3-amino-6,7-dimethoxy-2-(methoxycarbonyl)-1-(3,4,5-trimethoxyphenyl)naphthalene | 225516-15-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-amino-6,7-dimethoxy-2-(methoxycarbonyl)-1-(3,4,5-trimethoxyphenyl)naphthalene
• 英文别名: Methyl 3-amino-6,7-dimethoxy-1-(3,4,5-trimethoxyphenyl)naphthalene-2-carboxylate
• CAS: 225516-15-4
• 化学式: C₂₃H₂₅NO₇
• 分子量: 427.454
• InChiKey: MBWMGYJUVBNTQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  98.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-amino-6,7-dimethoxy-2-(methoxycarbonyl)-1-(3,4,5-trimethoxyphenyl)naphthalene 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 生成 [3-Amino-6,7-dimethoxy-1-(3,4,5-trimethoxy-phenyl)-naphthalen-2-yl]-methanol
  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：

  6,7-dimethoxy-2-(methoxycarbonyl)-1-(3,4,5-trimethoxyphenyl)naphthalene-3-carboxylic acid 在 盐酸 、 sodium azide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 生成 3-amino-6,7-dimethoxy-2-(methoxycarbonyl)-1-(3,4,5-trimethoxyphenyl)naphthalene
  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

文献信息

• 1-Arylnaphthalene Lignan:  A Novel Scaffold for Type 5 Phosphodiesterase Inhibitor
  作者：Tatsuzo Ukita、Yoshinori Nakamura、Akira Kubo、Yasuo Yamamoto、Masami Takahashi、Jun Kotera、Tomohiro Ikeo

  DOI：10.1021/jm9807048

  日期：1999.4.1

  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.