2-(苯氧基甲基)哌啶 | 220510-70-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-(苯氧基甲基)哌啶
• 英文名称: 2-(phenoxymethyl)piperidine
• CAS: 220510-70-3
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: XHTUKUBNEBMHAP-UHFFFAOYSA-N

物化性质

• 沸点：
  295.9±13.0 °C(Predicted)
• 密度：
  0.996±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  三光气 、 diphenyl(1H-1,2,3-triazol-4-yl)methanol 、 2-(苯氧基甲基)哌啶 在 N,N-二异丙基乙胺 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以25%的产率得到(4-(hydroxydiphenylmethyl)-2H-1,2,3-triazol-2-yl)(2-(phenoxymethyl)piperidin-1-yl)methanone
  参考文献：
  名称：

  Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

  摘要：

  Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2 -AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4 -substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5 -position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting -induced refeeding of mice, thereby emulating the effect of cannabinoid' CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

  DOI：

  10.1021/acs.jmedchem.6b01482
• 作为产物：
  描述：

  2-哌啶甲醇 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 32.5h， 生成 2-(苯氧基甲基)哌啶
  参考文献：
  名称：

  Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

  摘要：

  Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2 -AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4 -substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5 -position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting -induced refeeding of mice, thereby emulating the effect of cannabinoid' CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

  DOI：

  10.1021/acs.jmedchem.6b01482

文献信息

• [EN] CASPASES AND APOPTOSIS<br/>[FR] CASPASES ET APOPTOSE
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1999006367A1

  公开（公告）日：1999-02-11

  (EN) The present invention is to the novel compounds of Formula (I), their pharmaceutical compositions, and to the novel inhibition of caspases for use in the treatment of apoptosis, and disease states caused by excessive or inappropriate cell death.(FR) La présente invention concerne les nouveaux composés de formule (I), leurs compositions pharmaceutiques, ainsi que la nouvelle forme d'inhibition de caspases destinés à l'utilisation dans le traitement de l'apoptose et d'états pathogènes causés par une mort cellulaire excessive ou inappropriée.

  该发明涉及公式(I)的新化合物、它们的药物组合物，以及新的针对caspases的抑制剂，用于治疗由过度或不适当的细胞死亡引起的凋亡和疾病状态。
• Sulfonyl isatin compounds and methods of blocking apoptosis therewith
  申请人：SmithKline Beecham Corporation

  公开号：US06403792B1

  公开（公告）日：2002-06-11

  The present invention is to novel sulfonyl isatin compounds of Formula (I), their pharmaceutical compositions, and the novel inhibition of caspases for use in the treatment of apoptosis, and disease states caused by excessive or inappropriate cell death.

  本发明涉及一种新型的磺酰基异喹啉化合物（式（I）），它们的药物组合物，以及用于治疗细胞凋亡和由过度或不适当的细胞死亡引起的疾病状态的新型半胱氨酸蛋白酶抑制剂。
• Inhibitors of Ion Channels
  申请人：Marron Brian Edward

  公开号：US20130072471A1

  公开（公告）日：2013-03-21

  Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides substituted aryl sulfonamides, compositions comprising these compounds, as well as methods of using these compounds or compositions in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel.

  本发明提供了在通过抑制电压门控钠通道中的钠离子流来治疗疾病方面有用的化合物、组合物和方法。更具体地，本发明提供了取代芳基磺酰胺、包含这些化合物的组合物，以及使用这些化合物或组合物治疗中枢或外周神经系统疾病，特别是疼痛和慢性疼痛的方法，通过阻断与所示条件的发生或复发相关的钠通道来实现。本发明的化合物、组合物和方法特别适用于通过抑制电压门控钠通道中的离子流来治疗神经病性或炎症性疼痛。
• INHIBITORS OF ION CHANNELS
  申请人：Marron Brian Edward

  公开号：US20090143358A1

  公开（公告）日：2009-06-04

  Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides substituted aryl sulfonamides, compositions comprising these compounds, as well as methods of using these compounds or compositions in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel.

  本发明提供了化合物、组合物和方法，通过抑制电压门控钠通道中的钠离子流来治疗疾病。更具体地，本发明提供了取代芳基磺酰胺、包含这些化合物的组合物，以及使用这些化合物或组合物治疗中枢或外周神经系统疾病，特别是疼痛和慢性疼痛的方法，通过阻止与所示疾病的发生或复发有关的钠通道。本发明的化合物、组合物和方法特别适用于通过抑制电压门控钠通道中的离子流来治疗神经病理性或炎症性疼痛。
• Phenoxymethyl piperidine derivatives being sodium channle blockers
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0869119A1

  公开（公告）日：1998-10-07

  The present invention relates to phenoxymethyl piperidine derivatives, and pharmaceutically acceptable salts and N-oxides thereof, which are sodium channel blockers, and thus exhibit useful pharmacological properties, including utility for the treatment of neuropathic pain conditions. represented by formula I: where: R1 is hydrogen, (C1-4)alkyl, -(CH2)mcycloalkyl, -(CH2)mNR7R8, or -(CH2)mNR7SO2R9; m is 1 to 3; R7 and R8 are independently hydrogen or (C1-4)alkyl; and R9 is (C1-4)alkyl; R2,R3,R5, and R6 are independently hydrogen, (C1-4)alkyl, or halogen; R4 is hydrogen, (C1-4)alkyl, hydroxy, alkyloxy, fluoroalkyloxy, halogen, or phenyl or mono- or di-substituted phenyl, the substituents selected from alkyloxy, amino, nitro or acetylamino; provided that when R1 is hydrogen at least two of R2,R3,R4,R5, and R6 are other than hydrogen; and further provided that when R1 is methyl and R2,R3,R5 and R6 are hydrogen, R4 is other than fluoro; or a pharmaceutically acceptable salt or N-oxide thereof, as an individual isomer or as a racemic or non-racemic mixture of isomers.

  本发明涉及苯氧基甲基哌啶衍生物及其药学上可接受的盐和 N-氧化物，它们是钠通道阻滞剂，因此具有有用的药理特性，包括用于治疗神经性疼痛病症。 由式 I 表示： 其中 R1 是氢、(C1-4)烷基、-(CH2)m 环烷基、-(CH2)mNR7R8 或-(CH2)mNR7SO2R9； m 为 1 至 3； R7 和 R8 独立地为氢或 (C1-4)烷基；以及 R9 是 (C1-4)烷基； R2、R3、R5 和 R6 独立地是氢、(C1-4)烷基或卤素； R4 是氢、(C1-4)烷基、羟基、烷氧基、氟烷氧基、卤素或苯基或单取代或二取代苯基，取代基选自烷氧基、氨基、硝基或乙酰氨基； 当 R1 为氢时，R2、R3、R4、R5 和 R6 中至少有两个不是氢；当 R1 为甲基，R2、R3、R5 和 R6 为氢时，R4 不是氟； 或其药学上可接受的盐或 N-氧化物，作为单个异构体或作为异构体的外消旋或非外消旋混合物。