Pyrimidone derivatives, preparation thereof and use thereof

Claim 2

Pyrimidinone derivatives of the formula : wherein R 1 and R 2 are each lower alkyl, lower alkoxycarbonyl(lower)alkyl, carboxy(lower)alkyl or di(lower)alkylamino(lower)alkyl, R 3 and R 4 are each hydroxy, lower alkoxy, halo(lower)alkoxy, lower alkylthio, lower alkanesulfinyl, lower alkanesulfonyl, nitro, amino, di(lower)alkanesulfonylamino, lower alkoxycarbonyl(lower)alkoxy or carboxy(lower)alkoxy, or R3 and R 4 are taken together to form lower alkylenedioxy or lower alkylidenedioxy, R 5 is aryl optionally substituted with lower alkyl and/or sulfamoyl, and R 10 is hydrogen or sulfamoyl, provided that when both of R 1 and R 2 are lower alkyl and R 3 and R 4 are lower alkoxy, then R 10 is sulfamoyl, and pharmaceutically acceptable salts thereof.

Claim 3

A compound of claim 1, wherein R 5 is phenyl optionally substituted with lower alkyl and/or sulfamoyl. lower alkoxycarbonyl(lower)alkyl, carboxy(lower)alkyl or di(lower)alkylamino(lower)alkyl, R 3 and R 4 are each hydroxy, lower alkoxy, halo(lower)alkoxy, lower alkylthio, lower alkanesulfinyl, lower alkanesulfonyl, nitro, amino, di(lower)alkanesulfonylamino, lower alkoxycarbonyl(lower)alkoxy or carboxy(lower)alkoxy, or R 3 and R 4 are taken together to form lower alkylenedioxy or lower alkylidenedioxy, R 5 is aryl optionally substituted with lower alkyl and/or sulfamoyl, and R 10 is hydrogen or sulfamoyl, provided that when both of R 1 and R 2 are lower alkyl and R 3 and R 4 are lower alkoxy, then R 10 is sulfamoyl, or pharmaceutically acceptable salts thereof, which comprises (1) subjecting a compound of the formula: or its salt to a cleavage reaction of the lower alkyl groups for R 6 and R 7 to give a compound of the formula:

Claim 4

A compound of claim 2, wherein R 1 and R 2 are each methyl, ethyl, ethoxycarbonylmethyl, carboxymethyl, or dimethylaminopropyl, R 3 and R 4 are each hydroxy, methoxy, difluoromethoxy methylthio, methylsulfinyl, methylsulfonyl, nitro, amino, dimethanesulfonylamino, ethoxycarbonylmethoxy or carboxymethoxy, or R 3 and R 4 are taken together to form ethylenedioxy, methylenedioxy or isopropylidenedioxy, R 5 is phenyl optionally substituted with methyl and/or sulfamoyl, and R 10 is hydrogen or sulfamoyl, provided that when R 1 is methyl and R 2 is methyl or ethyl and R 3 and R 4 are methoxy, then R 10 is sulfamoyl.

Claim 5

A compound of claim 3, wherein R 1 is methyl, R 2 is methyl, ethyl, ethoxycarbonylmethyl, carboxymethyl or dimethylaminopropyl, R 3 is hydroxy, methoxy, difluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, nitro, amino, dimethanesulfonylamino, ethoxycarbonylmethoxy or carboxymethoxy, and R 4 is hydroxy, methoxy or difluoromethoxy.

Claim 6

A process for preparing pyrimidinone derivatives of the formula : wherein R 1 and R 2 are each lower alkyl, or its salt,in which R 1 1 R 2 , R 5 and R 10 are each as defined above, and R 6 and R 7 are each lower alkyl, or (2) reacting a compound of the formula : or its salt with a compound of the formula: to give a compound of the formula: or its salt, in which R 1 , R 2 , R 5 and R 10 are each as defined above, and X is a leaving group and Y is lower alkylene or lower alkylidene, or (3) reacting a compound of the formula: or its salt with a compound of the formula: or its reactive derivative at the carbonyl group to give a compound of the formula: or its salt, in which R 1 , R 2 , R 5 and R 10 are each as defined above, and R 8 and R 9 are each hydrogen or lower alkyl, or [4) reacting a compound of the formula: or its reactive derivative at the thioxo group or a salt thereof with a compound of the formula: R5 - N H 2 or its salt to give a compound of the formula: or its salt, in which R 1 ; R2, R 3 , R 4 , R 5 and R 10 are each as defined above, or (5) oxidizing a compound of the formula: or its salt to give a compound of the formula: or its salt, in which R 1 , R 2 , R 4 , R 5 and R 10 are each as defined above, R 3 a is lower alkylthio, and R 3 b is lower alkanesulfinyl or lower alkanesulfonyl, or (6) subjecting a compound of the formula: or its salt to introduction reaction of sulfamoyl group to give a compound of the formula: or its salt, in which R l , R 2 , R 3 and R 4 are each as defined above, R 5 a is aryl optionally substituted with lower alkyl and R 5 b is aryl optionally substituted with lower alkyl and sulfamoyl, or (7) reacting a compound of the formula: or its salt with a compound of the formula: to give a compound of the formula: or its salt, in which R l , R 3 , R 4 , R 5 , R 10 and X are each as defined above, and R 2 is lower alkoxycarbonyl(lower)alkyl or di(lower)-alkylamino(lower)alkyl, or (8) subjecting a compound of the formula: or its salt to hydrolysis reaction to give a compound of the formula: or its salt, in which R 1 , R 3 , R 4 , R 5 and R 10 are each as defined above, and R 2 b is lower alkoxycarbonyl(lower)alkyl and R 2 c is carboxy(lower)-alkyl, or (9) subjecting a compound of the formula: or its salt to reduction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 4 , R 5 and R 10 are each as defined above, or (10) subjecting a compound of the formula: or its salt to alkanesulfonylation reaction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 4 , R 5 and R 10 are each as defined above, and R 3 is di(lower)- alkanesulfonylamino, or (11) subjecting a compound of the formula: or its salt to alkylation reaction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 5 and R 10 are each as defined above, and R 3 b is lower alkoxy, or (12) reacting a compound of the formula: or its salt with a compound of the formula: to give a compound of the formula: or its salt, in which R 1 , R 2 , R 3 d , R 5 , R 10 and X are each as defined above, R 11 is lower alkoxycarbonyl(lower)alkyl and R 4 a is lower alkoxycarbonyl(lower)alkoxy, or (13) subjecting a compound of the formula: or its salt to hydrolysis reaction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 2 d , R 4 a , R and R 10 are each as defined above and R 4 b is carboxy(lower)alkoxy, or (14) reacting a compound of the formula: or its salt with a compound of the formula: X - R 12 to give a compound of the formula: or its salt, in which R l , R 2 , R5 , R 10 and X are eash as defined above and R 12 is halo(lower)-alkyl.

