4-amino-1H-pyrimidin-2-one based compounds, compositions comprising them and methods of their use

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Q is C or N;

X is a bond, NR 5 , N(C(O)R 5 ), N(C(O)OR 5 ), O, S, SO 2 , C, CH, or CH 2 ;

Y is a bond, C(O), C(O)NH, C(O)NH 2 CH 2 , SO 2 , NR 5 , N(C(O)R 5 ), N(C(O)OR 5 ), or CH 2 , with the proviso that Y is not a bond if X is a bond;

or X and Y are taken together to provide one bond between Z 1 and Q;

Z 1 is optionally substituted cycloalkyl, aryl, or heterocycle;

R 1 is hydrogen, halogen, —OH, —NH 2 , —NO 2 , —CN, or optionally substituted alkyl;

R 2 is hydrogen, halogen, or optionally substituted alkyl;

R 3 is hydrogen, halogen, —OR 6 or —NR 7 R 8 ;

R 4 is hydrogen, —C(O)(CH 2 ) n R 9 , —C(O)NH(CH 2 ) n R 9 , —NHC(O)(CH 2 ) n R 9 , or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl, or alkyl-heterocycle;

R 5 is hydrogen or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl or alkyl-heterocycle;

R 6 is hydrogen or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl or alkyl-heterocycle;

R 7 and R 8 are each independently hydrogen, or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl or alkyl-heterocycle, or taken together with the nitrogen atom to which they are attached, form an optionally substituted heterocycle;

R 9 is optionally substituted alkyl, aryl or heterocycle; and

n is 0-3.

2. The compound of claim 1 , which is of formula II:

3. A compound of formula VIII:

or a pharmaceutically acceptable salt thereof, wherein:

Q is C or N;

X is a bond, NR 5 , N(C(O)R 5 ), N(C(O)OR 5 ), O, S, SO 2 , C, CH, or CH 2 ;

Y is a bond, C(O), C(O)NH, C(O)NH 2 CH 2 , SO 2 , NR 5 , N(C(O)R 5 ), N(C(O)OR 5 ), or CH 2 , with the proviso that Y is not a bond if X is a bond;

or X and Y are taken together to provide one bond between Z 1 and Q;

Z 1 is optionally substituted cycloalkyl, aryl, or heterocycle;

R 1 is hydrogen, halogen, —OH, —NH 2 , —NO 2 , —CN, or optionally substituted alkyl;

R 2 is hydrogen, halogen, or optionally substituted alkyl;

R 3 is hydrogen, halogen, —OR 6 or —NR 7 R 8 ;

R 4 is hydrogen, —C(O)(CH 2 ) n R 9 , —C(O)NH(CH 2 ) n R 9 , —NHC(O)(CH 2 ) n R 9 , or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl, or alkyl-heterocycle;

R 5 is hydrogen or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl or alkyl-heterocycle;

R 6 is hydrogen or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl or alkyl-heterocycle;

R 7 and R 8 are each independently hydrogen, or optionally substituted alkyl, aryl, heterocycle, alkyl-aryl or alkyl-heterocycle, or taken together with the nitrogen atom to which they are attached, form an optionally substituted heterocycle;

R 9 is optionally substituted alkyl, aryl or heterocycle; and

n is 0-3;

with the proviso that Z 1 and R 4 taken together are not 4-methylphenyl when Q is N, X and Y taken together are SO 2 , and R 3 is —CH 2 CH 2 OH.

4. The compound of claim 3 , which is of formula IX:

5. The compound of claim 3 , wherein Z 1 is not substituted with anything other than R 4 .

6. The compound of claim 3 , wherein Z 1 is heteroaryl.

7. The compound of claim 6 , wherein Z 1 is pyridine, pyridazine, pyrimidine, pyrazine, quinoline, quinoxaline, or quinazoline.

8. The compound of claim 3 , wherein X is NR 5 and R 5 is hydrogen or methyl.

9. The compound of claim 3 , wherein Y is SO 2 or C(O).

10. The compound of claim 3 , wherein R 1 is hydrogen or halogen.

11. The compound of claim 3 , wherein R 2 is hydrogen.

12. The compound of claim 3 , wherein R 3 is hydrogen.

13. The compound of claim 3 , wherein R 4 is an optionally substituted heteroaryl.

14. The compound of claim 3 , wherein R 4 is an optionally substituted bicyclic heteroaryl.

15. The compound of claim 14 , wherein R 4 is quinoline, quinoxaline, quinazoline, 1,7-naphthyridine, benzofuran, benzo[b]thiophene, thieno[2,3-b]pyridine, thieno[2,3-c]pyridine, indole, isoindole, or pyrrolo[3,4-c]pyridine.

16. A pharmaceutical dosage form comprising a compound of claim 1 or 3 .

17. The dosage form of claim 16 , which further comprises an excipient or diluent.