(2-chloro-5-fluoro-pyrimidin-4-yl)-cyclopropyl-amine | 893772-23-1

• 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: (2-chloro-5-fluoro-pyrimidin-4-yl)-cyclopropyl-amine
• 英文别名: (2-chloro-5-fluoro-pyrimidin-4-yl)cyclopropylamine；2-chloro-N-cyclopropyl-5-fluoropyrimidin-4-amine
• CAS: 893772-23-1
• 化学式: C₇H₇ClFN₃
• mdl: MFCD07800343
• 分子量: 187.604
• InChiKey: QEMIWJUDZORNEP-UHFFFAOYSA-N

物化性质

• 沸点：
  352.5±27.0 °C(Predicted)
• 密度：
  1.553±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-吗啉基)苯胺 、 (2-chloro-5-fluoro-pyrimidin-4-yl)-cyclopropyl-amine 在 盐酸 作用下， 以 水 、 异丙醇 为溶剂， 反应 18.0h， 以58%的产率得到N4-cyclopropyl-5-fluoro-N2-(4-morpholinophenyl)-2,4-diaminepyrimidine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective Aurora A kinase inhibitors

  摘要：

  The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Here we synthesized 15 2,4diaminopyrimidines and evaluated their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects. These compounds generally exhibited more potent cytotoxicity against tumor cell lines compared with the VX-680 control, especially compound 11c, which showed the highest cytotoxicities, with IC50 values of 0.5-4.0 mu M. Compound 11c had more than 35-fold more selectivity for Aurora A over Aurora B, and molecular docking analysis indicated that compound 11c form better interaction with Aurora A both from the perspective of structure and energy. Furthermore, compound 11c induced G2/M cell cycle arrest in HeLa cells. This series of compounds has the potential for further development as selective Aurora A inhibitors for anticancer activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.044
• 作为产物：
  描述：

  2,4-二氯-5-氟嘧啶 、 环丙胺 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 生成 (2-chloro-5-fluoro-pyrimidin-4-yl)-cyclopropyl-amine
  参考文献：
  名称：

  VX-509（Decernotinib）的发现：一种有效的选择性Janus Kinase 3抑制剂，用于治疗自身免疫性疾病

  摘要：

  尽管存在几种治疗选择，但是仍然需要针对多种自身免疫疾病的更有效，安全和方便的治疗方法。靶向Janus酪氨酸激酶（JAKs）在细胞信号传导反应中起着重要作用，并且可以促进与疾病相关的异常免疫功能，它已成为开发新型自身免疫性疾病疗法的一种新颖且有吸引力的方法。我们针对免疫细胞中的关键信号激酶JAK3筛选了我们的化合物文库，并鉴定了多个支架对该支架表现出良好的抑制活性。选择了特定的目标支架1 H-吡咯并[2,3- b ]吡啶系列（7-氮杂吲哚），部分基于结合亲和力（K i）以及细胞效能的基础上。该化学系列的优化导致鉴定出一种新型，有效和选择性的JAK3抑制剂VX-509（地加罗非尼），与大鼠移植模型（HvG）相比，它在大鼠宿主体内显示出良好的疗效。基于这些发现，看来VX-509为治疗多种自身免疫性疾病提供了潜力。

  DOI：

  10.1021/acs.jmedchem.5b00301

文献信息

• [EN] IMIDAZOPYRIDINE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSINE KINASES<br/>[FR] DÉRIVÉS D'IMIDAZOPYRIDINE EN TANT QU'INHIBITEURS DE TYROSINES KINASES RÉCEPTRICES
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2009150240A1

  公开（公告）日：2009-12-17

  The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

  这项发明涉及新的双环杂环衍生物化合物，包括含有该化合物的药物组合物，以及利用该化合物治疗疾病，例如癌症。
• Heterocyclically Substituted Anilinopyrimidines
  申请人：Wasnaire Pierre

  公开号：US20110245249A1

  公开（公告）日：2011-10-06

  Heterocyclically substituted anilinopyrimidines of the formula (I) in which R 1 to R 12 and E1, E2, E3, L 1 , Y, Z and L 2 have the meanings given in the description, and agrochemically active salts thereof, their use and also methods and compositions for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on seed of plants, processes for preparing such compositions and treated seed and also their use for controlling phytopathogenic harmful fungi in agriculture, horticulture and forestry, in the protection of materials and in the domestic and hygiene field. The present invention furthermore relates to a process for preparing heterocyclically substituted anilinopyrimidinenes of the formula (I).

