5-羟基罗格列酮 | 257883-22-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 5-羟基罗格列酮
• 英文名称: p-Hydroxy-Rosiglitazone
• 英文别名: p-hydroxyrosiglitaonze；p-hydroxyrosiglitazone；5-(4-{2-[(5-hydroxy-pyridin-2-yl)-methyl-amino]-ethoxy}-benzyl)-thiazolidine-2,4-dione；p-Hydroxy rosiglitazone；5-[[4-[2-[(5-hydroxypyridin-2-yl)-methylamino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• CAS: 257883-22-0
• 化学式: C₁₈H₁₉N₃O₄S
• 分子量: 373.433
• InChiKey: AGQGGZNSVNKGDU-UHFFFAOYSA-N

物化性质

• 熔点：
  72-740C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

代谢

para-羟基罗格列酮是罗格列酮已知的人类代谢物。

Para-hydroxyrosiglitazone is a known human metabolite of rosiglitazone.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  罗格列酮 在 cytochrome P₄₅₀ reductase 、 cytochrome b5 、 cytochrome P₄₅₀ 2C₈ (Cyp₂C₈) wild type 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 5-羟基罗格列酮
  参考文献：
  名称：

  Drug metabolism by CYP2C8.3 is determined by substrate dependent interactions with cytochrome P450 reductase and cytochrome b5

  摘要：

  Genetic polymorphisms in CYP2C8 can influence the metabolism of important therapeutic agents and cause interindividual variation in drug response and toxicity. The significance of the variant CYP2C8*3 has been controversial with reports of higher in vivo but lower in vitro activity compared to CYP2C8*1. In this study, the contribution of the redox partners cytochrome P450 reductase (CPR) and cytochrome b5 to the substrate dependent activity of CYP2C8.3 (R139K, K399R) was investigated in human liver microsomes (HLMs) and Escherichia call expressed recombinant CYP2C8 proteins using amodiaquine, paclitaxel, rosiglitazone and cerivastatin as probe substrates. For recombinant CYP2C8.3, clearance values were two- to five-fold higher compared to CYP2C8.1. CYP2C8.3's higher k(cat) seems to be dominated by a higher, but substrate specific affinity, towards cytochrome b5 and CPR (K(D) and K(m,red)) which resulted in increased reaction coupling. A stronger binding affinity of ligands to CYP2C8.3, based on a two site binding model, in conjunction with a five fold increase in amplitude of heme spin change during binding of ligands and redox partners could potentially contribute to a higher k(cat), in HLMs, carriers of the CYP2C8*1/*3 genotype were as active as CYP2C8*1/*1 towards the CYP2C8 specific reaction amodiaquine N-deethylation. Large excess of cytochrome b5 compared to CYP2C8 in recombinant systems and HLMs inhibited metabolic clearance, diminishing the difference in k(cat) between the two enzymes, and may provide an explanation for the discrepancy to in vivo data. In silico studies illustrate the genetic differences between wild type and variant on the molecular level. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2011.06.027

文献信息

• Pharmaceutical compositions containing thiazolidinedione derivatives and process for their preparation
  申请人：SmithKline Beecham p.l.c.

  公开号：US20030125358A1

  公开（公告）日：2003-07-03

  A method for reducing post-ischaemic injury of the heart and/or improving the functional recovery of the heart following myocardial ischaemia which method comprises administration of an effective, non-toxic amount of a glucose uptake enhancer to a human or non-human mammal in need thereof

  一种减少心脏缺血后损伤和/或改善心肌缺血后心脏功能恢复的方法，该方法包括向需要的人或非人哺乳动物施用有效、无毒量的葡萄糖摄取增强剂
• PHARMACEUTICAL COMPOSITIONS CONTAINING THIAZOLIDINEDIONE DERIVATIVES AND PROCESS FOR THEIR PREPARATION
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1202991A1

  公开（公告）日：2002-05-08
• [EN] PHARMACEUTICAL COMPOSITIONS CONTAINING THIAZOLIDINEDIONE DERIVATIVES AND PROCESS FOR THEIR PREPARATION<br/>[FR] COMPOSITIONS PHARMACEUTIQUES CONTENANT DES DERIVES DE THIAZOLIDINEDIONE ET PROCEDE DE PREPARATION
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2001012628A1

  公开（公告）日：2001-02-22

  A pharmaceutical composition which composition comprises an effective non-toxic amount of a compound of formula (I), or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof, and/or a pharmaceutically acceptable solvate thereof, wherein: A1 represents OH or -OSO¿2OH; R?1 represents a hydrogen atom or a C¿1-6? alkyl group; and R?2 and R3¿ each represent hydrogen or R?2 and R3¿ together represent a bond; and a pharmaceutically acceptable carrier therefor; certain novel compounds used in such a composition and the use of such compounds and composition in medicine.