Imide and lactam derivatives of N-benzylpyroglutamyl- -phenylalanine as VCAM/VLA-4 antagonists

A series of imides and lactams derived from 4-amino-N-benzylpyroglutamyl- -phenylalanine was prepared and evaluated for activity as VCAM/VLA-4 antagonists. Imides were more potent than the corresponding lactams; several had subnanomolar IC50s in an ELISA based assay and were also highly effective at blocking VLA-4 expressing Ramos cell binding to VCAM coated plates.