2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido<6,1-a>isoquinolin-4-one | 75535-96-5

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido<6,1-a>isoquinolin-4-one
• 英文别名: 2-chloro-9,10-dimethoxy-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one；2-Chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido(6,1-a)isoquinolin-4-one；9,10-dimethoxy-2-chloro-6,7-dihydro-4H-pyrimido(6,1-a)isoquinolin-4-one；2-Chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido-[6,1-a]isoquinolin-4-one；2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one
• CAS: 75535-96-5
• 化学式: C₁₄H₁₃ClN₂O₃
• 分子量: 292.722
• InChiKey: BIJWXQNMLKVZJM-UHFFFAOYSA-N

物化性质

• 熔点：
  235-236 °C(Solv: ethanol (64-17-5))
• 沸点：
  470.0±55.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 储存条件：
  存储条件：2-8°C，密封保存，远离潮湿环境。

反应信息

• 作为反应物：
  描述：

  2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido<6,1-a>isoquinolin-4-one 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以51%的产率得到9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-pyrimido<6,1-a>isoquinolin-4-one
  参考文献：
  名称：

  Trequinsin, a potent new antihypertensive vasodilator in the series of 2-(arylimino)-3-alkyl-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-ones

  摘要：

  Series of 3-substituted-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido [6,1-a]isoquinoline-2,4-diones and 2-substituted-9,10-dimethoxy-6,7-dihydro-4H-pyrimido [6,1-a]isoquinolin-4-ones were synthesized and tested for blood pressure lowering properties in anesthetized normotensive cats and conscious spontaneously hypertensive rats. Several compounds in the 2-(arylamino)-9,10-dimethoxy-6,7-dihydro-4H-pyrimido [6,1-a]isoquinolin-4-one series display a high order of activity. The most active compounds are the alkyl derivatives of the 2-mesitylamino/2-mesitylimino tautomeric forms. The 2-(mesitylimino)-3-methyl analogue trequinsin is a potent antihypertensive agent and displays a hemodynamic profile characteristic of an arteriolar dilator. It is also a potent inhibitor of both cAMP phosphodiesterase and platelet aggregation.

  DOI：

  10.1021/jm00377a016
• 作为产物：
  描述：

  1-carbamidomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 sodium ethanolate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido<6,1-a>isoquinolin-4-one
  参考文献：
  名称：

  Trequinsin, a potent new antihypertensive vasodilator in the series of 2-(arylimino)-3-alkyl-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-ones

  摘要：

  Series of 3-substituted-9,10-dimethoxy-3,4,6,7-tetrahydro-2H-pyrimido [6,1-a]isoquinoline-2,4-diones and 2-substituted-9,10-dimethoxy-6,7-dihydro-4H-pyrimido [6,1-a]isoquinolin-4-ones were synthesized and tested for blood pressure lowering properties in anesthetized normotensive cats and conscious spontaneously hypertensive rats. Several compounds in the 2-(arylamino)-9,10-dimethoxy-6,7-dihydro-4H-pyrimido [6,1-a]isoquinolin-4-one series display a high order of activity. The most active compounds are the alkyl derivatives of the 2-mesitylamino/2-mesitylimino tautomeric forms. The 2-(mesitylimino)-3-methyl analogue trequinsin is a potent antihypertensive agent and displays a hemodynamic profile characteristic of an arteriolar dilator. It is also a potent inhibitor of both cAMP phosphodiesterase and platelet aggregation.

  DOI：

  10.1021/jm00377a016

文献信息

• Pyrimido (6,1-a)isoquinolin-4-one derivatives
  申请人：Hoechst Aktiengesellschaft

  公开号：US04482556A1

  公开（公告）日：1984-11-13

  What are disclosed are pyrimido (6,1-a)isoquinolin-4-one compounds useful as hypotensive agents, bronchodilators, and anti-allergenics, intermediates useful in their preparation, and methods for making the compounds and intermediates.

  披露的是嘧啶并[6,1-a]异喹啉-4-酮化合物，可用作降压剂、支气管扩张剂和抗过敏药物，以及其制备中有用的中间体，以及制备这些化合物和中间体的方法。
• Die Synthese von 6,7-Dihydro-2<i>H</i>-pyrimido[6, 1-<i>a</i>]isochinolin-4(3<i>H</i>)-onen und analogen Verbindungen und deren Wirkung als Blutpättchenaggregationshemmer
  作者：Frank Kienzle、Yves Bounameaux、Rudolf E. Minder、Reto Muggli

  DOI：10.1002/hlca.19860690722

  日期：1986.10.29

  Synthesis of 6,7-Dihydro-2H-pyrimido[6,1-a]isoquinolin-4(3H)-ones and Analogous Compounds and their Activity as Blood-Platelet Inhibitors

  6,7-二氢-2 H-嘧啶基[6,1 - a ]异喹啉-4（3 H）-ones及其类似化合物的合成及其作为血小板抑制剂的活性
• Derivatives of pyrimido[6,1-a]isoquinolin-4-one
  申请人：——

  公开号：US20030119813A1

  公开（公告）日：2003-06-26

  The invention provides compounds or salts thereof of the general formula (I): 1 wherein each of R 1 and R 2 independently represents a C 1-6 alkyl or C 2-7 acyl group; X represents OCH 2 or a group CR 3 R 4 ; wherein each of R 3 or R 4 independently represents a hydrogen atom or a C 1-3 alkyl group; R 5 represents a hydrogen atom or a C 1-3 alkyl, C 2-3 alkenyl or C 2-3 alkynyl group; R 6 represents a hydrogen atom or a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, amino, C 1-6 alkylamino, di(C 1-6 ) alkylamino or C 2-7 acylamino group; each of R 7 and R 8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkoxy, C 3-6 cycloalkyl; and R 9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkoxy or C 3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one).

