5-chloro-N-cyclooctylbenzofuran-2-carboxamide | 1432642-60-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 5-chloro-N-cyclooctylbenzofuran-2-carboxamide
• 英文别名: 5-chloro-N-cyclooctyl-benzofuran-2-carboxamide；5-chloro-N-cyclooctyl-1-benzofuran-2-carboxamide
• CAS: 1432642-60-8
• 化学式: C₁₇H₂₀ClNO₂
• 分子量: 305.804
• InChiKey: SBTRSJXIVBEZNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-氯苯并呋喃-2-甲酸乙酯 在 乙醇 、 1-羟基苯并三唑 、 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 3.67h， 生成 5-chloro-N-cyclooctylbenzofuran-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

文献信息

• Targeting Mycolic Acid Transport by Indole-2-carboxamides for the Treatment of <i>Mycobacterium abscessus</i> Infections
  作者：Alan P. Kozikowski、Oluseye K. Onajole、Jozef Stec、Christian Dupont、Albertus Viljoen、Matthias Richard、Tridib Chaira、Shichun Lun、William Bishai、V. Samuel Raj、Diane Ordway、Laurent Kremer

  DOI：10.1021/acs.jmedchem.7b00582

  日期：2017.7.13

  MmpL3. Biochemical analyses demonstrated that while de novo mycolic acid synthesis remained unaffected, the indolecarboxamides strongly inhibited the transport of trehalose monomycolate, resulting in the loss of trehalose dimycolate production and abrogating mycolylation of arabinogalactan. Our data introduce a hereto unexploited chemical structure class active against M. abscessus infections with promising

  脓肿分枝杆菌是一种快速生长的，具有多重耐药性的生物，已成为囊性纤维化（CF）患者的临床上重要的病原体。脓肿分支杆菌对最常见的抗生素的内在抗性严重限制了化学疗法的选择。在此，我们报道了一系列吲哚羧酰胺对脓肿分支杆菌的有效活性。铅化合物6和12在体外对广泛的脓肿分支杆菌均表现出强大的活性分离株和感染巨噬细胞。对吲哚甲酰胺的高抗性似乎与霉菌酸转运蛋白MmpL3中的A309P突变有关。生化分析表明，尽管从头霉菌酸的合成仍未受到影响，但吲哚甲酰胺强烈抑制了海藻糖一霉菌酸酯的运输，导致海藻糖二甲酸酯的产生损失并废除了阿拉伯半乳聚糖的霉菌酰化作用。我们的数据介绍了一种尚未利用的化学结构类别，可有效治疗脓肿分枝杆菌感染，并具有有望治疗CF患者的转化发展可能性。
• [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。
• 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.
• 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.