5-(2,4-dichlorophenyl)-2-(ethoxycarbonyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylic (ethyl carbonic) anhydride | 896459-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(2,4-dichlorophenyl)-2-(ethoxycarbonyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylic (ethyl carbonic) anhydride
• CAS: 896459-37-3
• 化学式: C₂₀H₁₇Cl₂N₃O₆
• 分子量: 466.277
• InChiKey: HWFJXTHUZHYTEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  109.09
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5-(2,4-dichlorophenyl)-2-(ethoxycarbonyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylic (ethyl carbonic) anhydride 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以430 mg的产率得到ethyl 5-(2,4-dichlorophenyl)-6-(hydroxymethyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxylate
  参考文献：
  名称：

  Discovery of 6-(Aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as Potent, Selective Dipeptidyl Peptidase-4 (DPP4) Inhibitors

  摘要：

  Continued structure activity relationship (SA R) exploration within our previously disclosed azolopyrimidine containing dipeptidyl peptidase-4 (DPP4) inhibitors led us to focus on an imidazolopyrimidine series in particular. Further study revealed that by replacing the aryl substitution on the imidazole ring with a more polar carboxylic ester or amide, these compounds displayed not only increased DPP4 binding activity but also significantly reduced human ether-a-go-go related gene (hERG) and sodium channel inhibitory activities. Additional incremental adjustment of polarity led to permeable molecules which exhibited favorable pharmacokinetic (PK) profiles in preclinical animal species. The active site binding mode of these compounds was determined by X-ray crystallography as exemplified by amide 24c. A subsequent lead molecule from this series, (+)-6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(1-ethyl-1H-pyrazol-5-yl)-7-methylimidazo[1,2-c]pyrimidine-2-carboxamide (24s), emerged as a potent, selective DPP4 inhibitor that displayed excellent PK profiles and in vivo efficacy in ob/ob mice.

  DOI：

  10.1021/jm100634a
• 作为产物：
  描述：

  5-(2,4-dichlorophenyl)-2-(ethoxycarbonyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylic acid 、 氯甲酸乙酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 5-(2,4-dichlorophenyl)-2-(ethoxycarbonyl)-7-methylimidazo[1,2-a]pyrimidine-6-carboxylic (ethyl carbonic) anhydride
  参考文献：
  名称：

  Discovery of 6-(Aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as Potent, Selective Dipeptidyl Peptidase-4 (DPP4) Inhibitors

  摘要：

  Continued structure activity relationship (SA R) exploration within our previously disclosed azolopyrimidine containing dipeptidyl peptidase-4 (DPP4) inhibitors led us to focus on an imidazolopyrimidine series in particular. Further study revealed that by replacing the aryl substitution on the imidazole ring with a more polar carboxylic ester or amide, these compounds displayed not only increased DPP4 binding activity but also significantly reduced human ether-a-go-go related gene (hERG) and sodium channel inhibitory activities. Additional incremental adjustment of polarity led to permeable molecules which exhibited favorable pharmacokinetic (PK) profiles in preclinical animal species. The active site binding mode of these compounds was determined by X-ray crystallography as exemplified by amide 24c. A subsequent lead molecule from this series, (+)-6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(1-ethyl-1H-pyrazol-5-yl)-7-methylimidazo[1,2-c]pyrimidine-2-carboxamide (24s), emerged as a potent, selective DPP4 inhibitor that displayed excellent PK profiles and in vivo efficacy in ob/ob mice.

  DOI：

  10.1021/jm100634a