4,6-dimethyl-2-(trichloromethyl)-1H-benzimidazole | 1432645-36-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4,6-dimethyl-2-(trichloromethyl)-1H-benzimidazole
• CAS: 1432645-36-7
• 化学式: C₁₀H₉Cl₃N₂
• 分子量: 263.554
• InChiKey: PJESACKCIOAJMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,6-dimethyl-2-(trichloromethyl)-1H-benzimidazole 在 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.17h， 生成 N-(1-adamantyl)-4,6-dimethyl-1H-benzo[d]imidazole-2-carboxamide
  参考文献：
  名称：

  Preliminary Structure–Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains

  摘要：

  Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure activity relationships (SARs). These efforts led to the identification of three molecules (12-14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis, with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay.

  DOI：

  10.1021/jm4003878
• 作为产物：
  描述：

  1,1,1-三氯丙烷-2-酮肟 、 3,5-二甲基-1,2-苯二胺 在 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 4,6-dimethyl-2-(trichloromethyl)-1H-benzimidazole
  参考文献：
  名称：

  [EN] INHIBITORS OF DRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS
  [FR] INHIBITEURS DE MYCOBACTERIUM TUBERCULOSIS RÉSISTANT AUX MÉDICAMENTS

  摘要：

  本发明提供了用于治疗结核病的新型吲哚酰胺化合物，包括用于治疗耐药性M-结核病的药物，含有吲哚酰胺的组合物以及使用吲哚酰胺与其他生物活性剂联合治疗需求的受试者的结核病的方法。

  公开号：

  WO2015164482A1

文献信息

• [EN] INHIBITORS OF DRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS<br/>[FR] INHIBITEURS DE MYCOBACTERIUM TUBERCULOSIS RÉSISTANT AUX MÉDICAMENTS
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2015164482A1

  公开（公告）日：2015-10-29

  The present invention provides novel indoleamide compounds for treating tuberculosis, including drug-resistant M-tuberculosis, compositions comprising the indoleamides and methods of using the indoleamides in conjunction with other biologically active agents for the treatment of tuberculosis in a subject in need thereof.

  本发明提供了用于治疗结核病的新型吲哚酰胺化合物，包括用于治疗耐药性M-结核病的药物，含有吲哚酰胺的组合物以及使用吲哚酰胺与其他生物活性剂联合治疗需求的受试者的结核病的方法。
• Preliminary Structure–Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
  作者：Oluseye K. Onajole、Marco Pieroni、Suresh K. Tipparaju、Shichun Lun、Jozef Stec、Gang Chen、Hendra Gunosewoyo、Haidan Guo、Nicole C. Ammerman、William R. Bishai、Alan P. Kozikowski

  DOI：10.1021/jm4003878

  日期：2013.5.23

  Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure activity relationships (SARs). These efforts led to the identification of three molecules (12-14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis, with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay.