Ethyl [2R,3R,4S]2-(4-Propoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate | 218271-42-2

• 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: Ethyl [2R,3R,4S]2-(4-Propoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate
• 英文别名: ethyl (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(4-propoxyphenyl)pyrrolidine-3-carboxylate
• CAS: 218271-42-2
• 化学式: C₂₃H₂₇NO₅
• 分子量: 397.471
• InChiKey: UWUDUSOQWXZGDU-QIJUGHKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ethyl [2R,3R,4S]2-(4-Propoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 3-吡咯烷羧酸,4-(1,3-苯并二噁唑-5-基)-1-[2-[(2,6-二乙基苯基)氨基]-2-羰基乙基]-2-(4-丙氧基苯基)-,(2R,3R,4S)-
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 4. Side Chain Conformational Restriction Leads to ET_B Selectivity

  摘要：

  When the dialkylacetamide side chain of the ETA-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ETB over ETA. By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ETB and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ETB receptor in modulating blood pressure; the observed hypertensive response to persistent ETB blockade is consistent with previous postulates and indicates that ETB-selective antagonists may not be suitable as agents for long-term systemic therapy.

  DOI：

  10.1021/jm990170q
• 作为产物：
  描述：

  Ethyl 4-(1,3-benzodioxol-5-yl)-2-(4-propoxyphenyl)pyrrolidine-3-carboxylate 生成 Ethyl [2R,3R,4S]2-(4-Propoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 4. Side Chain Conformational Restriction Leads to ET_B Selectivity

  摘要：

  When the dialkylacetamide side chain of the ETA-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ETB over ETA. By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ETB and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ETB receptor in modulating blood pressure; the observed hypertensive response to persistent ETB blockade is consistent with previous postulates and indicates that ETB-selective antagonists may not be suitable as agents for long-term systemic therapy.

  DOI：

  10.1021/jm990170q

文献信息

• Endothelin antagonists
  申请人：Abbott Laboratories

  公开号：US06124341A1

  公开（公告）日：2000-09-26

  A compound of the formula (I): ##STR1## or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

  公开了一种化合物的公式(I): ##STR1## 或其药学上可接受的盐，以及制备该化合物的过程和中间体，以及一种拮抗内皮素的方法。
• Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 4. Side Chain Conformational Restriction Leads to ET_B Selectivity
  作者：Thomas W. von Geldern、Andrew S. Tasker、Bryan K. Sorensen、Martin Winn、Bruce G. Szczepankiewicz、Douglas B. Dixon、William J. Chiou、Liming Wang、Jerry L. Wessale、Andy Adler、Kennan C. Marsh、Bach Nguyen、Terry J. Opgenorth

  DOI：10.1021/jm990170q

  日期：1999.9.1

  When the dialkylacetamide side chain of the ETA-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ETB over ETA. By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ETB and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ETB receptor in modulating blood pressure; the observed hypertensive response to persistent ETB blockade is consistent with previous postulates and indicates that ETB-selective antagonists may not be suitable as agents for long-term systemic therapy.