3-(4-(ethoxycarbonyl)piperidin-1-yl)propylamine

• 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: 3-(4-(ethoxycarbonyl)piperidin-1-yl)propylamine
• 英文别名: Ethyl 1-(3-aminopropyl)-4-piperidinecarboxylate；ethyl 1-(3-aminopropyl)piperidine-4-carboxylate
• 化学式: C₁₁H₂₂N₂O₂
• 分子量: 214.308
• InChiKey: POQYLKMTBDPINH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-(ethoxycarbonyl)piperidin-1-yl)propylamine 、 5-(N-methylcarboxamido)-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)pyridine-3-carboxylic acid 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 Ethyl 1-[3-[[2,6-dimethyl-5-(methylcarbamoyl)-4-(4-nitrophenyl)-1,4-dihydropyridine-3-carbonyl]amino]propyl]piperidine-4-carboxylate
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Dihydropyridine Antagonists for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  We report the synthesis and evaluation of novel alpha(1a) adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha(1a), antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a K-i of 2.8 nM, in agreement with the cloned human receptor binding data (K-i = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a K-i of 3.6 nM and confirmed it to be a potent antagonist (K-b = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP K-b/IUP K-b ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha(1a) adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha(1) antagonists such as prazosin and terazosin, with fewer side effects.

  DOI：

  10.1021/jm980506g
• 作为产物：
  描述：

  哌啶-4-甲酸乙酯 、 3-溴丙胺氢溴酸盐 在 potassium carbonate 、 potassium iodide 作用下， 以 1,4-二氧六环 为溶剂， 反应 36.0h， 以42%的产率得到3-(4-(ethoxycarbonyl)piperidin-1-yl)propylamine
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Dihydropyridine Antagonists for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  We report the synthesis and evaluation of novel alpha(1a) adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha(1a), antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a K-i of 2.8 nM, in agreement with the cloned human receptor binding data (K-i = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a K-i of 3.6 nM and confirmed it to be a potent antagonist (K-b = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP K-b/IUP K-b ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha(1a) adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha(1) antagonists such as prazosin and terazosin, with fewer side effects.

  DOI：

  10.1021/jm980506g