A new chemotype with promise against Trypanosoma cruzi

被引：3

作者：

Wang, Xiaofang ^{[1
]}

Cal, Monica ^{[2
,3
]}

Kaiser, Marcel ^{[2
,3
]}

Buckner, Frederick S. ^{[4
]}

Lepesheva, Galina, I ^{[5
]}

Sanford, Austin G. ^{[6
]}

Wallick, Alexander, I ^{[6
]}

Davis, Paul H. ^{[6
]}

Vennerstrom, Jonathan L. ^{[1
]}

机构：

[1] Univ Nebraska Med Ctr, Coll Pharm, 986025 Nebraska Med Ctr, Omaha, NE 68198 USA

[2] Swiss Trop Inst, Dept Med Parasitol & Infect Biol, Socinstr 57, CH-4002 Basel, Switzerland

[3] Univ Basel, CH-4003 Basel, Switzerland

[4] Univ Washington, Dept Med, 750 Republican St, Seattle, WA USA

[5] Vanderbilt Univ, Dept Biochem, 2200 Pierce Ave, Nashville, TN 37232 USA

[6] Univ Nebraska, Dept Biol, Omaha, NE 68182 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Chagas disease; Trypanosoma cruzi; SAR; DRUG DISCOVERY; SUBSTRATE; CYP51;

D O I：

10.1016/j.bmcl.2019.126778

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyridyl benzamide 2 is a potent inhibitor of Trypanosoma cruzi, but not other protozoan parasites, and had a selectivity-index of >= 10. The initial structure-activity relationship (SAR) indicates that benzamide and sulfonamide functional groups, and N-methylpiperazine and sterically unhindered 3-pyridyl substructures are required for high activity against T. cruzi. Compound 2 and its active analogs had low to moderate metabolic stabilities in human and mouse liver microsomes.

引用

页数：5

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