1-(4-Carbamoylpiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine

• 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: 1-(4-Carbamoylpiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine
• 英文别名: 1-[4-(3-Chloro-4-methoxy-benzylamino)-6-cyano-phthalazin-1-yl]-piperidine-4-carboxylic acid amide; hydrochloride；1-[4-[(3-chloro-4-methoxyphenyl)methylamino]-6-cyanophthalazin-1-yl]piperidine-4-carboxamide
• 化学式: C₂₃H₂₃ClN₆O₂
• 分子量: 450.928
• InChiKey: XSAKXVYXQWAYHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  哌啶-4-甲酰胺 、 1-chloro-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine 在 N-甲基吡咯烷酮 、 N,N-二异丙基乙胺 作用下， 反应 4.5h， 生成 1-(4-Carbamoylpiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine
  参考文献：
  名称：

  4-(3-Chloro-4-methoxybenzyl)aminophthalazines:  Synthesis and Inhibitory Activity toward Phosphodiesterase 5

  摘要：

  We synthesized various 4-(3-chloro-4-methoxybenzyl)aminophthalazines substituted at the 1- and 6-positions and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) and their vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F2 alpha (10(-5) M). The preferred substituents at the 1-position of the phthalazine were 4-hydroxypiperidino, 4-hydroxymethylpiperidino, 4-(2-hydroxyethyl)piperidino, and 4-oxopiperidino. Among these compounds, [4-(3-chloro-4-methoxybenzyl)amino-1-(4-hydroxy)piperidino]-6-phthalazinecarbonitrile monohydrochloride (13) exhibited potent PDE5 inhibitory activity (IC50 = 0.56 nM) with > 1700-fold high selectivity over other PDE isozymes (PDE1-4). Compound 13 exhibited the most potent vasorelaxant action (EC50 = 13 nM) in this series of compounds. Compound 13 reduced mean pulmonary arterial pressure by 29.9 +/- 3.1% when administered intravenously at 30 mu g/kg to the chronically hypoxic rats and had an apparent oral bioavailability of about 19.5% in rats and was selected for further biological evaluation.

  DOI：

  10.1021/jm9905054

文献信息

• FUSED PYRIDAZINE COMPOUND
  申请人：Eisai Co., Ltd.

  公开号：EP0722936A1

  公开（公告）日：1996-07-24

  A fused pyridazine compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof which exhibits an inhibitory activity against cyclic GMP phosphodiesterase (hereinafter referred to as "cGMP-PDE"). The compounds are useful as preventive and therapeutic agents for diseases for which a cGMP-PDE inhibiting action is efficacious, for example, ischemic heart diseases such as angina pectoris, myocardial infarct and chronic and acute cardiac failure, pulmonary hypertension, arteriosclerosis and bronchial asthma.

  由以下通式（I）代表的融合哒嗪化合物或其药理学上可接受的盐，对环 GMP 磷酸二酯酶（以下简称 "cGMP-PDE"）具有抑制活性。 这些化合物可作为 cGMP-PDE 抑制作用有效的疾病的预防和治疗药物，例如缺血性心脏病，如心绞痛、心肌梗塞、慢性和急性心力衰竭、肺动脉高压、动脉硬化和支气管哮喘。
• REMEDY FOR ERECTION FAILURE COMPRISING FUSED PYRIDAZINE COMPOUND
  申请人：Eisai Co., Ltd.

  公开号：EP0920868A1

  公开（公告）日：1999-06-09

  The present invnetion provides a remedy for erectile dysfunction. The active ingredient thereof is a fused pyridazine compound represented by the following formula (I) or a pharmacologically acceptable salt thereof: (wherein the ring C represents a 5 or 6 membered ring optionally having hetero atom(s); n is an integer of from 1 to 4; R1 represents a hydrogen, a halogen, a cyano, etc.; A represents a hydrogen, a halogen, an optionally substituted amino, etc.; X represents a group represented by the formula -N=, etc.; and Y represents the formula -CO-, an optionally substituted amino, etc).

  本发明提供了一种治疗勃起功能障碍的药物。其活性成分是由下式（I）代表的融合哒嗪化合物或其药理上可接受的盐： (其中环 C 代表任选具有杂原子的 5 或 6 成员环；n 是 1 至 4 的整数；R1 代表氢、卤素、氰基等；A 代表氢、卤素、任选取代的氨基等；X 代表式 -N= 所代表的基团等；Y 代表式 -CO-、任选取代的氨基等）。
• US5849741A
  申请人：——

  公开号：US5849741A

  公开（公告）日：1998-12-15
• US6218392B1
  申请人：——

  公开号：US6218392B1

  公开（公告）日：2001-04-17
• US6288064B1
  申请人：——

  公开号：US6288064B1

  公开（公告）日：2001-09-11