6-[5-(4-Ethyl-piperazine-1-sulfonyl)-2-propoxy-benzoylamino]-3-(3-fluoro-benzyl)-3H-benzoimidazole-5-carboxylic acid amide | 1026317-57-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-[5-(4-Ethyl-piperazine-1-sulfonyl)-2-propoxy-benzoylamino]-3-(3-fluoro-benzyl)-3H-benzoimidazole-5-carboxylic acid amide
• 英文别名: 6-[[5-(4-Ethylpiperazin-1-yl)sulfonyl-2-propoxybenzoyl]amino]-3-[(3-fluorophenyl)methyl]benzimidazole-5-carboxamide
• CAS: 1026317-57-6
• 化学式: C₃₁H₃₅FN₆O₅S
• 分子量: 622.721
• InChiKey: HLJNEHRUOPWECK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6-[5-(4-Ethyl-piperazine-1-sulfonyl)-2-propoxy-benzoylamino]-3-(3-fluoro-benzyl)-3H-benzoimidazole-5-carboxylic acid amide 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 生成 1-[[3-[1-[(3-fluorophenyl)methyl]-7,8-dihydro-8-oxo-1H-imidazo[4,5-g]quinazolin-6-yl]-4-propoxyphenyl]sulfonyl]-4-ethylpiperazine
  参考文献：
  名称：

  Optimization of Substituted N-3-Benzylimidazoquinazolinone Sulfonamides as Potent and Selective PDE5 Inhibitors

  摘要：

  A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described.

  DOI：

  10.1021/jm000336j
• 作为产物：
  描述：

  2-n-丙基氧基苯甲酸甲酯 在 氯磺酸 、 4-二甲氨基吡啶 、 lithium hydroxide 、 氯化亚砜 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 6-[5-(4-Ethyl-piperazine-1-sulfonyl)-2-propoxy-benzoylamino]-3-(3-fluoro-benzyl)-3H-benzoimidazole-5-carboxylic acid amide
  参考文献：
  名称：

  Optimization of Substituted N-3-Benzylimidazoquinazolinone Sulfonamides as Potent and Selective PDE5 Inhibitors

  摘要：

  A previous report from these laboratories identified the N-3-benzylimidazoquinazolinone nucleus as a more selective PDE5 inhibitor template compared to the pyrazolopyrimidine of sildenafil. This paper describes in detail the structure-activity relationships of a set of sulfonamide analogues, several of which are both more potent and more selective PDE5 inhibitors in vitro than sildenafil. The synthesis, in vitro enzyme activity and selectivity, and in vitro functional and preclinical pharmacokinetic assessment of molecules in this series are described.

  DOI：

  10.1021/jm000336j