1-(4-hydroxypiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine | 178308-65-1

• 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-hydroxypiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine
• 英文别名: 4-(3-chloro-4-methoxybenzyl)amino-6-cyano-1-(4-hydroxypiperidino)phthalazine；4-(3-Chloro-4-methoxybenzyl)amino-6-cyano-1-(4-hydroxypiperidino)phthalazin；E-4010；E-8010；Yze9gcm2BB；4-[(3-chloro-4-methoxyphenyl)methylamino]-1-(4-hydroxypiperidin-1-yl)phthalazine-6-carbonitrile
• CAS: 178308-65-1
• 化学式: C₂₂H₂₂ClN₅O₂
• 分子量: 423.902
• InChiKey: VDXZLVXFVYDBNH-UHFFFAOYSA-N

物化性质

• 沸点：
  714.1±60.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  94.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxypiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 14.0h， 生成 N₆,N₆-dimethyl-4-[(3-chloro-4-methoxybenzyl)amino]-1-(4-hydroxypiperidino)-6-phthalazinecarboxamide
  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
• 作为产物：
  描述：

  4-羟基哌啶 、 1-chloro-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine 在 N,N-二异丙基乙胺 作用下， 以 1-甲基-2-哌啶酮 为溶剂， 生成 1-(4-hydroxypiperidino)-4-(3-chloro-4-methoxybenzyl)amino-6-cyanophthalazine
  参考文献：
  名称：

  Remedy for erection failure comprising fused pyridazine compound

  摘要：

  该发明提供了一种治疗勃起功能障碍的药物。其活性成分是由以下式(I)表示的融合吡啶嗪化合物或其药理学上可接受的盐：（其中环C代表具有杂原子的5或6元环；n为1到4的整数；R1代表氢、卤素、氰基等；A代表氢、卤素、可选择取代的氨基等；X代表由式—N═表示的基团等；Y代表式—CO—、可选择取代的氨基等）。

  公开号：

  US06288064B1

文献信息

• Phthalazine derivatives and remedies for erectile dysfunction
  申请人：Eisai Co., Ltd.

  公开号：US06498159B1

  公开（公告）日：2002-12-24

  The present invention provides a phthalazine compound as a therapeutic agent for erectile dysfunction represented by the following formula, a pharmacologically acceptable salt thereof or a hydrate thereof: wherein R1 and R2 are the same as or different from each other and represent a halogen atom, a C1 to C4 alkyl group which may be substituted with a halogen atom, a C1 to C4 alkoxy group which may be substituted with a halogen atom or a cyano group; X represents a cyano group, a nitro group, a halogen atom, a hydroxyimino group which may be substituted or a heteroaryl group which may be substituted; Y represents a heteroaryl group, an aryl group which may be substituted, an alkynyl group which may substituted, an alkenyl group, an alkyl group, an optionally substituted saturated or unsaturated 4- to 8-membered amine ring, and the cyclic amine compound is a monocyclic compound, bicyclic compound or a spiro compound; l is an integer of 1 to 3; provided that the case where l is 1 or 2, X is a cyano group, a nitro group or a chlorine atom, R1 is a chlorine atom, R2 is a methoxy group and Y is a 5- or 6-membered amine ring substituted with a hydroxyl group is excluded.

  本发明提供了一种邻苯二氮杂环化合物，作为下式所代表的勃起功能障碍的治疗剂，其药理学上可接受的盐或水合物： 其中R1和R2相同或不同，分别代表卤素原子、可能被卤素原子取代的C1到C4烷基、可能被卤素原子取代的C1到C4烷氧基或氰基；X代表氰基、硝基、卤素原子、可能被取代的羟基亚胺基团或可能被取代的杂芳基团；Y代表杂芳基团、可能被取代的芳基团、可能被取代的炔基团、烯基团、烷基团、可选择地取代的饱和或不饱和的4-至8-成员氨基环，且环状胺化合物是单环化合物、双环化合物或螺环化合物；l为1到3的整数；但在l为1或2的情况下，X为氰基、硝基或氯原子，R1为氯原子，R2为甲氧基团，Y为取代羟基的5-或6-成员氨基环的情况除外。
• Fused pyridazine compounds
  申请人：Eisai Co., Ltd.

