三取代噻唑作为恶性疟原虫蛋白激酶G（PfPKG）的强效和选择性抑制剂。
Trisubstituted thiazoles as potent and selective inhibitors of Plasmodium falciparum protein kinase G (PfPKG).
作者信息
Tsagris Denise J, Birchall Kristian, Bouloc Nathalie, Large Jonathan M, Merritt Andy, Smiljanic-Hurley Ela, Wheldon Mary, Ansell Keith H, Kettleborough Catherine, Whalley David, Stewart Lindsay B, Bowyer Paul W, Baker David A, Osborne Simon A
机构信息
LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
LifeArc, Accelerator Building, Open Innovation Campus, Stevenage SG1 2FX, UK.
出版信息
Bioorg Med Chem Lett. 2018 Oct 15;28(19):3168-3173. doi: 10.1016/j.bmcl.2018.08.028. Epub 2018 Aug 27.
Abstract
A series of trisubstituted thiazoles have been identified as potent inhibitors of Plasmodium falciparum (Pf) cGMP-dependent protein kinase (PfPKG) through template hopping from known Eimeria PKG (EtPKG) inhibitors. The thiazole series has yielded compounds with improved potency, kinase selectivity and good in vitro ADME properties. These compounds could be useful tools in the development of new anti-malarial drugs in the fight against drug resistant malaria.
摘要
通过从已知的艾美球虫PKG（EtPKG）抑制剂进行模板跳跃，一系列三取代噻唑已被鉴定为恶性疟原虫（Pf）环鸟苷酸依赖性蛋白激酶（PfPKG）的有效抑制剂。噻唑系列已产生了具有提高的效力、激酶选择性和良好体外吸收、分布、代谢和排泄（ADME）特性的化合物。这些化合物可能是开发新型抗疟药物以对抗耐药性疟疾的有用工具。
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