3-(1-methylindol-3-yl)-4-{3-[((R)-2-hydroxy-2-hydroxymethyl)ethyloxy]phenyl}-1H-pyrrole-2,5-dione | 396090-78-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(1-methylindol-3-yl)-4-{3-[((R)-2-hydroxy-2-hydroxymethyl)ethyloxy]phenyl}-1H-pyrrole-2,5-dione
• 英文别名: 3-[3-[(2R)-2,3-dihydroxypropoxy]phenyl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione
• CAS: 396090-78-1
• 化学式: C₂₂H₂₀N₂O₅
• 分子量: 392.411
• InChiKey: PERSXWGSHFVFIB-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(1-methylindol-3-yl)-4-[3-((S)-2,2-dimethyl-1,3-dioxolan-4-ylmethyloxy)phenyl]-1H-pyrrole-2,5-dione 在 甲醇 、 对甲苯磺酸 作用下， 以63%的产率得到3-(1-methylindol-3-yl)-4-{3-[((R)-2-hydroxy-2-hydroxymethyl)ethyloxy]phenyl}-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Discovery of potent and bioavailable GSK-3β inhibitors

  摘要：

  Here we report on the discovery of a series of maleimides which have high potency and good selectivity for GSK-3 beta. The incorporation of polar groups afforded compounds with good bioavailability. The most potent compound 34 has an IC(50) of 0.6 nM for GSK-3 beta, over 100-fold selectivity against a panel of other kinases, and shows efficacy in rat osteoporosis models. The X-ray structure of GSK-3 beta protein with 34 bound revealed the binding mode of the template and provided insights for future optimization opportunities. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.038

文献信息

• 3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta
  申请人：——

  公开号：US20020052397A1

  公开（公告）日：2002-05-02

  This invention relates to inhibitors of glycogen synthase kinase- 3 &bgr;, methods of treating diseases characterized by an excess of Th 2 cytokines, and to 3 -indolyl- 4 -phenyl- 1 H-pyrrole- 2,5 -dione derivatives of Formula (I): 1 that are inhibitors of glycogen synthase kinase - 3 &bgr;, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.

  这项发明涉及抑制糖原合成酶激酶-3β的方法，用于治疗由Th2细胞因子过多引起的疾病，以及3-吲哚基-4-苯基-1H-吡咯-2,5-二酮衍生物的化合物(I)的方法：这些化合物是糖原合成酶激酶-3β的抑制剂，包含它们的药物组合物，使用它们的方法以及制备这些化合物的方法。
• US6479490B2
  申请人：——

  公开号：US6479490B2

  公开（公告）日：2002-11-12
• US7476676B2
  申请人：——

  公开号：US7476676B2

  公开（公告）日：2009-01-13
• Discovery of potent and bioavailable GSK-3β inhibitors
  作者：Leyi Gong、Don Hirschfeld、Yun-Chou Tan、J. Heather Hogg、Gary Peltz、Zafrira Avnur、Pete Dunten

  DOI：10.1016/j.bmcl.2010.01.038

  日期：2010.3

  Here we report on the discovery of a series of maleimides which have high potency and good selectivity for GSK-3 beta. The incorporation of polar groups afforded compounds with good bioavailability. The most potent compound 34 has an IC(50) of 0.6 nM for GSK-3 beta, over 100-fold selectivity against a panel of other kinases, and shows efficacy in rat osteoporosis models. The X-ray structure of GSK-3 beta protein with 34 bound revealed the binding mode of the template and provided insights for future optimization opportunities. (C) 2010 Elsevier Ltd. All rights reserved.