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

• 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: 1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-ylamine
• 英文别名: 1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinamine；1-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine
• 化学式: C₁₁H₁₅N₅
• 分子量: 217.274
• InChiKey: SOYJTCRGELSHIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  70.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-ylamine 在 羟胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 6.0h， 生成 (E)-3-(4-(((1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)amino)methyl)phenyl)-N-hydroxyacrylamide
  参考文献：
  名称：

  基于吡咯并[2,3-d]嘧啶和吡咯并[2,3-b]吡啶支架的组蛋白脱乙酰酶抑制剂的设计、合成和生物学评价

  摘要：

  我们设计并合成了一系列基于吡咯并[2,3- d ]嘧啶和吡咯并[2,3- b ]吡啶支架的HDAC抑制剂。化合物B3（灰色）对 HDAC 1、2、3、6 和 8 表现出有效的抑制活性。它对三种肿瘤细胞系表现出有效的抗增殖作用，比 SAHA 提高两到六倍。该系列为未来血液恶性肿瘤的治疗提供了有价值的先导化合物。

  DOI：

  10.1002/cmdc.202200683
• 作为产物：
  描述：

  4-羟基吡咯并[2,3-d]嘧啶 在 盐酸 、 三乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 6.5h， 生成 1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-ylamine
  参考文献：
  名称：

  WO2007/125321

  摘要：

  公开号：

文献信息

• [EN] ASK1 INHIBITING PYRROLOPYRIMIDINE DERIVATIVES<br/>[FR] DÉRIVÉS PYRROLOPYRIMIDINE INHIBANT ASK1
  申请人：CONVERGENCE PHARMACEUTICALS

  公开号：WO2012080735A1

  公开（公告）日：2012-06-21

  This invention relates to pyrrolopyrimidine derivatives of formula (I): where R1, X, p, R4, R2and R3are as defined herein, and their use as pharmaceuticals.

  这项发明涉及式(I)的吡咯吡嘧啶衍生物：其中R1、X、p、R4、R2和R3如本文所定义，并且它们作为药物的用途。
• 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。
• SUBSTITUTED PIPERIDINES HAVING PROTEIN KINASE INHIBITING ACTIVITY
  申请人：Woodhead Steven John

  公开号：US20100093748A1

  公开（公告）日：2010-04-15

  The invention provides PKA and PKB kinase-inhibiting compounds of the formula (I): or salts, solvates, tautomers or N-oxides thereof, wherein E is a five membered heteroaryl ring containing 1, 2, 3 or 4 heteroatoms selected from O, N and S provided that no more than 1 heteroatom may be other than N; q and r are each is 0 or 1; provided that q+r is 1 or 2; T is N or a group 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 ); Q 3 is a bond or a saturated C 1-3 hydrocarbon linker group optionally substituted by fluorine and hydroxy; G is NR 2 R 3 , CN or OH; m and n are each 0 or 1, provided that m+n is 1 or 2, and provided also that m or n are each 0 when the adjacent ring member of ring E is S or O; R 1a and R 1b are the same or different and each is hydrogen or a substituent R 10 ; or R 1a and R 1b together with the carbon atoms or heteroatoms to which they are attached form a 5 or 6-membered aryl or heteroaryl ring, wherein the aryl or heteroaryl rings are optionally substituted by one or more substituents R 10 ; and R 2 , R 3 , R 4 , R 5 , R 7 , R 6 , R 8 , and R 10 are as defined in the claims.

  本发明提供了式(I)的PKA和PKB激酶抑制化合物，或其盐、溶剂化物、互变异构体或N-氧化物，其中E是一个五元杂环芳基环，包含1、2、3或4个从O、N和S中选择的杂原子，但不得多于1个杂原子不是N；q和r各自为0或1；前提是q+r为1或2；T为N或CR5基团；J1-J2为N═C(R6)、(R7)C═N、(R8)N—C(O)、(R8)2C—C(O)、N═N或(R7)C═C(R6)；Q3为键或饱和的C1-3烃基连接基团，可选地被氟和羟基取代；G为NR2R3、CN或OH；m和n各自为0或1，前提是m+n为1或2，且当环E的相邻环成员为S或O时，m或n各自为0；R1a和R1b相同或不同，各自为氢或取代基R10；或R1a和R1b与它们所连接的碳原子或杂原子一起形成一个5或6元芳基或杂芳基环，其中芳基或杂芳基环可选地被一个或多个取代基R10取代；R2、R3、R4、R5、R7、R6、R8和R10如权利要求所定义。
• 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。