Methyl (RS)-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyano-phenoxy]-phenylacetate | 181039-95-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl (RS)-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyano-phenoxy]-phenylacetate
• 英文别名: Methyl 2-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyanophenoxy]-2-phenylacetate
• CAS: 181039-95-2
• 化学式: C₂₄H₁₉NO₆
• 分子量: 417.418
• InChiKey: ZYWMPMXQDLTRBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  87
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methyl (RS)-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyano-phenoxy]-phenylacetate 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 (RS)-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyanophenoxy]-phenylacetic acid
  参考文献：
  名称：

  Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

  摘要：

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.

  DOI：

  10.1021/jm990378b
• 作为产物：
  描述：

  扁桃酸 在 二溴亚砜 、 硫酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.17h， 生成 Methyl (RS)-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyano-phenoxy]-phenylacetate
  参考文献：
  名称：

  Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

  摘要：

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.

  DOI：

  10.1021/jm990378b

文献信息

• Substituted phenyl compounds with a substituent having a thienyl ring
  申请人：Rhone-Poulenc Rorer Limited

  公开号：US06124343A1

  公开（公告）日：2000-09-26

  This invention is directed to compounds of formula I ##STR1## wherein R.sup.1 is CN, CH.sub.2 CN, CH.dbd.CHCN, CHO, or CH.dbd.CHCO.sub.2 H; R.sup.2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted; R.sup.3 is halogen; R.sup.4 is optionally substituted aryl or optionally substituted heteroaryl; R.sup.5 is carboxy or an acid isostere; X is oxygen or sulphur; and n is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.

  这项发明涉及式I的化合物##STR1##其中R.sup.1为CN、CH.sub.2CN、CH.dbd.CHCN、CHO或CH.dbd.CHCO.sub.2H；R.sup.2为芳基低烷氧基、杂芳基低烷氧基、芳基低烷硫基或杂芳基低烷硫基，其中芳基和杂芳基中的每一个可选择地被取代；R.sup.3为卤素；R.sup.4为可选择地被取代的芳基或可选择地被取代的杂芳基；R.sup.5为羧基或酸异构体；X为氧或硫；n为零或1；或其N-氧化物、前药、溶剂化合物或药学上可接受的盐，这些化合物具有内皮素拮抗活性。该发明还涉及制备式I化合物及其药用的方法。
• US6048893
  申请人：——

  公开号：——

  公开（公告）日：——
• Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives
  作者：Peter C. Astles、Thomas J. Brown、Frank Halley、Caroline M. Handscombe、Neil V. Harris、Tahir N. Majid、Clive McCarthy、Iain M. McLay、Andrew Morley、Barry Porter、Alan G. Roach、Carol Sargent、Christopher Smith、Roger J. A. Walsh

  DOI：10.1021/jm990378b

  日期：2000.3.1

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.