N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation

…, C Cook, K Rowan, V Schwinge, R Campbell

Index: Chen, Li; Tilley, Jefferson; Trilles, Richard V.; Yun, Weiya; Fry, David; Cook, Charles; Rowan, Karen; Schwinge, Virginia; Campbell, Robert Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 2 p. 137 - 140

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Citation Number: 26

Abstract

A series of N-benzylpyroglutamyl-l-phenylalanine derivatives bearing carbamoyl substituents in the 3-or 4-positions was prepared and assayed for inhibition of the interaction between VCAM and VLA-4. Potent inhibition was observed in a number of analogues with substitution in the 4-position favored over the 3-position. A crystal structure of the key intermediate 25 indicates that it accesses a low energy conformation which closely ...