  公开号：US05849741A1

  公开（公告）日：1998-12-15

  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. ##STR1##

  以下是一种融合吡啶并嘧啶化合物，其化学式如下（I），或其药理学上可接受的盐，具有对环磷酸鸟苷磷酸二酯酶（以下简称“cGMP-PDE”）的抑制活性。这些化合物可用作预防和治疗剂，用于对于cGMP-PDE抑制活性有效的疾病，例如缺血性心脏病，如心绞痛，心肌梗死和慢性和急性心衰，肺动脉高压，动脉硬化和支气管哮喘。##STR1##
• Remedy for erection failure comprising fused pyridazine compound
  申请人：Eisai Co., Ltd.

  公开号：US06288064B1

  公开（公告）日：2001-09-11

  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).

  该发明提供了一种治疗勃起功能障碍的药物。其活性成分是由以下式(I)表示的融合吡啶嗪化合物或其药理学上可接受的盐：（其中环C代表具有杂原子的5或6元环；n为1到4的整数；R1代表氢、卤素、氰基等；A代表氢、卤素、可选择取代的氨基等；X代表由式—N═表示的基团等；Y代表式—CO—、可选择取代的氨基等）。
• Phthalazine compounds and therapeutic agents for erectile dysfunction
  申请人：Eisai Co., Ltd.

  公开号：US20030105074A1

  公开（公告）日：2003-06-05

  The present invention provides a phthalazine compound as a therapeutic agent for erectile dysfunction represented by the following formula, a pharmacologically acceptable salt thereof or a hydrate thereof: 1 wherein R 1 and R 2 are the same as or different from each other and represent a halogen atom, a C1 to C4 alkyl group which may be substituted with a halogen atom, a C1 to C4 alkoxy group which may be substituted with a halogen atom or a cyano group; X represents a cyano group, a nitro group, a halogen atom, a hydroxyimino group which may be substituted or a heteroaryl group which may be substituted; Y represents a heteroaryl group, an aryl group which may be substituted, an alkynyl group which may substituted, an alkenyl group, an alkyl group, an optionally substituted saturated or unsaturated 4- to 8-membered amine ring, and the cyclic amine compound is a monocyclic compound, bicyclic compound or a spiro compound; l is an integer of 1 to 3; provided that the case where l is 1 or 2, X is a cyano group, a nitro group or a chlorine atom, R 1 is a chlorine atom, R 2 is a methoxy group and Y is a 5- or 6-memberred amine ring substituted with a hydroxyl group is excluded.

  本发明提供了一种治疗勃起功能障碍的邻苯二氮杂环化合物，其化学式如下，其药理学上可接受的盐或水合物：1其中，R1和R2相同或不同，表示卤素原子、可能被卤素原子取代的C1到C4烷基、可能被卤素原子取代的C1到C4烷氧基或氰基；X表示氰基、硝基、卤素原子、可能被取代的羟肟基或可能被取代的杂环基；Y表示杂环基、可能被取代的芳基、可能被取代的炔基、烯基、烷基、可选取代的饱和或不饱和4-至8环胺环，所述的环胺化合物是单环化合物、双环化合物或螺环化合物；l是1到3的整数；但当l为1或2时，X为氰基、硝基或氯原子，R1为氯原子，R2为甲氧基，Y为取代有羟基的5-或6环胺环时，不在此范围内。
• USE OF A PDE 5 INHIBITOR FOR TREATING AND PREVENTING HYPOPIGMENTARY DISORDERS
  申请人：PEUKER Heidemarie

  公开号：US20110142956A1

  公开（公告）日：2011-06-16

  The invention relates to the use of PDE5 inhibitors for treating and/or preventing hypopigmentary disorders.

  本发明涉及使用PDE5抑制剂来治疗和/或预防低色素病。