N-(2-adamantyl)-4,6-dimethyl-1H-indole-2-carboxamide | 1432641-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(2-adamantyl)-4,6-dimethyl-1H-indole-2-carboxamide
• CAS: 1432641-86-5
• 化学式: C₂₁H₂₆N₂O
• 分子量: 322.45
• InChiKey: LTVQSXCKQLSNNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3,5-二甲基苯肼盐酸盐 在 对甲苯磺酸 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 N-(2-adamantyl)-4,6-dimethyl-1H-indole-2-carboxamide
  参考文献：
  名称：

  具有全抗分枝杆菌活性的吲哚-2-甲酰胺的设计、合成及评价

  摘要：

  目前针对非结核分枝杆菌（NTM）和结核病（TB）的治疗方案通常需要使用多种药物进行长期治疗，其中一些是广谱抗生素。尽管抗菌化合物取得了一些进展，但仍然需要针对特定​​分枝杆菌靶点的抗生素治疗。研究表明，MmpL3 是分枝杆菌酸转运至分枝杆菌细胞包膜所需的重要转运蛋白。在这里，我们合成了一系列 indole-2-carboxamides，它们可抑制 MmpL3，并对分枝杆菌物种具有有效的泛活性。这些化合物针对几种快速和缓慢生长的分枝杆菌进行了测试，包括脓肿分枝杆菌、马西分枝杆菌、博氏分枝杆菌、龟分枝杆菌、结核分枝杆菌、鸟分枝杆菌、爪蟾分枝杆菌和耻垢分枝杆菌。这些基于吲哚的化合物的靶标使其对分枝杆菌具有选择性，同时对金黄色葡萄球菌或铜绿假单胞菌没有表现出临床相关的杀菌活性。这些化合物针对人类细胞系 THP-1 进行了测试，显示出最小的体外细胞毒性和良好的选择性指数。显示和讨论的数据表明，先导吲哚-2-甲酰胺是作为

  DOI：

  10.1016/j.bmc.2017.05.015

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。
• INDOLE-BASED THERAPEUTICS
  申请人：Creighton University

  公开号：US20180036283A1

  公开（公告）日：2018-02-08

  Provided herein are indole-2-carboxamide compounds useful for the treatment of non-tuberculosis bacterial infections. Exemplary compounds provided herein are useful for the treatment of non-tuberculosis mycobacterial infections. Methods for preparing the indole-2-carboxamide compounds are also provided.

  本文提供了对非结核分枝杆菌感染治疗有用的吲哚-2-羧酰胺化合物。本文提供的示例化合物对非结核分枝杆菌感染的治疗有用。同时提供了制备吲哚-2-羧酰胺化合物的方法。
• Indole-based therapeutics
  申请人：Creighton University

  公开号：US10383848B2

  公开（公告）日：2019-08-20

  Provided herein are indole-2-carboxamide compounds useful for the treatment of non-tuberculosis bacterial infections. Exemplary compounds provided herein are useful for the treatment of non-tuberculosis mycobacterial infections. Methods for preparing the indole-2-carboxamide compounds are also provided.

  本文提供的吲哚-2-甲酰胺化合物可用于治疗非结核性细菌感染。本文提供的示例化合物可用于治疗非结核分枝杆菌感染。还提供了制备吲哚-2-甲酰胺化合物的方法。
• 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.
• INHIBITORS OF DRUG-RESISTANT MYCOBACTERIUM TUBERCULOSIS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20170044100A1

  公开（公告）日：2017-02-16

  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.