N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation
N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation
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DOI：
10.1016/s0960-894x(01)00711-9
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发表时间：
2002-01-21
影响因子：
2.7
通讯作者：
Campbell, R
中科院分区：
文献类型：
--
作者：
Chen, L;Tilley, J;Campbell, R
制备了一系列在3位或4位含有氨甲酰取代基的n -苄基焦戊酰- l-苯丙氨酸衍生物，并测定了它们对VCAM与vla4相互作用的抑制作用。在一些类似物中观察到有效的抑制作用，4位取代优于3位取代。关键中间体25的晶体结构表明，它获得的低能构象与结构表征的环肽的关键药效团密切匹配。(C) 2002 Elsevier Science Ltd.版权所有。
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. (C) 2002 Elsevier Science Ltd. All rights reserved.