4-氯-2-(1-哌啶)-5-噻唑甲醛 | 883107-61-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-氯-2-(1-哌啶)-5-噻唑甲醛
• 中文别名: 4-氯-2-(1-哌啶-4-醇)-5-噻唑甲醛
• 英文名称: 4-Chloro-2-(4-hydroxypiperidin-1-YL)thiazole-5-carbaldehyde
• 英文别名: 4-chloro-2-(4-hydroxypiperidin-1-yl)-1,3-thiazole-5-carbaldehyde
• CAS: 883107-61-7
• 化学式: C₉H₁₁ClN₂O₂S
• 分子量: 246.718
• InChiKey: QXAQQHPRPGAHJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8°C，惰性气体氛围

反应信息

• 作为反应物：
  描述：

  4-氯-2-(1-哌啶)-5-噻唑甲醛 在 三甲基铝 、 三乙胺 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 3.0h， 生成 N-(2-methylbenzo[d]oxazol-5-yl)-2-(4-hydroxypiperidin-1-yl)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-羟基哌啶 、 2,4-二氯噻唑-5-甲醛 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 4-氯-2-(1-哌啶)-5-噻唑甲醛
  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

• Fragment evolution for GPCRs: the role of secondary binding sites in optimization
  作者：Florent Chevillard、Ádám Kelemen、Jillian G. Baker、Vivien A. Aranyodi、Frank Balzer、Peter Kolb、György M. Keserű

  DOI：10.1039/d1cc04636e

  日期：——

  We developed a docking-based fragment evolution approach that extends orthosteric fragments towards a less conserved secondary binding pocket of GPCRs. Evaluating 13 000 extensions for the β1- and β2-adrenergic receptors we synthesized and tested 112 bitopic molecules. Our results confirmed the positive contribution of the secondary binding pocket to both potency and selectivity optimizations.

  我们开发了一种基于对接的片段进化方法，将正构片段扩展到不太保守的 GPCR 二级结合口袋。我们合成并测试了 112 个双位分子，评估了 13 000 次 β 1 - 和 β 2 -肾上腺素能受体的延伸。我们的结果证实了二级结合口袋对效力和选择性优化的积极贡献。
• 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.