ethyl 2-dimethylaminothieno<2,3-d>thiazole-5-carboxylate | 141764-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并噻唑类
• 英文名称: ethyl 2-dimethylaminothieno<2,3-d>thiazole-5-carboxylate
• 英文别名: Ethyl 2-(dimethylamino)thieno[2,3-d][1,3]thiazole-5-carboxylate
• CAS: 141764-90-1
• 化学式: C₁₀H₁₂N₂O₂S₂
• mdl: MFCD18453566
• 分子量: 256.349
• InChiKey: MRHJFVOQQHBNQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  98.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲氧苯胺 、 ethyl 2-dimethylaminothieno<2,3-d>thiazole-5-carboxylate 在 三甲基铝 作用下， 以 甲苯 为溶剂， 生成 2-(dimethylamino)-N-(4-methoxyphenyl)thieno[2,3-d]thiazole-5-carboxamide
  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
• 作为产物：
  描述：

  4-氯-2-二甲基氨基-1,3-噻唑-5-甲醛 、 巯基乙酸乙酯 在 三乙胺 、 sodium ethanolate 作用下， 以 二甲基亚砜 、 乙醇 为溶剂， 反应 3.0h， 生成 ethyl 2-dimethylaminothieno<2,3-d>thiazole-5-carboxylate
  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

• Athmani, Salah; Farhat, Mahmoud F.; Iddon, Brian, Journal of the Chemical Society. Perkin transactions I, 1992, # 8, p. 973 - 978
  作者：Athmani, Salah、Farhat, Mahmoud F.、Iddon, Brian

  DOI：——

  日期：——
• 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.