4-(2,4-二氯苄基)哌啶-4-胺 | 919112-72-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(2,4-二氯苄基)哌啶-4-胺
• 英文名称: 4-[(2,4-Dichlorophenyl)methyl]piperidin-4-amine
• CAS: 919112-72-4
• 化学式: C₁₂H₁₆Cl₂N₂
• 分子量: 259.178
• InChiKey: PJSLFVVWMGFIOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2,4-二氯苄基)哌啶-4-胺 、 6-chloro-7H-purin-8(9H)-one 生成 6-(4-amino-4-(2,4-dichlorobenzyl)piperidin-1-yl)-7H-purin-8(9H)-one
  参考文献：
  名称：

  PHARMACEUTICAL COMPOUNDS

  摘要：

  该发明提供了公式(I)的化合物： 或其盐、溶剂合物、互变异构体或N-氧化物，其中J1-J2为CH═CH，N═CH，CH═N，HN-C（O）或CH2CO；T为N或CH，GP如权利要求所定义。这些化合物具有作为PKA和PKB激酶抑制剂的活性，并可用于治疗癌症。

  公开号：

  US20100016340A1
• 作为产物：
  描述：

  1-Piperidinecarboxylic acid,4-[(2,4-dichlorophenyl)methyl]-4-[[(1,1-dimethylethyl)sulfinyl]amino]-,1,1-dimethylethyl ester 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 16.0h， 生成 4-(2,4-二氯苄基)哌啶-4-胺
  参考文献：
  名称：

  发现 4-Amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides 作为蛋白激酶 B (Akt) 的选择性口服活性抑制剂

  摘要：

  蛋白激酶 B（PKB 或 Akt）是调节生长和存活的细胞内信号通路的重要组成部分。通过 PKB 的信号传导在癌症中经常失调，因此 PKB 抑制剂具有作为抗肿瘤剂的潜力。一系列 4-benzyl-1-(7 H -pyrrolo[2,3 - d ]pyrimidin-4-yl)piperidin-4- amines中亲脂取代的优化提供了 ATP 竞争性的纳摩尔抑制剂，具有高达 150-与密切相关的激酶 PKA 相比，PKB 抑制的选择性倍数。尽管在细胞检测中具有活性，但含有 4-amino-4-benzylpiperidines 的化合物在体内进行代谢，导致快速清除和低口服生物利用度。哌啶和亲脂取代基之间的连接基团的变化鉴定了 4-amino-1-(7H -pyrrolo[2,3 - d ]pyrimidin-4-yl)piperidine-4-carboxamides 作为 PKB 的有效和

  DOI：

  10.1021/jm901788j

文献信息

• Ortho-Condensed Pyridine and Pyrimidine Derivatives (e.g., Purines) as Protein Kinases Inhibitors
  申请人：Berdini Valerio

  公开号：US20090247538A1

  公开（公告）日：2009-10-01

  The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q 1 is a bond or a saturated C 1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONR q or NR q CO where R q is hydrogen or methyl, or R q is a C 1-4 alkylene chain linked to R 1 or a carbon atom of Q 1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q 1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q 2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, 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 may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Q 2 is other than a bond; G is hydrogen, NR 2 R, OH or SH provided that when E is aryl or heteroaryl and Q 2 is a bond, then G is hydrogen; R 1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R 1 is hydrogen and G is NR 2 R 3 , then Q 2 is a bond; and R 2 , R 3 , R 4 , R 6 and R 8 are as defined in the claims.

