Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties
Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties
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DOI：
10.1016/j.bmcl.2011.02.006
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发表时间：
2011-04-01
影响因子：
2.7
通讯作者：
Wright, Jon
中科院分区：
文献类型：
--
作者：
Li, Xianfeng;Zhang, Suoming;Wright, Jon
我们合成并评价了一系列新的基于无环β 4-苯并氧杂硼杂环戊烯的HCV NS 3蛋白酶抑制剂。研究了结构-活性关系，导致在酶和基于细胞的复制子测定中鉴定出具有低纳摩尔效力的化合物5g和17。发现接头截短的化合物5 j在大鼠中表现出改善的吸收和口服生物利用度，表明分子量和极性表面积的进一步降低可以导致该新系列的改善的药物样性质。(C)2011爱思唯尔有限公司保留所有权利。
We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series. (C) 2011 Elsevier Ltd. All rights reserved.