苯甲脒衍生物对顶体蛋白酶抑制作用的构效关系。

Structure-activity relationships for the inhibition of acrosin by benzamidine derivatives.

作者信息

Parrish R F, Straus J W, Paulson J D, Polakoski K L, Tidwell R R, Geratz J D, Stevens F M

出版信息

J Med Chem. 1978 Nov;21(11):1132-6. doi: 10.1021/jm00209a008.

Abstract

A series, consisting of 52 benzamidine derivatives, was evaluated for inhibitory activity against homogeneous boar sperm acrosin. All of the compounds in the series proved to be more potent than benzamidine (Ki = 4.0 x 10(-6) M), with one of the derivatives, alpha-(4-amidino-2,6-diiodophenoxy)-3-nitrotoluene (compound 16), showing outstanding potency with a Ki value of 4.5 X 10(-8) M. Although all of the derivatives were effective acrosin inhibitors, structural specificity was observed within homologous groups of compounds. The information gained from this preliminary study should prove extremely beneficial in the design and synthesis of future acrosin inhibitors.

摘要

对由52种苯甲脒衍生物组成的系列化合物进行了抗纯合公猪精子顶体蛋白酶抑制活性评估。该系列中的所有化合物均被证明比苯甲脒（Ki = 4.0×10⁻⁶ M）更具效力，其中一种衍生物α-(4-脒基-2,6-二碘苯氧基)-3-硝基甲苯（化合物16）表现出卓越的效力，Ki值为4.5×10⁻⁸ M。尽管所有衍生物都是有效的顶体蛋白酶抑制剂，但在化合物的同系物组中观察到了结构特异性。从这项初步研究中获得的信息在未来顶体蛋白酶抑制剂的设计和合成中应会被证明极具益处。