1-(pyridin-2-yl)piperidin-4-yl methanesulfonate | 199117-80-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(pyridin-2-yl)piperidin-4-yl methanesulfonate
• 英文别名: methanesulfonic acid 3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl ester；(1-Pyridin-2-ylpiperidin-4-yl) methanesulfonate
• CAS: 199117-80-1
• 化学式: C₁₁H₁₆N₂O₃S
• 分子量: 256.326
• InChiKey: LPCYKMVWSAUMIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(pyridin-2-yl)piperidin-4-yl methanesulfonate 在 哌啶 、 potassium carbonate 、 苯甲酸 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 14.0h， 生成 (5Z)-5-[[4-(1-pyridin-2-ylpiperidin-4-yl)oxyphenyl]methylidene]-1,3-thiazolidine-2,4-dione
  参考文献：
  名称：

  Novel Euglycemic and Hypolipidemic Agents. 4. Pyridyl- and Quinolinyl-Containing Thiazolidinediones

  摘要：

  A series of substituted pyridyl- and quinolinyl-containing 2,4-thiazolidinediones having interesting cyclic amine as a linker have been synthesized. Both unsaturated thiazolidinediones 5 and saturated thiazolidinediones 6 and their various salts were evaluated in db/db mice for euglycemic and hypolipidemic effects and compared with BRL compound 11 and BRL-49653, respectively. Some of the potent compounds were converted to various salts in order to obtain improved activities. Among all the salts evaluated, the maleate salt of unsaturated TZD 5a was found to be a very potent euglycemic and hypolipidemic compound. Some of the more interesting compounds have also been evaluated in ob/ob mice and compared with rosiglitazone (maleate salt of BRL-49653). Oral glucose tolerance tests were performed in both db/db and ob/ob mice. Pharmacokinetic studies of 5a maleate are also reported. Receptor binding studies of PPAR gamma by 5a/5a maleate did not show any significant transactivation of PPAR alpha or PPAR gamma.

  DOI：

  10.1021/jm980622j
• 作为产物：
  描述：

  2-氯吡啶 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 1-(pyridin-2-yl)piperidin-4-yl methanesulfonate
  参考文献：
  名称：

  Novel Euglycemic and Hypolipidemic Agents. 4. Pyridyl- and Quinolinyl-Containing Thiazolidinediones

  摘要：

  A series of substituted pyridyl- and quinolinyl-containing 2,4-thiazolidinediones having interesting cyclic amine as a linker have been synthesized. Both unsaturated thiazolidinediones 5 and saturated thiazolidinediones 6 and their various salts were evaluated in db/db mice for euglycemic and hypolipidemic effects and compared with BRL compound 11 and BRL-49653, respectively. Some of the potent compounds were converted to various salts in order to obtain improved activities. Among all the salts evaluated, the maleate salt of unsaturated TZD 5a was found to be a very potent euglycemic and hypolipidemic compound. Some of the more interesting compounds have also been evaluated in ob/ob mice and compared with rosiglitazone (maleate salt of BRL-49653). Oral glucose tolerance tests were performed in both db/db and ob/ob mice. Pharmacokinetic studies of 5a maleate are also reported. Receptor binding studies of PPAR gamma by 5a/5a maleate did not show any significant transactivation of PPAR alpha or PPAR gamma.

  DOI：

  10.1021/jm980622j

文献信息

• [EN] NOVEL OXIME DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS D'OXIMES ET LEUR UTILISATION COMME MODULATEURS ALLOSTÉRIQUES DE RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE
  申请人：DOMAIN THERAPEUTICS

  公开号：WO2011051478A1

  公开（公告）日：2011-05-05

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGiuR4.

