5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol | 1239963-74-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol
• 英文别名: 5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2(3H)-thione；4-[2-(3,4-dimethoxyphenyl)propan-2-yl]-3-(4-fluorophenyl)-1H-imidazole-2-thione
• CAS: 1239963-74-6
• 化学式: C₂₀H₂₁FN₂O₂S
• 分子量: 372.463
• InChiKey: MXOVKXITXPTOES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 7.0h， 生成 5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-2-((2-phenoxyethyl)thio)-1H-imidazole
  参考文献：
  名称：

  Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

  摘要：

  TGR5 is a G protein -coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide -1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound 6g was found to have potent glucose lowering effects in vivo during an oral glucose tolerance test in DIO C57 mice with ED50 of 7.9 mg/kg and ED90 of 29.2 mg/ kg.

  DOI：

  10.1021/acsmedchemlett.5b00323
• 作为产物：
  描述：

  3-(3,4-dimethoxyphenyl)-3-methylbutan-2-ol 在 草酰氯 、 乌洛托品 、 tetra-N-butylammonium tribromide 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 64.5h， 生成 5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol
  参考文献：
  名称：

  Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

  摘要：

  TGR5 is a G protein -coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide -1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound 6g was found to have potent glucose lowering effects in vivo during an oral glucose tolerance test in DIO C57 mice with ED50 of 7.9 mg/kg and ED90 of 29.2 mg/ kg.

  DOI：

  10.1021/acsmedchemlett.5b00323

文献信息

• [EN] TRIAZOLE AND IMIDAZOLE DERIVATIVES FOR USE AS TGR5 AGONISTS IN THE TREATMENT OF DIABETES AND OBESITY<br/>[FR] DÉRIVÉS DE TRIAZOLE ET D'IMIDAZOLE DESTINÉS À ÊTRE UTILISÉS EN TANT QU'AGONISTES DE TGR5 DANS LE TRAITEMENT DU DIABÈTE ET DE L'OBÉSITÉ
  申请人：EXELIXIS INC

  公开号：WO2010093845A1

  公开（公告）日：2010-08-19

  The present invention comprises TGR5 agonists of structural formula I, wherein X, R1, R2, and R5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprises composition comprising the compounds, N-oxides, and/or pharmaceutically acceptable salts thereof. The invention also comprises use of the compounds and compositions for treating diseases in which TGR5 is a mediator or is implicated. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases in which TGR5 is a mediator or is implicated.

  本发明包括结构式I的TGR5激动剂，其中X、R1、R2和R5在此处定义，以及它们的N-氧化物和其药学上可接受的盐。该发明还包括包含这些化合物、N-氧化物和/或其药学上可接受的盐的组合物。该发明还包括利用这些化合物和组合物治疗TGR5是介质或涉及的疾病。该发明还包括利用这些化合物制造药物，特别是用于治疗TGR5是介质或涉及的疾病。
• [EN] 2-THIO-IMIDAZOLE DERIVATIVES AS TGR5 MODULATORS<br/>[FR] DÉRIVÉS DE 2-THIOL-IMIDAZOLE UTILES COMME MODULATEURS DE TGR5
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2013054338A1

  公开（公告）日：2013-04-18

  The present invention relates to compounds of the general Formula I their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers, prodrugs, their N-oxide, metabolites, polymorphs, use of these compounds in medicine for treating diabetes (TGR5 modulators) and the intermediates involved in their preparation.

  本发明涉及一般式I的化合物及其药学上可接受的盐、药学上可接受的溶剂化合物、对映体、非对映体、前药、它们的N-氧化物、代谢物、多型体，在医学上用于治疗糖尿病（TGR5调节剂）以及其制备中涉及的中间体。
• Practical and Efficient Synthesis of 2-Thio-imidazole Derivative—<b>ZY12201</b>: A Potent TGR5 Agonist
  作者：Vivek M. Joshi、Chandrakant Sojitra、Santosh Sasane、Mrigendra Shukla、Rakesh Chauhan、Vipin Chaubey、Sarika Jain、Kalpesh Shah、Hemant Mande、Shubhangi Soman、Padmaja Sudhakar Pamidimukkala、Shailesh R. Shah、Bipin Pandey、Kumar K. Singh、Sameer Agarwal

  DOI：10.1021/acs.oprd.0c00234

  日期：2020.8.21

  development for the synthesis of ZY12201, a novel TGR5 receptor agonist, as a potential clinical candidate is described. A practical, efficient, and scalable synthetic route provided ZY12201 in seven steps and 32% overall yield. The key step involves an inexpensive acetic acid-mediated cyclization of thiourea 6 for the construction of 2-thio-imidazole derivative 7. The developed process demonstrated cost-effective

  描述了用于潜在的临床候选物ZY12201（一种新型TGR5受体激动剂）的合成的早期可扩展方法开发。一条实用，高效且可扩展的合成路线以七个步骤提供了ZY12201，总产率为32％。关键步骤涉及廉价的乙酸介导的硫脲6的环化反应，以构建2-硫代咪唑衍生物7。所开发的工艺证明了ZY12201具有成本效益，高产量，可缩放规模且环保的特点。这种高产途径使我们能够快速合成大量纯度为99％的ZY12201，以支持体内和毒性研究。
• TRIAZOLE AND IMIDAZOLE DERIVATIVES FOR USE AS TGR5 AGONISTS IN THE TREATMENT OF DIABETES AND OBESITY
  申请人：Bollu Venkataiah

  公开号：US20120040985A1

  公开（公告）日：2012-02-16

  The present invention comprises TGR5 agonists of structural formula I, wherein X, R 1 , R 2 , and R 5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprises composition comprising the compounds, N-oxides, and/or pharmaceutically acceptable salts thereof. The invention also comprises use of the compounds and compositions for treating diseases in which TGR5 is a mediator or is implicated. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases in which TGR5 is a mediator or is implicated.

  本发明涉及结构式I的TGR5激动剂，其中X、R1、R2和R5如本文所定义，以及它们的N-氧化物和药学上可接受的盐。本发明还包括包含这些化合物、N-氧化物和/或药学上可接受的盐的组合物。本发明还包括使用这些化合物和组合物治疗TGR5是介质或被牵涉的疾病。本发明还包括使用这些化合物制造药物，特别是用于治疗TGR5是介质或被牵涉的疾病。
• Triazole and imidazole derivatives for use as TGR5 agonists in the treatment of diabetes and obesity
  申请人：Bollu Venkataiah

  公开号：US08785488B2

  公开（公告）日：2014-07-22

  The present invention comprises TGR5 agonists of structural formula I, wherein X, R1, R2, and R5 are defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprises composition comprising the compounds, N-oxides, and/or pharmaceutically acceptable salts thereof. The invention also comprises use of the compounds and compositions for treating diseases in which TGR5 is a mediator or is implicated. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases in which TGR5 is a mediator or is implicated.

  本发明包括结构式I的TGR5激动剂，其中X、R1、R2和R5在此定义，以及其N-氧化物和药学上可接受的盐。本发明还包括包含这些化合物、N-氧化物和/或药学上可接受的盐的组合物。本发明还包括使用这些化合物和组合物治疗TGR5是介质或涉及的疾病的用途。本发明还包括使用这些化合物制造药品，特别是用于治疗TGR5是介质或涉及的疾病。