1-[6,7-Dimethoxy-3-methoxycarbonyl-4-(3,4,5-trimethoxy-phenyl)-naphthalene-2-carbonyl]-piperidine-4-carboxylic acid ethyl ester | 225516-33-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基萘木脂素
• 英文名称: 1-[6,7-Dimethoxy-3-methoxycarbonyl-4-(3,4,5-trimethoxy-phenyl)-naphthalene-2-carbonyl]-piperidine-4-carboxylic acid ethyl ester
• 英文别名: ethyl 1-[6,7-dimethoxy-3-methoxycarbonyl-4-(3,4,5-trimethoxyphenyl)naphthalene-2-carbonyl]piperidine-4-carboxylate
• CAS: 225516-33-6
• 化学式: C₃₂H₃₇NO₁₀
• 分子量: 595.646
• InChiKey: LJLHVSDEOIFKQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-[6,7-Dimethoxy-3-methoxycarbonyl-4-(3,4,5-trimethoxy-phenyl)-naphthalene-2-carbonyl]-piperidine-4-carboxylic acid ethyl ester 在 甲醇 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 以78%的产率得到3-(4-Hydroxymethyl-piperidine-1-carbonyl)-6,7-dimethoxy-1-(3,4,5-trimethoxy-phenyl)-naphthalene-2-carboxylic acid methyl ester
  参考文献：
  名称：

  1-Arylnaphthalene Lignan:  A Novel Scaffold for Type 5 Phosphodiesterase Inhibitor

  摘要：

  1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 > 16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3,4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-carboxylate (35) (27q, EC50 = 0.10 mu M; 35, EC50 = 0.20 mu M) and was selected for further biological evaluation.

  DOI：

  10.1021/jm9807048
• 作为产物：
  描述：

  1-溴-2-(二甲氧基甲基)-4,5-二甲氧基苯 在 sodium hydroxide 、 正丁基锂 、 溶剂黄146 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.5h， 生成 1-[6,7-Dimethoxy-3-methoxycarbonyl-4-(3,4,5-trimethoxy-phenyl)-naphthalene-2-carbonyl]-piperidine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  1-Arylnaphthalene Lignan:  A Novel Scaffold for Type 5 Phosphodiesterase Inhibitor

  摘要：

  1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 > 16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3,4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-carboxylate (35) (27q, EC50 = 0.10 mu M; 35, EC50 = 0.20 mu M) and was selected for further biological evaluation.

  DOI：

  10.1021/jm9807048