Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents
Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents
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DOI：
10.1016/j.bmcl.2006.01.092
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发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Wyvratt, M
中科院分区：
文献类型：
--
作者：
Biftu, T;Feng, D;Wyvratt, M
化合物10a（IC50 110 pM）和21（IC50 40 pM）是迄今报道的柔嫩艾美耳球虫cGMP依赖性蛋白激酶活性的最有效抑制剂，并且当在饲料中以12.5和6.25 ppm水平施用于鸡时，在体内抗寄生虫测定中有效。然而，这两种化合物在艾姆斯微生物致突变试验中均为阳性，这排除了在缺乏阴性寿命啮齿动物致癌性研究的情况下将其进一步开发为抗原虫剂。(C)2006爱思唯尔有限公司保留所有权利。
Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies. (C) 2006 Elsevier Ltd. All rights reserved.