3-(2,1,3-benzothiadiazol-5-yl)-4-(3,4,5-trimethoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-one | 195505-56-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻二唑类
• 英文名称: 3-(2,1,3-benzothiadiazol-5-yl)-4-(3,4,5-trimethoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-one
• 英文别名: 3-(2,1,3-Benzothiadiazol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]furan-2-one
• CAS: 195505-56-7
• 化学式: C₂₇H₂₄N₂O₇S
• 分子量: 520.563
• InChiKey: ICXHSKRYFGHTBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-(2,1,3-benzothiadiazol-5-yl)-4-(3,4,5-trimethoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-one 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以100%的产率得到(Z)-2-Benzo[1,2,5]thiadiazol-5-yl-4-(4-methoxy-phenyl)-4-oxo-3-(3,4,5-trimethoxy-benzyl)-but-2-enoic acid
  参考文献：
  名称：

  2.Endothelin antagonists: Evaluation of 2,1,3-benzothiadiazole as a methylendioxyphenyl bioisoster

  摘要：

  The methylendioxyphenyl group is present in a number of endothelin receptor antagonists thus far reported. By means of a Kohonen neural network we discovered with a benzothiadiazole a bioisosteric replacement instead. This group should be devoid of the negative metabolic interactions with cytochrome P450 ascribed to methylendioxyphenyl in vivo. The synthesis of a potent benzothiadiazole analogue EMD 122801 together with in vitro studies of different methylendioxyphenyl, benzothiadiazole and benzofurazan derivatives is described. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10151-2
• 作为产物：
  描述：

  2-(3,4-二氨基苯基)乙酸乙酯 在 N-甲基吡咯烷酮 、 氯化亚砜 、 potassium tert-butylate 、 sodium methylate 、 N,N-二甲基甲酰胺 作用下， 以 甲醇 为溶剂， 生成 3-(2,1,3-benzothiadiazol-5-yl)-4-(3,4,5-trimethoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-one
  参考文献：
  名称：

  2.Endothelin antagonists: Evaluation of 2,1,3-benzothiadiazole as a methylendioxyphenyl bioisoster

  摘要：

  The methylendioxyphenyl group is present in a number of endothelin receptor antagonists thus far reported. By means of a Kohonen neural network we discovered with a benzothiadiazole a bioisosteric replacement instead. This group should be devoid of the negative metabolic interactions with cytochrome P450 ascribed to methylendioxyphenyl in vivo. The synthesis of a potent benzothiadiazole analogue EMD 122801 together with in vitro studies of different methylendioxyphenyl, benzothiadiazole and benzofurazan derivatives is described. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10151-2

文献信息

• [DE] ENDOTHELIN-REZEPTOR-ANTAGONISTEN<br/>[EN] ENDOTHELIN-RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR D'ENDOTHELINE
  申请人：MERCK PATENT GMBH

  公开号：WO1998042702A1

  公开（公告）日：1998-10-01

  (DE) Neue Verbindungen der Formel (I), worin R (a), (b) oder (c), X O oder S bedeuten, und R1, R2, R3, R4, R7 und n die in Patentanspruch (1) angegebene Bedeutung haben, und ihre Salze zeigen Endothelinrezeptor-antagonistische Eigenschaften.(EN) The invention relates to novel compounds of formula (I) wherein R means (a), (b) or (c), X means O or S and R1, R2, R3, R4, R7 and n have the meaning cited in claim 1. The invention further relates to the salts thereof. Said compounds display endothelin-receptor antagonistic properties.(FR) L'invention concerne de nouveaux composés de la formule (I) dans laquelle R désigne (a), (b) ou (c), X désigne O ou S et R, R1, R2, R3, R4, R7 et n ont la signification mentionnée dans la revendication 1, ainsi que leurs sels. Ces composés et leurs sels présentent des propriétés antagonistes vis-à-vis du récepteur d'endothéline.

  (德语) 新的连接形式（I），其中 R 指（a）、（b）或（c），X 指 O 或 S，而 R1、R2、R3、R4、R7 和 n 具有专利要求（1）中给出的含义，以及它们的盐显示 Endothelin-receptor 抗衡抗性特征。 (英语) The invention relates to novel compounds of formula (I) wherein R means (a), (b) or (c), X means O or S and R1, R2, R3, R4, R7 and n have the meaning cited in claim 1. The invention further relates to the salts thereof. The compounds and their salts display properties antagonistic to the endothelin receptor. (法语) L'invention concerne de nouveaux composés de la formule (I) dans laquelle R désigne (a), (b) ou (c), X désigne O ou S et R, R1, R2, R3, R4, R7 et n ont la signification mentionnée dans la revendication 1, ainsi que leurs sels. Ces composés et leurs sels présentent des propriétés antagonistes vis-à-vis du récepteur d'endothéline.
• 2,1,3-BENZOTHIA(OXA)DIAZOLDERIVATE MIT ENDOTHELINREZEPTOR-ANTAGONISTISCHER WIRKUNG
  申请人：MERCK PATENT GmbH

  公开号：EP0882030B1

  公开（公告）日：2001-09-12
• US6017939A
  申请人：——

  公开号：US6017939A

  公开（公告）日：2000-01-25
• 2.Endothelin antagonists: Evaluation of 2,1,3-benzothiadiazole as a methylendioxyphenyl bioisoster
  作者：Werner W.K.R Mederski、Mathias Osswald、Dieter Dorsch、Soheila Anzali、Maria Christadler、Claus-Jochen Schmitges、Claudia Wilm

  DOI：10.1016/s0960-894x(97)10151-2

  日期：1998.1

  The methylendioxyphenyl group is present in a number of endothelin receptor antagonists thus far reported. By means of a Kohonen neural network we discovered with a benzothiadiazole a bioisosteric replacement instead. This group should be devoid of the negative metabolic interactions with cytochrome P450 ascribed to methylendioxyphenyl in vivo. The synthesis of a potent benzothiadiazole analogue EMD 122801 together with in vitro studies of different methylendioxyphenyl, benzothiadiazole and benzofurazan derivatives is described. (C) 1997 Elsevier Science Ltd. All rights reserved.