Discovery and evaluation of novel nitrodihydroimidazooxazoles as promising anti-tuberculosis agents

被引：7

作者：

Tao, Xin ^{[1
,2
]}

Gao, Chao ^{[1
]}

Huang, Zhi-Gang ^{[3
]}

Luo, Wei ^{[3
]}

Liu, Kun-Lin ^{[1
]}

Peng, Cui-Ting ^{[4
]}

Ding, Charles Z. ^{[3
]}

Li, Jian ^{[3
]}

Chen, Shu-Hui ^{[3
]}

Yu, Luo-Ting ^{[1
]}

机构：

[1] Sichuan Univ, West China Hosp, Canc Ctr, Dept Biotherapy, Chengdu 610041, Sichuan, Peoples R China

[2] Changzhou Yinsheng Pharm Co Ltd, Weitang Chem Ind Zone, Changzhou 213000, Peoples R China

[3] WuXi AppTec Co Ltd, Waigaoqiao Free Trade Zone, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China

[4] Sichuan Univ, West China Univ Hosp 2, Dept Obstet & Gynecol, Chengdu, Sichuan, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 17期

基金：

中国博士后科学基金;

关键词：

Nitroimidazoles; Antitubercular agents; Physicochemical properties; TUBERCULOSIS DRUG; IN-VITRO; ANALOGS; DELAMANID; LINKER; NITROIMIDAZOLES; DERIVATIVES; METABOLISM;

D O I：

10.1016/j.bmcl.2019.06.055

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New analogues of antitubercular drug Delamanid were prepared, seeking drug candidates with enhanced aqueous solubility and high efficacy. The strategy involved replacement of phenoxy linker proximal to the 2-nitroimidazooxazole of Delamanid by piperidine fused 5 or 6-membered ring heterocycles (ring A). The new compounds were all more hydrophilic than Delamanid, and several class of analogues showed remarkable activities against M. bovis. And among these series, the tetrahydro-naphthyridine-linked nitroimidazoles displayed excellent antimycobacterial activity against both replicating (MABA) and nonreplicating (LORA) M. tb H37Rv and low cytotoxicity. Compared to Delamanid, these new compounds (6, 7, 45) demonstrated dramatically improved physicochemical properties and are suitable for further in vitro and in vivo evaluation.

引用

页码：2511 / 2515

页数：5

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