5-[[4-[[(2S)-1-[(2,5,7,8-tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl]pyrrolidin-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-[[4-[[(2S)-1-[(2,5,7,8-tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl]pyrrolidin-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• 化学式: C₃₆H₄₂N₂O₅S
• 分子量: 614.806
• InChiKey: NSEGOJXLVQTIAC-GNDAZDRNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2R/S)-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl]carbinol 在 palladium on activated charcoal 盐酸 、 氢溴酸 、 氢气 、 sodium acetate 、 sodium hydride 、 三乙胺 、 sodium nitrite 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 120.0 ℃ 、413.68 kPa 条件下， 反应 34.0h， 生成 5-[[4-[[(2S)-1-[(2,5,7,8-tetramethyl-6-phenylmethoxy-3,4-dihydrochromen-2-yl)methyl]pyrrolidin-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
  参考文献：
  名称：

  Novel Antidiabetic and Hypolipidemic Agents. 5. Hydroxyl versus Benzyloxy Containing Chroman Derivatives

  摘要：

  Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1,3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPAR gamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.

  DOI：

  10.1021/jm9805541

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
• Novel Antidiabetic and Hypolipidemic Agents. 5. Hydroxyl versus Benzyloxy Containing Chroman Derivatives
  作者：K. Anji Reddy、B. B. Lohray、V. Bhushan、A. Sekar Reddy、N. V. S. Rao Mamidi、P. Papi Reddy、V. Saibaba、N. Jaipal Reddy、A. Suryaprakash、Parimal Misra、Reeba K. Vikramadithyan、R. Rajagopalan

  DOI：10.1021/jm9805541

  日期：1999.8.1

  Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1,3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPAR gamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.