IP Library Granted Patent US 7,317,014
Granted Patent B2
US 7,317,014 · App. 10/469,647 · Granted Jan 8, 2008

Bio-active pyrimidine molecules

Assignees: Orchid Research Laboratories, Ltd.; Bexel Pharmaceuticals Inc.
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Quick Facts
Patent No.
US 7,317,014
App. No.
10/469,647
Granted
Jan 8, 2008
Kind
B2
Abstract

The present invention relates to novel derivatives of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their hydrates, their solvates, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them. The present invention more particularly provides novel pyrimidine derivatives of the general formula (I)

Claims (119)

1. A pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine of the structure

wherein R 5 , R 6 , R 7 , may be same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (i) when at least one N is substituted, the substitution is not an alkyl, wherein in structure (iv) R 6 and R 7 are not hydrogen or an alkyl group, and wherein when one of R 6 and R 7 is a haloakyl group, the other is not a haloalkyl group and when one of R 6 and R 7 is an amino group the other is not an alkoxy, amino or amino substituted alkyl group.

2. A pyrimidine compound selected from the group consisting of:

4-Chloro-5,6-diphenyl-2-(trifluoromethyl)pyrimidine;

4-Chloro-6-(4-methylphenyl)-5-phenyl-2-(trifluoromethyl)pyrimidine;

4-Chloro-6-(4-fluorophenyl)-5-phenyl-2-(trifluoromethyl)pyrimidine;

4-Chloro-6-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)pyrimidine;

4-Chloro-5-(4-chlorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine;

4-Chloro-5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine;

2,4-Dichloro-5,6-diphenylpyrimidine;

2,4-Dichloro-6-(4-methylphenyl)-5-phenylpyrimidine;

6-(4-Chlorophenyl)-2,4-dichloro-5-phenylpyrimidine;

5-(4-Chlorophenyl)-2,4-dichloro-6-phenylpyrimidine;

2,4-Dichloro-5-(4-methoxyphenyl)-6-phenylpyrimidine;

2,4-Dichloro-5-[4-(methylthio)phenyl]-6-phenylpyrimidine;

2,4-Dichloro-6-(4-chlorophenyl)-5-[4-(methylthio)phenyl]pyrimidine;

2,4-Dichloro-5-(4-chlorophenyl)-6-(4-methylphenyl)pyrimidine;

4-Azido-5,6-diphenyl-2-(trifluoromethyl)pyrimidine;

4-Azido-6-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)pyrimidine;

4-Azido-5-(4-chlorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine;

4-Azido-5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine;

2,4-Diazido-5,6-diphenylpyrimidine;

2,4-Diazido-5-(4-chlorophenyl)-6-phenylpyrimidine;

4-Hydrazino-5,6-diphenyl-2-(trifluoromethyl)pyrimidine;

4-Hydrazino-6-(4-methylphenyl)-5-phenyl-2-(trifluoromethyl)pyrimidine;

4-Hydrazino-6-(4-fluorophenyl)-5-phenyl-2-(trifluoromethyl)pyrimidine;

4-Hydrazino-6-[4-(methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)pyrimidine;

5-(4-Chlorophenyl)-4-hydrazino-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine;

5-(4-Fluorophenyl)-4-hydrazino-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine;

2-Chloro-5,6-diphenyl-4-hydrazinopyrimidine;

2-Chloro-4-hydrazino-5-[4-(methylthio)phenyl]-6-phenylpyrimidine;

2,4-Dihydrazino-5,6-diphenylpyrimidine;

2,4-Dihydrazino-5-[4-(methylthio)phenyl]-6-phenylpyrimidine;

N′-[5,6-Diphenyl-2-(trifluoromethyl)pyrimidin-4-yl]acetohydrazide;

N′-[6-(4-Methylphenyl)-5-phenyl-2-(trifluoromethyl)pyrimidin-4-yl]acetohydrazide;

N′-[6-(4-Fluorophenyl)-5-phenyl-2-(trifluoromethyl)pyrimidin-4-yl]acetohydrazide;

