C-phenyl-C-[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-yl]-methylamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: C-phenyl-C-[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-yl]-methylamine
• 英文别名: C-phenyl-C-[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methylamine；4-Piperidinemethanamine,a-phenyl-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-；phenyl-[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methanamine
• 化学式: C₁₈H₂₁N₅
• 分子量: 307.398
• InChiKey: QZUZDXQRPMHXBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-羟基吡咯并[2,3-d]嘧啶 在 盐酸 、 甲醇 、 水 、 三乙胺 、 三氯氧磷 作用下， 以 正丁醇 为溶剂， 反应 62.5h， 生成 C-phenyl-C-[1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-yl]-methylamine
  参考文献：
  名称：

  WO2007/125315

  摘要：

  公开号：

文献信息

• Identification of 4-(4-Aminopiperidin-1-yl)-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidines as Selective Inhibitors of Protein Kinase B through Fragment Elaboration
  作者：John J. Caldwell、Thomas G. Davies、Alastair Donald、Tatiana McHardy、Martin G. Rowlands、G. Wynne Aherne、Lisa K. Hunter、Kevin Taylor、Ruth Ruddle、Florence I. Raynaud、Marcel Verdonk、Paul Workman、Michelle D. Garrett、Ian Collins

  DOI：10.1021/jm701437d

  日期：2008.4.1

  inhibitor-PKA-PKB chimera complexes efficiently guided improvements in the potency and selectivity of the compounds, resulting in the identification of nanomolar 6-(piperidin-1-yl)purine, 4-(piperidin-1-yl)-7-azaindole, and 4-(piperidin-1-yl)pyrrolo[2,3- d]pyrimidine inhibitors of PKBbeta with antiproliferative activity and showing pathway inhibition in cells. A divergence in the binding mode was seen

  基于片段的筛选确定7-氮杂吲哚为蛋白激酶B抑制剂支架。使用抑制剂-PKA-PKB嵌合体复合物的反复结晶学方法对片段进行精细加工，可有效指导化合物效力和选择性的提高，从而鉴定出纳摩尔级的6-（哌啶-1-基）嘌呤，4-（哌啶-1-基）纳摩尔。 ）-7-氮杂吲哚和PKBbeta的4-（哌啶-1-基）吡咯并[2,3-d]嘧啶抑制剂具有抗增殖活性，并在细胞中表现出途径抑制作用。在包含4-氨基甲基哌啶和含4-氨基哌啶的分子之间观察到结合模式的差异。用4-氨基哌啶衍生物观察到PKB对PKA的选择性，大多数PKB选择性抑制剂（30倍）显示出PKA和PKA-PKB嵌合体之间的结合构象显着不同。
• Pharmaceutical Compounds
  申请人：Davies Thomas Glanmor

  公开号：US20090253718A1

  公开（公告）日：2009-10-08

  The invention provides a compound having 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 ); A is an optionally substituted saturated C 1-7 hydrocarbon 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 , one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH 2 , O, S or NH and G is a C 1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R 1 is hydrogen or an aryl or heteroaryl group; R 2 and R 3 are each hydrogen, optionally substituted C 1-4 hydrocarbyl or optionally substituted C 1-4 acyl; or NR 2 R 3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR 2 R 3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C 1-4 alkyl; or NR 2 R 3 and the adjacent carbon atom of linker group A together form a cyano group; or R 1 , A and NR 2 R 3 together form a cyano group; and R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from hydrogen and various substituents 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.