  该发明提供了通式(I)的化合物或其盐： 其中R1和R2分别代表C1-6烷基或C2-7酰基基团；X代表OCH2或CR3R4基团；其中R3或R4分别代表氢原子或C1-3烷基基团；R5代表氢原子或C1-3烷基、C2-3烯基或C2-3炔基团；R6代表氢原子或C1-6烷基、C2-6烯基、C2-6炔基、氨基、C1-6烷基氨基、双(C1-6)烷基氨基或C2-7酰氨基团；R7和R8分别代表氢或卤原子或羟基、三氟甲基、C1-6烷基、C2-6烯基、C2-6炔基、C2-7酰基、C1-6烷基硫基、C1-6烷氧基、C3-6环烷基；R9代表氢或卤原子或羟基、三氟甲基、C1-6烷基、C2-6烯基、C2-6炔基、C2-7酰基、C1-6烷基硫基、C1-6烷氧基或C3-6环烷基。该化合物或其盐可用于治疗哮喘等呼吸系统疾病。该发明的化合物比已知的三氮杂环化合物trequinsin（9,10-二甲氧基-3-甲基-2-间甲苯基亚基-2,3,6,7-四氢-4H-嘧啶并［6,1-a］异喹啉-4-酮）具有更长的作用持续时间。
• Derivatives of pyrimido[6.1-a]isoquinolin-4-one
  申请人：——

  公开号：US20030036542A1

  公开（公告）日：2003-02-20

  The invention provides compounds or salts thereof of the general formula (I): 1 wherein each of R 1 and RX independently represents a C 1-6 alkyl or C 2-7 acyl group; X represents OCH 2 or a group CR 3 R 4 ; wherein each of R 3 or R 4 independently represents a hydrogen atom or a C 1-3 alkyl group; R 5 represents a hydrogen atom or a C 1-3 alkyl, C 2-3 alkenyl or C 2-3 alkynyl group; R 6 represents a hydrogen atom or a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, amino, C 1-6 alkylamino, di(C 1-6 ) alkylamino or C 2-7 acylamino group; each of R 7 and R 8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkoxy, C 3-6 cycloalkyl; and R 9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkoxy or C 3-6 cycloalkyl group. The compounds or salts thereof are useful for treatment of respiratory disorders such as asthma. Compounds of the invention have a longer duration of action than the known compound trequinsin (9,10-dimethoxy-3 methyl-2-mesitylimino-2,3,6,7-tetrahydro- 4 -H-pyrimido[6,1-a]isoquinolin-4-one).

  该发明提供了通式（I）的化合物或其盐： 其中，R1和RX分别独立表示C1-6烷基或C2-7酰基；X表示OCH2或CR3R4基团；R3或R4分别独立表示氢原子或C1-3烷基；R5表示氢原子或C1-3烷基、C2-3烯基或C2-3炔基；R6表示氢原子或C1-6烷基、C2-6烯基、C2-6炔基、氨基、C1-6烷基氨基、二（C1-6）烷基氨基或C2-7酰氨基；R7和R8分别独立表示氢或卤素原子、羟基、三氟甲基、C1-6烷基、C2-6烯基、C2-6炔基、C2-7酰基、C1-6烷基硫基、C1-6烷氧基、C3-6环烷基；R9表示氢或卤素原子、羟基、三氟甲基、C1-6烷基、C2-6烯基、C2-6炔基、C2-7酰基、C1-6烷基硫基、C1-6烷氧基或C3-6环烷基。该化合物或其盐可用于治疗哮喘等呼吸系统疾病。该发明的化合物比已知的化合物特雷昆辛（9,10-二甲氧基-3-甲基-2-间二甲苯亚基-2,3,6,7-四氢-4H-嘧啶并［6,1-a］异喹啉-4-酮）具有更长的作用持续时间。
• Processes for the manufacture of pyrimido[6,1-a]isoquinolinones
  申请人：Hoechst Aktiengesellschaft

  公开号：US04400506A1

  公开（公告）日：1983-08-23

  What are disclosed are compounds of the formula ##STR1## wherein, X is oxygen, sulfur, or halogen, useful as intermediates in the preparation of certain pyrimido(6,1-a)isoquinolin-4-ones having pharmaceutical utilities, and methods for making said intermediates.

  所披露的是具有以下公式的化合物 ##STR1## 其中，X为氧、硫或卤素，可用作某些具有药用价值的嘧啶并[6,1-a]异喹啉-4-酮的制备中间体，并提供制备该中间体的方法。