against VLA-4.
Doherty
George A
GA
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. george_doherty@merck.com
Kamenecka
Theodore
T
McCauley
Ermenegilda
E
Van Riper
Gail
G
Mumford
Richard A
RA
Tong
Sharon
S
Hagmann
William K
WK
D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D010649:Phenylalanine