2-chloro-N-cyclobutyl-5-(trifluoromethyl)pyrimidin-4-amine | 1187590-86-8

• 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-N-cyclobutyl-5-(trifluoromethyl)pyrimidin-4-amine
• 英文别名: (2-chloro-5-trifluoromethyl-pyrimidin-4-yl)-cyclobutyl-amine；2-chloro-N-cyclobutyl-5-trifluoromethylpyrimidin-4-amine
• CAS: 1187590-86-8
• 化学式: C₉H₉ClF₃N₃
• 分子量: 251.639
• InChiKey: JYUNMGCHCKSBCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-氨基-7-氮杂吲哚 、 2-chloro-N-cyclobutyl-5-(trifluoromethyl)pyrimidin-4-amine 在 溶剂黄146 作用下， 反应 0.33h， 以50 mg的产率得到N⁴-cyclobutyl-N²-(1H-pyrrolo[2,3-b]pyridin-5-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer

  摘要：

  Inhibition of autophagy, the major cellular recycling pathway in mammalian cells, is a promising strategy for the treatment of triple-negative breast cancer (TNBC). We previously reported SBI-0206965, a small molecule inhibitor of unc-51-like autophagy activating kinase 1 (ULK1), which is a key regulator of autophagy initiation. Herein, we describe the design, synthesis, and characterization of new dual inhibitors of ULK1 and ULK2 (ULK1/2). One inhibitor, SBP-7455 (compound 26), displayed improved binding affinity for ULK1/2 compared with SBI-0206965, potently inhibited ULK1/2 enzymatic activity in vitro and in cells, reduced the viability of TNBC cells and had oral bioavailability in mice. SBP-7455 inhibited starvation-induced autophagic flux in TNBC cells that were dependent on autophagy for survival and displayed synergistic cytotoxicity with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib against TNBC cells. These data suggest that combining ULK1/2 and PARP inhibition may have clinical utility for the treatment of TNBC.

  DOI：

  10.1021/acs.jmedchem.0c00873
• 作为产物：
  描述：

  环丁基胺 、 2,4-二氯-5-三氟甲基嘧啶 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.17h， 生成 2-chloro-N-cyclobutyl-5-(trifluoromethyl)pyrimidin-4-amine
  参考文献：
  名称：

  Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer

  摘要：

  Inhibition of autophagy, the major cellular recycling pathway in mammalian cells, is a promising strategy for the treatment of triple-negative breast cancer (TNBC). We previously reported SBI-0206965, a small molecule inhibitor of unc-51-like autophagy activating kinase 1 (ULK1), which is a key regulator of autophagy initiation. Herein, we describe the design, synthesis, and characterization of new dual inhibitors of ULK1 and ULK2 (ULK1/2). One inhibitor, SBP-7455 (compound 26), displayed improved binding affinity for ULK1/2 compared with SBI-0206965, potently inhibited ULK1/2 enzymatic activity in vitro and in cells, reduced the viability of TNBC cells and had oral bioavailability in mice. SBP-7455 inhibited starvation-induced autophagic flux in TNBC cells that were dependent on autophagy for survival and displayed synergistic cytotoxicity with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib against TNBC cells. These data suggest that combining ULK1/2 and PARP inhibition may have clinical utility for the treatment of TNBC.

  DOI：

  10.1021/acs.jmedchem.0c00873

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 Anilinopyrimides
  申请人：Greul Jörg Nico

  公开号：US20110245242A1

  公开（公告）日：2011-10-06

  Heterocyclically substituted anilinopyrimidines of the formula (I) in which R 1 to R 10 and L 1 , L 2 , E1, E2, E3, Y and Z 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R10和L1、L2、E1、E2、E3、Y和Z的含义如描述中所示，以及其农药活性盐，它们的用途以及用于控制植物或植物种子中和/或上的植物病原有害真菌的方法和组合物，制备这种组合物的过程以及处理后的种子以及它们在农业、园艺和林业中用于控制植物病原有害真菌，在材料保护以及家庭和卫生领域。此外，本发明还涉及制备公式（I）中的杂环取代苯基嘧啶的方法。
• 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。
• Alkoxy- and Alkylthio-Substituted Anilinopyrimidines
  申请人：Greul Jörg Nico

  公开号：US20110245284A1

  公开（公告）日：2011-10-06

  Alkoxy- and alkylthio-substituted anilinopyrimidines of the formula (I) in which R 1 to R 14 and E1, E2, E3, X and Y have the meanings given in the description, and agrochemically active salts thereof, their use, and methods and compositions for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on seeds of plants, processes for preparing such compositions and treated seeds and also their use for controlling phytopathogenic hal inful 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 the preparation of alkoxy- and alkylthio-substituted anilinopyrimidines of the formula (I).

  配方（I）中的烷氧基和烷硫基取代的苯胺嘧啶化合物，其中R1至R14和E1、E2、E3、X和Y的含义如描述中所示，以及其农用活性盐、它们的用途，用于控制植物或种子中和/或上的植物病原有害真菌的方法和组合物，用于制备这种组合物的过程和处理过的种子，以及它们在农业、园艺和林业中控制植物病原有害真菌、保护材料以及在家庭和卫生领域中的用途。本发明还涉及一种制备配方（I）中的烷氧基和烷硫基取代的苯胺嘧啶化合物的方法。
• Diaminopyrimidines as crop protection agents
  申请人：Greul Jörg Nico

  公开号：US20110105472A1

  公开（公告）日：2011-05-05

  Use of diaminopyrimidines of the formula (I) in which R 1 to R 11a,b,c and X 1 , X 2 have the meanings given in the description, and also agrochemically active salts thereof as crop protection agents. Diaminopyrimidines of the formulae (Ia), (Ib) and (Ic) in which R 8a , R 8b , R 8c , and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11a,b,c and X 1 , X 2 have the meanings given in the description, and also agrochemically active salts thereof and their use for controlling animal pests and/or phytopathogenic harmful fungi.

  使用公式（I）中的二氨基嘧啶，其中R1至R11a，b，c和X1，X2具有描述中给出的含义，以及其农业化学活性盐作为作物保护剂。公式（Ia），（Ib）和（Ic）的二氨基嘧啶中，R8a，R8b，R8c，以及R1，R2，R3，R4，R5，R6，R7，R8，R9，R10，R11a，b，c和X1，X2具有描述中给出的含义，以及其农业化学活性盐及其用于控制动物害虫和/或植物病原真菌。