Piperidine derivatives

1. A compound of formula I:

or a pharmaceutically acceptable salt or hydrate thereof; wherein:

R a and R b independently represent H, F, C 1-4 -alkyl or phenyl provided R a and R b are not both phenyl;

Z is selected from:

(a) a spiro-linked moiety of formula:

where m and n are integers of from 0-4 such that m+n is 3 or 4;

(b) a moiety CH—NR 1 R 2 where R 1 and R 2 independently represent H or C 1-6 alkyl, or together with the nitrogen atom to which they are attached complete a non-aromatic N-heterocyclyl group of 5 or 6 ring atoms bearing 0-3 substituents selected from C 1-4 -alkyl, halogen, CF 3 , OR 3 and CO 2 R 3 , or said N-heterocyclyl group may be fused to a benzene ring which bears 0-3 substituents selected from C 1-4 -alkyl, halogen, CF 3 , OR 3 and CO 2 R 3 , where R 3 represents H or C 1-4 alkyl, and

(c) a moiety CH-Het where Het represents a 5-membered heteroaryl group which optionally bears a substituent selected from halogen, C 1-4 -alkyl, CF 3 and phenyl;

W represents N or CH,

V represents S, CR 4 ═CR 5 , CR 4 ═N or N═CR 4 ; with the proviso that when V represents N═CR 4 , W represents CH;

R 4 and R 5 independently represent H or (CH 2 ) p —X, where p is 0 or 1 and X represents halogen, 5- or 6-membered heteroaryl, CN, CF 3 , R 6 , OR 6 , N(R 6 ) 2 , SO 2 R 6 , CO 2 R 6 or CON(R 6 ) 2 where each R 6 independently represents H, phenyl, C 1-4 -alkyl or hydroxyC 1-4 -alkyl; or R 4 and R 5 together may complete a fused 5- or 6-membered carbocyclic or heterocyclic ring; and

Ar represents a phenyl ring bearing from 2 to 4 substituents selected from:

(a) C 1-6 alkyl;

(b) C 3-6 cycloalkyl;

(d) C 3-6 cyclo alkylC 1-6 alkyl;

(e) C 2-6 alkenyl;

(f) mono-or bicyclic aryl groups of up to 10 ring atoms, optionally bearing up to 2 substituents selected from halogen, CF 3 and C 1-6 alkyl;

(g) OR 7 ;

(h) CO 2 R 7 ;

(i) N(R 7 ) 2

(j) SR 7 ; and

(k) CF 3 ;

where each R 7 represents C 1-6 alkyl or two R 7 groups attached to the same nitrogen may complete an N-heterocyclyl group bearing 0-2 substituents selected from halogen, CF 3 , C 1-4 -alkyl and C 1-4 alkoxy;

or the ring represented by Ar may be fused to a mono- or bicyclic carbocyclic or heterocyclic ring system of up to 10 ring atoms.

2. A compound according to claim 1 or a pharmaceutically acceptable salt or hydrate thereof, wherein W is N and V is selected from S, CR 4 ═CR 5 and CR 4 ═N.

3. A compound according to claim 1 or a pharmaceutically acceptable salt or hydrate thereof, wherein Ar represents:

where R 8 represents C 1-6 alkyl; and

R 9 and R 10 independently represent:

H;

C 1-6 alkyl;

OR 7 where R 7 represents C 1-6 alkyl;

CO 2 R 7 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where the two R 7 groups complete an N-heterocyclyl group bearing 0-2 substituents selected from halogen, CF 3 , C1-4alkyl and C1-4alkoxy;

CF 3 ; or

mono-or bicyclic aryl groups of up to 10 ring atoms, optionally bearing up to 2 substituents selected from halogen, CF 3 and C 1-6 alkyl;

with the proviso that at least one of R 9 and R 10 is other than H.

4. A compound of formula II:

or a pharmaceutically acceptable salt or hydrate thereof; wherein

R a and R b independently represent H, F, C 1-4 -alkyl or phenyl provided R a and R b are not both phenyl;

R 4 and R 5 independently represent H or (CH 2 ) p —X, where p is 0 or 1 and X represents halogen, 5- or 6-membered heteroaryl, CN, CF 3 , R 6 , OR 6 , N(R 6 ) 2 , SO 2 R 6 , CO 2 R 6 or CON(R 6 ) 2 where each R 6 independently represents H, phenyl, C 1-4 -alkyl or hydroxyC 1-4 alkyl; or R 4 and R 5 together may complete a fused 5- or 6-membered carbocyclic or heterocyclic ring;

R 8 represents C 1-6 alkyl; and R 9 and R 10 independently represent:

H;

C 1-6 alkyl;

OR 7 where R 7 represents C 1-6 alkyl;

CO 2 R 7 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where the two R 7 groups complete an N-heterocyclyl group bearing 0-2 substituents selected from halogen, CF 3 , C 1-4 -alkyl and C 1-4 -alkoxy;

CF 3 ; or

mono-or bicyclic aryl groups of up to 10 ring atoms, optionally bearing up to 2 substituents selected from halogen, CF 3 and C 1-6 alkyl;

with the proviso that at least one of R 9 and R 10 is other than H; and Z 1 represents a spiro-linked moiety of formula:

where m and n are integers of from 0-4 such that m+n is 3 or 4.

