3-amino-pyrazole derivatives useful against tuberculosis

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

wherein:

Het is a 5 to 10-membered heteroaromatic ring;

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 C 1-2 alkyl,

R 2 is selected from H, C 1-2 alkyl, OH, —CH 2 OH and C 1-2 alkoxy;

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

R 4 is selected from C 1-3 alkyl and haloC 1-3 alkyl;

R 5 is selected from H, C 1-3 alkyl and haloC 1-3 alkyl;

R 6 and R 7 are either

(i) each independently selected from H, C 1-3 alkyl and C 1-3 alkoxy; or

(ii) R 6 and R 7 together with the ring to which they are attached form a 9-membered bicylic ring;

p is 0-3; and

R A is selected from H and C 1-3 alkyl.

2. A compound of Formula (I*) or a pharmaceutically acceptable salt thereof, which is a compound of Formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound has the absolute stereochemistry:

3. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Het is selected from pyridyl, thiazolyl, quinolinyl, oxazolyl, imidazopyridyl, pyrazolyl, isoxazolyl, imidazolyl and isothiazolyl.

4. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Z is N.

5. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is CH 3 .

6. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is selected from H and OH.

7. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 4 is CH 3 .

8. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 5 is selected from H and CH 3 .

9. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 6 and R 7 are each independently selected from H and CH 3 .

10. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R A is selected from H and CH 3 .

11. A compound selected from:

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

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

or a pharmaceutically acceptable salt thereof.

12. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , for use in therapy.

13. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , for use in the treatment of tuberculosis.

14. A method of treatment of tuberculosis in a mammal, 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 according to claim 1 .

15. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof according to claim 1 , and one or more pharmaceutically acceptable carriers, excipients or diluents.

16. A compound which is (1S)-1-(4-methyl-1,3-thiazol-2-yl)-1-[5-({1-[(2-methyl-1,3-thiazol-4-yl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]ethanol or a salt thereof.

17. A compound which is (1S)-1-(4-methyl-1,3-thiazol-2-yl)-1-[5-({1-[(2-methyl-1,3-thiazol-4-yl)methyl]-1H-pyrazol-3-yl}amino)-1,3,4-thiadiazol-2-yl]ethanol.

18. The method of claim 14 wherein said mammal is a human.