N-(5-benzyloxy-2,4,6,7-tetramethylbenzofuran-3-ylmethyl)-(3R)-chloropiperidine | 199108-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: N-(5-benzyloxy-2,4,6,7-tetramethylbenzofuran-3-ylmethyl)-(3R)-chloropiperidine
• 英文别名: (3R)-3-chloro-1-[(2,4,6,7-tetramethyl-5-phenylmethoxy-1-benzofuran-3-yl)methyl]piperidine
• CAS: 199108-91-3
• 化学式: C₂₅H₃₀ClNO₂
• 分子量: 411.972
• InChiKey: DZNUTTOMBRJTOG-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  25.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(5-benzyloxy-2,4,6,7-tetramethylbenzofuran-3-ylmethyl)-(3R)-chloropiperidine 在 哌啶 、 potassium carbonate 、 苯甲酸 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 15.0h， 生成 (5Z)-5-[[4-[(3R)-1-[(2,4,6,7-tetramethyl-5-phenylmethoxy-1-benzofuran-3-yl)methyl]piperidin-3-yl]oxyphenyl]methylidene]-1,3-thiazolidine-2,4-dione
  参考文献：
  名称：

  Novel Antidiabetic and Hypolipidemic Agents. 3. Benzofuran-Containing Thiazolidinediones

  摘要：

  Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2-ylmethoxy]phenylene]-thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.

  DOI：

  10.1021/jm980549x
• 作为产物：
  描述：

  L-脯氨醇 在 氯化亚砜 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 N-(5-benzyloxy-2,4,6,7-tetramethylbenzofuran-3-ylmethyl)-(3R)-chloropiperidine
  参考文献：
  名称：

  Novel Antidiabetic and Hypolipidemic Agents. 3. Benzofuran-Containing Thiazolidinediones

  摘要：

  Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2-ylmethoxy]phenylene]-thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.

  DOI：

  10.1021/jm980549x

文献信息

• [EN] NOVEL HETEROCYCLIC COMPOUNDS HAVING ANTIDIABETIC, HYPOLIPIDAEMIC, ANTIHYPERTENSIVE PROPERTIES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX COMPOSES HETEROCYCLIQUES PRESENTANT DES PROPRIETES ANTIDIABETIQUES, HYPOLIPIDEMIANTES, ANTIHYPERTENSIVES, LEUR PROCEDE DE PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：WO1997041121A1

  公开（公告）日：1997-11-06

  (EN) The present invention relates to novel antidiabetic compounds, their tautomeric forms, their derivatives, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. This invention particularly relates to novel azolidinedione derivatives of general formula (I), and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutical compositions containing them.(FR) La présente invention concerne des nouveaux composés antidiabétiques, leurs formes tautomères, leurs dérivés, leurs stéréoisomères, leurs polymorphes, leurs sels pharmaceutiquement acceptables, leurs solvates pharmaceutiquement acceptables et des compositions pharmaceutiquement acceptables les contenant. L'invention concerne notamment de nouveaux dérivés d'azolidinediène de la formule générale (I) et leurs sels pharmaceutiquement acceptables, solvates pharmaceutiquement acceptables et des compositions pharmaceutiques les contenant.

  本发明涉及新型抗糖尿病化合物，它们的互变异构体，它们的衍生物，它们的立体异构体，它们的多晶形式，它们的药学上可接受的盐，它们的药学上可接受的溶剂和包含它们的药学上可接受的组合物。本发明特别涉及一般式(I)的新型噁唑烷二酮衍生物，以及它们的药学上可接受的盐、药学上可接受的溶剂和包含它们的药物组合物。
• NOVEL HETEROCYCLIC COMPOUNDS HAVING ANTIDIABETIC, HYPOLIPIDAEMIC, ANTIHYPERTENSIVE PROPERTIES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：Dr. Reddy's Laboratories Ltd.

  公开号：EP0894089B9

  公开（公告）日：2003-04-02
• US5889032A
  申请人：——

  公开号：US5889032A

  公开（公告）日：1999-03-30
• Novel Antidiabetic and Hypolipidemic Agents. 3. Benzofuran-Containing Thiazolidinediones
  作者：K. Anji Reddy、B. B. Lohray、V. Bhushan、A. C. Bajji、K. Vivekananda Reddy、P. Rajamohan Reddy、T. Hari Krishna、I. Nageswara Rao、H. Kumar Jajoo、N. V. S. Mamidi Rao、Ranjan Chakrabarti、T. Dileepkumar、R. Rajagopalan

  DOI：10.1021/jm980549x

  日期：1999.6.1

  Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2-ylmethoxy]phenylene]-thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.