5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-2-((2-phenoxyethyl)thio)-1H-imidazole | 1430211-24-7

• 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)-2-((2-phenoxyethyl)thio)-1H-imidazole
• 英文别名: 5-[2-(3,4-Dimethoxyphenyl)propan-2-yl]-1-(4-fluorophenyl)-2-(2-phenoxyethylsulfanyl)imidazole；5-[2-(3,4-dimethoxyphenyl)propan-2-yl]-1-(4-fluorophenyl)-2-(2-phenoxyethylsulfanyl)imidazole
• CAS: 1430211-24-7
• 化学式: C₂₈H₂₉FN₂O₃S
• 分子量: 492.614
• InChiKey: LWMPGIHLGCXIOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(3,4-dimethoxyphenyl)-3-methylbutan-2-one 在 乌洛托品 、 tetra-N-butylammonium tribromide 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 69.0h， 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

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。
• Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist
  作者：Sameer Agarwal、Amit Patil、Umesh Aware、Prashant Deshmukh、Brijesh Darji、Santosh Sasane、Kalapatapu V. V. M. Sairam、Priyanka Priyadarsiny、Poonam Giri、Harilal Patel、Suresh Giri、Mukul Jain、Ranjit C. Desai

  DOI：10.1021/acsmedchemlett.5b00323

  日期：2016.1.14

  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.