5-[4-[2-[4-methyl-1-oxo-1,2-dihydrophthalazin-2-yl]ethoxy]phenylmethylene]thiazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-[4-[2-[4-methyl-1-oxo-1,2-dihydrophthalazin-2-yl]ethoxy]phenylmethylene]thiazolidine-2,4-dione
• 英文别名: (5Z)-5-[[4-[2-(4-methyl-1-oxophthalazin-2-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione
• 化学式: C₂₁H₁₇N₃O₄S
• 分子量: 407.45
• InChiKey: HWTVWYSIMDNUEI-PDGQHHTCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-[4-[2-[4-methyl-1-oxo-1,2-dihydrophthalazin-2-yl]ethoxy]phenylmethylene]thiazolidine-2,4-dione 在 palladium on activated charcoal 氢气 作用下， 以 1,4-二氧六环 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 以80%的产率得到PHT46
  参考文献：
  名称：

  Novel phthalazinone and benzoxazinone containing thiazolidinediones as antidiabetic and hypolipidemic agents

  摘要：

  We report here the synthesis of a series of 5-[4-[2-[substituted phthalazinones-2(or 4)yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and 5-[4-[2-[2,3-benzoxazine-4-one-2-yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and their plasma glucose and plasma triglyceride lowering activity in db/db mice. In vitro PPAR gamma transactivation assay was performed in HEK 293T cells. In vitro and in vivo pharmacological studies showed that the phthalazinone analogue has better activity. PHT46 (compound 5a), the best compound in this series, showed better in vitro PPAR gamma transactivation potential than troglitazone and pioglitazone. In insulin resistant db/db mice, PHT46 showed better plasma glucose and triglyceride lowering activity than the standard drugs. Pharmacokinetic study in Wistar rats showed good systemic exposure of PHT46. Subchronic toxicity study in Wistar rats did not show any treatment-related adverse effect. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(01)01257-0
• 作为产物：
  描述：

  4-(2-溴乙氧基)苯甲醛 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 25.5h， 生成 5-[4-[2-[4-methyl-1-oxo-1,2-dihydrophthalazin-2-yl]ethoxy]phenylmethylene]thiazolidine-2,4-dione
  参考文献：
  名称：

  Novel phthalazinone and benzoxazinone containing thiazolidinediones as antidiabetic and hypolipidemic agents

  摘要：

  We report here the synthesis of a series of 5-[4-[2-[substituted phthalazinones-2(or 4)yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and 5-[4-[2-[2,3-benzoxazine-4-one-2-yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and their plasma glucose and plasma triglyceride lowering activity in db/db mice. In vitro PPAR gamma transactivation assay was performed in HEK 293T cells. In vitro and in vivo pharmacological studies showed that the phthalazinone analogue has better activity. PHT46 (compound 5a), the best compound in this series, showed better in vitro PPAR gamma transactivation potential than troglitazone and pioglitazone. In insulin resistant db/db mice, PHT46 showed better plasma glucose and triglyceride lowering activity than the standard drugs. Pharmacokinetic study in Wistar rats showed good systemic exposure of PHT46. Subchronic toxicity study in Wistar rats did not show any treatment-related adverse effect. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(01)01257-0

文献信息

• THIAZOLIDINEDIONE AND OXAZOLIDINEDIONE DERIVATIVES HAVING ANTIDIABETIC, HYPOLIPIDAEMIC AND ANTIHYPERTENSIVE PROPERTIES
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：EP0971917B1

  公开（公告）日：2002-02-06
• Novel phthalazinone and benzoxazinone containing thiazolidinediones as antidiabetic and hypolipidemic agents
  作者：Gurram R Madhavan、Ranjan Chakrabarti、Sunil K.B Kumar、Parimal Misra、Rao N.V.S Mamidi、V Balraju、Katneni Kasiram、Ravi K Babu、Juluri Suresh、Braj B Lohray

  DOI：10.1016/s0223-5234(01)01257-0

  日期：2001.8

  We report here the synthesis of a series of 5-[4-[2-[substituted phthalazinones-2(or 4)yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and 5-[4-[2-[2,3-benzoxazine-4-one-2-yl]ethoxy]phenylmethyl]thiazolidine-2,4-diones and their plasma glucose and plasma triglyceride lowering activity in db/db mice. In vitro PPAR gamma transactivation assay was performed in HEK 293T cells. In vitro and in vivo pharmacological studies showed that the phthalazinone analogue has better activity. PHT46 (compound 5a), the best compound in this series, showed better in vitro PPAR gamma transactivation potential than troglitazone and pioglitazone. In insulin resistant db/db mice, PHT46 showed better plasma glucose and triglyceride lowering activity than the standard drugs. Pharmacokinetic study in Wistar rats showed good systemic exposure of PHT46. Subchronic toxicity study in Wistar rats did not show any treatment-related adverse effect. (C) 2001 Editions scientifiques et medicales Elsevier SAS.