4-Chloro-5,6-dimethoxy-quinazoline | 155960-95-5

• 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-Chloro-5,6-dimethoxy-quinazoline
• 英文别名: 4-Chloro-5,6-dimethoxyquinazoline
• CAS: 155960-95-5
• 化学式: C₁₀H₉ClN₂O₂
• 分子量: 224.647
• InChiKey: UCMRHISAKHYUPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Chloro-5,6-dimethoxy-quinazoline 、 3,4-亚甲二氧基苄胺 在 sodium carbonate 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 以74%的产率得到4-(3,4-Methylenedioxybenzyl)amino-5,6-dimethoxyquinazoline
  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：

  5,6-Dimethoxy-3H-quinazolin-4-one 在 三氯氧磷 作用下， 反应 3.0h， 以57%的产率得到4-Chloro-5,6-dimethoxy-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

文献信息

• 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：——
• SUBSTITUTED HETEROAROMATIC COMPOUNDS AND THEIR USE IN MEDICINE
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0782570A1

  公开（公告）日：1997-07-09
• [EN] SUBSTITUTED HETEROAROMATIC COMPOUNDS AND THEIR USE IN MEDICINE<br/>[FR] COMPOSES HETEROAROMATIQUES SUBSTITUES ET LEUR UTILISATION EN MEDECINE
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1996009294A1

  公开（公告）日：1996-03-28

  (EN) The invention is directed towards substituted heteroaromatic compounds which are protein tyrosine kinase inhibitors, in particular substituted quinolines and quinazolines. Methods of their preparation, pharmaceutical compositions including such compounds and their use in medicine, for example in the treatment of psoriasis, fibrosis, atherosclerosis, restenosis, auto-immune disease, allergy, asthma, transplantation rejection, inflammation, thrombosis, nervous system diseases, and cancer.(FR) On décrit des composés hétéroaromatiques substitués qui sont des inhibiteurs des tyrosines kinases, notamment des quinolines et quinazolines substituées. On décrit également des procédés de préparation de ces composés, des compositions pharmaceutiques comprenant de tels composés ainsi que l'utilisation de ceux-ci en médecine, par exemple dans le traitement du psoriasis, des fibroses, de l'athérosclérose, de la resténose, des maladies auto-immunes, des allergies, de l'asthme, du rejet de greffon, des inflammations, de la thrombose, des maladies du système nerveux et du cancer.
• Cyclic GMP Phosphodiesterase Inhibitors. 2. Requirement of 6-Substitution of Quinazoline Derivatives for Potent and Selective Inhibitory Activity
  作者：Yasutaka Takase、Takao Saeki、Nobuhisa Watanabe、Hideyuki Adachi、Shigeru Souda、Isao Saito

  DOI：10.1021/jm00039a024

  日期：1994.6

  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,