4-(2-(trifluoromethyl)phenyl)pyrimidin-2-amine | 1159820-24-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-(2-(trifluoromethyl)phenyl)pyrimidin-2-amine
• 英文别名: 2-Amino-4-(2-trifluoromethylphenyl)pyrimidine；4-[2-(trifluoromethyl)phenyl]pyrimidin-2-amine
• CAS: 1159820-24-2
• 化学式: C₁₁H₈F₃N₃
• 分子量: 239.2
• InChiKey: UTMQFRVOXZKELB-UHFFFAOYSA-N

物化性质

• 沸点：
  403.5±55.0 °C(Predicted)
• 密度：
  1.351±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-acetyl-4-morpholino-2-oxo-2H-benzopyran-7-yltrifluoromethanesulfonate 、 4-(2-(trifluoromethyl)phenyl)pyrimidin-2-amine 在 palladium diacetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 甲苯 为溶剂， 以43%的产率得到3-acetyl-4-morpholino-7-((4-(2-(trifluoromethyl)phenyl)pyrimidin-2-yl)amino)-2H-chromen-2-one
  参考文献：
  名称：

  Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity

  摘要：

  Specific inhibition of CDK9 is considered a promising strategy for developing effective anticancer therapeutics. However, most of the reported CDK9 inhibitors are still at an early stage of development and lack selectivity against other CDKs. Herein, we discovered coumarin derivative 30i as a potent CDK9 inhibitor with high selectivity (8300-fold over CDK7). Binding mode analysis illustrated that the substituent coumarin moiety is a critical group for CDK9 selectivity by occupying a flexible hinge/alpha D region, which is sterically hindered in other CDKs. Compound 30i showed excellent cellular antiproliferative activity, moderate pharmacokinetic property and low hERG inhibition. Moreover, 30i significantly induced tumour growth inhibition in a dose-dependent manner without causing an obvious loss of body weight in an MV4-11 xenograft mice model. Altogether, these results suggest that 30i may serve as a potential acute myeloid leukaemia (AML) therapeutics by selectively targeting CDK9. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112424
• 作为产物：
  描述：

  2-氨基-4-氯嘧啶 、 2-(三氟甲基)苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以55%的产率得到4-(2-(trifluoromethyl)phenyl)pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity

  摘要：

  Specific inhibition of CDK9 is considered a promising strategy for developing effective anticancer therapeutics. However, most of the reported CDK9 inhibitors are still at an early stage of development and lack selectivity against other CDKs. Herein, we discovered coumarin derivative 30i as a potent CDK9 inhibitor with high selectivity (8300-fold over CDK7). Binding mode analysis illustrated that the substituent coumarin moiety is a critical group for CDK9 selectivity by occupying a flexible hinge/alpha D region, which is sterically hindered in other CDKs. Compound 30i showed excellent cellular antiproliferative activity, moderate pharmacokinetic property and low hERG inhibition. Moreover, 30i significantly induced tumour growth inhibition in a dose-dependent manner without causing an obvious loss of body weight in an MV4-11 xenograft mice model. Altogether, these results suggest that 30i may serve as a potential acute myeloid leukaemia (AML) therapeutics by selectively targeting CDK9. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112424

文献信息

• [EN] SUBSTITUTED TRIAZOLE AND IMIDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS<br/>[FR] DÉRIVÉS DE TRIAZOLE ET D'IMIDAZOLE SUBSTITUÉS EN TANT QUE MODULATEURS DE GAMMA SECRÉTASE
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2011006903A1

  公开（公告）日：2011-01-20

  The present invention is concerned with novel substituted triazole and imidazole derivatives of Formula (I) wherein R1, R2, A1, A2, A3, A4, X, and Het1 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

  本发明涉及具有以下式（I）的新型取代三唑和咪唑衍生物，其中R1、R2、A1、A2、A3、A4、X和Het1的含义如权利要求中所定义。根据本发明的化合物可用作γ-分泌酶调节剂。该发明还涉及制备这种新型化合物的方法，包含所述化合物作为活性成分的药物组合物，以及将所述化合物用作药物的用途。
• SUBSTITUTED TRIAZOLE AND IMIDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
  申请人：Janssen Pharmaceuticals Inc.

  公开号：EP2454239B1

  公开（公告）日：2014-08-13
• NOVEL SUBSTITUTED TRIAZOLE AND IMIDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
  申请人：Wu Tongfei

  公开号：US20120135981A1

  公开（公告）日：2012-05-31

  The present invention is concerned with novel substituted triazole and imidazole derivatives of Formula (I) wherein R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , X, and Het 1 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
• US8946266B2
  申请人：——

  公开号：US8946266B2

  公开（公告）日：2015-02-03
• [EN] ANTI VIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX
  申请人：PASTEUR INSTITUT KOREA

  公开号：WO2010046780A2

  公开（公告）日：2010-04-29

  There is provided small molecule anti-human immunodeficiency virus (anti-HIV) compounds as well as a phenotypic cell-based high throughput screening (HTS) assay for their identification.