5. A compound according to claim 4 or a pharmaceutically acceptable salt or hydrate thereof, wherein:

m=n=2; or

m is 0 and n is 3; or

m is 1 and n is 2.

6. A compound of formula III:

or a pharmaceutically acceptable salt or hydrate thereof; wherein

R 1 and R 2 independently represent H or C 1-6 alkyl, or together with the nitrogen atom to which they are attached complete a non-aromatic N-heterocyclyl group of 5 or 6 ring atoms bearing 0-3 substituents selected from C 1-4 -alkyl, halogen, CF 3 , OR 3 and CO 2 R 3 , or said N-heterocyclyl group may be fused to a benzene ring which bears 0-3 substituents selected from C 1-4 alkyl, halogen, CF 3 , OR 3 and CO 2 R 3 , where R 3 represents H or C 1-4 -alkyl;

R 4 and R 5 independently represent H or (CH 2 ) p —X, where p is 0 or 1 and X represents halogen, 5- or 6-membered heteroaryl, CN, CF 3 , R 6 , OR 6 , N(R 6 ) 2 SO 2 R 6 CO 2 R 6 or CON(R 6 ) 2 where each R 6 independently represents H, phenyl, C 1-4 -alkyl or hydroxyC 1-4 -alkyl; or R 4 and R 5 together may complete a fused 5- or 6-membered carbocyclic or heterocyclic ring; and

R 8 represents C 1-6 alkyl; and R 9 and R 10 independently represent:

H;

C 1-6 alkyl;

OR 7 where R 7 represents C 1-6 alkyl;

CO 7 R 7 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where the two R 7 groups complete an N-heterocyclyl group bearing 0-2 substituents selected from halogen, CF 3 , C 1-4 -alkyl and C 1-4 -alkoxy;

CF 3 ; or

mono-or bicyclic aryl groups of up to 10 ring atoms, optionally bearing up to 2 substituents selected from halogen, CF 3 and C 1-6 alkyl;

with the proviso that at least one of R 9 and R 10 is other than H.

7. A compound according to claim 6 or a pharmaceutically acceptable salt or hydrate thereof, wherein R 1 and R 2 complete an optionally substituted or benzo-fused N-heterocyclyl group of 5 or 6 ring atoms.

8. A compound according to claim 3 of formula IV:

and pharmaceutically acceptable salts and hydrates thereof; wherein

R a and R b independently represent H, F, C 1-4 -alkyl or phenyl provided R a and R b are not both phenyl;

R 4 and R 5 independently represent H or (CH 2 ) p —X, where p is 0 or 1 and X represents halogen, 5- or 6-membered heteroaryl, CN, CF 3 , R 6 , OR 6 , N(R 6 ) 2 , SO 2 R 6 , CO 2 R 6 or CON(R 6 ) 2 where each R 6 independently represents H, phenyl, C 1-4 -alkyl or hydroxyC 1-4 alkyl; or R 4 and R 5 together may complete a fused 5- or 6-membered carbocyclic or heterocyclic ring;

R 8 represents C 1-6 alkyl; and R 9 and R 10 independently represent:

H;

C 1-6 alkyl;

OR 7 where R 7 represents C 1-6 alkyl;

CO 2 R 7 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where R 7 represents C 1-6 alkyl;

N(R 7 ) 2 where the two R 7 groups complete an N-heterocyclyl group bearing 0-2 substituents selected from halogen, CF 3 , C 1-4 -alkyl and C 1-4 -alkoxy;

CF 3 ; or

mono-or bicyclic aryl groups of up to 10 ring atoms, optionally bearing up to 2 substituents selected from halogen, CF 3 and C 1-6 alkyl;

with the proviso that at least one of R 9 and R 10 is other than H; and

Het represents a 5-membered heteroaryl group which optionally bears a substituent selected from halogen, C 1-4 -alkyl, CF 3 and phenyl.

9. A compound according to claim 8 or a pharmaceutically acceptable salt or hydrate thereof, wherein Het comprises at least one ring nitrogen.

10. A compound according to claim 9 or a pharmaceutically acceptable salt or hydrate thereof, wherein Het is bonded to the remainder of the molecule through a ring nitrogen.

11. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt or hydrate thereof and a pharmaceutically acceptable carrier.