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. A series of N-arylated phenylalanine derivatives has been synthesized and has been shown to be potent inhibitors of the integrin VLA-4. Both aryl and heteroaryl derivatives were examined. Substitution of the meta position of either the aryl or heteroaryl ring with hydrogen bond acceptors provided the most potent compounds in this series.