4-methoxy-N-(2-(piperidin-1-yl)thieno[2,3-d]thiazol-5-yl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-methoxy-N-(2-(piperidin-1-yl)thieno[2,3-d]thiazol-5-yl)benzamide
• 英文别名: 4-methoxy-N-(2-piperidin-1-ylthieno[2,3-d][1,3]thiazol-5-yl)benzamide
• 化学式: C₁₈H₁₉N₃O₂S₂
• 分子量: 373.5
• InChiKey: YZLKQVUKGCCYOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-2-(1-哌啶)-5-噻唑甲醛 在 盐酸 、 叠氮磷酸二苯酯 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 4-methoxy-N-(2-(piperidin-1-yl)thieno[2,3-d]thiazol-5-yl)benzamide
  参考文献：
  名称：

  Discovery of thienothiazolocarboxamide analogues as novel anti-tubercular agent

  摘要：

  In order to identify anti-tubercular agents with a novel scaffold, commercial libraries of small organic compounds were screened against a fluorescent strain of Mycobacterium tuberculosis H37Rv, using a dual phenotypic assay. Compounds were assessed against bacteria replicating in broth medium, as well as inside macrophages, and thienothiazolocarboxamide (TTCA) scaffold was identified as hit in both assays, with submicromolar inhibitory concentrations. Derivatives of TTCA were further synthesized and evaluated for their inhibitory effects on M.tuberculosis H37Rv. In the present study we report the structure-activity relationship of these TTCA derivatives. Compounds 28, 32 and 42 displayed good anti-tubercular activities, as well as favorable ADME and PK properties. Compound 42 exhibited excellent oral bioavailability in mice with high distribution to lungs, within 1 h. It was found to be efficacious in a dose dependent manner in a murine model of M. tuberculosis infection. Hence, compound 42 is now under evaluation as a potential lead candidate for treatment of tuberculosis.

  DOI：

  10.1016/j.bmc.2020.115797

文献信息

• [EN] ANTI-INFECTIVE COMPOUNDS<br/>[FR] COMPOSÉS ANTI-INFECTIEUX
  申请人：PASTEUR INSTITUT KOREA

  公开号：WO2015193506A1

  公开（公告）日：2015-12-23

  The present invention relates to small molecule compounds having the general formula (I): wherein A is a moiety selected from the group consisting of formulae (A) to (K) and their use in the treatment of bacterial infections, in particular Tuberculosis.

  本发明涉及具有通式（I）的小分子化合物，其中A是从式（A）到（K）组成的基团之一，并且其在治疗细菌感染，特别是结核病中的用途。
• ANTI-INFECTIVE COMPOUNDS
  申请人：Institut Pasteur Korea

  公开号：EP3157904B1

  公开（公告）日：2020-11-18
• Discovery of thienothiazolocarboxamide analogues as novel anti-tubercular agent
  作者：Guanghai Jin、Young Mi Kim、Aram Lee、Junghwan Choi、Sunhee Kang、Mooyoung Seo、Jeong Jea Seo、Sumi Lee、Juhee Kang、Jaeseung Kim、Sinyoung Park、Minjeong Woo、Virgínia Carla de Almeida Falcão、Honggun Lee、Jinyeong Heo、David Shum、Kaapjoo Park、Vincent Delorme、Inhee Choi

  DOI：10.1016/j.bmc.2020.115797

  日期：2020.12

  In order to identify anti-tubercular agents with a novel scaffold, commercial libraries of small organic compounds were screened against a fluorescent strain of Mycobacterium tuberculosis H37Rv, using a dual phenotypic assay. Compounds were assessed against bacteria replicating in broth medium, as well as inside macrophages, and thienothiazolocarboxamide (TTCA) scaffold was identified as hit in both assays, with submicromolar inhibitory concentrations. Derivatives of TTCA were further synthesized and evaluated for their inhibitory effects on M.tuberculosis H37Rv. In the present study we report the structure-activity relationship of these TTCA derivatives. Compounds 28, 32 and 42 displayed good anti-tubercular activities, as well as favorable ADME and PK properties. Compound 42 exhibited excellent oral bioavailability in mice with high distribution to lungs, within 1 h. It was found to be efficacious in a dose dependent manner in a murine model of M. tuberculosis infection. Hence, compound 42 is now under evaluation as a potential lead candidate for treatment of tuberculosis.