4-hydroxy-4-pyrimidin-2-yl-piperidine-1-carboxylic acid tert-butyl ester | 182416-02-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-hydroxy-4-pyrimidin-2-yl-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-hydroxy-4-pyrimidin-2-ylpiperidine-1-carboxylic acid tert-butyl ester；N-tert-butoxycarbonyl-4-hydroxy-4-(2-pyrimidinyl)piperidine；N-butoxycarbonyl-4-hydroxy-4-(2-pyrimidinyl)piperidine；N-t-butoxycarbonyl-4-hydroxy-4-(2-pyrimidinyl)piperidine；tert-butyl 4-hydroxy-4-pyrimidin-2-ylpiperidine-1-carboxylate
• CAS: 182416-02-0
• 化学式: C₁₄H₂₁N₃O₃
• 分子量: 279.339
• InChiKey: QKPZLLSIRXTNTG-UHFFFAOYSA-N

物化性质

• 沸点：
  407.0±45.0 °C(Predicted)
• 密度：
  1.210±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  75.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-hydroxy-4-pyrimidin-2-yl-piperidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 吡啶 、 氢气 、 三氟乙酸 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 63.0h， 生成 2-(哌啶-4-基)嘧啶
  参考文献：
  名称：

  Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of Piclozotan

  摘要：

  A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D, and alpha(1)-adrenergic receptors. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-y]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.046
• 作为产物：
  描述：

  1-Boc-哌啶 、 2-(三丁基锡)嘧啶 在 正丁基锂 、 水 作用下， 以 正己烷 、 四氢呋喃 为溶剂， 反应 0.5h， 以448 mg的产率得到4-hydroxy-4-pyrimidin-2-yl-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  NOVEL COMPOUNDS

  摘要：

  这项发明涉及公式I的化合物，它们作为mGlu5受体活性的正向变构调节剂的用途，含有这些化合物的药物组合物，以及将其用作治疗和/或预防与谷氨酸功能障碍相关的神经和精神障碍，如精神分裂症或认知功能下降，如痴呆症或认知障碍的药剂的方法。A、B、X、R1、R2、R3在描述中给出了它们的含义。

  公开号：

  US20130143870A1

文献信息

• Pyrimidine derivatives and their salts, useful for making benzoxazepine derivatives
  申请人：Suntory Limited

  公开号：US06337397B1

  公开（公告）日：2002-01-08

  A benzoxazepine derivative having the general formula (I) and its salts and medicaments containing the same as effective ingredients: wherein, n is an integer of 2 to 5, R1 indicates a hydrogen atom, halogen atom, C1 to C4 lower alkyl group, C1 to C4 lower alkoxyalkyl group, C1 to C4 halogenoalkyl group, cyano group, or ester group, R2 indicates a hydrogen atom, halogen atom, C1 to C4 lower alkyl group, C1 to C4 lower alkoxy group, or hydroxy group, a dotted line indicates the presence or absence of a binding bond, W indicates C, CH, or CH2 or a nitrogen atom, provided that, when W is a nitrogen atom, Z is bonded to W and the dotted line indicates the absence of a bond, and Z indicates an unsubstituted or substituted aromatic hydrocarbon ring group or an unsubstituted or substituted heterocyclic group).

  一种具有通式（I）的苯并噁唑啉衍生物及其盐和含有其作为有效成分的药物： 其中，n为2至5的整数，R1表示氢原子、卤原子、C1至C4的低碳基团、C1至C4的低碳氧基碳基团、C1至C4的卤代烷基团、氰基或酯基，R2表示氢原子、卤原子、C1至C4的低碳基团、C1至C4的低碳氧基团或羟基，虚线表示结合键的存在或缺失，W表示C、CH或CH2或氮原子，但当W为氮原子时，Z与W结合，虚线表示缺少结合，Z表示未取代或取代的芳香烃环基团或未取代或取代的杂环基团。
• [EN] 1,2,4 -TRIAZOLES AS ALLOSTERIC MODULATORS OF MGLU5 RECEPTOR ACTIVITY FOR THE TREATMENT OF SCHIZOPHRENIA OF DEMENTIA<br/>[FR] 1,2,4-TRIAZOLES COMME MODULATEURS ALLOSTÉRIQUES DE L'ACTIVITÉ DES RÉCEPTEURS MGLU5 POUR LE TRAITEMENT DE LA SCHIZOPHRÉNIE OU DE LA DÉMENCE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013083741A1

  公开（公告）日：2013-06-13

  This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.

