N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation.
Basic Information
ID: ALA1135363
Journal: Bioorg Med Chem Lett
Title: N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation.
Authors: Chen L, Tilley J, Trilles RV, Yun W, Fry D, Cook C, Rowan K, Schwinge V, Campbell R.
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 matches key pharmacophores of a structurally characterized cyclic peptide.
CiteXplore: 11755339
DOI: 10.1016/s0960-894x(01)00711-9
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