  本发明提供了一种用作蛋白激酶B抑制剂的化合物，该化合物是公式（I）的化合物或其盐、溶剂化物、互变异构体或N-氧化物，其中T为N或CR5；J1-J2为N═C(R6)、(R7)C═N、(R8)N—C(O)、(R8)2C—C(O)、N═N或(R7)C═C(R6)；E为5或6个环成员的单环碳环或杂环基团，所述杂环基团中含有最多3个选自O、N和S的杂原子；Q1为键或饱和的C1-3碳氢化合物连接基团，连接基团中的一个碳原子可以被氧或氮原子取代，或者相邻的一对碳原子可以被CONRq或NRqCO取代，其中Rq为氢或甲基，或者Rq为C1-4烷基链，与R1或Q1的一个碳原子连接形成环状基团；连接基团Q1的碳原子可以选择地带有一个或多个氟和羟基取代基；Q2为键或含有1至3个碳原子的饱和碳氢化合物连接基团，其中连接基团中的一个碳原子可以选择地被氧或氮原子取代；连接基团的碳原子可以选择地带有一个或多个氟和羟基取代基团，但当羟基存在时，不得位于与G基团相对的碳原子a上；并且当E为芳基或杂芳基时，Q2不是键；G为氢、NR2R或OH或SH，但当E为芳基或杂芳基且Q2为键时，G为氢；R1为氢或芳基或杂芳基，但当R1为氢且G为NR2R3时，Q2为键；而R2、R3、R4、R6和R8如权利要求中所定义。
• PURINE AND DEAZAPURINE DERIVATIVES AS PHARMACEUTICAL COMPOUNDS
  申请人：Davies Thomas Glanmor

  公开号：US20100022564A1

  公开（公告）日：2010-01-28

  The invention provides a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q 1 is a bond or a saturated C 1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONR q or NR q CO where R q is hydrogen or methyl, or R q is a C 1-4 alkylene chain linked to R 1 or a carbon atom of Q 1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q 1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q 2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, 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 may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom α with respect to the G group; and provided that when E is aryl or heteroaryl, then Q 2 is other than a bond; G is hydrogen, NR 2 R 3 , OH or SH provided that when E is aryl or heteroaryl and Q 2 is a bond, then G is hydrogen; R 1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R 1 is hydrogen and G is NR 2 R 3 , then Q 2 is a bond; and R 2 , R 3 R 4 , R 6 and R 8 are as defined in the claims, wherein the compound is for use in: (a) the treatment or prophylaxis of a disease or condition in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase P70S6K is indicated; and/or (b) the treatment of a subject or patient population in which the modulation (e.g. inhibition) of ROCK kinase or protein kinase P70S6K is indicated.

  本发明提供了化合物(I)或其盐、溶剂化物、互变异构体或N-氧化物，其中T为N或CR5；J1-J2为N═C(R6)、(R7)C═N、(R8)N—C(O)、(R8)2C—C(O)、N═N或(R7)C═C(R6)；E为由5个或6个环成的单环碳环或杂环基团，其中杂环基团中最多含有3个从O、N和S中选择的杂原子；Q1为键或饱和的C1-3烃基连接基团，其中连接基团中的一个碳原子可以选择性地被氧或氮原子替换，或者相邻的一对碳原子可以被CONRq或NRqCO替换，其中Rq为氢或甲基，或者Rq为C1-4烷基链，与R1或Q1的碳原子连接形成环状结构；连接基团Q1的碳原子可以选择性地带有一个或多个氟和羟基取代基；Q2为键或含有1至3个碳原子的饱和烃基连接基团，其中连接基团中的一个碳原子可以选择性地被氧或氮原子替换；连接基团的碳原子可以选择性地带有一个或多个氟和羟基取代基团，但当羟基取代基团存在时，不得位于与G基团相对的α碳原子上；当E为芳基或杂芳基时，Q2不是键；G为氢、NR2R3、OH或SH，但当E为芳基或杂芳基且Q2为键时，G为氢；R1为氢或芳基或杂芳基基团，但当R1为氢且G为NR2R3时，Q2为键；R2、R3、R4、R6和R8如权利要求所定义，其中该化合物用于：(a)治疗或预防需要调节（例如抑制）ROCK激酶或蛋白激酶P70S6K的疾病或病情；和/或(b)治疗需要调节（例如抑制）ROCK激酶或蛋白激酶P70S6K的受试者或患者群体。
• ORTHO-CONDENSED PYRIDINE AND PYRIMIDINE DERIVATIVES (E.G., PURINES) AS PROTEIN KINASES INHIBITORS
  申请人：ASTEX THERAPEUTICS LIMITED

