3-(6-Methylimidazo[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

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 3-(6-Methylimidazo[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
• 化学式: C₂₉H₂₈N₆O₃
• 分子量: 508.58
• InChiKey: UAZPEMYGGMNSTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  38
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.31
• 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-(二丁氧基甲基)-4-氟-1-硝基苯 在 palladium on activated charcoal 盐酸 、 potassium tert-butylate 、 氢气 、 sodium hydride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 12.67h， 生成 3-(6-Methylimidazo[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
  参考文献：
  名称：

  Substituted 3-Imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino- [6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as Highly Selective and Potent Inhibitors of Glycogen Synthase Kinase-3

  摘要：

  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.

  DOI：

  10.1021/jm049768a

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.