(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) | 298680-25-8

• 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-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one)
• 英文别名: 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；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；ensifentrine；RPL554；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；2-[9,10-dimethoxy-4-oxo-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-3-yl]ethylurea
• CAS: 298680-25-8
• 化学式: C₂₆H₃₁N₅O₄
• 分子量: 477.563
• InChiKey: CSOBIBXVIYAXFM-UHFFFAOYSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO: 2mg/mL, clear (Warmed)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

(E/Z)-Ensifentrine 是一种同时作用于PDE3和PDE4的双重抑制剂，能够减少炎性细胞进入气道，并在体内外模型中展现出支气管扩张及抗炎活性。

反应信息

• 作为反应物：
  描述：

  (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) 、 1,2-乙二磺酸 以 N,N-二甲基乙酰胺 为溶剂， 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 ethane-1,2-disulfonate
  参考文献：
  名称：

  WO2023/76205

  摘要：

  公开号：
• 作为产物：
  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

文献信息

• 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。
• Derivatives of pyrimido[6,1-a]isoquinolin-4-one
  申请人：Rhinopharma Limited

  公开号：US07105663B2

  公开（公告）日：2006-09-12

  Compounds of general formula (I) wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6)alkylamino or C2-7 acylamino group, each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkythio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 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 CR3R4, wherein each of R3 and R4 independently represents a hydrogen atom or a C1-3 alkyl group; each of R10 and R11 independently represents a hydrogen atom, a C1-3 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，二（C1-6）烷基氨基或C2-7酰氨基基团，R7和R8分别独立地表示氢或卤素原子或羟基，三氟甲基，C1-6烷基，C2-6烯基，C2-6炔基，C2-7酰，C1-6烷硫基，C1-6烷氧基，C3-6环烷基；R9表示氢或卤素原子或羟基，三氟甲基，C1-6烷基，C2-6烯基，C2-6炔基，C2-7酰，C1-6烷硫基，C1-6烷氧基或C3-6环烷基；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；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；对于治疗哮喘等呼吸系统疾病有用。本发明的化合物比已知的trequinsin（9,10-二甲氧基-3-甲基-2-间苯基亚胺基-2,3,6,7-四氢-4H-嘧啶并[6,1-a]-异喹啉-4-酮）具有更长的作用时间，并且不具有trequinsin的非常苦的味道。
• Derivatives of pyrimido[6.1-a]isoquinolin-4-one
  申请人：Vernalis Limited

  公开号：US06794391B2

  公开（公告）日：2004-09-21

  The invention provides compounds or salts thereof of the general formula (I): wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; X represents OCH2 or a group CR3R4; wherein each of R3 or R4 independently represents a hydrogen atom or a C1-3 alkyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy or C3-6 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).

  本发明提供的化合物或其盐的一般式（I）如下：其中，R1和R2各自表示C1-6烷基或C2-7酰基；X表示OCH2或CR3R4基团；其中，R3或R4各自表示氢原子或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酰胺基；R7和R8各自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。该化合物或其盐对于治疗哮喘等呼吸系统疾病非常有用。本发明的化合物比已知化合物trequinsin（9,10-二甲氧基-3-甲基-2-间苯基亚氨基-2,3,6,7-四氢-4H-嘧啶[6,1-a]异喹啉-4-酮）具有更长的作用时间。
• Derivatives of pyrimido[6, 1-A]isoquinolin-4-one
  申请人：Verona Pharma PLC

  公开号：US07378424B2

  公开（公告）日：2008-05-27

  The invention provides compounds or salts thereof of the general formula (I): wherein each of R1 and R2 independently represents a C1-6 alkyl or C2-7 acyl group; X represents OCH2 or a group CR3R4; wherein each of R3 or R4 independently represents a hydrogen atom or a C1-3 alkyl group; R5 represents a hydrogen atom or a C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl group; R6 represents a hydrogen atom or a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, amino, C1-6 alkylamino, di(C1-6) alkylamino or C2-7 acylamino group; each of R7 and R8 independently represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy, C3-6 cycloalkyl; and R9 represents a hydrogen or halogen atom or a hydroxy, trifluoromethyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-7 acyl, C1-6 alkylthio, C1-6 alkoxy or C3-6 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).

  本发明提供了一般式（I）的化合物或其盐： 其中R1和R2各自独立表示C1-6烷基或C2-7酰基；X表示OCH2或CR3R4基团；其中R3或R4各自独立表示氢原子或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，双（C1-6）烷基氨基或C2-7酰氨基；R7和R8各自独立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。该化合物或其盐用于治疗呼吸系统疾病，如哮喘。本发明的化合物比已知的化合物trequinsin（9,10-二甲氧基-3-甲基-2-苯并咪唑基-2,3,6,7-四氢-4H-嘧啶[6,1-a]异喹啉-4-酮）具有更长的作用时间。
• DERIVATIVES OF PYRIMIDO [6,1-A] ISOQUINOLIN-4-ONE
  申请人：Oxford Alexander William

  公开号：US20120302533A1

  公开（公告）日：2012-11-29

  The present invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their application as inhibitors of phosphodiesterase (PDE) isoenzymes. More particularly the invention relates to derivatives of pyrimido[6,1-a]isoquinolin-4-one and their use in medicine for example as bronchodilators with anti-inflammatory properties.

  本发明涉及嘌呤并[6,1-a]异喹啉-4-酮的衍生物及其作为磷酸二酯酶（PDE）同工酶抑制剂的应用。更具体地，本发明涉及嘌呤并[6,1-a]异喹啉-4-酮的衍生物及其在医学上的应用，例如作为具有抗炎作用的支气管扩张剂。