3-咪唑并[1,2-a]吡啶-3-基-4-[1,2,3,4-四氢-2-(1-哌啶基羰基)吡咯并[3,2,1-jk][1,4]苯并二氮杂卓-7-基]-1H-吡咯-2,5-二酮 | 603281-60-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 3-咪唑并[1,2-a]吡啶-3-基-4-[1,2,3,4-四氢-2-(1-哌啶基羰基)吡咯并[3,2,1-jk][1,4]苯并二氮杂卓-7-基]-1H-吡咯-2,5-二酮
• 英文名称: LY2090314
• 英文别名: 3-Imidazo[1,2-a]pyridin-3-yl-4-[10-(piperidine-1-carbonyl)-1,10-diazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-3-yl]pyrrole-2,5-dione
• CAS: 603281-60-3
• 化学式: C₂₈H₂₆N₆O₃
• 分子量: 494.553
• InChiKey: HHSIUHRARDLCPM-UHFFFAOYSA-N

物化性质

• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  37
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-咪唑[1,2-A]吡啶-3-基-乙酰胺 在 盐酸 、 TEA 、 potassium tert-butylate 、 乙硫醇 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-咪唑并[1,2-a]吡啶-3-基-4-[1,2,3,4-四氢-2-(1-哌啶基羰基)吡咯并[3,2,1-jk][1,4]苯并二氮杂卓-7-基]-1H-吡咯-2,5-二酮
  参考文献：
  名称：

  The development of potent and selective bisarylmaleimide GSK3 inhibitors

  摘要：

  Many 3-aryl-4-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl)maleimides exhibit potent GSK3 inhibitory activity (<100 nM IC50), although few show significant selectivity (>100x) versus CDK2, CDK4, or PKCbetaII. However, combining 3-(imidazo[1,2-a]pyridin-3-yl), 3-(pyrazolo[1,5-a]pyridin-3-yl) or aza-analogs with a 4-(2-acyl-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl)) group on the maleimide resulted in very potent inhibitors of GSK3 (less than or equal to5 nM) with >160 to >10,000-fold selectivity versus CDK2/4 and PKCbetaII, These compounds also inhibited tau phosphorylation in cells and were effective in lowering plasma glucose in a rat model of type 2 diabetes (ZDF rat). (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.12.063

文献信息

• Substituted 3-Imidazo[1,2-<i>a</i>]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino- [6,7,1-<i>hi</i>]indol-7-yl)pyrrole-2,5-diones as Highly Selective and Potent Inhibitors of Glycogen Synthase Kinase-3
  作者：Thomas A. Engler、James R. Henry、Sushant Malhotra、Brian Cunningham、Kelly Furness、Joseph Brozinick、Timothy P. Burkholder、Michael P. Clay、Joshua Clayton、Clive Diefenbacher、Eric Hawkins、Philip W. Iversen、Yihong Li、Terry D. Lindstrom、Angela L. Marquart、Johnathan McLean、David Mendel、Elizabeth Misener、Daniel Briere、John C. O'Toole、Warren J. Porter、Steven Queener、Jon K. Reel、Rebecca A. Owens、Richard A. Brier、Thomas E. Eessalu、Jill R. Wagner、Robert M. Campbell、Renee Vaughn

  DOI：10.1021/jm049768a

  日期：2004.7.1

  Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
• TGFß SIGNALING INDEPENDENT NAÏVE INDUCED PLURIPOTENT STEM CELLS, METHODS OF MAKING AND USE
  申请人：HONG GUAN Ltd.

  公开号：US20170191038A1

  公开（公告）日：2017-07-06

  Provided is a cocktail of factors for converting/reprogramming non-naïve pluripotent stem cells into TGFβ signaling-independent (TSI) naïve induced pluripotent stem cells (iPSCs). Also provided are methods for reprograming a non-naïve PSC into a TSI naïve iPSC by contacting the cell to be reprogrammed with effective amounts of compounds for a sufficient period of time to reprogram the cell into a TSI naïve iPSC.
• [EN] COMPOSITIONS AND METHODS FOR GENERATING HAIR CELLS BY UPREGULATING JAG-1<br/>[FR] COMPOSITIONS ET MÉTHODES POUR GÉNÉRER DES CELLULES CILIÉES PAR LA RÉGULATION À LA HAUSSE DE JAG-1
  申请人：FREQUENCY THERAPEUTICS INC

  公开号：WO2020037323A1

  公开（公告）日：2020-02-20

  Provided are compositions and methods comprising Jag-1 agonists for increasing proliferation of cochlear supporting cells or vestibular supporting cells, and related methods of treating hearing or balance disorders.
• The development of potent and selective bisarylmaleimide GSK3 inhibitors
  作者：Thomas A. Engler、Sushant Malhotra、Timothy P. Burkholder、James R. Henry、David Mendel、Warren J. Porter、Kelly Furness、Clive Diefenbacher、Angela Marquart、Jon K. Reel、Yihong Li、Joshua Clayton、Brian Cunningham、Johnathan McLean、John C. O’Toole、Joseph Brozinick、Eric Hawkins、Elizabeth Misener、Daniel Briere、Richard A. Brier、Jill R. Wagner、Robert M. Campbell、Bryan D. Anderson、Renee Vaughn、Donald B. Bennett、Timothy I. Meier、James A. Cook

  DOI：10.1016/j.bmcl.2004.12.063

  日期：2005.2

  Many 3-aryl-4-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl)maleimides exhibit potent GSK3 inhibitory activity (<100 nM IC50), although few show significant selectivity (>100x) versus CDK2, CDK4, or PKCbetaII. However, combining 3-(imidazo[1,2-a]pyridin-3-yl), 3-(pyrazolo[1,5-a]pyridin-3-yl) or aza-analogs with a 4-(2-acyl-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl)) group on the maleimide resulted in very potent inhibitors of GSK3 (less than or equal to5 nM) with >160 to >10,000-fold selectivity versus CDK2/4 and PKCbetaII, These compounds also inhibited tau phosphorylation in cells and were effective in lowering plasma glucose in a rat model of type 2 diabetes (ZDF rat). (C) 2005 Elsevier Ltd. All rights reserved.