N-methyl-7-nitro-2-(piperidine-1-carbonyl)benzo[d]thiazole-5-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: N-methyl-7-nitro-2-(piperidine-1-carbonyl)benzo[d]thiazole-5-carboxamide
• 英文别名: N-methyl-7-nitro-2-(piperidine-1-carbonyl)-1,3-benzothiazole-5-carboxamide
• 化学式: C₁₅H₁₆N₄O₄S
• 分子量: 348.382
• InChiKey: BPJSCOVCTXPMQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-chloro-3,5-dinitro-N-methylbenzamide 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 N-methyl-7-nitro-2-(piperidine-1-carbonyl)benzo[d]thiazole-5-carboxamide
  参考文献：
  名称：

  Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure–activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose 2′-oxidase

  摘要：

  We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1), the key enzyme involved in arabinogalactan synthesis. Specific target linkage and mode of binding were established using co-crystallization and protein mass spectrometry studies. Most importantly, the current study provides insights on the utilization of systematic medicinal chemistry approaches to mitigate safety liabilities while improving potency during progression from an initial genotoxic hit, the benzothiazole N-oxides (BTOs) to the lead-like AMES negative, crowded benzothiazoles (cBTs). These findings offer opportunities for development of safe clinical candidates against tuberculosis. The design strategy adopted could find potential application in discovery of safe drugs in other therapy areas too. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.11.017

文献信息

• Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure–activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose 2′-oxidase
  作者：Sudhir Landge、Amrita B. Mullick、Kavitha Nagalapur、João Neres、Venkita Subbulakshmi、Kannan Murugan、Anirban Ghosh、Claire Sadler、Mick D. Fellows、Vaishali Humnabadkar、Jyothi Mahadevaswamy、Prakash Vachaspati、Sreevalli Sharma、Parvinder Kaur、Meenakshi Mallya、Suresh Rudrapatna、Disha Awasthy、Vasan K. Sambandamurthy、Florence Pojer、Stewart T. Cole、Tanjore S. Balganesh、Bheemarao G. Ugarkar、V. Balasubramanian、Balachandra S. Bandodkar、Manoranjan Panda、Vasanthi Ramachandran

  DOI：10.1016/j.bmc.2015.11.017

  日期：2015.12

  We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1), the key enzyme involved in arabinogalactan synthesis. Specific target linkage and mode of binding were established using co-crystallization and protein mass spectrometry studies. Most importantly, the current study provides insights on the utilization of systematic medicinal chemistry approaches to mitigate safety liabilities while improving potency during progression from an initial genotoxic hit, the benzothiazole N-oxides (BTOs) to the lead-like AMES negative, crowded benzothiazoles (cBTs). These findings offer opportunities for development of safe clinical candidates against tuberculosis. The design strategy adopted could find potential application in discovery of safe drugs in other therapy areas too. (c) 2015 Elsevier Ltd. All rights reserved.