Ethyl 2-(4-butanoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate | 178609-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: Ethyl 2-(4-butanoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate
• 英文别名: Ethyl 2-[1-(1,3-benzodioxol-5-yl)-2-nitroethyl]-3-oxohexanoate
• CAS: 178609-47-7
• 化学式: C₁₇H₂₁NO₇
• 分子量: 351.356
• InChiKey: KOCFTZPDWGWGLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 2-(4-butanoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate 在 镍 sodium hydroxide 、 氢气 、 溴甲酚绿 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 生成 trans,trans-2-propyl-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
• 作为产物：
  描述：

  5-((E)-2-nitroethenyl)-1,3-benzodioxole 、 丁酰乙酸乙酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲苯 为溶剂， 生成 Ethyl 2-(4-butanoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate
  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

文献信息

• [EN] ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES D'ENDOTHELINE
  申请人：ABBOTT LABORATORIES

  公开号：WO1996006095A1

  公开（公告）日：1996-02-29

  (EN) 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.(FR) Composé de formule (I) ou sel pharmaceutiquement acceptable dudit composé, ainsi que procédés et intermédiaires destinés à la préparation dudit composé, et procédé permettant d'obtenir un effet antagoniste par rapport à l'endothéline.

  揭示了化合物式(I)或其药学上可接受的盐，以及其制备过程中的中间体和制备方法，并且揭示了拮抗内皮素的方法。
• 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。
• Processes for preparing endothelin antagonists
  申请人：Abbott Laboratories

  公开号：EP1186603A2

  公开（公告）日：2002-03-13

  Processes for preparing endothelin antagonists of formula (I) and pharmaceutically acceptable salts thereof and processes for preparing intermediates thereof.

  制备式(I)内皮素拮抗剂及其药学上可接受的盐的工艺，以及制备其中间体的工艺。
• 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。
• ENDOTHELIN ANTAGONISTS
  申请人：Abbott Laboratories

  公开号：EP0776324B1

  公开（公告）日：2002-06-12