Discovery of nonbenzamidine factor VIla inhibitors using a biaryl acid scaffold
Discovery of nonbenzamidine factor VIla inhibitors using a biaryl acid scaffold
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DOI：
10.1016/j.bmcl.2013.06.028
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发表时间：
2013-09-15
影响因子：
2.7
通讯作者：
Seiler, Steven M.
中科院分区：
文献类型：
--
作者：
Bolton, Scott A.;Sutton, James C.;Seiler, Steven M.
在这封信中，我们描述了几个nonamidine类似物的联芳酸因子VIla抑制剂1含有弱碱性或非碱性P1基团的合成。2-发现氨基异喹啉是苯甲脒基团（化合物2）的极好替代物，其中相对于大多数其它相关丝氨酸蛋白酶维持了对因子VIla的有效抑制。在未预料到的结果中，间苯甲酰胺P1（化合物21 a和21 b）被证明是可行的苯甲脒替代物，尽管其对因子VIIa的效力损失了20-40倍。(C)2013由Elsevier Ltd.出版
In this Letter, we describe the synthesis of several nonamidine analogs of biaryl acid factor VIla inhibitor 1 containing weakly basic or nonbasic P1 groups. 2-Aminoisoquinoline was found to be an excellent surrogate for the benzamidine group (compound 2) wherein potent inhibition of factor VIla is maintained relative to most other related serine proteases. In an unanticipated result, the m-benzamide P1 (compounds 21a and 21b) proved to be a viable benzamidine replacement, albeit with a 20-40 fold loss in potency against factor Vlla. (C) 2013 Published by Elsevier Ltd.