1-(叔丁氧基羰基)-4-(4-氯苄基)哌啶-4-羧酸 | 170284-71-6

• 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: 1-(叔丁氧基羰基)-4-(4-氯苄基)哌啶-4-羧酸
• 英文名称: 1-(tert-butoxycarbonyl)-4-(4-chlorobenzyl)piperidine-4-carboxylic acid
• 英文别名: 4-[(4-chlorophenyl)methyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid
• CAS: 170284-71-6
• 化学式: C₁₈H₂₄ClNO₄
• 分子量: 353.846
• InChiKey: MRYZLPQGWRXSTE-UHFFFAOYSA-N

物化性质

• 沸点：
  480.8±35.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(叔丁氧基羰基)-4-(4-氯苄基)哌啶-4-羧酸 在 盐酸 、 甲醇 、 sodium hydroxide 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 正丁醇 为溶剂， 反应 75.0h， 生成 4-[(4-氯苯基)甲基]-1-(7H-吡咯并[2,3-D]嘧啶-4-基)-4-哌啶胺
  参考文献：
  名称：

  WO2007/125321

  摘要：

  公开号：
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 20.0h， 生成 1-(叔丁氧基羰基)-4-(4-氯苄基)哌啶-4-羧酸
  参考文献：
  名称：

  一种综合的生物学方法，可指导流感病毒PA核酸内切酶的金属螯合抑制剂的开发。

  摘要：

  流感病毒PA核酸内切酶可裂解带帽的细胞前mRNA，从而引发病毒mRNA的合成，是新型抗流感病毒治疗方法的有希望的靶标。该酶的催化中心位于PA（PA-Nter）的N端，含有两个（或可能一个或三个）Mg（2+）或Mn（2+）离子，这对于其催化功能至关重要。对PA抑制剂的研究引起了极大的兴趣，这些抑制剂经过优化设计，可以占据活性位点并螯合金属离子。我们在这里集中于一系列包含不同支架的β-二酮酸（DKA）和DKA生物立体异构化合物，并在用PA-Nter的酶法测定中确定了它们的构效关系，以建立三维药效团模型。此外，我们开发了一种基于分子信标（MB）的PA-Nter分析，使我们能够比较Mn（2+）和Mg（2+）的抑制作用，后者可能是生物学上相关的辅助因子。这种实时MB检测使我们能够测量PA-Nter的酶动力学或进行高通量筛选。发现几种DKA衍生物可强烈抑制PA-Nter，IC50值可与原型L-742,

  DOI：

  10.1124/mol.114.095588

文献信息

• QUINAZOLINE DERIVATIVES AS NK3 RECEPTOR ANTAGONISTS
  申请人：Knust Henner

  公开号：US20100125078A1

  公开（公告）日：2010-05-20

  The present invention relates to a compounds of formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , and n are as defined herein and to a pharmaceutically active salt, a racemic mixture, an enantiomer, an optical isomer or a tautomeric form thereof. The present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

  本发明涉及一种具有以下式I的化合物 其中 R 1 ，R 2 ，R 3 ，R 4 ，R 5 和n如本文所定义，并且涉及其药用活性盐，外消旋混合物，对映体，光学异构体或其互变异构体形式。本化合物是治疗抑郁症、疼痛、精神病、帕金森病、精神分裂症、焦虑症和注意力缺陷多动障碍（ADHD）的高潜力NK-3受体拮抗剂。
• 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：Saxty Gordon

  公开号：US20090124610A1

  公开（公告）日：2009-05-14

  Compounds of the formula (I), and salts, solvates, tautomers and N-oxide thereof, wherein TG is selected from groups (1) and (2): wherein the asterisk (*) represents the point of attachment of the group E to the group X; R 1a is an optionally substituted aryl or heteroaryl group; R 1b is hydrogen or a group R1a; X is an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 are heteroatoms selected from O, N and S; and A, E, R 2 , R 3 , R 4 , Q 1 and Q 2 are as defined in the claims; provided that when E is aryl or heteroaryl, then Q 2 is other than a bond; and further provided that the moiety (a) is other than a group (BG1) or (BG2); wherein (BG1) and (BG2) are each optionally substituted; T is N or CR Z ; J 1 -J 2 is selected from N═C(R Z ), (R Z )C═N, (R Z )N—C(O), (R Z ) 2 C—C(O), N═N and (R Z )C═C(R 6 ); J 4 -J 3 is a group N═C(R Z ) or a group (R Z )N—CO; and R Z is hydrogen or a substituent. The compounds of the formula (I) have PKA and PKB kinase inhibiting activity and are useful in the treatment of cancers.

  公式（I）的化合物及其盐、溶剂化物、互变异构体和N-氧化物，其中TG从（1）和（2）组中选择：其中星号（*）表示E基团连接到X基团的连接点；R1a是可选取代的芳基或杂环芳基基团；R1b是氢或R1a基团；X是具有8至12个环成员的可选取代的双环杂环基团，其中最多5个是O、N和S的杂原子；A、E、R2、R3、R4、Q1和Q2如权利要求所定义；但是当E是芳基或杂环芳基时，Q2不是键；并且进一步提供，所述基团（a）不是（BG1）或（BG2）基团；其中（BG1）和（BG2）均为可选取代基团；T为N或CRZ；J1-J2选自N═C（RZ）、（RZ）C═N、（RZ）N—C（O）、（RZ）2C—C（O）、N═N和（RZ）C═C（R6）；J4-J3是N═C（RZ）基团或（RZ）N—CO基团；RZ是氢或取代基团。公式（I）的化合物具有PKA和PKB激酶抑制活性，并且在治疗癌症方面有用。
• 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。