  公式(I)中的杂环取代苯基嘧啶，其中R1至R12和E1、E2、E3、L1、Y、Z和L2具有描述中给出的含义，以及其农用活性盐，它们的用途以及控制植物或种子中和/或植物中和/或植物种子上的植物病原真菌的方法和组合物，用于制备这种组合物的过程以及受处理的种子，以及其在农业、园艺和林业中控制植物病原真菌的用途，在材料保护以及家庭和卫生领域。本发明还涉及制备公式(I)中的杂环取代苯基嘧啶的方法。
• DIAMINOPYRIMIDINES AS FUNGICIDES
  申请人：Greul Joerg Nico

  公开号：US20100081679A1

  公开（公告）日：2010-04-01

  Use of diaminopyrimidines of the formula (I) in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X 1 , X 2 and A have the meanings given in the description, and also agrochemically active salts thereof as fungicides. Diaminopyrimidines of the formulae (Ia), (Ib), (Ic), (Id), (Ie), (If) in which R 8a , R 8b , R 8c , R 8d , R 8e , R 8f , R 3b , R 3c , R 3e , X 1b , X 1c , X 1e and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X 1 , X 2 and A have the meanings given in the description, and also agrochemically active salts thereof and their use for controlling unwanted microorganisms.

  使用公式(I)中的二氨基嘧啶，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和X1、X2和A具有描述中给出的含义，以及其作为杀菌剂的农药活性盐。公式(Ia)、(Ib)、(Ic)、(Id)、(Ie)、(If)中的二氨基嘧啶，其中R8a、R8b、R8c、R8d、R8e、R8f、R3b、R3c、R3e、X1b、X1c、X1e和R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和X1、X2和A具有描述中给出的含义，以及其作为农药活性盐的使用以及用于控制不受欢迎的微生物。
• PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
  申请人：Bhattacharya Kumar Samit

  公开号：US20080234303A1

  公开（公告）日：2008-09-25

  The present invention relates to a compound of the formula 1 or a pharmaceutically acceptable salt thereof, wherein Ar is a group of formula and R 1 , R 2 , R 13 , A, K, M, L 1 , L 2 , X, Y 1 , Y 2 , Q, salt thereof, wherein R 1 , R 2 , R 13 , A, K, L 1 , L 2 , W, X, Z 1 , Z 2 , Y 1 , Y 2 , Z 1 , Z 2 , M, Q, W, X, m, p and q are as defined herein. Such novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. The invention also relates to a method of using such compounds in the treatment of abnormal cell growth in mammals, especially humans, and to pharmaceutical compositions containing such compounds.

  本发明涉及式1的化合物或其药学上可接受的盐，其中Ar是式的基团，而R1、R2、R13、A、K、M、L1、L2、X、Y1、Y2、Q、其盐、R1、R2、R13、A、K、L1、L2、W、X、Z1、Z2、Y1、Y2、Z1、Z2、M、Q、W、X、m、p和q的定义如本文所述。这些新型嘧啶衍生物在哺乳动物中治疗异常细胞增长，如癌症方面具有用途。本发明还涉及使用这些化合物在哺乳动物，特别是人类中治疗异常细胞增长的方法，以及含有这些化合物的制药组合物。
• IMIDAZOPYRIDINE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSINE KINASES
  申请人：Berdini Valerio

  公开号：US20120208791A1

  公开（公告）日：2012-08-16

  The invention relates to new bicyclic heterocyclic derivative compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

  本发明涉及新的双环杂环衍生物化合物，涉及包含该化合物的药物组合物以及涉及使用该化合物治疗疾病，例如癌症的用途。