methyl 2-(4-benzyloxyphenyl)-1,2-dihydro-6,7-dimethoxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-3-isoquinolinecarboxylate | 260407-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 2-(4-benzyloxyphenyl)-1,2-dihydro-6,7-dimethoxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-3-isoquinolinecarboxylate
• 英文别名: Methyl 6,7-dimethoxy-1-oxo-2-(4-phenylmethoxyphenyl)-4-(3,4,5-trimethoxyphenyl)isoquinoline-3-carboxylate
• CAS: 260407-27-0
• 化学式: C₃₅H₃₃NO₉
• 分子量: 611.648
• InChiKey: NZPZJFGJYSSPGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-benzyloxyphenyl)-1,2-dihydro-6,7-dimethoxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-3-isoquinolinecarboxylate 在 10percent Pd/C 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到2-(4-Hydroxy-phenyl)-6,7-dimethoxy-1-oxo-4-(3,4,5-trimethoxy-phenyl)-1,2-dihydro-isoquinoline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Novel, Potent, and Selective Phosphodiesterase 5 Inhibitors:  Synthesis and Biological Activities of a Series of 4-Aryl-1-isoquinolinone Derivatives

  摘要：

  A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-iso-quinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)- 3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC50 = 1.0 nM) with high isozyme selectivities (IC50 ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC30 = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.

  DOI：

  10.1021/jm000558h
• 作为产物：
  描述：

  3,4-dimethoxy-6-(3,4,5-trimethoxybenzoyl)benzoic acid 在 盐酸 、 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 methyl 2-(4-benzyloxyphenyl)-1,2-dihydro-6,7-dimethoxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-3-isoquinolinecarboxylate
  参考文献：
  名称：

  Novel, Potent, and Selective Phosphodiesterase 5 Inhibitors:  Synthesis and Biological Activities of a Series of 4-Aryl-1-isoquinolinone Derivatives

  摘要：

  A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-iso-quinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)- 3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC50 = 1.0 nM) with high isozyme selectivities (IC50 ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC30 = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.

  DOI：

  10.1021/jm000558h

文献信息

• Novel, Potent, and Selective Phosphodiesterase 5 Inhibitors:  Synthesis and Biological Activities of a Series of 4-Aryl-1-isoquinolinone Derivatives
  作者：Tatsuzo Ukita、Yoshinori Nakamura、Akira Kubo、Yasuo Yamamoto、Yasunori Moritani、Kunio Saruta、Takanori Higashijima、Jun Kotera、Michino Takagi、Kohei Kikkawa、Kenji Omori

  DOI：10.1021/jm000558h

  日期：2001.6.1

  A novel class of potent and selective phosphodiesterase 5 (PDE5) inhibitors, 4-aryl-1-iso-quinolinone derivatives, which have been designed by the comparison of the structure of cGMP and a previously reported 1-arylnaphthalene lignan, was disclosed. Among these compounds, methyl 2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)- 3-isoquinoline carboxylate dihydrochloride (36a) exhibited potent PDE5 inhibitory activity (IC50 = 1.0 nM) with high isozyme selectivities (IC50 ratio: PDE1/PDE5 = 1300, PDE2/PDE5 > 10 000, PDE3/PDE5 > 10 000, PDE4/PDE5 = 4700, PDE6/PDE5 = 28). Compound 36a also showed the most potent relaxant effect on isolated rabbit corpus cavernosum (EC30 = 7.9 nM). Compound 63 (T-1032), the sulfate form of 36a, was selected for further biological and pharmacological evaluation of erectile dysfunction.