Claim 7

A process for preparing pyrimidinone derivatives of the formula : wherein R 1 and R 2 are each lower alkyl, or its salt,in which R 1 1 R 2 , R 5 and R 10 are each as defined above, and R 6 and R 7 are each lower alkyl, or (2) reacting a compound of the formula : or its salt with a compound of the formula: to give a compound of the formula: or its salt, in which R 1 , R 2 , R 5 and R 10 are each as defined above, and X is a leaving group and Y is lower alkylene or lower alkylidene, or (3) reacting a compound of the formula: or its salt with a compound of the formula: or its reactive derivative at the carbonyl group to give a compound of the formula: or its salt, in which R 1 , R 2 , R 5 and R 10 are each as defined above, and R 8 and R 9 are each hydrogen or lower alkyl, or [4) reacting a compound of the formula: or its reactive derivative at the thioxo group or a salt thereof with a compound of the formula: R5 - N H 2 or its salt to give a compound of the formula: or its salt, in which R 1 ; R2, R 3 , R 4 , R 5 and R 10 are each as defined above, or (5) oxidizing a compound of the formula: or its salt to give a compound of the formula: or its salt, in which R 1 , R 2 , R 4 , R 5 and R 10 are each as defined above, R 3 a is lower alkylthio, and R 3 b is lower alkanesulfinyl or lower alkanesulfonyl, or (6) subjecting a compound of the formula: or its salt to introduction reaction of sulfamoyl group to give a compound of the formula: or its salt, in which R l , R 2 , R 3 and R 4 are each as defined above, R 5 a is aryl optionally substituted with lower alkyl and R 5 b is aryl optionally substituted with lower alkyl and sulfamoyl, or (7) reacting a compound of the formula: or its salt with a compound of the formula: to give a compound of the formula: or its salt, in which R l , R 3 , R 4 , R 5 , R 10 and X are each as defined above, and R 2 is lower alkoxycarbonyl(lower)alkyl or di(lower)-alkylamino(lower)alkyl, or (8) subjecting a compound of the formula: or its salt to hydrolysis reaction to give a compound of the formula: or its salt, in which R 1 , R 3 , R 4 , R 5 and R 10 are each as defined above, and R 2 b is lower alkoxycarbonyl(lower)alkyl and R 2 c is carboxy(lower)-alkyl, or (9) subjecting a compound of the formula: or its salt to reduction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 4 , R 5 and R 10 are each as defined above, or (10) subjecting a compound of the formula: or its salt to alkanesulfonylation reaction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 4 , R 5 and R 10 are each as defined above, and R 3 is di(lower)- alkanesulfonylamino, or (11) subjecting a compound of the formula: or its salt to alkylation reaction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 5 and R 10 are each as defined above, and R 3 b is lower alkoxy, or (12) reacting a compound of the formula: or its salt with a compound of the formula: to give a compound of the formula: or its salt, in which R 1 , R 2 , R 3 d , R 5 , R 10 and X are each as defined above, R 11 is lower alkoxycarbonyl(lower)alkyl and R 4 a is lower alkoxycarbonyl(lower)alkoxy, or (13) subjecting a compound of the formula: or its salt to hydrolysis reaction to give a compound of the formula: or its salt, in which R 1 , R 2 , R 2 d , R 4 a , R and R 10 are each as defined above and R 4 b is carboxy(lower)alkoxy, or (14) reacting a compound of the formula: or its salt with a compound of the formula: X - R 12 to give a compound of the formula: or its salt, in which R l , R 2 , R5 , R 10 and X are eash as defined above and R 12 is halo(lower)-alkyl.

Claim 8

A pharmaceutical composition comprising, as an active ingredient, the compound of claim 1, in association with a non-toxic, pharmaceutically acceptable carrier or excipient.

Claim 9

Use of the compound of claim 1 as a medicament.

Claim 10

Use of the compound of claim 1 for the manufacture of a medicament for treating a heart disease and an allergic disease.

Claim 11

A compound of the formula: wherein R 1 d and R2 are lower alkyl, R 3 e is lower alkylthio or nitro and R 4 c is lower alkoxy, and salt thereof.

Claim 12

A compound of the formula: wherein R 1 d and R2 are lower alkyl, R 3 e is lower alkylthio or nitro and R 4 c is lower alkoxy, and salt thereof.