  本发明提供了一般式（I）的新羟肟衍生物，包含它们的药物组合物以及它们用于治疗和/或预防与改变的谷氨酸信号和/或功能有关的疾病，和/或在哺乳动物中改变谷氨酸水平或信号会影响的疾病。本发明进一步提供了一般式（I）的新羟肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新羟肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向变构调节剂，更具体地说是mGluR4的正向变构调节剂。
• [EN] THIAZOLIDINEDIONE COMPOUNDS HAVING ANTIDIABETIC, HYPOLIPIDAEMIC, ANTIHYPERTENSIVE PROPERTIES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] COMPOSES DE THIAZOLIDINEDIONE PRESENTANT DES PROPRIETES ANTIDIABETIQUES, HYPOLIPIDEMIANTES, ANTIHYPERTENSIVES, LEUR PROCEDE DE PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：WO1997041120A1

  公开（公告）日：1997-11-06

  (EN) Novel thiazolidinedione antidiabetic compounds, their tautomeric forms, their derivatives, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceuticals acceptable compositions containing them; methods for preparing the antidiabetic compounds and their uses.(FR) L'invention concerne de nouveaux composés antidiabétiques de thiazolidinedione, leurs formes tautomères, leurs dérivés, leurs stéréoisomères, leurs polymorphes, leurs sels pharmaceutiquement acceptables, leurs solvates pharmaceutiquement acceptables et des compositions pharmaceutiquement acceptables les contenant, des procédés de préparation des composés antidiabétiques et leurs utilisations.

  (中) 一种新的噻唑烷酮类抗糖尿病化合物、它们的互变异构体、衍生物、立体异构体、多晶形态、药用可接受的盐、药用可接受的溶剂和含有它们的药用可接受的组合物；制备抗糖尿病化合物的方法及其用途。
• Novel Oxime Derivatives and Their Use As Allosteric Modulators of Metabotropic Glutamate Receptors
  申请人：Schann Stephan

  公开号：US20120277212A1

  公开（公告）日：2012-11-01

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

  本发明提供了一般式（I）的新的肟衍生物，以及包含它们的制药组合物，以及它们用于治疗和/或预防与改变谷氨酸信号和/或功能相关的疾病和/或与哺乳动物中谷氨酸水平或信号改变有关的疾病的用途。本发明还提供了一般式（I）的新的肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经和/或精神障碍。在特定实施例中，本发明的新的肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向异构调节剂，更具体地说是mGluR4的正向异构调节剂。
• Oxime derivatives and their use as allosteric modulators of metabotropic glutamate receptors
  申请人：Schann Stephan

  公开号：US08962627B2

  公开（公告）日：2015-02-24

  The present invention provides new oxime derivatives of the general formula (I), pharmaceutical compositions containing them and their use for the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals. This invention further provides new oxime derivatives of the general formula (I) consisting of modulators of nervous system receptors sensitive to glutamate, which makes them particularly suitable for the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders. In particular embodiments, the new oxime derivatives of the invention are modulators of metabotropic glutamate receptors (mGluRs). The invention further provides positive allosteric modulators of mGluRs and more specifically positive alSosteric modulators of mGluR4.

  本发明提供了一般式（I）的新的肟衍生物、包含它们的药物组合物以及它们用于治疗和/或预防与改变谷氨酸信号和/或功能有关的疾病和/或可以受到哺乳动物谷氨酸水平或信号改变影响的疾病的用途。本发明还提供了一般式（I）的新的肟衍生物，它们是对谷氨酸敏感的神经系统受体的调节剂，因此特别适用于治疗和/或预防急性和慢性神经系统和/或精神疾病。在特定实施例中，本发明的新的肟衍生物是代谢型谷氨酸受体（mGluRs）的调节剂。本发明还提供了mGluRs的正向变构调节剂，更具体地说是mGluR4的正向变构调节剂。
• THIAZOLIDINEDIONE COMPOUNDS HAVING ANTIDIABETIC, HYPOLIPIDAEMIC, ANTIHYPERTENSIVE PROPERTIES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：EP0923580A1

  公开（公告）日：1999-06-23