6-methoxy-4-(piperidin-4-yl)quinazoline | 1044931-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-methoxy-4-(piperidin-4-yl)quinazoline
• 英文别名: 6-Methoxy-4-piperidin-4-ylquinazoline
• CAS: 1044931-27-2
• 化学式: C₁₄H₁₇N₃O
• 分子量: 243.308
• InChiKey: AFJFULLYEXVSNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methoxy-4-(piperidin-4-yl)quinazoline 、 4-(三氟甲氧基)苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以19%的产率得到(4-(6-methoxyquinazolin-4-yl)piperidin-1-yl)(4-(trifluoromethoxy)phenyl)methanone
  参考文献：
  名称：

  Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5

  摘要：

  The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction, and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis, and cell survival. We could demonstrate that inhibition of ERKS kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.

  DOI：

  10.1021/acs.jmedchem.8b01606
• 作为产物：
  描述：

  4-氯-6-甲氧基喹唑啉 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 10% palladium hydroxide on charcoal 、 氢气 、 sodium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 20.0~100.0 ℃ 、303.99 kPa 条件下， 反应 5.5h， 生成 6-methoxy-4-(piperidin-4-yl)quinazoline
  参考文献：
  名称：

  Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5

  摘要：

  The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction, and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis, and cell survival. We could demonstrate that inhibition of ERKS kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.

  DOI：

  10.1021/acs.jmedchem.8b01606

文献信息

• ALKYLQUINOLINE AND ALKYLQUINAZOLINE KINASE MODULATORS
  申请人：Baindur Nand

  公开号：US20060281772A1

  公开（公告）日：2006-12-14

  The invention is directed to alkylquinoline and alkylquinazoline compounds of Formula I: wherein R 1 , R 2 , R 3 , B, Z, G, Q and X are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

  该发明涉及Formula I的烷基喹啉和烷基喹噁啉化合物： 其中R1、R2、R3、B、Z、G、Q和X如本文所定义，所述化合物的用途为蛋白酪氨酸激酶调节剂，特别是FLT3和/或c-kit和/或TrkB的抑制剂，所述化合物的用途为在细胞或受试者中减少或抑制FLT3和/或c-kit和/或TrkB的激酶活性，以及所述化合物的用途为预防或治疗受试者的细胞增殖紊乱和/或与FLT3和/或c-kit和/或TrkB相关的紊乱。本发明还涉及包括本发明化合物的药物组合物，以及治疗癌症和其他细胞增殖紊乱等疾病的方法。
• [EN] IDENTIFICATION AND USE OF ERK5 INHIBITORS<br/>[FR] IDENTIFICATION ET UTILISATION D'INHIBITEURS D'ERK5
  申请人：BAYER AG

  公开号：WO2019170543A1

  公开（公告）日：2019-09-12

  The present invention covers heterocyclic compounds of general formula (I) in which T, U, Y, Z, R1 and R3 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer disorders, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式(I)的杂环化合物，其中T、U、Y、Z、R1和R3如本文所定义，制备所述化合物的方法，用于制备所述化合物的中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病，特别是癌症疾病的药物组合物的用途，作为唯一活性成分或与其他活性成分组合使用。
• Synergistic Modulation of Flt3 Kinase Using Alkylquinolines and Alkylquinazolines
  申请人：Baumann Andrew Christian

  公开号：US20070004660A1

  公开（公告）日：2007-01-04

  The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from alkylquinoline and alkylquinazoline compounds of Formula I′: where R 1 , R 2 , R 3 , Z, G, Q and X are as defined herein. Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.

  本发明涉及一种抑制细胞或主体中FLT3酪氨酸激酶活性或表达或减少FLT3激酶活性或表达的方法，包括给予一种法尼酰转移酶抑制剂和一种从式I'的烷基喹啉和烷基喹唑啉化合物中选择的FLT3激酶抑制剂：其中R1、R2、R3、Z、G、Q和X如本文所定义。本发明包括治疗和预防方法，用于治疗或预防患有细胞增殖性疾病或与FLT3相关的疾病的患者。
• INTERMEDIATES USEFUL IN THE SYNTHESIS OF ALKYLQUINOLINE AND ALKYLQUINAZOLINE KINASE MODULATORS, AND RELATED METHODS OF SYNTHESIS
  申请人：Baindur Nand

  公开号：US20070021436A1

  公开（公告）日：2007-01-25

  The invention is directed to alkylquinoline and alkylquinazoline compounds of Formula C: wherein R 1 , R 2 , R 99 , and X are as defined herein, the use of such compounds in the sysnthesis of protein tyrosine kinase inhibitors, particularly inhibitors of FLT3 and/or c-kit and/or TrkB.

  本发明涉及公式C的烷基喹啉和烷基喹唑啉化合物，其中R1，R2，R99和X如本文所定义，以及在合成蛋白酪氨酸激酶抑制剂，特别是FLT3和/或c-kit和/或TrkB抑制剂中使用这些化合物的方法。
• INTERMEDIATES USEFUL IN THE SYNTHESIS OF ALKYLQUINOLINE AND ALKYLQUINAZOLINE KINASE MODULATORS AND RELATED METHODS OF SYNTHESIS
  申请人：Janssen Pharmaceutica NV

  公开号：EP1891040A1

  公开（公告）日：2008-02-27