2-((2-((2,6-difluorobenzyl)oxy)ethyl)thio)-5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole | 1430210-40-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-((2-((2,6-difluorobenzyl)oxy)ethyl)thio)-5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole
• 英文别名: 2-[2-[(2,6-Difluorophenyl)methoxy]ethylsulfanyl]-5-[2-(3,4-dimethoxyphenyl)propan-2-yl]-1-(4-fluorophenyl)imidazole；2-[2-[(2,6-difluorophenyl)methoxy]ethylsulfanyl]-5-[2-(3,4-dimethoxyphenyl)propan-2-yl]-1-(4-fluorophenyl)imidazole
• CAS: 1430210-40-4
• 化学式: C₂₉H₂₉F₃N₂O₃S
• 分子量: 542.622
• InChiKey: YYUYPNGMKLCURX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,6-二氟溴苄 、 5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol 、 2-溴乙醇 在 potassium carbonate 作用下， 以 丙酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以61%的产率得到2-((2-((2,6-difluorobenzyl)oxy)ethyl)thio)-5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole
  参考文献：
  名称：

  Evaluation of novel TGR5 agonist in combination with Sitagliptin for possible treatment of type 2 diabetes

  摘要：

  TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes. (C)2018C)2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.04.011

文献信息

• [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。
• Evaluation of novel TGR5 agonist in combination with Sitagliptin for possible treatment of type 2 diabetes
  作者：Sameer Agarwal、Santosh Sasane、Jeevan Kumar、Prashant Deshmukh、Hitesh Bhayani、Poonam Giri、Suresh Giri、Shubhangi Soman、Neelima Kulkarni、Mukul Jain

  DOI：10.1016/j.bmcl.2018.04.011

  日期：2018.6

  TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes. (C)2018C)2018 Elsevier Ltd. All rights reserved.