N″-[6-[4-(Methylsulfonyl)phenyl]-5-phenyl-2-(trifluoromethyl)pyrimidin-4-yl]acetohydrazide;

N′-[5-(4-Chlorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidin-4-yl]acetohydrazide;

N′-[5-(6-Fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidin-4-yl]acetohydrazide;

N′-[5-(4-Chlorophenyl)-[6-(4-methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidin-4-yl]trifluoroacetohydrazide;

4-Chloro- 1,6-diphenylpyrimidine-2(1H)-one;

4-Azido-6-[(4-methylthio)phenyl]-1-phenylpyrimidin-2(1H)-one;

4-[3-(4-Chlorophenyl)-2-oxo-6-trifluoromethyl-2,3-dihydro-pyrimidin-4-yl]benzenesulfonamide;

6-(4-Methylsulfonylphenyl)-1-p-tolyl-4-(trifluoromethy)pyrimidin-2(1H)-one;

4-Azido-6-(4-methylsulfonylphenyl)-1-p-tolyl-pyrimidin-2(1H)-one;

4-(6-Azido-3-methoxyphenyl-2-oxo-2,3-dihydropyrimidin-4-yl)benzenesulfonamide;

4-(6-Azido-4-methoxyphenyl-2-oxo-2,3-dihydropyrimidin-4-yl)benzenesulfonamide;

2-Chloro-5-(4-chlorophenyl)-4-methylthio-6-[(4-methylthio)phenyl]pyrimidine;

6-[(4-Methylthio)phenyl]-1-phenyl-4-(trifluoromethyl)pyrimidin-2(1H)-one;

4-(2-Oxo-3-phenyl-6-trifluoromethyl-2,3-dihydropyrimidin-4-yl)benzenesulfonamide;

4-Methylthio-5,6-bis(p-tolyl)pyrimidine;

4-Methylthio-5,6-diphenyl-pyrimidin-2-ol;

4-Methylsulfonyl-5,6-bis(p-tolyl)pyrimidine;

1,6-Diphenyl-4-(trifluoromethyl)pyrimidin-2(1H)-one;

4-(2-Hydroxy-6-methylthio-5-phenylpyrimidin-4-yl)benzenesulfonamide;

4-Methylthio-6-[(4-methylthio)phenyl]-5-phenylpyrimidine;

2-Chloro-4-methylthio-5,6-bis(p-tolyl)pyrimidine;

2-Chloro-4-methylthio-6-[(4-methylthio)phenyl]-5-p-tolyl-pyrimidine;

5-(4-Bromophenyl)-2-chloro-4-methylthio-6-[(4-methylthio)phenyl]pyrimidine;

5-(2-Bromophenyl)-4-methylthio-6-[(4-methylthio)phenyl]pyrimidin-2-ol;

4-(2-Chloro-6-methylthio-5-phenylpyrimidin-4-yl)benzenesulfonamide;

2-Chloro-4,5-bis-(4-methoxyphenyl)-6-(methylthio)pyrimidine;

2-Chloro-4-methylthio-6-[(4-methylthio)phenyl]-5-phenylpyrimidine;

2,4-Diazido-6[(4-methylthio)phenyl)]-5-phenylpyrimidine;

2,4-Diazido-5-(4-bromophenyl)-6-(4-methylthiophenyl)pyrimidine;

4-Chloro-6-[(4-methylsulfonyl)phenyl]-1-phenylpyrimidin-2(1H)-one;

4-Azido-1-(2-fluorophenyl)-6-[(4-methylthio)phenyl]-pyrimidin-2(1H)-one;

2-[(4-Methylsulfonyl)phenyl]-6-trifluoromethyl-3-[(4-trifluoromethyl)phenyl]-3,4-dihydropyrimidin-4-ol;

5-(3-Fluorophenyl)-4-methylthio-6-[(4-methylthio)phenyl]pyrimidin-2-ol, and

4-(6-Hydroxy-6-methyl-2-p-tolyl-4-trifluoromethyl-6H-pyrimidin-1-yl)benzenesulfonamide.

3. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; R 5 , R 6 , may be same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the process comprising condensing a compound of formula (Ia) using a solvent in an acidic condition in the presence of a phase transfer catalyst and under cooling to reflux conditions,

wherein all symbols are as defined above with a compound of the formula (Ib)

where all symbols are as defined above.

4. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine of the structure

wherein R 6 represents halogen atom, R 5 , R 7 , may be same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (i) when at least one N is substituted, the substitution is not an alkyl, and wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl, the other is not a haloalkyl; the process comprising converting the compound of formula (Ic) using a reagent, in the presence or absence of a solvent, and in the presence or absence of DMF, N,N-dimethyl aniline or N,N-diethyl aniline at a temperature of from 20° C. to reflux temperature, in a range of from 2 hours to 5 hours,

wherein all symbols are as defined earlier.

5. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine of the formula

wherein any of R 7 represents halogen atom and R 6 represents hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl; the process comprising converting the compound of formula (Id) using a reagent in the presence or absence of a solvent, and in the presence or absence of DMF, N,N-dimethyl aniline or N,N-diethyl aniline at a temperature of from 20° C. to reflux temperature, in a range of from 2 hours to 12 hours,

wherein R 6 is as defined above.

6. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine of the structure

wherein R 6 represents azido, hydrazine or hydrazine derivatives, R 5 and R 7 are same or different and represent hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (i) when at least one N is substituted, the substitution is not an alkyl, and wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl; the process comprising converting the compound of formula (Ie) in a presence of one or more equivalents of a metal azide or a hydrazine and a solvent, at a temperature of from 80° C. to 100° C. from 0.5 hour to 18 hours,

wherein R 6 represents halogen atom and all other symbols are as defined above.

7. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives;

wherein R 5 , R 6 , R 7 , may be same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the process comprising reacting a compound of the formula (If)

where all symbols are as defined above, with a compound of formula (Ig) using an agent selected from the group consisting of polyphosphoric acid, phosphorous pentoxide and sulfuric acid in a solvent, under acid or base catalyzed conditions in the presence of a phase transfer catalyst, and under cooling to reflux conditions,

where all symbols are as defined above.

8. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives;

wherein R 5 , R 6 , are same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives, wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl; the process comprising:

i) reacting a compound of formula (Ih)

where all symbols are as defined earlier with a compound of formula (Ii) in a solvent under acid or base catalyzed conditions, in the presence of a phase transfer catalyst, and under cooling to reflux conditions,

where R 6 is as defined earlier to produce compound of formula (Ij)

and

ii) converting the compound of formula (Ij) to produce compound of formula (I), where all symbols are as defined earlier, by reacting with suitable nucleophilic reagent.

9. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein R 1 , R 2 , R 3 and R 4 may be same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine of the structure

wherein any one of R 5 , R 6 , R 7 , represent hydrazine derivatives and the other R 5 , R 6 , R 7 , are same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (i) when at least one N is substituted, the substitution is not an alkyl, and wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl; the process comprising reacting the compound of formula (I) wherein any one of R 5 , R 6 , R 7 represent hydrazine, using a reagent in a solvent an at from room temperature to reflux temperatures of the solvent.

10. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein any one of R 1 , R 2 , R 3 and R 4 represent alkylsulfonyl, alkylsulfinyl, aryl sulfinyl or arylsulfonyl and the other R 1 , R 2 , R 3 and R 4 are same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine derivative of the structure

wherein any one of R 5 , R 6 , R 7 , represent alkylsulfonyl, alkylsulfinyl, aryl sulfinyl or arylsulfonyl and the other R 5 , R 6 , R 7 , are same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (i) when at least one N is substituted, the substitution is not an alkyl, and wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl; the process comprising reacting the compound of formula (I) wherein the groups any of the groups R 1 , R 2 , R 3 , R 4 , R 5 , R 6 represent alkylthio or arylthio and all other symbols are as defined above, using a reagent in a solvent that does not adversely invluence the reaction, and under cooling to refluxing conditions.

