ethyl 4-hydroxy-2-(pyridin-2-yl)thiazole-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-hydroxy-2-(pyridin-2-yl)thiazole-5-carboxylate
• 化学式: C₁₁H₁₀N₂O₃S
• 分子量: 250.278
• InChiKey: MVHXDDPUVDJBML-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  72.31
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-hydroxy-2-(pyridin-2-yl)thiazole-5-carboxylate 在 吡啶 、 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 26.0h， 生成 ethyl 4-(4-(benzylamino)piperidin-1-yl)-2-(pyridin-2-yl)thiazole-5-carboxylate
  参考文献：
  名称：

  Thiazole–aminopiperidine hybrid analogues: Design and synthesis of novel Mycobacterium tuberculosis GyrB inhibitors

  摘要：

  A series of ethyl-4-(4-((substituted benzyl)amino)piperidin-1-yl)-2-(phenyl/pyridyl)thiazole-5-carboxy lates was designed by molecular hybridization and synthesized from aryl thioamides in five steps. The compounds were evaluated for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antituberculosis activity and cytotoxicity. Among the twenty four compounds studied, ethyl-4-(44(4-fluorobenzypamino)piperidin-1-y1)-2-phenylthiazole-5-carboxylate (14) was found to be the promising compound which showed activity against all test with MS GyrB IC50 of 24.0 +/- 2.1 mu M, 79% inhibition of MTB DNA gyrase at 50 tM, MTB MIC of 28.44 mu M, and not cytotoxic at 50 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.09.025
• 作为产物：
  描述：

  吡啶-2-羧硫酸胺 、 溴代丙二酸二乙酯 以 乙醇 为溶剂， 生成 ethyl 4-hydroxy-2-(pyridin-2-yl)thiazole-5-carboxylate
  参考文献：
  名称：

  作为高效TGR5激动剂的4-苯氧基噻唑-5-甲酰胺的发现及其与构效关系的研究。

  摘要：

  一种由武田G蛋白偶联受体5（TGR5）激动剂刺激内源性胰高血糖素样肽1（GLP-1）分泌的新疗法可能是治疗2型糖尿病的更好选择。一系列的4-苯氧基噻唑-5-羧酰胺被开发为高效的TGR5激动剂，使用了基于4-苯氧基烟酰胺骨架的生物等位取代策略。广泛研究了底部苯环和噻唑环上的结构-活性关系，并且2-甲基-噻唑衍生物30c和30e在体外对人TGR5表现出最佳的效价，EC50值约为1 nM。虽然具有出色的体外效能，但2-甲基噻唑在高微粒体清除率方面存在缺陷。

  DOI：

  10.1248/cpb.c15-00905

文献信息

• Enabling the (3 + 2) cycloaddition reaction in assembling newer anti-tubercular lead acting through the inhibition of the gyrase ATPase domain: lead optimization and structure activity profiling
  作者：Variam Ullas Jeankumar、Rudraraju Srilakshmi Reshma、Renuka Janupally、Shalini Saxena、Jonnalagadda Padma Sridevi、Brahmam Medapi、Pushkar Kulkarni、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1039/c4ob02049a

  日期：——

  Exploring the Gyrase ATPase platform to tailor novel anti-tubercular leads.

  探索旋转酶ATP酶平台，以定制新型抗结核药物前导。
• Synthesis and structure–activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors
  作者：Andreas Reichelt、Julie M. Bailis、Michael D. Bartberger、Guomin Yao、Hong Shu、Matthew R. Kaller、John G. Allen、Margaret F. Weidner、Kathleen S. Keegan、Jennifer H. Dao

  DOI：10.1016/j.ejmech.2014.04.013

  日期：2014.6

  The Cell division cycle 7 (Cdc7) protein kinase is essential for DNA replication and maintenance of genome stability. We systematically explored thiazole-based compounds as inhibitors of Cdc7 kinase activity in cancer cells. Our studies resulted in the identification of a potent, selective Cdc7 inhibitor that decreased phosphorylation of the direct substrate MCM2 in vitro and in vivo, and inhibited DNA synthesis and cell viability in vitro.
• Discovery and Structure–Activity Relationship Study of 4-Phenoxythiazol-5-carboxamides as Highly Potent TGR5 Agonists
  作者：Zhixiang Chen、Mengmeng Ning、Qingan Zou、Hua Cao、Yangliang Ye、Ying Leng、Jianhua Shen

  DOI：10.1248/cpb.c15-00905

  日期：——

  secretion by Takeda G-protein-coupled receptor 5 (TGR5) agonists might be a superior alternative for the treatment of type 2 diabetes mellitus. A series of 4-phenoxythiazol-5-carboxamides were developed as highly potent TGR5 agonists using a bioisosteric replacement strategy based on the scaffold of 4-phenoxynicotinamides. The structure-activity relationship on the bottom phenyl ring and the thiazole ring

  一种由武田G蛋白偶联受体5（TGR5）激动剂刺激内源性胰高血糖素样肽1（GLP-1）分泌的新疗法可能是治疗2型糖尿病的更好选择。一系列的4-苯氧基噻唑-5-羧酰胺被开发为高效的TGR5激动剂，使用了基于4-苯氧基烟酰胺骨架的生物等位取代策略。广泛研究了底部苯环和噻唑环上的结构-活性关系，并且2-甲基-噻唑衍生物30c和30e在体外对人TGR5表现出最佳的效价，EC50值约为1 nM。虽然具有出色的体外效能，但2-甲基噻唑在高微粒体清除率方面存在缺陷。
• Thiazole–aminopiperidine hybrid analogues: Design and synthesis of novel Mycobacterium tuberculosis GyrB inhibitors
  作者：Variam Ullas Jeankumar、Janupally Renuka、Peddi Santosh、Vijay Soni、Jonnalagadda Padma Sridevi、Priyanka Suryadevara、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.ejmech.2013.09.025

  日期：2013.12

  A series of ethyl-4-(4-((substituted benzyl)amino)piperidin-1-yl)-2-(phenyl/pyridyl)thiazole-5-carboxy lates was designed by molecular hybridization and synthesized from aryl thioamides in five steps. The compounds were evaluated for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antituberculosis activity and cytotoxicity. Among the twenty four compounds studied, ethyl-4-(44(4-fluorobenzypamino)piperidin-1-y1)-2-phenylthiazole-5-carboxylate (14) was found to be the promising compound which showed activity against all test with MS GyrB IC50 of 24.0 +/- 2.1 mu M, 79% inhibition of MTB DNA gyrase at 50 tM, MTB MIC of 28.44 mu M, and not cytotoxic at 50 mu M. (C) 2013 Elsevier Masson SAS. All rights reserved.