Fused pyrazole derivatives being protein kinase inhibitors

1. A compound of Formula (I):

or a salt or solvate thereof:

wherein

Z is N;

a is 1 or 2;

b is 1, 2or 3;

c is 1, 2 or 3;

each R 1 is independently selected from groups of the formula

—(X) d —(CH 2 ) e —R 5

wherein

d is 0 or 1;

e is 0 to 6;

X is O, NR 6 or S(O) f where f is 0, 1 or 2;

R 5 is hydrogen, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, heterocyclyl, aryl, heteroaryl, hydroxyl, cyano, nitro, trihalomethyl, NR 7 R 8 , C 6 H 4 NR 7 R 8 , C 6 H 4 (CH 2 )NR 7 R 8 , C(O)R 7 , C(O)NR 7 R 8 , OC(O)R 7 , OC(O)NR 7 R 8 , CO 2 R 7 , OCO 2 R 7 , SO 2 R 7 , SO 2 NR 7 R 8 , C(═NR 7 )NR 7 R 8 , NR 7 (C═NR 7 )NR 7 R 8 , NHC(O)R 7 or N(C 1-3 alkyl)C(O)R 7 ;

each R 2 is independently selected from hydrogen, cyano, halogen, trihalomethyl, OC 1-6 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, S(O) g C 1-6 alkyl where g is 0, 1 or 2, NC 1-6 alkyl(C 1-6 alkyl), hydroxyl or nitro;

each R 4 is independently selected from groups of the formula

—(Y) d —(CH 2 ) e —R 3

wherein

d is 0 or 1;

e is 0 to 6;

Y is O or S(O) f where f is 0, 1 or 2;

R 3 is hydrogen, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, heterocyclyl, aryl, heteroaryl, hydroxyl, cyano, nitro, trihalomethyl, phthalamido, C 6 H 4 NR 7 R 8 , C 6 H 4 (CH 2 )NR 7 R 8 , C(O)R 7 , C(O)NR 7 R 8 , OC(O)R 7 , OC(O)NR 7 R 8 , CO 2 R 7 , OCO 2 R 7 , SO 2 R 7 , SO 2 NR 7 R 8 or C(═NR 7 )NR 7 R 8 ;

R 6 is H, C 1-6 alkyl, C 2-6 alkenyl, aryl, heteroaryl, C 3-12 cycloalkyl, or heterocyclyl;

R 7 and R 8 are each independently H, C 1-8 alkyl, C 2-6 alkenyl, SO 2 C 1-6 alkyl, (CH 2 ) m —C 3-12 cycloalkyl, (CH 2 ) m -aryl, (CH 2 ) m -heterocyclyl, (CH 2 ) m -heteroaryl, wherein m=0, 1 or 2, or may, together with the nitrogen atom to which they are bound, form a heterocyclyl group; and

wherein any of said alkyl, alkenyl and alkynyl groups may be optionally substituted with up to three members selected from halogen, hydroxyl, oxo, cyano, NR 7 R 8 , C 1-6 alkyl, OC 1-6 alkyl, S(O)C 1-6 alkyl, S(O) 2 C 1-6 alkyl and SO 2 NR 7 R 8 ; and

wherein any of said cycloalkyl, heterocyclyl, aryl, and heteroaryl groups may be optionally substituted with substituents selected from a group consisting of C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylsulfenyl, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, hydroxy, oxo, mercapto, nitro, cyano, halogen, C 1-6 perfluoroalkyl, amino optionally substituted by C 1-6 alkyl, carbamoyl optionally substituted by C 1-6 alkyl, NR 7 R 8 , carboxy and aminosulfonyl optionally substituted by C 1-6 alkyl;

with the proviso that (R 2 ) b , (R 1 ) a and (R 4 ) c cannot all represent solely hydrogen substitution;

and with the proviso that when (R 2 ) b represents solely hydrogen or methyl substitution, (R 4 ) c cannot represent solely hydrogen substitution;

and with the proviso that R 4 may not be located on the 7-position of the pyrazolopyridine ring system as numbered below:

2. A compound according to claim 1 wherein a is 1.

3. A compound according to claim 1 wherein R 1 is in the 2-position of the pyrimidinyl ring.

4. A compound according to claim 1 wherein R 1 is —NR 6 —(CH 2 ) e —R 5 .

5. A compound according to claim 1 wherein b is 1.

6. A compound according to claim 1 wherein R 2 is selected from hydrogen, cyano, halogen, trihalomethyl and OC 1-6 alkyl.

7. A compound according to claim 1 wherein R 2 is fluoro.

8. A compound according to claim 1 wherein R 2 is in the 4-position of the phenyl ring.

9. A compound according to claim 1 wherein c is 1.

10. A compound according to claim 1 wherein R 4 is in the 6-position of the pyrazolopyridine ring.

11. A compound according to claim 1 wherein R 4 is selected from C 1-6 alkyl, halogen, cyano and trihalomethyl.

12. 3-(4-[2-(4-Fluorophenyl)-6-trifluoromethylpyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinylamino)-1-propanol or a salt or solvate thereof.

13. A pharmaceutical composition comprising a compound according to claim 1 , in admixture with one or more pharmaceutically acceptable carriers, diluents or excipients.