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US 2004/0171828 A1Published application
Derivatives of pyrimido[6,1-a]isoquinolin-4-one
AssigneeVernalis Limited
InventorsAlexander William Oxford, David Jack
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AssigneeVernalis Limited
InventorsAlexander William Oxford, David Jack
Estimating the term…
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. 1
A compound of general formula I:
A compound of general formula I wherein, independently or in any compatible combination:
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-(N′-isopropylcarbamoyl)-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-[1-(N′-methyl-2-nitroethenamine)]-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-[1-(N′-isopropyl-2-nitroethenamine)]-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-[1-(N′,N′-dimethyl-2-nitroethenamine)]-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-(N′-phenylcarbamoyl)-2-aminoethyl]-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-2-one.
9,10-Dimethoxy-3-[2-guanidinoethyl]-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.
9,10-Dimethoxy-3-[N-(N′-nitro)-2-guanidinoethyl]-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.
3-[N-(N′-Cyclohexylcarbamoyl)-2-aminoethyl]-9,10-dimethoxy-2-(2,4,6-trimethyl-phenylimino3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.
3-(N-Carbamoyl-2-aminoethyl)-9,10-dimethoxy-2-(2-methylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.
3-N-Carbamoyl-2-aminoethyl)-2-(2,6-diisopropylphenylimino)-9,10-dimethoxy-3,4,6,7-tetrahydro- 2H-pyrimido[6,1-a]isoquinolin-4-one.
3-(N-Carbamoyl-4-aminobutyl)-9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.
3-[N-(N′-Cyano-N″-methyl)-2-guanidinoethyl]-9,10-dimethoxy-2-(2,4,6-trimethyl-phenylimino)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one.
A composition comprising a compound of general formula I and a veterinarily or pharmaceutically acceptable carrier or diluent.
A compound of general formula I for use in medicine.
A compound of general formula I for use as an inhibitor of a phosphodiesterase isoenzyme.
A compound of general formula I for use in the prevention or treatment of a disease in which raising the intracellular concentration of cAMP is desirable.
A compound of general formula I for use in the prevention or treatment of asthma.
A compound of general formula I for use in the prevention or treatment of chronic obstructive pulmonary disease (COPD).
The use of a compound of general formula I in the manufacture of an inhibitor of a type III/IV phosphodiesterase isoenzyme.
The use of a compound of general formula I in the manufacture of a bronchodilator.
The use of a compound of general formula I in the manufacture of an anti-asthmatic.
The use of a compound of general formula I in the manufacture of a medicament for the prevention or treatment of chronic obstructive pulmonary disease (COPD).
A method for the treatment or prevention of a disease in a mammal where a phosphodiesterase isoenzyme inhibitor and/or a bronchodilator would be expected to be of benefit, which method comprises administering to said mammal an effective, non-toxic amount of a compound of general formula I.
A method for the treatment or prevention of asthma in a mammal, which method comprises administering to said mammal an effective, non-toxic amount of a compound of general formula I.
A method for the treatment or prevention of chronic obstructive pulmonary disease (COPD) in a mammal, which method comprises administering to said mammal an effective, non-toxic amount of a compound of general formula I.
A compound substantially as hereinbefore described in any of the examples.
A process substantially as hereinbefore described in any of the examples.
Dependencies are inferred from the claim text.