11. A process for the preparation of a pyrimidine compound of the formula (I)

and their pharmaceutically acceptable salts, wherein any one of R 1 , R 2 , R 3 and R 4 represent sulfamoyl and the other R 1 , R 2 , R 3 and R 4 are same or different and independently represent hydrogen, hydroxy, nitro, nitroso, formyl, azido, halo or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heterocyclyl, acyl, acyloxy, cycloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; A represents pyrimidine of the structure

wherein any one of R 5 , R 6 , R 7 , represent sulfamoyl and the other R 5 , R 6 , R 7 , are same or different and represent, hydrogen, nitro, nitroso, formyl, azido, halo, or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, cycloalkyl, haloalkyl, amino, hydrazine, monoalkylamino, dialkylamino, acylamino, alkylsufonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, alkylthio, arylthio, alkoxycarbonyl, aryloxycarbonyl, alkoxyalkyl, sulfamoyl, carboxylic acid and its derivatives; the pyrimidine group may be attached to the phenyl through carbon or nitrogen atom, wherein in structure (i) when at least one N is substituted, the substitution is not an alkyl, and wherein in structure (iv) R 6 and R 7 are not hydrogen and when one of R 6 and R 7 is a haloalkyl, the other is not a haloalkyl; the process comprising reacting the compound of formula (D wherein the groups any of the groups R 1 , R 2 , R 3 , R 4 , R 5 , R 6 represent alkylsulfonyl and all other symbols are as defined above, using a reagent in the presence of sodium acetate and water, at a temperature of from 0° C. to room temperature for a time of from 2 hours to 4 hours, wherein the reagent is hydroxylamine-O-sulfonic acid.

12. A pharmaceutical composition, which comprises a compound of formula (I)

as defined in claim 1 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

13. A pharmaceutical composition as claimed in claim 12 , in the form of a tablet, capsule, powder, syrup, solution, aerosol or suspension.

14. A pharmaceutical composition which comprises a compound as claimed in claim 2 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

15. A method for treatment of pain, rheumatoid arthritis, breast cancer, lung cancer or CNS cancer, the method comprising administering the compound of formula (I) as claimed in claim 1 , together with a pharmaceutically acceptable carrier, diluent, excipient or solvate to a patient in need thereof.

16. A method for treatment of pain, rheumatoid arthritis, breast cancer, lung cancer or CNS cancer, the method comprising administering the compound as claimed in claim 2 , together with a pharmaceutically acceptable carrier, diluent, excipient or solvate to a patient in need thereof.

17. A method for treatment of pain, rheumatoid arthritis, breast cancer, lung cancer, or CNS cancer, the method comprising administering the composition as claimed in claim 12 to a patient in need thereof.

18. A method for treatment of a pain disorder, comprising administering the compound of formula (I) as claimed in claim 1 .

19. A method for treatment of a pain disorder, comprising administering the compound as claimed in claim 2 .

20. A method for treatment of a pain disorder, comprising administering the composition as claimed in claim 12 .

Assignments (5)
RECORD TO CORRECT NATURE OF CONVEYANCE ON A CHANGE NAME DOCUMENT PREVIOUSLY RECORDED ON FEBRUARY 12, 2013, REEL 029824/FRAME 0502 Recorded Feb 27, 2013
From: ORCHID RESEARCH LABORATORIES LIMITED
To: ORCHID CHEMICALS & PHARMACEUTICALS LIMITED
Reel/Frame 029921/0877 →
CHANGE OF NAME Recorded Feb 12, 2013
From: ORCHID RESEARCH LABORATORIES LIMITED
To: ORCHID CHEMICALS & PHARMACEUTICALS LIMITED
Reel/Frame 029824/0502 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 3, 2008
From: BEXEL PHARMACEUTICALS INC.
To: ORCHID RESEARCH LABORATORIES
Reel/Frame 021194/0419 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2006
From: ORCHID RESEARCH LABORATORIES LTD.
To: BEXEL PHARMACEUTICALS INC.
Reel/Frame 017330/0759 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2006
From: ORCHID CHEMICALS & PHARMACEUTICALS, LTD.
To: ORCHID RESEARCH LABORATORIES LTD.
Reel/Frame 017330/0816 →
Priority Claims (1)
IN 548/MAS/2002 · Jul 22, 2002 · national
Continuity (1)
Related Publication 20050107413A1 · May 19, 2005