methyl 2-(1-pyrrolidinylmethyl)piperidine-5-carboxylate

• 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: methyl 2-(1-pyrrolidinylmethyl)piperidine-5-carboxylate
• 英文别名: cis-Methyl 6-(pyrrolidinylmethyl)-3-piperidinecarboxylate；Methyl 6-(pyrrolidin-1-ylmethyl)piperidine-3-carboxylate
• 化学式: C₁₂H₂₂N₂O₂
• 分子量: 226.319
• InChiKey: NJQJPXCPDAVHAV-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：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(1-pyrrolidinylmethyl)piperidine-5-carboxylate 在 氨 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 cis-1-<(3,4-dichlorophenyl)acetyl>-6-(1-pyrrolidinylmethyl)-3-piperidinecarboxamide
  参考文献：
  名称：

  New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus

  摘要：

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

  DOI：

  10.1021/jm00081a009
• 作为产物：
  描述：

  6-(溴甲基)烟酸甲酯 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 以 四氯化碳 为溶剂， 22.0 ℃ 、101.33 kPa 条件下， 反应 0.25h， 生成 methyl 2-(1-pyrrolidinylmethyl)piperidine-5-carboxylate
  参考文献：
  名称：

  New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus

  摘要：

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

  DOI：

  10.1021/jm00081a009

文献信息

• New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus
  作者：David I. C. Scopes、Norman F. Hayes、David E. Bays、David Belton、John Brain、Dearg S. Brown、Duncan B. Judd、Andrew B. McElroy、Clive A. Meerholz

  DOI：10.1021/jm00081a009

  日期：1992.2

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.