5-[1-{4-[2-(Methyl-pyrazin-2-yl-amino)-ethoxy]-phenyl}-meth-(Z)-ylidene]-thiazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-[1-{4-[2-(Methyl-pyrazin-2-yl-amino)-ethoxy]-phenyl}-meth-(Z)-ylidene]-thiazolidine-2,4-dione
• 英文别名: (5Z)-5-[[4-[2-[methyl(pyrazin-2-yl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione
• 化学式: C₁₇H₁₆N₄O₃S
• 分子量: 356.405
• InChiKey: FGBHIENLRYOSLT-UVTDQMKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 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-[1-{4-[2-(Methyl-pyrazin-2-yl-amino)-ethoxy]-phenyl}-meth-(Z)-ylidene]-thiazolidine-2,4-dione 在 甲醇 、 碘 、 magnesium 作用下， 反应 2.0h， 以2%的产率得到5-{4-[2-(Methyl-pyrazin-2-yl-amino)-ethoxy]-benzyl}-thiazolidine-2,4-dione
  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
• 作为产物：
  描述：

  2-[Methyl(2-pyrazinyl)amino]-1-ethanol 在 哌啶乙酸盐 、 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 20.0h， 生成 5-[1-{4-[2-(Methyl-pyrazin-2-yl-amino)-ethoxy]-phenyl}-meth-(Z)-ylidene]-thiazolidine-2,4-dione
  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

• [EN] INHIBITORS OF THE NOTCH TRANSCRIPTIONAL ACTIVATION COMPLEX AND METHODS FOR USE OF THE SAME<br/>[FR] INHIBITEURS DU COMPLEXE D'ACTIVATION DE TRANSCRIPTION DU RÉCEPTEUR NOTCH ET PROCÉDÉS D'UTILISATION DE CES DERNIERS
  申请人：UNIV MIAMI

  公开号：WO2016154255A1

  公开（公告）日：2016-09-29

  Disclosed herein are inhibitors of the Notch transcriptional activation complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: Formula (I), wherein the substituents are as described.

  本文披露了Notch转录激活复合物的抑制剂，以及它们在治疗或预防疾病（如癌症）中的使用方法。本文描述的抑制剂可以包括式（I）的化合物及其药用可接受盐：式（I），其中取代基如所述。
• Inhibitors of the Notch transcriptional activation complex and methods for use of the same
  申请人：UNIVERSITY OF MIAMI

  公开号：US10501413B2

  公开（公告）日：2019-12-10

  Disclosed herein are inhibitors of the Notch transcriptional activation complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: Formula (I), wherein the substituents are as described.

  本文公开了 Notch 转录激活复合物的抑制剂，以及将其用于治疗或预防癌症等疾病的方法。本文所述的抑制剂可包括式（I）化合物及其药学上可接受的盐类：式 (I)，其中取代基如所述。
• INHIBITORS OF THE NOTCH TRANSCRIPTIONAL ACTIVATION COMPLEX AND METHODS FOR USE OF THE SAME
  申请人：SPYVEE Mark

  公开号：US20180086700A1

  公开（公告）日：2018-03-29

  Disclosed herein are inhibitors of the Notch transcriptional activation complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically acceptable salts thereof: Formula (I), wherein the substituents are as described.
• [[.omega.-(Heterocyclylamino)alkoxy]benzyl]-2,4-thiazolidinediones as potent antihyperglycemic agents
  作者：Barrie C. C. Cantello、Michael A. Cawthorne、Graham P. Cottam、Peter T. Duff、David Haigh、Richard M. Hindley、Carolyn A. Lister、Stephen A. Smith、Peter L. Thurlby

  DOI：10.1021/jm00049a017

  日期：1994.11

  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.