(Pyrazol-3-yl)-1,3,4-thiadiazol-2-amine and (pyrazol-3-yl)-1,3,4-thiazol-2-amine compounds

1. A method of treating tuberculosis in a mammal, which method comprises the administration to a mammal in need of such treatment an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof,

wherein:

either X is N and Y is CR 5 ; or X is C and Y is S;

Z is selected from N and CH;

R 1 is selected from H and Me,

R 2 is selected from H, OH, OMe and Me;

each R 3 is independently selected from C 1-3 alkyl, F, Cl, Br, CF 3 and NH 2 ;

R 4 is selected from Me, CF 3 , NO 2 and CHF 2 ;

R 5 is selected from H, Me and CHF 2 ;

R 6 is selected from H and Me; and

p is 0-3.

2. The method of claim 1 wherein in the compound R 1 is Me,

3. The method of treatment according to claim 1 wherein the compound is selected from:

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[1-(3-methyl-1H-pyrazol-1-yl)ethyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3-methyl-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[1-(5-methyl-3-nitro-1H-pyrazol-1-yl)ethyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-{1-[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]ethyl}-1,3,4-thiaoliazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[1-(3-methyl-1H-pyrazol-1-yl)ethyl]-1,3,4-thiadiazol-2-amine

5-{1-[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]ethyl}-N-[1-(phenylmethyl)-1H-pyrazol-3-yl]-1,3,4-thiadiazol-2-amine

5-[1-(3-methyl-1H-pyrazol-1-yl)ethyl]-N-[1-(phenylmethyl)-1H-pyrazol-3-yl]-1,3,4-thiadiazol-2-amine

5-{[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]methyl}-N-[1-(phenylmethyl)-1H-pyrazol-3-yl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-{[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]methyl}-1,3,4-thiadiazol-2-amine

N-{1-[(2,6-dichlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3-nitro-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5(3-nitro-1H-pyrazol-1-yl)methyl-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(5-methyl-3-nitro-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3-nitro-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2,6-dichlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2,6-dichlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[1-(3-methyl-1H-pyrazol-1-yl)ethyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-{[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]methyl}-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2,6-dichlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(3-methyl-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(5-methyl-3-nitro-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chlorophenyl)methyl]-1H-pyrazol-3-yl}-5-{[3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1,3,4-thiadiazol-2-amine

5-[(3-methyl-1H-pyrazol-1-yl)methyl]-N-[1-(phenylmethyl)-1H-pyrazol-3-yl]-1,3,4-thiadiazol-2-amine

N[1-(phenylmethyl)-1H-pyrazol-3-yl]-5-{[3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1,3,4-thiadiazol-2-amine

5-[(5-methyl-3-nitro-1H-pyrazol-1-yl)methyl]-N-[1-(phenylmethyl)-1H-pyrazol-3-yl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-{[3-(trifluoromethyl)-1H-pyrazol-1-yl]methyl}-1,3,4-thiadiazol-2-amine

5-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]-N-[1-(phenylmethyl)-1H-pyrazol-3-yl]-1-1,3,4-thiadiazol-2-amine and

N-{1-[(2,6-dichlorophenyl)methyl]-1H-pyrazol-3-yl}-5-[1-(5-methyl-3-nitro-1H-pyrazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine,

or a pharmaceutically acceptable salt thereof for use in therapy.

4. The method of claim 1 wherein the mammal is a human.

5. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:

wherein:

either X is N and Y is CR 5 ; or X is C and Y is S;

Z is selected from N and CH;

R 1 is Me,

R 2 is selected from H, OH, and OMe;

each R 3 is independently selected from C 1-3 alkyl, F, Cl, Br, CF 3 and NH 2 ;

R 4 is Me;

R 5 is selected from H, Me and CHF 2 ;

R 6 is selected from H and Me; and

p is 0-3.

6. The compound of claim 5 selected from:

N-{1-[(2-chloro--6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(1S)-1-(3-methyl-1H-pyrazol-1-yl)ethyl]-1,3,4-thiadiazol-2-amine

N-{1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}-5-[(1S)-1-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]1,3,4-thiadiazol-2-amine

(1S)-1-[5-({1-[(2-chloro-6-fluorophenyl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol

(1S)-1-[5-({1-[(2,6-difluorophenyl)methyl]-1H-pyrazol-3-yl}amino)- 1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol,

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 which is (1S)-1-[5-({1-[(2,6-difluorophenyl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]-1-(4-methyl-1,3-thiazol-2-yl)ethanol, or a pharmaceutically acceptable salt thereof.

8. The compound of claim 6 which is (1S)-1-[5-({1-[(2,6-difluorophenyl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]-(4-methyl-1,3-thiazol-2-yl)ethanol.

9. A method of treatment of tuberculosis in mammals, which method comprises the administration to a mammal in need of such treatment an effective amount of a compound or a pharmaceutically acceptable salt thereof as defined in claim 5 .

10. The method as claimed in claim 9 wherein the mammal is a human.

11. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof as defined in claim 5 and one or more pharmaceutically acceptable carriers, excipients or diluents.

12. A combination comprising a compound of Formula (1*) or pharmaceutically acceptable salt thereof as defined in claim 5 together with one or more additional therapeutic agents.

13. The combination as claimed in claim 12 wherein the one or more additional therapeutic agent is an anti-tuberculosis agent.

14. A compound of Formula (I), or a pharmaceutically acceptable salt thereof,

wherein:

X is C and Y is S;

Z is selected from N and CH;

R 1 is selected from H and Me,

R 2 is selected from H, OH, OMe and Me;

each R 3 is independently selected from C 1-3 alkyl, F, Cl, Br, CF 3 and NH 2 ;

R 4 is selected from Me, CF 3 , NO 2 and CHF 2 ;

R 6 is selected from H and Me; and

p is 0-3.

15. The compound or a pharmaceutically acceptable salt thereof as claimed in claim 14 wherein R 1 is Me.

16. The compound or a pharmaceutically acceptable salt thereof as claimed in claim 15 wherein R 2 is selected from H, OH and OMe and which has the absolute stereochemistry shown in Formula (I*):

17. A method of treatment of tuberculosis in mammals, which method comprises the administration to a mammal in need of such treatment an effective amount of a compound, or a pharmaceutically acceptable salt thereof, as defined in claim 16 .

18. The method as claimed in claim 17 , wherein the mammal is a human.

19. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof as defined in claim 16 and one or more pharmaceutically acceptable carriers, excipients or diluents.

20. A combination comprising a compound or pharmaceutically acceptable salt thereof as claimed in claim 16 together with one or more additional therapeutic agents.

21. A combination as claimed in claim 20 , wherein the one or more additional therapeutic agent is an anti-tuberculosis agent.