trans,trans-2-(4-ethylphenylphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylate

• 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: trans,trans-2-(4-ethylphenylphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylate
• 英文别名: 4-Benzo[1,3]dioxol-5-yl-1-dibutylcarbamoylmethyl-2-(4-ethyl-phenyl)-pyrrolidine-3-carboxylic acid；(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-ethylphenyl)pyrrolidine-3-carboxylic acid
• 化学式: C₃₀H₄₀N₂O₅
• 分子量: 508.658
• InChiKey: KDKGYZPRCNXIRY-USOMCTOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  79.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对乙基苯甲酸 在 镍 sodium hydroxide 、 氢气 、 溴甲酚绿 、 sodium cyanoborohydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 生成 trans,trans-2-(4-ethylphenylphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Discovery of a series of pyrrolidine-based endothelin receptor antagonists with enhanced ETA receptor selectivity

  摘要：

  Endothelins, ET-1, ET-2, and ET-3 are potent vasoconstricting and mitogenic 21-amino acid bicyclic peptides, which exert their effects upon binding to the ETA and ETB receptors. The ETA receptor mediates vasoconstriction and smooth muscle cell proliferation, and the ETB receptor mediates different effects in different tissues, including nitric oxide release from endothelial cells, and vasoconstriction in certain vascular cell types. Selective antagonists of endothelin receptor subtypes may prove useful in determining the role of endothelin in various tissue types and disease states, and hence as therapeutic agents for such diseases. The pyrrolidine carboxylic acid A-127722 has been disclosed as a potent and ETA-selective antagonist, and is currently undergoing clinical trials. In our efforts to find antagonists with altered selectivity (ETA-selective, ETB-selective, or nonselective), we investigated the SAR of the 2-substituent on the pyrrolidine. Compounds with alkyl groups at the 2-position possessed ETA selectivity improved over A-127722 (1400-fold selective), with the best of these compounds showing nearly 19,000-fold selectivity. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00022-x