5-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzyl]-2,4-thiazolidinedione | 122320-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 5-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzyl]-2,4-thiazolidinedione
• 英文别名: 5-(4-[2-(N-methyl-N-(2-benzoxazolyl)amino)ethoxy] benzyl)-2,4-thiazolidinedione；BRL 48482；5-<<4-<2-(2-benzoxazolylmethylamino)ethoxy>phenyl>methyl>-2,4-thiazolidinedione；5-(4-<2-ethoxy>benzyl)thiazolidine-2,4-dione；5-(4-[2-(N-methyl-N-(2-benzoxazolyl)amino)ethoxy]benzyl)-2,4-thiazolidinedione；5-[4-[2-(N-benzoxazol-2-yl)-N-methylamino]ethoxy]benzyl]thiazolidine-2,4-dione；5-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
• CAS: 122320-46-1
• 化学式: C₂₀H₁₉N₃O₄S
• 分子量: 397.455
• InChiKey: ZYKPNHFCNSVFNF-UHFFFAOYSA-N

物化性质

• 密度：
  1.377±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzyl]-2,4-thiazolidinedione 以 sodium hydroxide 、 乙酸乙酯 为溶剂， 生成 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-mercaptopropanoic acid
  参考文献：
  名称：

  Heterocyclic compounds and their use in the treatment of Type-II diabetes

  摘要：

  一种具有以下结构的化合物：A.sup.1 --X--(CH.sub.2).sub.n --O--A.sup.2 --A.sup.3 --CO.R.sup.2 (I)或其互变异构体和/或其药学上可接受的盐，和/或其药学上可接受的溶剂，其中：A.sup.1代表取代或未取代的芳香杂环基团；A.sup.2代表具有三个可选取代基团的苯环；A.sup.3代表具有式--(CH.sub.2).sub.m --CHR.sup.1 --的基团，其中R.sup.1代表卤素原子或式S(O).sub.p A.sup.4的基团，其中A.sup.4代表氢、取代或未取代的烷基、芳基、芳基烷基、烷基羰基或芳香杂环基团，p代表零或整数1或2，m代表零或范围在1到5之间的整数，或A.sup.3代表具有式--CH.dbd.CR.sup.1 --的基团，其中R.sup.1如上定义；R.sup.2代表OR.sup.3，其中R.sup.3代表氢、烷基、芳基或芳基烷基，或R.sup.2代表--NR.sup.4 R.sup.5，其中R.sup.4和R.sup.5各自独立地代表氢或烷基，或R.sup.4和R.sup.5与它们连接的氮原子一起形成杂环环；X代表O、S或NR，其中R代表氢原子、烷基、酰基、芳基烷基，其中芳基可能是取代或未取代的，或取代或未取代的芳基；n代表范围在2到6之间的整数；一种制备这种化合物的方法，包括这种化合物的药物组合物和这种化合物及组合物在医学中的用途。

  公开号：

  US05589492A1
• 作为产物：
  描述：

  2-氯苯并恶唑 在 palladium on activated charcoal 吡啶 、 氢气 、 哌啶乙酸盐 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 26.0h， 生成 5-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]benzyl]-2,4-thiazolidinedione
  参考文献：
  名称：

  [[.omega.-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents

  摘要：

  A series of [(ureidoethoxy)benzyl]-2,4-thiazolidinediones and [[(heterocyclylamino)alkoxy]-benzyl]-2,4-thiazolidinediones was synthesized from the corresponding aldehydes. Compounds from the urea series, exemplified by 16, showed antihyperglycemic potency comparable with known agents of the type such as pioglitazone and troglitazone (CS-045). The benzoxazole 49, a cyclic analogue of 16, was a very potent enhancer of insulin sensitivity, and by modification of the aromatic heterocycle, an aminopyridine, 37, was identified as a lead compound from SAR studies. Evaluation of antihyperglycemic activity together with effects on blood hemoglobin content, to determine the therapeutic index, was performed in 8-day repeat administration studies in genetically obese C57 Bl/6 ob/ob mice. From these studies, BRL 49653 (37) has been selected, on the basis of antihyperglycemic potency combined with enhanced selectivity against reductions in blood hemoglobin content, for further evaluation.

  DOI：

  10.1021/jm00049a017

文献信息

• Substituted thiazolidinedione derivatives
  申请人：BEECHAM GROUP PLC

  公开号：EP0842925A1

  公开（公告）日：1998-05-20

  Compounds of formula (I): or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A1 represents a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.

  式(I)的化合物，或其互变异构体，或其药学上可接受的盐，或其药学上可接受的溶剂化物，其中：A1代表取代或未取代的芳香杂环基团；R1代表氢原子、烷基团、酰基团、芳基烷基团，其中芳基部分可以是取代或未取代的，或取代或未取代的芳基基团；R2和R3各自代表氢，或R2和R3一起代表键；A2代表苯环，最多具有五个取代基；n代表在2到6范围内的整数；包含这种化合物的药学组合物以及这种化合物和组合物在医学上的用途。
• NOVEL COMPOUNDS
  申请人：Beecham Group p.1.c.

