4-(3,4-Methylenedioxybenzyl)amino-6-ethoxycarbonylquinazoline | 150450-64-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-(3,4-Methylenedioxybenzyl)amino-6-ethoxycarbonylquinazoline
• 英文别名: 4-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-quinazoline-6-carboxylic acid ethyl ester；ethyl 4-(1,3-benzodioxol-5-ylmethylamino)quinazoline-6-carboxylate
• CAS: 150450-64-9
• 化学式: C₁₉H₁₇N₃O₄
• 分子量: 351.362
• InChiKey: MQMLSCZNCLYVPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3,4-Methylenedioxybenzyl)amino-6-ethoxycarbonylquinazoline 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 生成 6-(hydroxymethyl)-4-<<3,4-(methylenedioxy)benzyl>amino>quinazoline
  参考文献：
  名称：

  Cyclic GMP Phosphodiesterase Inhibitors. 2. Requirement of 6-Substitution of Quinazoline Derivatives for Potent and Selective Inhibitory Activity

  摘要：

  We synthesized various 4-[[3,4-(methylenedioxy)benzyl]amino]quinazolines substituted at the 5-to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta, Monosubstitution at the 6-position was essential for the inhibitory activity, and the preferred substituents were compact and hydrophobic: methoxy (3b, IC50 = 0.23 mu M), methyl (3c, 0.10 mu M), chloro (3d, 0.019 mu M), thiomethyl (3f, 0.031 mu M), and cyano (3p, 0.090 mu M) groups. Compounds 3b-d,f,p lacked inhibitory activity toward other PDE isozymes (all IC50 values > 100 mu M), and their relaxing activities in porcine coronary arteries were well correlated with the inhibitory activities toward cGMP-PDE (r = 0.88, p < 0.05). One of these compounds, 3b, elevated the intracellular cGMP level in isolated porcine coronary arteries without causing any change in the cAMP level. We consider that this series of compounds dilates coronary arteries via potent and specific inhibition of cGMP-PDE,

  DOI：

  10.1021/jm00039a024
• 作为产物：
  描述：

  ethyl 4-oxo-3,4-dihydroquinazoline-6-carboxylate 在 sodium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 3.0h， 生成 4-(3,4-Methylenedioxybenzyl)amino-6-ethoxycarbonylquinazoline
  参考文献：
  名称：

  Cyclic GMP Phosphodiesterase Inhibitors. 2. Requirement of 6-Substitution of Quinazoline Derivatives for Potent and Selective Inhibitory Activity

  摘要：

  We synthesized various 4-[[3,4-(methylenedioxy)benzyl]amino]quinazolines substituted at the 5-to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta, Monosubstitution at the 6-position was essential for the inhibitory activity, and the preferred substituents were compact and hydrophobic: methoxy (3b, IC50 = 0.23 mu M), methyl (3c, 0.10 mu M), chloro (3d, 0.019 mu M), thiomethyl (3f, 0.031 mu M), and cyano (3p, 0.090 mu M) groups. Compounds 3b-d,f,p lacked inhibitory activity toward other PDE isozymes (all IC50 values > 100 mu M), and their relaxing activities in porcine coronary arteries were well correlated with the inhibitory activities toward cGMP-PDE (r = 0.88, p < 0.05). One of these compounds, 3b, elevated the intracellular cGMP level in isolated porcine coronary arteries without causing any change in the cAMP level. We consider that this series of compounds dilates coronary arteries via potent and specific inhibition of cGMP-PDE,

  DOI：

  10.1021/jm00039a024

文献信息

• NITROGENOUS HETEROCYCLIC COMPOUND
  申请人：Eisai Co., Ltd.

  公开号：EP0607439A1

  公开（公告）日：1994-07-27

  A nitrogenous heterocyclic compound represented by general formula (I) or a pharmacologically acceptable salt thereof, efficacious in treating various ischemic cardiac diseases, wherein ring A represents a benzene, pyridine or cyclohexane ring; ring B represents a pyridine, pyrimidine or imidazole ring; R¹, R², R³ and R⁴ represent each hydrogen, halogen, lower alkoxy, etc.; R⁵ represents -NR¹¹R¹² (wherein R¹¹ and R¹² represent each hydrogen, lower alkyl, etc.), etc.; and R⁶ represents (a) (wherein R¹⁹ represents hydrogen, lower alkyl, etc.; R²⁰, R²¹ and R²² represent each hydrogen, halogen, hydroxy, etc.; and r represents an integer of 0.1 to 8), etc.

  一种由通式(I)代表的含氮杂环化合物或其药理学上可接受的盐，可有效治疗各种缺血性心脏病，其中环 A 代表苯环、吡啶环或环己烷环；环 B 代表吡啶环、嘧啶环或咪唑环；R¹、R²、R³ 和 R⁴ 分别代表氢、卤素、低级烷氧基等；R⁵ 代表 -NR¹R¹² (其中 R¹¹ 和 R¹² 分别代表氢、低级烷基等)；以及 R⁶ 代表 -NR¹R¹² (其中 R¹¹ 和 R¹² 分别代表氢、低级烷基等)。R⁵代表-NR¹R¹²（其中 R¹¹ 和 R¹² 分别代表氢、低级烷基等）等；以及 R⁶ 代表（a）（其中 R¹⁹ 代表氢、低级烷基等；R²⁰、R²¹ 和 R²² 分别代表氢、卤素、羟基等；以及 r 代表 0.1 至 8 的整数）等。
• Takase Yasutaka, Saeki Takao, Watanabe Nobuhisa, Adachi Hideyuki, Souda S+, J. Med. Chem, 37 (1994) N 13, S 2106-2111
  作者：Takase Yasutaka, Saeki Takao, Watanabe Nobuhisa, Adachi Hideyuki, Souda S+

  DOI：——

  日期：——
• US5576322A
  申请人：——

  公开号：US5576322A

  公开（公告）日：1996-11-19
• US5693652A
  申请人：——

  公开号：US5693652A

  公开（公告）日：1997-12-02
• US5801180A
  申请人：——

  公开号：US5801180A

  公开（公告）日：1998-09-01