Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring. Inhibitors of arginine-specific esteroproteases.
Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring. Inhibitors of arginine-specific esteroproteases.
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二芳基脒衍生物，其一个或两个芳基部分由吲哚或类吲哚环组成。
DOI：
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发表时间：
1978
影响因子：
7.3
通讯作者：
H. Loewe
中科院分区：
文献类型：
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作者：
R. Tidwell;J. Geratz;O. Dann;G. Volz;D. Zeh;H. Loewe
对62个二芳胺衍生物的抗蛋白水解活性进行了评价。除两种化合物外，其余化合物的一个或两个氨基取代芳基部分为吲哚环或类吲哚环。后者包括茚、苯并咪唑、苯并呋喃、苯[β]噻吩和其他几种相关的含氮杂环。其中一些化合物对凝血酶、胰蛋白酶和胰激肽素表现出相当大的抑制效力。在双（5-氨基-2-苯并咪唑）甲烷（化合物42）中发现了一种出色的胰蛋白酶抑制剂，其Ki值为1.7 X 10(-8) M（pH）。摄氏8.1度，37度)。另一种衍生物1,2-二（4-氨基-2-苯并呋喃基）乙烷（化合物21）被证明是一种非常有效的整体凝血过程抑制剂。从一般的结构活性角度来看，这些化合物表明，低分子量抑制剂的微小结构变化可以导致抗蛋白水解活性的特异性和效力的显着变化。
A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other related nitrogen-containing heterocycles. Several of the compounds exhibited considerable inhibitory potency against thrombin, trypsin, and pancreatic kallikrein. An outstanding inhibitor of trypsin was found in bis(5-amidino-2-benzimidazolyl)methane (compound 42) with a Ki value of 1.7 X 10(-8) M(pH. 8.1, 37 degrees C). Another derivative, 1,2-di(4-amidino-2-benzofuranyl)ethane (compound 21), proved to be a highly effective inhibitor of the overall blood clotting process. From a general structure-activity standpoint these compounds demonstrate that minor structural variations of low-molecular-weight inhibitors can result in significant changes in specificity and potency with regard to antiproteolytic activity.