N4-(4-(trifluoromethyl)phenyl)-9H-indeno[2,1-d]pyrimidine-2,4-diamine | 1126602-58-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N4-(4-(trifluoromethyl)phenyl)-9H-indeno[2,1-d]pyrimidine-2,4-diamine
• 英文别名: N4-(4-trifluoromethyl-phenyl)-9H-indeno[2,1-d]pyrimidine-2,4-diamine；4-N-[4-(trifluoromethyl)phenyl]-9H-indeno[2,1-d]pyrimidine-2,4-diamine
• CAS: 1126602-58-1
• 化学式: C₁₈H₁₃F₃N₄
• 分子量: 342.323
• InChiKey: LREDHDABOIKCQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1,2-苯二乙腈 在 4-二甲氨基吡啶 、 硫酸 、 potassium tert-butylate 、 sodium 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 、 叔丁醇 为溶剂， 反应 18.0h， 生成 N4-(4-(trifluoromethyl)phenyl)-9H-indeno[2,1-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents

  摘要：

  We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfonation of the 4-position followed by displacement with appropriately substituted anilines afforded the target compounds. These compounds were potent inhibitors of platelet-derived growth factor receptor beta (PDGFR beta) and inhibited angiogenesis in the chicken embryo chorioallantonic membrane (CAM) assay compared to standards. In addition, compound 7 had a two digit nanomolar GI(50) against nine tumor cell lines, a submicromolar GI(50) against 29 of other tumor cell lines in the preclinical NCI 60 tumor cell line panel. Compound 7 also demonstrated significant in vivo inhibition of tumor growth and angiogenesis in a B16-F10 syngeneic mouse melanoma model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.068

文献信息

• Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents
  作者：Aleem Gangjee、Ying Zhao、Michael A. Ihnat、Jessica E. Thorpe、Lora C. Bailey-Downs、Roy L. Kisliuk

  DOI：10.1016/j.bmc.2012.05.068

  日期：2012.7

  We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfonation of the 4-position followed by displacement with appropriately substituted anilines afforded the target compounds. These compounds were potent inhibitors of platelet-derived growth factor receptor beta (PDGFR beta) and inhibited angiogenesis in the chicken embryo chorioallantonic membrane (CAM) assay compared to standards. In addition, compound 7 had a two digit nanomolar GI(50) against nine tumor cell lines, a submicromolar GI(50) against 29 of other tumor cell lines in the preclinical NCI 60 tumor cell line panel. Compound 7 also demonstrated significant in vivo inhibition of tumor growth and angiogenesis in a B16-F10 syngeneic mouse melanoma model. (C) 2012 Elsevier Ltd. All rights reserved.