  本发明提供了具有以下式子（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）; A为最大链长为5个原子的选择性取代的饱和C1-7碳氢链连接基，在R1和NR2R3之间延伸，最大链长为4个原子，在E和NR2R3之间延伸，链连接基中的一个碳原子可以被氧或氮取代; E为单环或双环的碳环或杂环基团或一个无环的X-G基团，其中X为CH2，O，S或NH，G为一个C1-4烷基链，其中一个碳原子可以被O，S或NH取代; R1为氢或芳基或杂环基团; R2和R3分别为氢，选择性取代的C1-4烃基或选择性取代的C1-4酰基; 或NR2R3形成咪唑基团或具有4-7个环成员的饱和单环杂环基团; 或NR2R3和A一起形成一个被C1-4烷基取代的饱和单环杂环基团; 或NR2R3和链连接基A的相邻碳原子一起形成氰基团; 或R1，A和NR2R3一起形成氰基团; R4，R5，R6，R7和R8各自独立地选择氢和各种在权利要求中定义的取代基，其中该化合物用于：（a）治疗或预防调节ROCK激酶或蛋白激酶p70S6K所示的疾病或情况; 和/或（b）治疗调节ROCK激酶或蛋白激酶p70S6K所示的受试者或患者人群。
• Ortho-Condensed Pyridine and Pyrimidine Derivatives (e.g., Purines) as Protein Kinases Inhibitors
  申请人：Berdini Valerio

  公开号：US20090099213A1

  公开（公告）日：2009-04-16

  The invention provides a compound for use in the prophylaxis or treatment of a disease state or condition mediated by protein kinase B, the compound having 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 ); A is an optionally substituted saturated C 1-7 hydrocarbon 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 , one of the carbon atoms in the linker group being optionally replaced by oxygen or nitrogen; E is a monocyclic or bicyclic carbocyclic or heterocyclic group or an acyclic group X-G wherein X is CH 2 , O, S or NH and G is a C 1-4 alkylene chain wherein one of the carbon atoms is optionally replaced by O, S or NH; R 1 is hydrogen or an aryl or heteroaryl group; R 2 and R 3 are each hydrogen, optionally substituted C 1-4 hydrocarbyl or optionally substituted C 1-4 acyl; or NR 2 R 3 forms an imidazole group or a saturated monocyclic heterocyclic group having 4-7 ring members; or NR 2 R 3 and A together form a saturated monocyclic heterocyclic group having 4-7 ring members which is optionally substituted by C 1-4 alkyl; or NR 2 R 3 and the adjacent carbon atom of linker group A together form a cyano group; or R 1 , A and NR 2 R 3 together form a cyano group; and R 4 , R 5 , R 6 , R 7 and R 8 are each independently selected from hydrogen and various substituents as defined in the claims.

  本发明提供了一种化合物，可用于预防或治疗由蛋白激酶B介导的疾病状态或病况，该化合物具有以下式（I）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）；A为一个可选取代的饱和C1-7碳链连接基团，其最大链长为5个原子，延伸在R1和NR2R3之间，并且最大链长为4个原子，延伸在E和NR2R3之间，连接基团中的一个碳原子可被氧或氮取代；E为单环或双环碳环或杂环基团或一个无环基团X-G，其中X为CH2，O，S或NH，G为C1-4烷基链，其中一个碳原子可被O，S或NH取代；R1为氢或芳基或杂芳基团；R2和R3分别为氢，可选取代的C1-4烃基或可选取代的C1-4酰基；或NR2R3形成咪唑基团或具有4-7个环成员的饱和单环杂环基团；或NR2R3和A一起形成具有4-7个环成员的饱和单环杂环基团，该基团可选取代为C1-4烷基；或NR2R3和连接基团A的相邻碳原子一起形成氰基团；或R1，A和NR2R3一起形成氰基团；R4，R5，R6，R7和R8各自独立地选择氢和各种定义中定义的取代基。
• WO2006/46023
  申请人：——

  公开号：——

  公开（公告）日：——
• ORTHO- CONDENSED PYRIDINE AND PYRIMIDINE DERIVATIVES (E. G. PURINES) AS PROTEIN KINASES INHIBITORS
  申请人：Astex Therapeutics Limited

  公开号：EP1812003A1

  公开（公告）日：2007-08-01