ethyl 3-(3,4-difluorophenyl)-5-(4-methoxyphenyl)-3,4-dihydro-2H-pyrrole-4-carboxylate | 1027967-97-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: ethyl 3-(3,4-difluorophenyl)-5-(4-methoxyphenyl)-3,4-dihydro-2H-pyrrole-4-carboxylate
• CAS: 1027967-97-0
• 化学式: C₂₀H₁₉F₂NO₃
• 分子量: 359.373
• InChiKey: CIYHCROZXHIKID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3,4-difluorophenyl)-5-(4-methoxyphenyl)-3,4-dihydro-2H-pyrrole-4-carboxylate 在 盐酸 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 、 ethyl (2R,3S,4S)-4-(3,4-difluorophenyl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylate 、 、
  参考文献：
  名称：

  Potent and Selective Non-Benzodioxole-Containing Endothelin-A Receptor Antagonists

  摘要：

  The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N-dibutylacetamido)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid acid (A-127722). This is a potent antagonist, binding to the ET(A) and ET(B) receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p-anisyl, were potent compounds with IC(50)s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ET(A) receptor. Additionally, the compounds showed enhanced selectivity, binding to the ET(B) receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.

  DOI：

  10.1021/jm960077r
• 作为产物：
  描述：

  (E)-1,2-difluoro-4-(2-nitrovinyl)benzene 在 W-2 Raney Ni 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 乙酸乙酯 、 异丙醇 为溶剂， 生成 ethyl 3-(3,4-difluorophenyl)-5-(4-methoxyphenyl)-3,4-dihydro-2H-pyrrole-4-carboxylate
  参考文献：
  名称：

  Potent and Selective Non-Benzodioxole-Containing Endothelin-A Receptor Antagonists

  摘要：

  The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N-dibutylacetamido)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid acid (A-127722). This is a potent antagonist, binding to the ET(A) and ET(B) receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p-anisyl, were potent compounds with IC(50)s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ET(A) receptor. Additionally, the compounds showed enhanced selectivity, binding to the ET(B) receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.

  DOI：

  10.1021/jm960077r

文献信息

• Potent and Selective Non-Benzodioxole-Containing Endothelin-A Receptor Antagonists
  作者：Andrew S. Tasker、Bryan K. Sorensen、Hwan-Soo Jae、Martin Winn、Thomas W. von Geldern、Douglas B. Dixon、William J. Chiou、Brian D. Dayton、Samuel Calzadila、Lisa Hernandez、Kennan C. Marsh、J. Ruth WuWong、Terry J. Opgenorth

  DOI：10.1021/jm960077r

  日期：1997.1.1

  The benzodioxole ((methylenedioxy)benzene) group is present in a number of endothelin (ET) receptor antagonists thus far reported. As part of our own endothelin antagonist program we have developed (2R*,3R*,4S*)-1-(N,N-dibutylacetamido)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid acid (A-127722). This is a potent antagonist, binding to the ET(A) and ET(B) receptor subtypes with affinities (IC50) of 0.4 and 520 nM, respectively, and also contains the aforementioned benzodioxole. While this compound was seemingly optimized at its N-terminus, no effort had been directed toward understanding the contributions to binding affinity or receptor subtype selectivity conferred by the benzodioxole. Substitution by 1- or 2-naphthyl yielded weak antagonists. Oxygenated benzenes, such as p-anisyl, were potent compounds with IC(50)s in the low-nanomolar range. Simple deletion of either of the two oxygen atoms (dihydrobenzofurans) yielded extremely potent agents, possessing subnanomolar affinity for the ET(A) receptor. Additionally, the compounds showed enhanced selectivity, binding to the ET(B) receptor subtype in the micromolar range. This paper describes the development of this novel class of compounds.