基于中心噻吩骨架的α(v)β(3)拮抗剂。

alpha(v)beta(3) Antagonists based on a central thiophene scaffold.

作者信息

Peyman A, Scheunemann K, Will D W, Knolle J, Wehner V, Breipohl G, Stilz H U, Carniato D, Ruxer J, Gourvest J, Auberval M, Doucet B, Baron R, Gaillard M, Gadek T R, Bodary S

机构信息

Aventis Pharma Deutschland GmbH, D-65926, Frankfurt, Germany.

出版信息

Bioorg Med Chem Lett. 2001 Aug 6;11(15):2011-5. doi: 10.1016/s0960-894x(01)00357-2.

DOI:10.1016/s0960-894x(01)00357-2

PMID:11454469

Abstract

A series of novel, highly potent alpha(v)beta(3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta-amino acids were explored with respect to inhibition of alpha(v)beta(3) mediated cell adhesion and selectivity versus alpha(IIb)beta(3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.

摘要

描述了一系列基于噻吩支架且含有酰基胍作为精氨酸模拟物的新型高效α(v)β(3)拮抗剂。针对α(v)β(3)介导的细胞黏附抑制以及与α(IIb)β(3)结合的选择性，研究了许多结构特征，如环状胍与开链胍以及各种亲脂性侧链、氨基甲酸酯、磺酰胺和β-氨基酸。此外，发现化合物19在骨质疏松症的TPTX模型中具有活性。