Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis: Part 2. Synthesis of rigid pyrazolones

被引：154

作者：

Castagnolo, Daniele ^{[1
]}

Manetti, Fabrizio ^{[1
]}

Radi, Marco ^{[1
]}

Bechi, Beatrice ^{[1
]}

Pagano, Mafalda ^{[1
]}

De Logu, Alessandro ^{[2
]}

Meleddu, Rita ^{[2
]}

Saddi, Manuela ^{[2
]}

Botta, Maurizio ^{[1
]}

机构：

[1] Univ Siena, I-53100 Siena, Italy

[2] Univ Cagliari, Dipartimento Sci & Tecnol Biomed, Sez Microbiol Med, I-09123 Cagliari, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 15期

关键词：

Tuberculosis; Pyrazolones; Pyrazole; SAR study; ANTIMYCOBACTERIAL AGENTS; DERIVATIVES; BM212;

D O I：

10.1016/j.bmc.2009.05.058

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 mu g/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity. (C) 2009 Elsevier Ltd. All rights reserved.

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收藏

页码：5716 / 5721

页数：6

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