(2R,3R,4S)-1-[2-(dibutylamino)-2-oxoethyl]-4-(2,3-dihydro-1-benzofuran-5-yl)-2-(3-fluoro-4-methylphenyl)pyrrolidine-3-carboxylic acid | 380180-51-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,3R,4S)-1-[2-(dibutylamino)-2-oxoethyl]-4-(2,3-dihydro-1-benzofuran-5-yl)-2-(3-fluoro-4-methylphenyl)pyrrolidine-3-carboxylic acid
• CAS: 380180-51-8
• 化学式: C₃₀H₃₉FN₂O₄
• 分子量: 510.649
• InChiKey: QEEBBVPPVYZDDG-USOMCTOXSA-N

物化性质

• 沸点：
  650.6±55.0 °C(predicted)
• 密度：
  1.173±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,3-二氢苯并呋喃-5-甲醛 在 RaNi sodium hydroxide 、 potassium tert-butylate 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 反应 43.5h， 生成 (2R,3R,4S)-1-[2-(dibutylamino)-2-oxoethyl]-4-(2,3-dihydro-1-benzofuran-5-yl)-2-(3-fluoro-4-methylphenyl)pyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 5. Highly Selective, Potent, and Orally Active ET_A Antagonists

  摘要：

  The synthesis and structure-activity relationships (SAR) of a series of pyrrolidine-3-carboxylic acids as endothelin antagonists are described. The data shows an increase in selectivity when the methoxy of Atrasentan (ABT-627) is replaced with methyl, and the benzodioxole is replaced with dihydrobenzofuran. Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ETA-selective antagonist.

  DOI：

  10.1021/jm010237l

文献信息

• Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 5. Highly Selective, Potent, and Orally Active ET_A Antagonists
  作者：Hwan-Soo Jae、Martin Winn、Thomas W. von Geldern、Bryan K. Sorensen、William J. Chiou、Bach Nguyen、Kennan C. Marsh、Terry J. Opgenorth

  DOI：10.1021/jm010237l

  日期：2001.11.1

  The synthesis and structure-activity relationships (SAR) of a series of pyrrolidine-3-carboxylic acids as endothelin antagonists are described. The data shows an increase in selectivity when the methoxy of Atrasentan (ABT-627) is replaced with methyl, and the benzodioxole is replaced with dihydrobenzofuran. Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ETA-selective antagonist.