9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one | 76536-66-8

• 物质功能分类: 有机原料 - 酮类化合物
• 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: 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one
• 英文别名: 9,10-Dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one
• CAS: 76536-66-8
• 化学式: C₂₃H₂₅N₃O₃
• 分子量: 391.47
• InChiKey: FJVQNSDTSROABN-UHFFFAOYSA-N

物化性质

• 熔点：
  287-288 °C
• 沸点：
  559.2±60.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one 在 氨 、 氢气 、 lithium carbonate 、 potassium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 丁酮 为溶剂， 20.0~65.0 ℃ 、900.02 kPa 条件下， 反应 144.0h， 生成 (9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one)
  参考文献：
  名称：

  [EN] NEW COMPOUND AND PROCESS
  [FR] NOUVEAU COMPOSÉ ET PROCÉDÉ

  摘要：

  本发明涉及一种式(A)的嘧啶并[6,1-a]异喹啉-4-酮化合物的新型腈衍生物。本发明还涉及一种制备式(A)化合物的方法。本发明还涉及一种包括还原式(A)化合物的方法。本发明的化合物在生产RPL554等化合物中具有用途。

  公开号：

  WO2018020249A1
• 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 、 氯仿 为溶剂， 反应 32.0h， 生成 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-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。
• 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。
• [EN] DERIVATIVES OF PYRIMIDO[6,1-a]ISOQUINOLIN-4-ONE<br/>[FR] DERIVES DE PYRIMIDO [6,1-A] ISOQUINOLEIN-4-ONE ET LEUR UTILISATION EN MEDECINE
  申请人：VANGUARD MEDICA LTD

  公开号：WO2000058308A1

  公开（公告）日：2000-10-05

  Compounds of general formula (I) wherein each of R?1 and R2¿ independently represents a C¿1-6? alkyl or C2-7 acyl group; R?5¿ represents a hydrogen atom or a C¿1-3? alkyl, C2-3 alkenyl or C2-3 alkynyl group; R?6¿ represents a hydrogen atom or a C¿1-6? alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R?7 and R8¿ independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C¿1-6? alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy, C3-6 cycloalkyl; and R?9¿ represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C¿1-6? alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy or C3-6 cycloalkyl group; X represents OCH2 or a group CR?3R4¿, wherein each of R?3 and R4¿ independently represents a hydrogen atom or a C¿1-3? alkyl group; each of R?10 and R11¿ independently represents a hydrogen atom, a C¿1-3? alkyl, C3-6 cycloalkyl or phenyl group; y represents an oxygen atom or a group CHNO2, NCN, NH or NNO2, n is an integer from 2 to 4; or a salt 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) and do not have trequinsin's very bitter taste.

  通式（I）的化合物其中R1和R2分别独立地表示C1-6烷基或C2-7酰基基团；R5表示氢原子或C1-3烷基，C2-3烯基或C2-3炔基基团；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，双（C1-6）烷基氨基或C2-7酰基氨基基团；R7和R8分别独立地表示氢或卤原子或羟基，三氟甲基，C1-6烷基，C2-6烯基，C2-6炔基，C2-7酰基，C1-6烷硫基，C1-6烷氧基，C3-6环烷基；R9表示氢或卤原子或羟基，三氟甲基，C1-6烷基，C2-6烯基，C2-6炔基，C2-7酰基，C1-6烷硫基，C1-6烷氧基或C3-6环烷基基团；X表示OCH2或CR3R4基团，其中R3和R4分别独立地表示氢原子或C1-3烷基基团；R10和R11分别独立地表示氢原子，C1-3烷基，C3-6环烷基或苯基；y表示氧原子或CHNO2，NCN，NH或NNO2基团，n为2到4的整数；或其盐；用于治疗哮喘等呼吸系统疾病。与已知化合物trequinsin（9,10-二甲氧基-3-甲基-2-二苯基亚胺-2,3,6,7-四氢-4H-嘧啶[6,1-a]异喹啉-4-酮）相比，本发明化合物具有更长的作用时间，并且不具有trequinsin非常苦的味道。
• Pyrimido(6-1-a)isoquinolin-4-one derivatives
  申请人：Hoechst Aktiengesellschaft

  公开号：US04598148A1

  公开（公告）日：1986-07-01

  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 method for making the compounds and intermediates.

  公开的是吡咯并[6,1-a]异喹啉-4-酮化合物，用作降压剂、支气管扩张剂和抗过敏剂，其制备中有用的中间体，以及制备该化合物和中间体的方法。