4-(4-Bromo-phenyl)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester | 857531-82-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(4-Bromo-phenyl)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-(4-Bromo-phenyl)-4-(4-hydroxy-phenyl)piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-(4-bromophenyl)-4-(4-hydroxyphenyl)piperidine-1-carboxylate
• CAS: 857531-82-9
• 化学式: C₂₂H₂₆BrNO₃
• 分子量: 432.357
• InChiKey: AYRCQEYIRSRBFV-UHFFFAOYSA-N

物化性质

• 沸点：
  516.2±50.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-Bromo-phenyl)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester 、 3-methoxypropyl p-toluenesulfonate 在 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 4.0h， 生成 4-(4-Bromo-phenyl)-4-[4-(3-methoxy-propoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] PYRAZOLE DERIVATIVES AS PROTEIN KINASE MODULATORS
  [FR] DERIVES DE PYRAZOLE SERVANT DE MODULATEURS DE PROTEINE KINASE

  摘要：

  该发明提供了具有蛋白激酶B抑制活性的化合物，其化学式为：（I），其中A是一个饱和的含有1至7个碳原子的烷基链连接基团，该连接基团在R1和NR2R3之间延伸的最大链长为5个原子，在E和NR2R3之间延伸的最大链长为4个原子，其中连接基团中的一个碳原子可以选择性地被氧原子或氮原子取代；连接基团A的碳原子可以选择性地携带来自酮基、氟和羟基的一个或多个取代基，前提是当存在羟基时，该羟基不位于相对于NR2R3基团的碳原子a处，且当存在酮基时，该酮基位于相对于NR2R3基团的碳原子a处；E是一个单环或双环的碳环或杂环基团；R1是芳基或杂芳基团；R2、R3、R4和R5如权利要求中所定义。还提供了含有这些化合物的药物组合物，制备这些化合物的方法以及它们作为抗癌剂的用途。

  公开号：

  WO2005061463A1
• 作为产物：
  描述：

  4-[1-(4-Bromo-phenyl)-2-methylamino-ethyl]-phenol 生成 4-(4-Bromo-phenyl)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  PHARMACEUTICAL COMBINATIONS COMPRISING PYRAZOLE DERIVATIVES AS PROTEIN KINASE MODULATORS

  摘要：

  该发明提供了一种组合物，包括一个辅助化合物（例如一个、两个或更多个辅助化合物）和具有蛋白激酶B抑制活性的式（I）化合物：其中A是含有1至7个碳原子的饱和碳氢链连接基团，连接基团在R1和NR2R3之间延伸的最大链长为5个原子，在E和NR2R3之间延伸的最大链长为4个原子，其中连接基团中的一个碳原子可以选择性地被氧原子或氮原子取代；连接基团A的碳原子可以选择性地携带来自酮基、氟和羟基的一个或多个取代基，前提是当羟基存在时，不位于相对于NR2R3基团的碳原子a处，且当酮基存在时，位于相对于NR2R3基团的碳原子a处；E是单环或双环碳环或杂环基团；R是芳基或杂芳基团；R2、R3、R4和R5如权利要求中所定义。还提供了患者包装、药物配套和包装以及含有这些组合物的组合物、制备这些组合物的方法以及它们作为抗癌剂的联合治疗中的用途。

  公开号：

  US20100166699A1

文献信息

• PYRAZOLE DERIVATIVES AS PROTEIN KINASE MODULATORS
  申请人：Berdini Valerio

  公开号：US20110144080A1

  公开（公告）日：2011-06-16

  The invention provides compounds of the formula: (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R 1 and NR 2 R 3 and a maximum chain length of 4 atoms extending between E and NR 2 R 3 , wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR 2 R 3 group and provided that the oxo group when present is located at a carbon atom a with respect to the NR 2 R 3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R 1 is an aryl or heteroaryl group; and R 2 , R 3 , R 4 and R 5 are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

  本发明提供具有蛋白激酶B抑制活性的式(I)化合物：其中A是饱和的碳氢链连接基，含有1至7个碳原子，连接基在R1和NR2R3之间的最大链长为5个原子，在E和NR2R3之间的最大链长为4个原子，其中连接基中的一个碳原子可以选择性地被氧或氮原子取代；连接基A的碳原子可以选择性地带有一个或多个取代基，所述取代基选自氧代、氟代和羟基，但当羟基存在时，不得位于相对于NR2R3基团的碳原子a处，当氧代基存在时，必须位于相对于NR2R3基团的碳原子a处；E是单环或双环碳环或杂环基团；R1是芳基或杂环基团；R2、R3、R4和R5如权利要求所定义。还提供了含有该化合物的药物组合物，制备该化合物的方法以及其作为抗癌剂的用途。
• PHARMACEUTICAL COMPOUNDS
  申请人：Davies Thomas Glanmor

  公开号：US20100130464A1

  公开（公告）日：2010-05-27

  The invention provides compounds of the formula (I) having ROCK kinase and/or protein kinase p70S6K inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR 2 R 3 and a maximum chain length of 4 atoms extending between E and NR 2 R 3 , wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the NR 2 R 3 group and provided that the oxo group when present is located at a carbon atom α with respect to the NR 2 R 3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R 1 is an aryl or heteroaryl group; and R 2 , R 3 , R 4 and R 5 are as defined in the claims.

