1-(2-cyanoethyl)-4-(N,N-dimethylaminomethyl)-4-phenylpiperidine | 219553-48-7

• 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: 1-(2-cyanoethyl)-4-(N,N-dimethylaminomethyl)-4-phenylpiperidine
• 英文别名: 1-(2-cyanoethyl)-N,N-dimethyl-4-phenylpiperidine-4-carboxamide
• CAS: 219553-48-7
• 化学式: C₁₇H₂₃N₃O
• 分子量: 285.389
• InChiKey: VASHGYXOOAIODY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-cyanoethyl)-4-(N,N-dimethylaminomethyl)-4-phenylpiperidine 在 盐酸 、 硼烷 作用下， 生成 3-<4-(N,N-dimethylaminomethyl)-4-phenylpiperidin-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
• 作为产物：
  描述：

  4-苯基-4-哌啶羧酸对甲基苯磺酸 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 1-(2-cyanoethyl)-4-(N,N-dimethylaminomethyl)-4-phenylpiperidine
  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