鉴定磺酰基嘧啶类新型选择性醛固酮合成酶（CYP11B2）抑制剂

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2024-06-04 DOI:10.1016/j.bmc.2024.117775

Masaki Meguro , Satoru Miyauchi , Yukiko Kanao-Arisumi , Satoru Naito , Kanae Suzuki , Shinichi Inoue , Keisuke Yamada , Tsuyoshi Homma , Kiyoshi Chiba , Futoshi Nara , Shinji Furuzono

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引用次数: 0

摘要

研究发现，4-[(5-[2-甲基-5-(甲磺酰基)戊-2-基]磺酰基嘧啶-4-基)氨基]苯腈 2 是一种新型强效醛固酮合成酶抑制剂。研究发现，化合物 2 对人类 CYP11B2 的抑制作用在纳摩尔范围内，并在呋塞米处理的猴模型中显示出降低醛固酮的作用。虽然人 CYP11B2 与人 CYP11B1 具有高同源性序列，但化合物 2 在体外的选择性比人 CYP11B1 高 80 多倍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Identification of sulfonylpyrimidines as novel selective aldosterone synthase (CYP11B2) inhibitors

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Identification of sulfonylpyrimidines as novel selective aldosterone synthase (CYP11B2) inhibitors

4-[(5-[2-Methyl-5-(methylsulfonyl)pentan-2-yl]sulfonylpyrimidin-4-yl)amino]benzonitrile 2 was identified as a novel potent aldosterone synthase inhibitor. Compound 2 was found to inhibit human CYP11B2 in the nanomolar range, and showed an aldosterone-lowering effect in a furosemide-treated cynomolgus monkey model. Although human CYP11B2 has the high homology sequence with human CYP11B1, compound 2 showed more than 80 times higher selectivity over human CYP11B1 in vitro.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.