2-(azepan-1-yl)-N-(5-phenyl-1H-pyrazol-3-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(azepan-1-yl)-N-(5-phenyl-1H-pyrazol-3-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
• 化学式: C₂₂H₂₆N₆
• 分子量: 374.489
• InChiKey: QXOLJHUEQFNGSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  69.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二氯-5,6-三甲基嘧啶 在 三乙胺 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 60.0h， 生成 2-(azepan-1-yl)-N-(5-phenyl-1H-pyrazol-3-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine
  参考文献：
  名称：

  Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor

  摘要：

  A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2- amino ring, 4-pyrazolo moieties and size of fused saturated ring with the central pyrimidine core. A stepwise optimization by combination of active fragments led to discovery of compound 6f and 6k, two structures with IGF-1R IC50 of 20 nM and 10 nM, respectively. 6f was further profiled for its anti cancer activity across various cell lines and pharmacokinetic studies in Sprague Dawley rats. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.053

文献信息

• [EN] BICYCLIC HETEROCYCLIC COMPOUNDS AS MULTI-KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES BICYCLIQUES UTILISÉS COMME INHIBITEURS DE PLUSIEURS KINASES
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015028848A1

  公开（公告）日：2015-03-05

  The present invention provides bicyclic heterocyclic compounds (the compounds of formula I, or an isotopic form, a stereoisomer or a tautomer or a pharmaceutically acceptable salt, a solvate, a polymorph, a prodrug or N-oxide thereof and processes for their preparation. The invention further relates to pharmaceutical compositions containing said compounds and their use in the treatment of diseases or disorders associated with abnormal protein kinase activity.

  本发明提供了双环杂环化合物（式I的化合物，或同位素形式、立体异构体、互变异构体或药学上可接受的盐、溶剂合物、多晶型、前药或N-氧化物及其制备方法。本发明还涉及含有所述化合物的药物组合物以及它们在治疗与异常蛋白激酶活性相关的疾病或紊乱中的用途。
• Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor
  作者：Valmik Aware、Nitin Gaikwad、Sambhaji Chavan、Sonal Manohar、Julie Bose、Smriti Khanna、Chandrika B-Rao、Neeta Dixit、Kishori Sharan Singh、Anagha Damre、Rajiv Sharma、Sambhaji Patil、Abhijit Roychowdhury

  DOI：10.1016/j.ejmech.2014.12.053

  日期：2015.3

  A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2- amino ring, 4-pyrazolo moieties and size of fused saturated ring with the central pyrimidine core. A stepwise optimization by combination of active fragments led to discovery of compound 6f and 6k, two structures with IGF-1R IC50 of 20 nM and 10 nM, respectively. 6f was further profiled for its anti cancer activity across various cell lines and pharmacokinetic studies in Sprague Dawley rats. (C) 2015 Elsevier Masson SAS. All rights reserved.