  公开号：US20140303177A1

  公开（公告）日：2014-10-09

  The invention provides a compound for use as a protein kinase B inhibitor, the compound being a compound of the formula (I) or salts, solvates, tautomers or N-oxides thereof, wherein T is N or CR 5 ; J 1 -J 2 is N═C(R 6 ), (R 7 )C═N, (R 8 )N—C(O), (R 8 ) 2 C—C(O), N═N or (R 7 )C═C(R 6 ); E is a monocyclic carbocyclic or heterocyclic group of 5 or 6 ring members, the heterocyclic group containing up to 3 heteroatoms selected from O, N and S; Q 1 is a bond or a saturated C 1-3 hydrocarbon linker group, one of the carbon atoms in the linker group being optionally be replaced by an oxygen or nitrogen atom, or an adjacent pair of carbon atoms may be replaced by CONR q or NR q CO where R q is hydrogen or methyl, or R q is a C 1-4 alkylene chain linked to R or a carbon atom of Q 1 to form a cyclic moiety; and wherein the carbon atoms of the linker group Q 1 may optionally bear one or more substituents selected from fluorine and hydroxy; Q 2 is a bond or a saturated hydrocarbon linker group containing from 1 to 3 carbon atoms, 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 may optionally bear one or more substituents selected from fluorine and hydroxy, provided that the hydroxy group when present is not located at a carbon atom a with respect to the G group; and provided that when E is aryl or heteroaryl, then Q 2 is other than a bond; G is hydrogen, NR 2 R 3 , OH or SH provided that when E is aryl or heteroaryl and Q 2 is a bond, then G is hydrogen; R 1 is hydrogen or an aryl or heteroaryl group, with the proviso that when R is hydrogen and G is NR 2 R 3 , then Q is a bond; and R 2 , R 3 , R 4 , R 6 and R 8 are as defined in the claims.

  本发明提供了一种用作蛋白激酶B抑制剂的化合物，该化合物是公式(I)的化合物或其盐、溶剂化合物、互变异构体或N-氧化物，其中T为N或CR5；J1-J2为N═C(R6)、(R7)C═N、(R8)N—C(O)、(R8)2C—C(O)、N═N或(R7)C═C(R6)；E为5或6个环元素的单环碳环或杂环基团，其中杂环基团最多包含3个从O、N和S中选择的杂原子；Q1为键或饱和的C1-3烃基连接基团，连接基团中的一个碳原子可以被氧或氮原子替换，或者相邻的一对碳原子可以被CONRq或NRqCO替换，其中Rq为氢或甲基，或者Rq为C1-4烷基链，连接到R或Q1的碳原子以形成环状基团；连接基团Q1的碳原子可以选择地带有一个或多个氟和羟基取代基；Q2为键或含有1至3个碳原子的饱和烃基连接基团，其中连接基团中的一个碳原子可以选择地被氧或氮原子替换；连接基团的碳原子可以选择地带有一个或多个氟和羟基取代基，但当存在羟基时，其不位于与G基团相关的碳原子a上；并且当E为芳基或杂芳基时，Q2不是键；G为氢、NR2R3、OH或SH，但当E为芳基或杂芳基且Q2为键时，G为氢；R1为氢或芳基或杂芳基，但当R为氢且G为NR2R3时，Q为键；而R2、R3、R4、R6和R8如权利要求所定义。
• ORTHO- CONDENSED PYRIDINE AND PYRIMIDINE DERIVATIVES (E. G. PURINES) AS PROTEIN KINASES INHIBITORS
  申请人：Astex Therapeutics Limited

  公开号：EP1812004B1

  公开（公告）日：2011-06-22
• Ortho-condensed pyridine and pyrimidine derivatives ( e.g. purines ) as protein kinases inhibitors
  申请人：Astex Therapeutics Limited

  公开号：EP2272517B1

  公开（公告）日：2014-10-01