  本发明提供了式（I）的化合物，具有ROCK激酶和/或蛋白激酶p70S6K抑制活性：其中A是一个饱和的碳氢化合物链连接基，含有1至7个碳原子，链连接基在R1和NR2R3之间具有最大链长为5个原子，在E和NR2R3之间具有最大链长为4个原子，其中链连接基中的一个碳原子可以选择性地被氧或氮原子替换；链连接基A的碳原子可以选择性地带有一个或多个取代基，所述取代基选自氧代、氟代和羟基，但当羟基存在时，不得位于相对于NR2R3基团的碳原子a上，当氧代基存在时，必须位于相对于NR2R3基团的碳原子α上；E是一个单环或双环的碳环或杂环基团；R1是一个芳基或杂芳基团；R2、R3、R4和R5如权利要求所定义。
• Pharmaceutical compounds
  申请人：Astex Therapeutics Limited

  公开号：US08343953B2

  公开（公告）日：2013-01-01

  The invention provides compounds of the formula (I) having ROCK kinase and/or protein kinase p70S6K inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom α with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom α with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R1 is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims.

  本发明提供了具有ROCK激酶和/或蛋白激酶p70S6K抑制活性的式（I）化合物：其中A是饱和的含有1至7个碳原子的烃链连接基，该连接基在R1和NR2R3之间具有最大链长为5个原子，在E和NR2R3之间具有最大链长为4个原子，其中连接基中的一个碳原子可以选择性地被氧或氮原子取代；连接基A的碳原子可以选择性地带有一个或多个取代基，所述取代基包括氧代、氟代和羟基，前提是当羟基存在时，其不位于相对于NR2R3基团的α碳原子上，当氧代基存在时，其位于相对于NR2R3基团的α碳原子上；E是单环或双环碳环或杂环基团；R1是芳基或杂芳基团；R2、R3、R4和R5如权利要求所定义。
• Pyrazole derivatives as protein kinase modulators
  申请人：Berdini Valerio

  公开号：US08691806B2

  公开（公告）日：2014-04-08

  The invention provides compounds of the formula (I) having protein kinase B inhibiting activity: Also provided are pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anticancer agents.

  本发明提供了具有蛋白激酶B抑制活性的式(I)的化合物：还提供了含有该化合物的药物组合物，制备该化合物的方法以及其作为抗癌剂的用途。
• Pharmaceutical combinations comprising pyrazole derivatives as protein kinase modulators
  申请人：Thompson Neil Thomas

  公开号：US08541461B2

  公开（公告）日：2013-09-24

  The invention provides a combination comprising an ancillary compound (e.g. one, two or more ancillary compounds) and a compound of the formula (I) having protein kinase B inhibiting activity: wherein A is a saturated hydrocarbon linker group containing from 1 to 7 carbon atoms, the linker group having a maximum chain length of 5 atoms extending between R1 and NR2R3 and a maximum chain length of 4 atoms extending between E and NR2R3, wherein one of the carbon atoms in the linker group may optionally be replaced by an oxygen or nitrogen atom; and wherein the carbon atoms of the linker group A may optionally bear one or more substituents selected from oxo, fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom α with respect to the NR2R3 group and provided that the oxo group when present is located at a carbon atom α with respect to the NR2R3 group; E is a monocyclic or bicyclic carbocyclic or heterocyclic group; R1 is an aryl or heteroaryl group; and R2, R3, R4 and R5 are as defined in the claims. Also provided are patient packs, pharmaceutical kits and packs and compositions containing the combinations, methods for preparing the combinations and their use in combination therapy as anticancer agents.

  本发明提供了一种组合物，包括一个辅助化合物（例如，一个、两个或更多个辅助化合物）和一种具有蛋白激酶B抑制活性的式（I）化合物：其中A是一个饱和的含有1-7个碳原子的碳链连接基团，该连接基团在R1和NR2R3之间具有最大为5个原子的链长，在E和NR2R3之间具有最大为4个原子的链长，其中连接基团中的一个碳原子可以选择性地被氧原子或氮原子取代；连接基团A的碳原子可以选择性地带有一个或多个取代基，所述取代基被选择自氧代基、氟代基和羟基，但当羟基存在时，不能位于相对于NR2R3基团的α碳原子上，当氧代基存在时，必须位于相对于NR2R3基团的α碳原子上；E是一个单环或双环的碳环或杂环基团；R1是一个芳基或杂芳基团；R2、R3、R4和R5如权利要求所定义。还提供了患者包装、药物套装和包装以及含有这些组合物的组合物，制备这些组合物的方法以及它们作为抗癌剂的联合治疗中的使用方法。