(2S)-3-[1-(3,5-difluorobenzyl)-1H-imidazol-4-yl]-2-{[4-(2-naphthyl)pyrimidin-2-yl]amino}propan-1-ol | 1084834-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2S)-3-[1-(3,5-difluorobenzyl)-1H-imidazol-4-yl]-2-{[4-(2-naphthyl)pyrimidin-2-yl]amino}propan-1-ol
• 英文别名: (2S)-3-[1-[(3,5-difluorophenyl)methyl]imidazol-4-yl]-2-[(4-naphthalen-2-ylpyrimidin-2-yl)amino]propan-1-ol
• CAS: 1084834-22-9
• 化学式: C₂₇H₂₃F₂N₅O
• 分子量: 471.509
• InChiKey: WKOJEUFMVANARS-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  75.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2S)-3-(1H-imidazol-4-yl)-2-{[4-(2-naphthyl)pyrimidin-2-yl]amino}propan-1-ol 、 3,5-二氟溴苄 在 sodium hydride 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 (2S)-3-[1-(3,5-difluorobenzyl)-1H-imidazol-4-yl]-2-{[4-(2-naphthyl)pyrimidin-2-yl]amino}propan-1-ol
  参考文献：
  名称：

  Hit to lead studies on (hetero)arylpyrimidines—Agonists of the canonical Wnt-β-catenin cellular messaging system

  摘要：

  A series of (hetero)arylpyrimidines agonists of the Wnt-beta-catenin cellular messaging system have been prepared. These compounds show activity in U2OS cells transfected with Wnt-3 alpha, TCF-luciferase, Dkk-1 and tk-Renilla. Selected compounds show minimal GSK-3 beta inhibition indicating that the Wnt-beta-catenin agonism activity most likely comes from interaction at Wnt-3 alpha/Dkk-1. Two examples 1 and 25 show in vivo osteogenic activity in a mouse calvaria model. One example 1 is shown to activate non-phosphorylated beta-catenin formation in bone. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.093

文献信息

• HETEROARYL/ARYL PYRIMIDINE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM
  申请人：BURSAVICH Matthew Gregory

  公开号：US20080287452A1

  公开（公告）日：2008-11-20

  The present invention relates to heteroaryl/aryl pyrimidine analogs, methods of making aryl/heteroaryl pyrimidine analogs, compositions comprising a aryl/heteroaryl pyrimidine analog, and methods for treating canonical Wnt-β-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a heteroaryl/aryl pyrimidine analog.

  本发明涉及杂环芳基/芳基嘧啶类似物，制备芳基/杂环芳基嘧啶类似物的方法，包含芳基/杂环芳基嘧啶类似物的组合物，以及治疗与经典Wnt-β-连环蛋白细胞信息传递系统相关疾病的方法，包括向需要的受试者施用有效量的杂环芳基/芳基嘧啶类似物。
• Hit to lead studies on (hetero)arylpyrimidines—Agonists of the canonical Wnt-β-catenin cellular messaging system
  作者：Adam M. Gilbert、Matthew G. Bursavich、Nippa Alon、Bheem M. Bhat、Frederick J. Bex、Michael Cain、Valerie Coleburn、Virginia Gironda、Paula Green、Diane B. Hauze、Yogendra Kharode、Girija Krishnamurthy、Matthew Kirisits、Ho-Sun Lam、Yao-Bin Liu、Sabrina Lombardi、Jeanne Matteo、Richard Murrills、John A. Robinson、Sally Selim、Michael Sharp、Raymond Unwalla、Usha Varadarajan、Weiguang Zhao、Paul J. Yaworsky

  DOI：10.1016/j.bmcl.2009.10.093

  日期：2010.1

  A series of (hetero)arylpyrimidines agonists of the Wnt-beta-catenin cellular messaging system have been prepared. These compounds show activity in U2OS cells transfected with Wnt-3 alpha, TCF-luciferase, Dkk-1 and tk-Renilla. Selected compounds show minimal GSK-3 beta inhibition indicating that the Wnt-beta-catenin agonism activity most likely comes from interaction at Wnt-3 alpha/Dkk-1. Two examples 1 and 25 show in vivo osteogenic activity in a mouse calvaria model. One example 1 is shown to activate non-phosphorylated beta-catenin formation in bone. (C) 2009 Elsevier Ltd. All rights reserved.