Structure-Activity Relationship Study of Benzamides as Mycobacterium tuberculosis QcrB Inhibitors

被引：0

作者：

Lynde, Brock E. ^{[1
]}

Mattos, Jared ^{[1
]}

Chemaly, Danielle M. ^{[1
]}

Deshpande, Aditi ^{[1
]}

Pogula, Sreekanth Reddy ^{[1
]}

Greve, Eric ^{[1
]}

Chowdhury, Sultan ^{[1
]}

Parish, Tanya ^{[1
,2
]}

机构：

[1] Seattle Childrens Res Inst, Ctr Global Infect Dis Res, Seattle, WA 98101 USA

[2] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2025年

关键词：

tuberculosis; aerobic respiration; antibacterial; mycobacteria; PHENOXYALKYLBENZIMIDAZOLES; DISCOVERY; DESIGN; Q203;

D O I：

10.1021/acsmedchemlett.5c00252

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We previously identified a morpholinobenzamide series with potent activity against Mycobacterium tuberculosis. We conducted structure-activity relationship studies focusing on removing the metabolically labile morpholine group while retaining antibacterial activity. We identified potent benzamides 16 (IC90 = 0.13 mu M) and 22f (IC90 = 0.09 mu M) with a thiophene and methyl substituents replacing the morpholine at the C-5 position. These analogs had high selectivity (selectivity index = 300 and 278, respectively) and low cytotoxicity (HepG2 CC50 of 39 and 25 mu M, respectively). Compound 16 demonstrated a good metabolic stability in human liver microsomes.

引用

页数：9

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