3-(morpholin-4-yl)-4-(trifluoromethyl)benzoic acid | 1369965-92-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 3-(morpholin-4-yl)-4-(trifluoromethyl)benzoic acid
• 英文别名: 3-morpholino-4-(trifluoromethyl)benzoic acid；3-morpholin-4-yl-4-(trifluoromethyl)benzoic acid
• CAS: 1369965-92-3
• 化学式: C₁₂H₁₂F₃NO₃
• 分子量: 275.227
• InChiKey: UKEXSXZLCOHDQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-(4-aminophenyl)(1-(2-((2-hydroxypropyl)amino)pyrimidin-4-yl)-1H-imidazol-2-yl)methanone 、 3-(morpholin-4-yl)-4-(trifluoromethyl)benzoic acid 在 N-[(dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[4-[1-[2-[[(2S)-2-hydroxypropyl]amino]pyrimidin-4-yl]imidazole-2-carbonyl]phenyl]-3-morpholin-4-yl-4-(trifluoromethyl)benzamide
  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。
• Design, synthesis, and in vitro evaluation of N-(3-(3-alkyl-1H-pyrazol-5-yl) phenyl)-aryl amide for selective RAF inhibition
  作者：Hoyong Jung、Jinwoong Kim、Daseul Im、Hyungwoo Moon、Jung-Mi Hah

  DOI：10.1016/j.bmcl.2019.01.003

  日期：2019.2

  Notorious oncogenic BRAF V600E plays a significant role in the signal transduction of the MAPK pathway, which is involved in tumor growth, especially in melanoma. Much effort has been made to suppress BRAF V600E through small molecules like vemurafenib and dabrafenib, but the MAPK pathway remains active through paradoxical activation, where CRAF transmits the signal of the MAPK pathway either alone or along with BRAF V600E. Therefore, we designed and synthesized a new series of N-(3-(3-alkyl-1H-pyrazol-5-yl) phenyl)-aryl amide/urea analogues that showed potent inhibitory activities against BRAF V600E and CRAF. Compound 7c exhibited particularly superior selectivity toward BRAF V600E and CRAF over 30 other protein kinases, implying that this chemotype could be investigated as a BRAF paradox breaker. (C) 2019 Elsevier Ltd. All rights reserved.
• Discovery of highly selective CRAF inhibitors, 3-carboxamido-2H-indazole-6-arylamide: In silico FBLD design, synthesis and evaluation
  作者：Waqar Aman、Junghun Lee、Minjung Kim、Songyi Yang、Hoyong Jung、Jung-Mi Hah

  DOI：10.1016/j.bmcl.2016.01.037

  日期：2016.2

  The recent success of vemurafenib shows the importance of selective BRAF V600E inhibition in melanoma. However, paradoxical activation by structurally diverse ATP-competitive RAF kinase inhibitors strongly suggests that selective CRAF inhibitors, not BRAF inhibitors, would be ideal for some Ras mutation cancer treatment. In this respect, we approached designing selective CRAF inhibitors starting from in silico fragment screening and synthesized a 3-carboxamido-2H-indazole-6-arylamide scaffold. Most of the compounds showed potent antiproliferative activity against the WM3629 melanoma cell line and the most promising compound, compound 10d, was found to be a potent and selective CRAF inhibitor with an IC50 value of 38.6 nM, which shows greater than 270-fold selectivity over BRAF kinase (9.45 mu M). (C) 2016 Elsevier Ltd. All rights reserved.
• N-(5-ARYLAMIDO-2-METHYLPHENYL)-5-METHYLISOOXAZOLE-4-CARBOXAMIDE DERAVATIVE, PHARMACEUTICAL ACCEPTABLE SALT THEREOF, METHOD FOR PREPARATION THEROF AND FMS KINASE INHIBITOR COMPRISING THE SAME AS ANACTIVE INGREDIENT
  申请人：Industry-University Cooperation Foundation Hanyang University ERICA Campus

  公开号：US20170273947A1

  公开（公告）日：2017-09-28

  The present invention relates to N-(5-arylamido-2-methylphenyl)-5-methylisoquoxazole-4-carboxamide derivative, or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising same. The compound according to the present invention exhibits an FMS kinase inhibitory activity and thus can be used as pharmaceutical composition for preventing and treating diseases associated therewith.
• US9540348B2
  申请人：——

  公开号：US9540348B2

  公开（公告）日：2017-01-10