(S)-1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(1-(2-((2-hydroxypropyl)amino)pyrimidin-4-yl)-1H-imidazole-2-carbonyl)phenyl)urea | 1220701-49-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(1-(2-((2-hydroxypropyl)amino)pyrimidin-4-yl)-1H-imidazole-2-carbonyl)phenyl)urea
• 英文别名: (S)-1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(1-(2-(2-hydroxypropylamino)pyrimidin-4-yl)-1H-imidazole-2-carbonyl)phenyl)urea；1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[1-[2-[[(2S)-2-hydroxypropyl]amino]pyrimidin-4-yl]imidazole-2-carbonyl]phenyl]urea
• CAS: 1220701-49-4
• 化学式: C₂₅H₂₁ClF₃N₇O₃
• 分子量: 559.935
• InChiKey: UPSKPAPDLKEKDD-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (1H-imidazol-2-yl)(4-nitrophenyl)methanone 在 盐酸 、 铁粉 、 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 (S)-1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(1-(2-((2-hydroxypropyl)amino)pyrimidin-4-yl)-1H-imidazole-2-carbonyl)phenyl)urea
  参考文献：
  名称：

  Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

  摘要：

  The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 91, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50 = 38.3 nM and 8.79 nM). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.030

文献信息

• Imidazole-1-yl pyrimidine derivatives, or pharmacutically acceptable salt thereof, and pharmaceutic composition comprising the same as an active ingredient
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus

  公开号：US20160200706A1

  公开（公告）日：2016-07-14

  The present invention relates to a novel imidazole-1-yl pyrimidine derivative, a pharmaceutically acceptable salt thereof, and a pharmaceutic composition comprising the same. Since the imidazole-1-yl pyrimidine derivative according to the present invention shows the inhibition activity selectively to BRAF, BRAF mutants, or CRAF, it can be used to a pharmaceutic composition for preventing or treating cancer.

  本发明涉及一种新型咪唑-1-基嘧啶衍生物，其药用盐以及包含该衍生物的药物组合物。由于根据本发明，咪唑-1-基嘧啶衍生物显示出对BRAF、BRAF突变体或CRAF的选择性抑制活性，因此可用于预防或治疗癌症的药物组合物。
• [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.
• US9540348B2
  申请人：——

  公开号：US9540348B2

  公开（公告）日：2017-01-10
• Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors
  作者：Minjung Kim、Junghun Lee、Kyungjin Jung、Hyangmi Kim、Waqar Aman、Jae-Sang Ryu、Jung-Mi Hah

  DOI：10.1016/j.bmcl.2014.05.030

  日期：2014.8

  The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 91, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50 = 38.3 nM and 8.79 nM). (C) 2014 Elsevier Ltd. All rights reserved.