  这项发明涉及公式（I）化合物的用途，它们作为mGlu5受体活性的正变构调节剂，包含这些化合物的药物组合物，以及使用它们作为治疗和/或预防与谷氨酸功能障碍相关的神经和精神障碍的方法，如精神分裂症或认知衰退，例如痴呆或认知障碍。A、B、X、R1、R2、R3的含义在描述中给出。
• E-fluoro-4-(pyridin-2-yl)-piperidine-1-carboxamide derivatives and related compounds which modulate the function of the vanilloid-1 receptor (vr1) for the treatment of pain
  申请人：Bayliss Tracy

  公开号：US20070135423A1

  公开（公告）日：2007-06-14

  Compounds of formula (I): wherein: A 1 is phenyl, a six-membered aromatic heterocycle containing one, two or three nitrogen atoms, or a five-membered aromatic heterocycle containing up to four heteroatoms chosen from O, N and S, at most one heteroatom being O or S; A 2 is phenyl, a six-membered aromatic heterocycle containing one, two or three nitrogen atoms, or a five-membered aromatic heterocycle containing up to four heteroatoms chosen from O, N and S, at most one heteroatom being O or S; L is a bond or C 1-6 alkylene; R 1 and R 2 independently chosen from hydrogen and C 1-6 alkyl or R 1 and R 2 may, together, form a methylene or ethylene bridge; W is halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; X is O, S or NR 3 or X, together with the atom to which it is attached, and Y, form an unsaturated five-membered ring together with A 2 ; Y is a bond, C 1-4 alkylene, NH or NH(CH 2 ) 1-3 ; or a pharmaceutically acceptable salt thereof; other substituents are defined in claim 1 ; which are useful as therapeutic compounds, particularly in the treatment of pain and other conditions ameliorated by the modulation of the function of the vanilloid-1 receptor (VR1).

  式(I)的化合物：其中：A1是苯基，含有一个、两个或三个氮原子的六元芳杂环，或含有最多四个来自O、N和S的杂原子的五元芳杂环，至多一个杂原子为O或S；A2是苯基，含有一个、两个或三个氮原子的六元芳杂环，或含有最多四个来自O、N和S的杂原子的五元芳杂环，至多一个杂原子为O或S；L是键或C1-6烷基；R1和R2独立选择自氢和C1-6烷基，或R1和R2可共同形成亚甲基或乙烯基桥；W是卤素、C1-6烷基、卤代C1-6烷基、C1-6烷氧基或卤代C1-6烷氧基；X是O、S或NR3或X与其所连接的原子和Y共同形成一个不饱和的五元环，并与A2一起；Y是键、C1-4烷基、NH或NH(CH2)1-3；或其药学上可接受的盐；其他取代基在权利要求书中有定义；它们在治疗疼痛和其他通过调节vanilloid-1受体（VR1）功能改善的疾病中特别有用。
• Compounds
  申请人：Grauert Matthias

  公开号：US08741892B2

  公开（公告）日：2014-06-03

  This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.

  本发明涉及I式化合物，其用作mGlu5受体活性的正向变构调节剂，含有该化合物的制药组合物，以及将其用作治疗和/或预防与谷氨酸功能失调有关的神经和精神障碍，如精神分裂症或认知衰退，如痴呆或认知障碍的药物的方法。其中，A、B、X、R1、R2、R3在描述中给出了其含义。
• New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects
  作者：Katsuhide Kamei、Noriko Maeda、Ryoko Katsuragi-Ogino、Makoto Koyama、Mika Nakajima、Toshio Tatsuoka、Tomochika Ohno、Teruyoshi Inoue

  DOI：10.1016/j.bmcl.2005.04.059

  日期：2005.6

  A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D-2 and alpha(1)-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model. (c) 2005 Elsevier Ltd. All rights reserved.