  公开号：US20020049240A1

  公开（公告）日：2002-04-25

  Compounds of formula (I): 1 or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: A 1 represents a substituted or unsubstituted aromatic heterocyclyl group; R 1 represents a hydrocarbon atom, an alkyl group, an acyl grup, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R 2 and R 3 each represent hydrogen, or R 2 and R 3 together represent a bond; A 2 represents a benzene ring having a total up to five substituents; and n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.

  化合物的式子（I）：其中1或其互变异构体，或其药学上可接受的盐，或其药学上可接受的溶剂盐，其中：A1代表取代或未取代的芳香杂环基团；R1代表碳氢原子，烷基，酰基，苯基烷基，其中芳基部分可能被取代或未取代，或者是取代或未取代的芳基基团；R2和R3分别代表氢，或者R2和R3一起代表一个键；A2代表苯环，具有最多五个取代基；n代表在2到6之间的整数；包含这种化合物的药物组合物以及这种化合物和组合物在医学上的用途。
• Use of thiazolidinediones for the treatment of atherosclerosis and eating disorders
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1306086A2

  公开（公告）日：2003-05-02

  The use 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 a substituted or unsubstituted aromatic heterocyclyl group; R1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; R2 and R3 each represent hydrogen, or R2 and R3 together represent a bond; A2 represents a benzene ring having in total up to five substituents; and n represents an integer in the range of from 2 to 6, for the manufacture of a medicament for use in the treatment and/or prophylaxis of atherosclerosis and/or for the regulation of appetite and food intake.

  使用式(I)化合物： 或其同分异构体和/或其药学上可接受的盐和/或其药学上可接受的溶液，其中 A1 代表取代或未取代的芳香杂环基团； R1 代表氢原子、烷基、酰基、芳烷基（其中芳基可以是取代或未取代的）或取代或未取代的芳基； R2 和 R3 各自代表氢，或 R2 和 R3 共同代表键； A2 代表一个苯环，其上总共有最多五个取代基；以及 n 代表 2-6 之间的整数，用于制造治疗和/或预防动脉粥样硬化和/或调节食欲和食物摄入的药物。
• Anti-Alzheimer's disease treatment of subjects identified by detecting the presence of a genetic variant in the TOMM40 gene at rs10524523
  申请人：Zinfandel Pharmaceuticals, Inc.

  公开号：EP2789695A1

  公开（公告）日：2014-10-15

  Provided herein is a method for identifying a genetic variant that is associated with development of a condition of interest (e.g., Alzheimer's disease), and genetic variants so identified. Methods of treatment with an active agent (e.g., with a particular active agent and/or at an earlier age) is also provided, upon detecting a genetic variant described herein. In some embodiments, the genetic variant is a deletion/insertion polymorphism (DIP) of the TOMM40 gene. Kits for determining if a subject is at increased risk of developing late onset Alzheimer's disease is also provided. Kits for determining if a subject is responsive to treatment for a condition of interest with an active agent are further provided..

  本文提供了一种用于鉴定与相关疾病（如阿尔茨海默病）发展相关的基因变异体的方法，以及所鉴定的基因变异体。还提供了在检测到本文所述基因变异体后使用活性制剂（如使用特定活性制剂和/或在较早年龄使用）进行治疗的方法。在某些实施方案中，基因变异是 TOMM40 基因的缺失/插入多态性（DIP）。还提供了用于确定受试者患晚期阿尔茨海默病的风险是否增加的试剂盒。还提供了用于确定受试者是否对活性制剂治疗相关疾病有反应的试剂盒。
• Method of identifying disease risk factors
  申请人：Zinfandel Pharmaceuticals, Inc.

  公开号：US10865449B2

  公开（公告）日：2020-12-15

  Provided herein is a method for identifying a genetic variant that is associated with development of a condition of interest (e.g., Alzheimer's disease), and genetic variants so identified. Methods of treatment with an active agent (e.g., with a particular active agent and/or at an earlier age) is also provided, upon detecting a genetic variant described herein. In some embodiments, the genetic variant is a deletion/insertion polymorphism (DIP) of the TOMM40 gene. Kits for determining if a subject is at increased risk of developing late onset Alzheimer's disease is also provided. Kits for determining if a subject is responsive to treatment for a condition of interest with an active agent are further provided.

  本文提供了一种用于鉴定与相关疾病（如阿尔茨海默病）发展相关的基因变异体的方法，以及所鉴定的基因变异体。还提供了在检测到本文所述基因变异体后使用活性制剂（如使用特定活性制剂和/或在较早年龄使用）进行治疗的方法。在某些实施方案中，基因变异是 TOMM40 基因的缺失/插入多态性（DIP）。还提供了用于确定受试者患晚期阿尔茨海默病的风险是否增加的试剂盒。还提供了用于确定受试者是否对活性制剂治疗相关疾病有反应的试剂盒。