methyl 2-(4-hexenoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate | 195707-98-3

• 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: methyl 2-(4-hexenoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate
• 英文别名: methyl 2-[1-(1,3-benzodioxol-5-yl)-2-nitroethyl]-3-oxooct-6-enoate
• CAS: 195707-98-3
• 化学式: C₁₈H₂₁NO₇
• 分子量: 363.367
• InChiKey: JKBJHQCGSJUWGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  methyl 2-(4-hexenoyl)-4-nitro-3-(1,3-benzodioxole-5-yl)butyrate 在 镍 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 21.0h， 生成 4-Benzo[1,3]dioxol-5-yl-2-pentyl-4,5-dihydro-3H-pyrrole-3-carboxylic acid methyl ester
  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 、 methyl 3-oxo-6-octenoate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 0.33h， 以82%的产率得到methyl 2-(4-hexenoyl)-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

• Endothelin antagonists
  申请人：Abbott Laboratories

  公开号：US05622971A1

  公开（公告）日：1997-04-22

  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.

  公开了一种式(I)的化合物： ##STR1## 或其药学上可接受的盐，以及其制备过程和中间体，以及一种拮抗内皮素的方法。
• Treatment of diseases using endothelin antagonists
  申请人：Abbott Laboratories

  公开号：US06380241B1

  公开（公告）日：2002-04-30

  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.

  本发明揭示了化合物(I)的公式或其药学上可接受的盐，以及其制备过程中的中间体和方法，以及拮抗内皮素的方法。
• Discovery of a series of pyrrolidine-based endothelin receptor antagonists with enhanced ETA receptor selectivity
  作者：Steven A Boyd、Robert A Mantei、Andrew S Tasker、Gang Liu、Bryan K Sorensen、Kenneth J Henry Jr、Thomas W von Geldern、Martin Winn、Jinshyun R Wu-Wong、William J Chiou、Douglas B Dixon、Charles W Hutchins、Kennan C Marsh、Bach Nguyen、Terry J Opgenorth

  DOI：10.1016/s0968-0896(99)00022-x

  日期：1999.6

  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.