3-[3-(2,3-dihydroxy- propylamino)-phenyl]-4-(5-fluoro-1-methyl-1h-indol-3-yl)-pyrrole-2,5-dione | 396091-16-0

• 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-[3-(2,3-dihydroxy- propylamino)-phenyl]-4-(5-fluoro-1-methyl-1h-indol-3-yl)-pyrrole-2,5-dione
• 英文别名: 3-[3-(2,3-Dihydroxy-propylamino)-phenyl]-4-(5-fluoro-1-methyl-1H-indol-3-YL)-pyrrole-2,5-dione；3-[3-(2,3-dihydroxypropylamino)phenyl]-4-(5-fluoro-1-methylindol-3-yl)pyrrole-2,5-dione
• CAS: 396091-16-0
• 化学式: C₂₂H₂₀FN₃O₄
• 分子量: 409.417
• InChiKey: RPGZQOOZHIEPJW-UHFFFAOYSA-N

物化性质

• 沸点：
  754.2±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  30
• 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：
  104
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 甲醇 、 对甲苯磺酸 作用下， 反应 18.0h， 以66%的产率得到3-[3-(2,3-dihydroxy- propylamino)-phenyl]-4-(5-fluoro-1-methyl-1h-indol-3-yl)-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

• [EN] USE OF A GSK-3BETA INHIBITOR IN THE MANUFACTURE OF A MEDICAMENT FOR INCREASING BONE FORMATION<br/>[FR] UTILISATION D'UN INHIBITEUR DE GSK-3 BETA DANS LA FABRICATION D'UN MEDICAMENT POUR ACCROITRE LA FORMATION OSSEUSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2003057202A1

  公开（公告）日：2003-07-17

  This invention relates to the use of inhibitors of glycogen synthase kinase-3β to increase bone formation.

  本发明涉及使用糖原合酶激酶-3β抑制剂来增加骨形成。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• 3-INDOLYL-4-PHENYL-1H-PYRROLE-2,5-DIONE DERIVATIVES AS INHIBITORS OF GLYCOGEN SYNTHASE KINASE-3BETA
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1307447A2

  公开（公告）日：2003-05-07
• USE OF A GSK-3BETA INHIBITOR IN THE MANUFACTURE OF A MEDICAMENT FOR INCREASING BONE FORMATION
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1465610B1

  公开（公告）日：2008-12-31
• ADVANCED DRUG DEVELOPMENT AND MANUFACTURING
  申请人：Los Alamos National Security, LLC

  公开号：EP2084519A2

  公开（公告）日：2009-08-05