Ethyl 2-(3-Fluoro-4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate | 195510-46-4

• 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 2-(3-Fluoro-4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate
• 英文别名: Ethyl 4-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)pyrrolidine-3-carboxylate
• CAS: 195510-46-4
• 化学式: C₂₁H₂₂FNO₅
• 分子量: 387.408
• InChiKey: GKMSZRFWEOVKNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 2-(3-Fluoro-4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate 在 盐酸 、 sodium hydroxide 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 ethyl (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-(2-bromoethyl)-2-(3-fluoro-4-methoxyphenyl)pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 2. Sulfonamide-Based ET_A/ET_B Mixed Antagonists

  摘要：

  When the N,N-dialkylacetamide side chain of the highly ETA-selective endothelin antagonist ABT-627 (1; [2R,3R,4S]-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(N,N-dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylic acid; A-147627) is replaced by N,S-dialkylsulfonamidoethyl, the resultant analogs retain ETA affinity, but exhibit substantial ETB affinity as well. Structure-activity studies reveal that modifications in the length of the two alkyl groups, and in the substitution on the anisyl ring, are important in optimizing this ''balanced'' antagonist profile. In particular the combination of an N-n-propyl group, an S-alkyl chain between four and six carbons in length, and a fluorine atom ortho to the aromatic OCH3 provides compounds with sub-nanomolar affinities for both receptor subtypes, and with ETA/ETB ratios close to 1. A number of these compounds also exhibit oral bioavailabilities (in rats) in the 30-50% range and have substantial plasma half-lives. The balanced receptor-binding profile of these potent and orally bioavailable compounds complements the ETA selectivity observed with 1.

  DOI：

  10.1021/jm970101g
• 作为产物：
  描述：

  3-氟-4-甲氧基苯乙酮 在 Ra-Ni 氢气 、 sodium hydride 、 sodium cyanoborohydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 溶剂黄146 、 异丙醇 为溶剂， 生成 Ethyl 2-(3-Fluoro-4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 2. Sulfonamide-Based ET_A/ET_B Mixed Antagonists

  摘要：

  When the N,N-dialkylacetamide side chain of the highly ETA-selective endothelin antagonist ABT-627 (1; [2R,3R,4S]-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(N,N-dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylic acid; A-147627) is replaced by N,S-dialkylsulfonamidoethyl, the resultant analogs retain ETA affinity, but exhibit substantial ETB affinity as well. Structure-activity studies reveal that modifications in the length of the two alkyl groups, and in the substitution on the anisyl ring, are important in optimizing this ''balanced'' antagonist profile. In particular the combination of an N-n-propyl group, an S-alkyl chain between four and six carbons in length, and a fluorine atom ortho to the aromatic OCH3 provides compounds with sub-nanomolar affinities for both receptor subtypes, and with ETA/ETB ratios close to 1. A number of these compounds also exhibit oral bioavailabilities (in rats) in the 30-50% range and have substantial plasma half-lives. The balanced receptor-binding profile of these potent and orally bioavailable compounds complements the ETA selectivity observed with 1.

  DOI：

  10.1021/jm970101g

文献信息

• Endothelin antagonists
  申请人：Winn Martin

  公开号：US20060229280A1

  公开（公告）日：2006-10-12

  A compound of the formula (I): 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.

  公开了化合物(I)的公式或其药学上可接受的盐，以及其制备过程和中间体，以及拮抗内皮素的方法。
• Benzo-1,3-dioxolyl- and benzofuranyl substituted pyrrolidine derivatives as endothelin antagonists
  申请人：ABBOTT LABORATORIES

  公开号：EP1609790A2

  公开（公告）日：2005-12-28

  A compound of formula (I), 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.

  本研究公开了一种式 (I) 的化合物或其药学上可接受的盐，以及其制备工艺和中间体，以及一种拮抗内皮素的方法。
• NOVEL BENZO-1,3-DIOXOLYL- AND BENZOFURANYL SUBSTITUTED PYRROLIDINE DERIVATIVES AS ENDOTHELIN ANTAGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：EP0885215B1

  公开（公告）日：2006-04-19
• US6162927A
  申请人：——

  公开号：US6162927A

  公开（公告）日：2000-12-19
• US6946481B1
  申请人：——

  公开号：US6946481B1

  公开（公告）日：2005-09-20