PIPERAZINE DERIVATIVES FOR TREATMENT OF AD AND RELATED CONDITIONS

1 . A compound of formula I:

or a pharmaceutically acceptable salt or hydrate thereof; wherein:

R 1 and R 2 are attached at the same ring position or at different ring positions and independently represent H, F, C 1-4 alkyl or phenyl provided R 1 and R 2 are not both phenyl; or R 1 and R 2 which are attached at the same ring position may together represent ═O; or R 1 and R 2 which are attached at different ring positions may represent carbon atoms which together with the intervening atoms complete a 5- or 6-membered ring;

R 3 represents H, t-butoxycarbonyl, phenyl or pyridyl, said phenyl or pyridyl optionally bearing 1 or 2 substituents independently selected from C 1-4 alkoxy and halogen;

W represents N or CR 4a ,

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 CR 4a ;

R 4 , R 4a and R 5 independently represent H or (CH 2 ) m —X, where m is 0 or 1 and X represents halogen, CN, CF 3 , R 6 , OR 6 , N(R 6 ) 2 , NHCOR 6 , SO 2 R 6 , CO 2 R 6 or CON(R 6 ) 2 , or X represents phenyl or 5-membered heteroaryl either of which optionally bears up to two substituents independently selected from halogen, C 1-4 alkyl and CF 3 ;

or R 4 and R 5 together may complete a fused 5- or 6-membered carbocyclic or heterocyclic ring which optionally bears up to two substituents independently selected from oxo, halogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkylsulfonyl and CF 3 ;

each R 6 independently represents H or C 1-6 alkyl which optionally bears a substituent selected from CF 3 , C 1-4 alkoxy, di(C 1-4 alkyl)amino, C 3-6 cycloalkyl, and 5- or 6-membered heterocyclyl, said heterocyclyl optionally bearing up to two substituents independently selected from halogen, C 1-4 alkyl and CF 3 ;

or two R 6 groups attached to the same nitrogen atom may complete a 4-, 5- or 6-membered heterocyclic ring which optionally bears up to two substituents independently selected from halogen, C 1-4 alkyl and CF 3 ; and

Ar represents a phenyl or 5- or 6-membered heteroaryl ring bearing from 2 to 4 substituents selected from:

(a) C 1-6 alkyl which is optionally substituted with OH or CF 3 ;

(b) C 3-6 cycloalkyl;

(d) C 3-6 cycloalkylC 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 ;

(k) CF 3 ;

(l) CN;

(m) halogen;

(n) CON(C 1-4 alkyl) 2 ;

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 wherein R 1 and R 2 independently represent H or methyl.

3 . A compound according to claim 1 wherein R 3 represents phenyl or pyridyl which bears a methoxy substituent in the para position.

4 . A compound according to claim 1 wherein W is N and V is selected from S, CR 4 ═CR 5 and CR 4 ═N.

5 . A compound according to claim 1 wherein Ar represents:

where R 8 represents C 1-6 alkyl; and R 9 , R 10 an R 11 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 that R 11 is other than H.

6 . A compound according to claim 5 of formula II:

or a pharmaceutically acceptable salt or hydrate thereof.

7 . A compound according to claim 5 of formula III:

or a pharmaceutically acceptable salt or hydrate thereof.

8 . A compound according to claim 5 of formula IV:

or a pharmaceutically acceptable salt or hydrate thereof.

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

10 - 11 . (canceled)

12 . A method for treating or preventing a disease associated with deposition of Aβ in the brain comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or hydrate thereof.

13 . The method according to claim 12 wherein said disease is selected from Alzheimer's disease, cerebral amyloid angiopathy, HCHWA-D, multi-infarct dementia, dementia pugilistica and Down syndrome.