Ethyl 4-(1,3-benzodioxol-5-yl)-2-(4-ethoxy-3-fluorophenyl)pyrrolidine-3-carboxylate | 1027305-47-0

• 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 4-(1,3-benzodioxol-5-yl)-2-(4-ethoxy-3-fluorophenyl)pyrrolidine-3-carboxylate
• CAS: 1027305-47-0
• 化学式: C₂₂H₂₄FNO₅
• 分子量: 401.435
• InChiKey: HIKXIRBDOAPFJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 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 4-(1,3-benzodioxol-5-yl)-2-(4-ethoxy-3-fluorophenyl)pyrrolidine-3-carboxylate 在 sodium hydroxide 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 6.5h， 生成 (2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-2-(4-ethoxy-3-fluoro-phenyl)-1-{2-[(pentane-1-sulfonyl)-propyl-amino]-ethyl}-pyrrolidine-3-carboxylic acid
  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：

  5-((E)-2-nitroethenyl)-1,3-benzodioxole 在 Ra-Ni 氢气 、 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 4-(1,3-benzodioxol-5-yl)-2-(4-ethoxy-3-fluorophenyl)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