RhII-Catalyzed De-symmetrization of Ethane-1,2-dithiol and Propane-1,3-dithiol Yields Metallo-β-lactamase Inhibitors

被引：9

作者：

Krasavin, Mikhail ^{[1
]}

Zhukovsky, Daniil ^{[1
]}

Solovyev, Igor ^{[1
]}

Barkhatova, Darina ^{[1
]}

Dar'in, Dmitry ^{[1
]}

Frank, Denia ^{[2
]}

Martinelli, Giada ^{[2
]}

Weizel, Lilia ^{[3
]}

Proschak, Anna ^{[3
]}

Rotter, Marco ^{[3
]}

Kramer, Jan S. ^{[3
]}

Brunst, Steffen ^{[3
]}

Wichelhaus, Thomas A. ^{[2
]}

Proschak, Ewgenij ^{[3
]}

机构：

[1] St Petersburg State Univ, Inst Chem, 26 Univ Skii Prospect, Peterhof 198905, Russia

[2] Univ Hosp Frankfurt, Inst Med Microbiol & Infect Control, Paul Ehrlich Str 40, D-60596 Frankfurt, Germany

[3] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Max von Laue Str 9, D-60438 Frankfurt, Germany

来源：

CHEMMEDCHEM | 2021年 / 16卷 / 22期

关键词：

multiresistant bacteria; metallo beta lactamases; thiol inhibitors; Rh(II) catalysis; diazo compounds; DIAZO; KETONES;

D O I：

10.1002/cmdc.202100344

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo-beta-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity.

引用

页码：3410 / 3417

页数：8