Troglitazone quinone

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: Troglitazone quinone
• 英文别名: 5-{4-[2-hydroxy-2-methyl-4-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)butoxy]benzyl}-2,4-dioxothiazolidine；5-[[4-[2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• 化学式: C₂₄H₂₇NO₆S
• 分子量: 457.547
• InChiKey: QUTRCNCTMKKAPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Troglitazone quinone 在 sodium borohydrid 作用下， 以 磷酸酐 、 ice-water 、 乙醇 为溶剂， 生成 troglitazone quinol
  参考文献：
  名称：

  Thiazolidine derivatives with anti-diabetic activity, their preparation

  摘要：

  公式（I）的化合物：其中：A是公式（II）或（III）的基团：W是亚甲基，羰基或>C.dbd.N--OV，其中V是氢，磺酰基，酰基或烷基；U是亚甲基，或者W不存在且U是A和--CR.sup.1（OH）之间的碳-碳双键；R.sup.1，R.sup.2，R.sup.3和R.sup.4分别为氢或烷基；Y.sup.1和Y.sup.2分别为氢或羟基保护基团；n为1、2或3，其盐在哺乳动物中具有抗糖尿病活性。还提供了它们的制备方法。

  公开号：

  US05143930A1
• 作为产物：
  描述：

  曲格列酮 在 乙酸铵 作用下， 以 乙腈 为溶剂， 生成 Troglitazone quinone
  参考文献：
  名称：

  通过库仑电极上的流式电化学反应成功制备了曲格列酮代谢物。

  摘要：

  开发了一种使用库仑电极的简单，快速，有效的系统来制备药物代谢物。痕量反应物通常在电化学反应中产生，不适用于足够的产物制备以获得NMR和其他光谱数据以进行化学结构确认或从产物的药理活性筛选测试中获得数据。在开发的系统（称为“流内电化学反应系统”）中，曲格列酮将药物溶解在挥发性流动溶剂中，并在优化条件下泵入库仑电极中，并蒸发了出水。无需进一步纯化，即可在数小时内获得毫克量的曲格列酮纯氧化产物。获得的量足以用于（1）H-和（13）C-NMR分析，通过该分析可以确认结构，并且发现其与在人血浆中检测到的曲格列酮的代谢物之一相同。该系统对于制备药代动力学研究和毒物动力学研究所需量的标准化合物将很有用。

  DOI：

  10.1248/cpb.55.1207

文献信息

• Thiazolidine derivatives with anti-diabetic activity, their preparation and their use
  申请人：Sankyo Company Limited

  公开号：EP0441605A2

  公开（公告）日：1991-08-14

  Compounds of formula (I) : [in which : A is a group of formula (II) or (III) : W is methylene, carbonyl or >C=N-OV, where V is hydrogen, sulpho, acyl or alkyl ; U is methylene, or W is absent and U is a carbon-carbon double bond between A and -CR1(OH)-; R1, R2, R3 and R4 are each hydrogen or alkyl ; Y1 and Y' are each hydrogen or a hydroxy-protecting group ; and n is 1, 2 or 3] and salts thereof have anti-diabetic activity in mammals. Methods of preparing them are also provided.

  式 (I) 的化合物： [其中：A 是式 (II) 或 (III) 的基团： W为亚甲基、羰基或 >C=N-OV，其中 V 为氢、亚砜基、酰基或烷基；U 为亚甲基，或不含 W，且 U 为 A 与-CR1(OH)-之间的碳碳双键；R1、R2、R3 和 R4 各为氢或烷基；Y1 和 Y' 各为氢或羟基保护基团；n 为 1、2 或 3]及其盐类在哺乳动物中具有抗糖尿病活性。还提供了制备它们的方法。
• Thiazolidine compounds, their preparation and their therapeutic uses
  申请人：Sankyo Company Limited

  公开号：EP0549365B1

  公开（公告）日：1995-08-09
• Enzyme-Induction Dependent Bioactivation of Troglitazone and Troglitazone Quinone In Vivo
  作者：Justice N. Tettey、James L. Maggs、W. Garth Rapeport、Munir Pirmohamed、B. Kevin Park

  DOI：10.1021/tx0001981

  日期：2001.8.1

  Troglitazone (TGZ), a 2,4-thiazolidinedione antidiabetic, causes hepatotoxicity in 1.9% of patients. TGZ is an inducer of, and substrate for, hepatic P450 3A. Microsomal metabolism yields a benzoquinone (TGZQ) and reactive intermediates. Kassahun et al. [Kassahun et al. (2001) Chem. Res. Toxicol. 14, 62-70] have trapped the intermediates as thioester, thioether, and disulfide conjugates of glutathione and found five conjugates in rat bile. The thioether was substituted in the chromane moiety. We have investigated the effect of the P450 3A inducer, dexamethasone (DEX), on metabolism of TGZ and TGZQ in rats and assessed the compounds' cytotoxicity. TGZ-glucuronide and sulfonate were confirmed as principal biliary metabolites of TGZ (50 mg/kg, iv). Bile from noninduced animals also contained a TGZ-glutathione thioether adduct (ML3) but it was substituted in the thiazolidinedione moiety. Pretreatment with DEX (50 mg/kg/day for 3 days) resulted in a 2-5-fold increase in the biliary concentration of ML3 and a 2-fold increase in the concentration of TGZQ, which was commensurate with the induction of hepatic P450 3A. Three of the known glutathione-conjugated metabolites were also found. TGZQ (50 mg/kg, iv) was metabolized to an analogue of one of the TGZ-glutathione thioesters and a glutathione adduct of TGZQ hydroquinone after DEX pretreatment. TGZ quinol glucuronide was a biliary metabolite of TGZ and TGZQ. Its formation would represent deactivation of TGZQ. TGZ was toxic to rat hepatocytes and Hep-G2 cells at concentrations exceeding 50 and 25 muM, respectively, after 24 h. In contrast, TGZQ was nontoxic to rat hepatocytes and toxic to Hep G2 cells only at concentrations exceeding 100 muM. Our results show that TGZQ as well as TGZ yields reactive metabolites in vivo, and that bioactivation is enhanced by induction of P450 3A. However, hepatotoxicity is unlikely to be due to either TGZQ or its metabolites.
• Thiazolidine compounds containing a quinone group, their preparation and their therapeutic uses
  申请人：Sankyo Company Limited

  公开号：EP0549366B1

  公开（公告）日：1998-04-15
• US5143930A
  申请人：——

  公开号：US5143930A

  公开（公告）日：1992-09-01