Pyrimidinedione derivatives

1. A compound of formula (Ia):

its tautomeric forms, its stereoisomers and their pharmaceutically acceptable salts, wherein X and Y may be same or different and independently represent oxygen, sulfur or NR, wherein R represents hydrogen, hydroxyl, acyl, alkyl, alkoxy, aryl, amino, hydroxylamino, alkylamino, arylamino, acylamino, or alkoxyamino group; the ring represented by B is selected from aryl and heteroaryl; R 3 represents SR 7 , wherein R 7 represents alkyl or aryl; S(O) p R 8 , wherein R 8 represents alkyl, amino or aryl group and p represents an integer of 1 or 2; R 4 represents hydrogen, halogen, hydroxyl, nitro, cyano, azido, nitroso, amino, formyl, alkyl, haloalkyl, acyl, alkoxy, monoalkylamino, dialkylamino, acylamino, alkoxycarbonyl, alkylsulfonyl, alkylsulfinyl, alkylthio, sulfamoyl, alkoxyalkyl groups or carboxylic acids or its derivatives; R 5 and R 6 may be same or different and independently represent hydrogen, halogen, hydroxyl, formyl, cyano, nitroso, nitro, amino, alkyl, acyl, monoalkylamino, dialkylamino, arylamino, acylamino, alkoxyalkyl or COR 9 , wherein R 9 represents hydroxy, amino, halogen, alkoxy, aryloxy, monoalkylamino, dialkylamino, or arylamino groups; n is an integer and represents 0 to 2.

2. A method of reducing inflammation, inhibiting TNF-α, inhibiting 11-6 or inhibiting COX-2 in a mammal comprising administering to the mammal in need thereof an effective amount of pyrimidinedione derivatives of the formula (I)

their their tautomeric forms, their stereoisomers, their solvates, their pharmaceutically acceptable salts and their pharmaceutically acceptable compositions, wherein X and Y may be same or different and independently represent oxygen, sulfur or NR, wherein R represents hydrogen, hydroxyl, acyl, alkyl, alkoxy, aryl, amino, hydroxylamino, alkylamino, arylamino, acylamino, or alkoxyamino group; the rings represented by A and B are selected from aryl and heteroaryl; R 1 and R 3 are different and represent hydrogen or SR 7 , wherein R 7 represents alkyl or aryl; S(O) p R 8 , wherein R 8 represents alkyl, amino or aryl group and p represents an integer of 1 or 2; R 2 and R 4 may be same or different and independently represent hydrogen, halogen, hydroxyl, nitro, cyano, azido, nitroso, amino, formyl, alkyl, haloalkyl, acyl, alkoxy, monoalkylamino, dialkylamino, acylamino, alkoxycarbonyl, alkylsulfonyl, alkylsulfinyl, alkylsulfanyl, sulfamoyl, alkoxyalkyl groups or carboxylic acids or its derivatives; R 5 and R 6 may be same or different and independently represent hydrogen, halogen, hydroxyl, formyl, cyano, nitro, nitroso, amino, alkyl, acyl, monoalkylamino, dialkylamino, arylamino, acylamino, alkoxyalkyl or COR 9 , wherein R 9 represents hydroxyl, amino, halogen, alkoxy, aryloxy, monoalkylamino, dialkylamino, or arylamino groups; m is an integer and is in the range of 0 to 2; n is an integer in the range of 0 to 2, inclusive.

3. The method as claimed in claim 2 , wherein the ring systems represented by A and B are selected from phenyl, naphthyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, piperidinyl, piperazinyl, pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, benzopyranyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyrolyl, benzoxadiazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, benzothienyl, benzofuranyl and indolyl.

4. A method of reducing inflammation, inhibiting TNF-α, inhibiting IL-6 or inhibiting COX-2 in a mammal comprising administering to the mammal in need thereof an effective amount of one or more compounds selected from the group consisting of:

1-(4-Methylsulfanyl-phenyl)-6-phenyl-pyrimidin-2,4-(1H)-dione;

6-(4-Methylphenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Ethylphenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

1-(4-Methylphenyl)-6-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

1-(4-Bromophenyl)-6-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chlorophenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chloro-3-methylphenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(3-Chloro-4-methylphenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Fluoro-3-methylphenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Fluorophenyl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Methylsulfanyl-phenyl)-1-phenyl-pyrimidin-2,4-(1H)-dione;

6-(4-Methylphenyl)-1-(3-chloro-4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Methoxy-3-methylphenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Methylphenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Ethylphenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chlorophenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chloro-3-methylphenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chlorophenyl)-1-(3-methoxy-4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(3-Chloro-4-methylphenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Fluorophenyl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

1-(4-Methylsulfonyl-phenyl)-6-phenyl-pyrimidin-2,4-(1H)-dione;

1-(4-Methylsulfanyl-phenyl)-6-(pyridin-2-yl)-pyrimidin-2,4-(1H)-dione;

6-(4-Methylpyridin-2-yl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chloropyridin-2-yl)-1-(4-methylsulfanyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Methylsulfanyl-phenyl)-1-(pyridin-2-yl)-pyrimidin-2,4-(1H)-dione;

1-(4-Methylsulfonyl-phenyl)-6-(pyridin-2-yl)-pyrimidin-2,4-(1H)-dione;

6-(4-Methylpyridin-2-yl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

6-(4-Chloropyridin-2-yl)-1-(4-methylsulfonyl-phenyl)-pyrimidin-2,4-(1H)-dione;

4-(2,4-Dioxo-6-(4-methylphenyl)-3,4-dihydro-2H-pyrimidin-1-yl)-benzenesulfonamide;

4-(2,4-Dioxo-6-phenyl-3,4-dihydro-2H-pyrimidin-1-yl)-benzenesulfonamide;

4-[6-(4-Bromo-phenyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-benzenesulfonamide;

4-(2,6-Dioxo-3-phenyl-1,2,3,6-tetrahydro-pyrimidin-4-yl)-benzenesulfonamide;

4-(2,6-Dioxo-3-(4-methylsulfanyl-phenyl)-1,2,3,6-tetrahydro-pyrimidin-4-yl)-benzenesulfonamide and

4-[3-(4-Chloro-phenyl)-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl]-benzenesulfonamide.

5. The method of claim 2 , wherein the activity of plasma concentration or the production of either or in combination of the following TNF-α, IL-1, IL-6, IL-8 and IL-12 are inhibited.

6. The method of claim 2 , wherein prostaglandins production is decreased.

7. The method of claim 2 , wherein cyclooxygenase enzyme activity is decreased.

8. The method of claim 4 , wherein the activity of plasma concentration or the production of either or in combination of the following TNF-α, IL-1, IL-6, IL-8 and IL-12 are inhibited.

9. The method of claim 4 , wherein prostaglandins production is decreased.

10. The method of claim 4 , wherein cyclooxygenase enzyme activity is decreased.