Triazole derivatives for treatment of Alzheimer's disease

1. A compound of formula I:

or a pharmaceutically acceptable salt or hydrate thereof; wherein:

W represents phenyl or 5- or 6-membered heteroaryl comprising up to 3 heteroatoms selected from N, O and S, wherein the phenyl or heteroaryl is optionally fused to a further 5- or 6-membered carbocyclic, or 5- or 6-membered heterocyclic ring, W optionally bearing up to 3 R 1 substituents; or when X is a bond W may represent CN and when X is CO W may represent a piperazin-1-yl or piperidin-1-yl ring;

each R 1 independently represents halogen, OH, amino, CF 3 , C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 2-6 acylamino, N—C 1-4 alkoxycarbamoyl, C 1-6 alkoxy, C 1-6 alkylcarbonyl, or C 1-6 alkyl which is optionally substituted with OH or C 1-4 alkoxy;

X represents a bond, (CH 2 ) n O, (CH 2 ) n NH, CO or (CH 2 ) n NHCO where each n is 0 or 1;

Y represents a phenyl or 5- or 6-membered heteroaryl ring which optionally bears up to 3 R 2 substituents; or when X is a bond and W is not CN, Y may represent C≡C or a C 3-6 cycloalkyl ring; or when X is a bond or CO, Y may represent piperidin-4-yl;

or the moiety W-X-Y may represent a fused-ring system consisting of 2 or 3 fused rings selected from the group consisting of;

with the proviso that if X is a bond and W represents an imidazole, triazole or pyrazole ring which is linked to Y through N, then Y does not represent

where Y1 and Y2 each independently represents N or CR 2 ;

each R 2 independently represents halogen, CN, OH, C 1-6 alkyl, or C 1-6 alkoxy, said alkyl and alkoxy optionally having up to 3 fluorine substituents or a cyclopropyl substituent;

Z represents CH 2 , CH 2 —CH 2 , O, S, NH, CH 2 —O, CH 2 —S or CH 2 —NH;

R 9 represent H, C 1-6 alkyl, C 2-6 alkenyl, polyfluoroC 1-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-4 alkyl, C 1-4 alkoxyC 1-4 alkyl, aminoC 1-4 alkyl, C 1-4 alkylcarbonyl, polyfluoroC 1-4 alkylcarbonyl, C 1-4 alkylsulfonyl, phenyl, phenylsulfonyl, benzoyl, benzyl, naphthylmethyl or pyridylmethyl, where said phenyl and the aromatic portions of said phenylsulfonyl, benzoyl, benzyl, naphthylmethyl and pyridylmethyl optionally bear up to 3 substituents selected from halogen, C 1-4 alkyl, C 1-4 alkoxy and CF 3 ;

each R 10 independently represents halogen, OH, C 1-4 alkyl, C 2-4 alkenyl, polyfluoroC 1-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, polyfluoroC 1-4 alkoxy, C 1-4 alkylcarbonyl, polyfluoroC 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylthio, C 1-4 alkylsulfonyl, SO 2 NR 2 , CONR 2 or NR 2 where each R is independently H or C 1-4 alkyl or the two R groups together with the nitrogen to which they are attached complete a ring selected from azetidine, pyrrolidine, piperidine, piperazine and morpholine; or phenyl or benzyl either of which optionally is substituted with halogen, C 1-4 alkyl, C 1-4 alkoxy or CF 3 ;

or two R 10 groups attached to adjacent ring positions optionally complete a fused benzene, naphthalene, cyclopentane, cyclohexane, pyridine, thiophene or furan ring which optionally bears up to 2 substituents independently selected from halogen, NO 2 , CN, OH, phenyl, C 1-4 alkyl, C 2-4 alkenyl, polyfluoroC 1-4 alkyl, C 3-4 cycloalkyl, C 3-6 cycloalkylC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, polyfluoroC 1-4 alkoxy, C 1-4 alkylcarbonyl, polyfluoroC 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylthio, C 1-4 alkylsulfonyl, SO 2 NR 2 , CONR 2 or NR 2 where each R is independently H or C 1-4 alkyl;

or two R 10 groups attached to non-adjacent ring positions optionally complete a CH 2 or CH 2 CH 2 bridge.

2. A compound according to claim 1 of formula II:

or a pharmaceutically acceptable salt or hydrate thereof; wherein

x is 0, 1 or 2;

y is 0, 1 or 2;

R 11 represents methyl or phenyl with the proviso that x is not 2 when R 11 is phenyl; and

each R 12 is independently selected from phenyl, NO 2 halogen, C 1-4 alkyl, polyfluoroC 1-4 alkyl, C 1-4 alkoxy and polyfluoroC 1-4 alkoxy with the provision that not more than one R 12 represents phenyl or NO 2 .

3. A compound according to claim 2 or a pharmaceutically acceptable salt or hydrate thereof, wherein R 9 represents CH 2 CF 3 , x is 0, y is 0 or 1 and R 12 represents F.

4. A compound according to claim 1 or a pharmaceutically acceptable salt or hydrate thereof, wherein Y is ring selected from phenyl, pyridine, pyrimidine, thiophene, furan, thiazole and imidazole and optionally bears up to 2 R 2 substituents.

5. A compound according to claim 4 or a pharmaceutically acceptable salt or hydrate thereof, wherein each R 2 independently represents H, F or C 1-4 alkoxy.

6. A compound according to claim 1 or a pharmaceutically acceptable salt or hydrate thereof, wherein W represents phenyl, naphthalene, tetrahydronaphthalene, quinoline, methylenedioxyphenyl, pyridine, pyridazine, pyrimidine, or a 5-membered heteroaryl selected from pyrrole, furan, thiophene, pyrazole, imidazole, oxazole, isoxazole, thiazole, isothiazole, triazole, oxadiazole or thiadiazole, and a benzo- or pyrido-fused analogue of said 5-membered heteroaryl, any of which optionally bears up to two R 1 substituents.

7. A compound according to claim 6 or a pharmaceutically acceptable salt or hydrate thereof, wherein W represents 4-pyridyl which optionally bears up to 2 substituents selected from F, Cl, CF 3 , C 1-4 alkyl, and C 1-4 alkoxy, X is a bond, and Y represents 1,4-phenylene which optionally bears up to 2 substituents selected from F, Cl, CF 3 , C 1-4 alkyl, and C 1-4 alkoxy.

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