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一种具有抗克氏锥虫潜力的新型化学型。

A new chemotype with promise against Trypanosoma cruzi.

机构信息

College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, United States.

Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH-4003 Basel, Switzerland.

出版信息

Bioorg Med Chem Lett. 2020 Jan 1;30(1):126778. doi: 10.1016/j.bmcl.2019.126778. Epub 2019 Oct 31.

DOI:10.1016/j.bmcl.2019.126778
PMID:31706668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6892603/
Abstract

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.

摘要

吡啶基苯甲酰胺 2 是一种有效的克氏锥虫抑制剂，但对其他原生动物寄生虫无效，其选择性指数≥10。初步的结构-活性关系（SAR）表明，苯甲酰胺和磺酰胺官能团以及 N-甲基哌嗪和空间位阻的 3-吡啶基亚结构是对抗克氏锥虫高活性所必需的。化合物 2 及其活性类似物在人肝微粒体和鼠肝微粒体中的代谢稳定性较低至中等。

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