(S)-N-(3-(1-(2-(2-hydroxypropylamino)pyrimidin-4-yl)-1H-imidazol-2-yl)phenyl)-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide | 1220701-23-4

• 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: (S)-N-(3-(1-(2-(2-hydroxypropylamino)pyrimidin-4-yl)-1H-imidazol-2-yl)phenyl)-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide
• 英文别名: N-[3-[1-[2-[[(2S)-2-hydroxypropyl]amino]pyrimidin-4-yl]imidazol-2-yl]phenyl]-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide
• CAS: 1220701-23-4
• 化学式: C₂₉H₃₁F₃N₈O₂
• 分子量: 580.613
• InChiKey: DKFAHLYMYSORAF-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  3-(4-methyl-piperazin-1-yl)-5-trifluoromethyl-benzoic acid 、 (S)-1-(4-(2-(3-aminophenyl)-1H-imidazol-1-yl)pyrimidin-2-ylamino)propan-2-ol 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-N-(3-(1-(2-(2-hydroxypropylamino)pyrimidin-4-yl)-1H-imidazol-2-yl)phenyl)-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

  摘要：

  The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC50 = 0.62 and 4.49 mu M, respectively) and turned out to be a selective and potent CRAF inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.064

文献信息

• [EN] IMIDAZOLE DERIVATIVES AND COMPOSITIONS FOR TREATING MELANOMA<br/>[FR] DÉRIVÉS D'IMIDAZOLE ET COMPOSITIONS POUR LE TRAITEMENT D'UN MÉLANOME
  申请人：KOREA INST SCI & TECH

  公开号：WO2011049274A1

  公开（公告）日：2011-04-28

  The present invention relates to novel imidazole derivatives or pharmaceutically acceptable salts thereof, preparation methods thereof and pharmaceutical compositions for prevention and treatment of melanoma containing the same as active ingredients. The novel imidazole derivatives or pharmaceutically acceptable salts thereof according to the present invention have excellent inhibitory effects on various protein kinases, which cause melanoma, such as B-RAF, C-RAF, Aurora-A, BTK, Flt3, Ret, KDR/VEGFR2, P38a/MAPK14, RAF1, FMS, and the like, so they can be used for the prevention and treatment of melanoma.

  本发明涉及新型咪唑衍生物或其药学上可接受的盐、其制备方法和包含其作为活性成分的预防和治疗黑色素瘤的制药组合物。本发明的新型咪唑衍生物或其药学上可接受的盐对引起黑色素瘤的各种蛋白激酶具有出色的抑制作用，如B-RAF、C-RAF、Aurora-A、BTK、Flt3、Ret、KDR/VEGFR2、P38a/MAPK14、RAF1、FMS等，因此它们可用于预防和治疗黑色素瘤。
• Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines
  作者：Junghun Lee、Hwan Kim、Hana Yu、Jae Yoon Chung、Chang-Hyun Oh、Kyung Ho Yoo、Taebo Sim、Jung-Mi Hah

  DOI：10.1016/j.bmcl.2010.01.064

  日期：2010.3

  The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC50 = 0.62 and 4.49 mu M, respectively) and turned out to be a selective and potent CRAF inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.