Cyclohexyl sulphones as gamma-secretase inhibitors

1. A compound of formula I:

wherein n is 1 or 2;

R 1 represents CF 3 or C 1-6 alkyl, C 2-6 alkenyl, C 3-9 cycloalkyl or C 3-6 cycloalkylC 1-6 alkyl, any of which may bear up to 2 substituents selected from halogen, CN, CF 3 , OR 3 , COR 3 , CO 2 R 3 , OCOR 4 , SO 2 R 4 , N(R 5 ) 2 , and CON(R 5 ) 2 ,

or R 1 represents aryl, arylC 1-6 alkyl, C-heterocyclyl or C-heterocyclylC 1-6 alkyl;

R 2 represents H or C 1-4 alkyl;

R 3 represents H, C 1-4 alkyl, phenyl or heteroaryl;

R 4 represents C 1-4 alkyl, phenyl or heteroaryl;

R 5 represents H or C 1-4 alkyl, or two R 5 groups together with a nitrogen atom to which they are mutually attached complete an azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine or thiomorpholine-1,1-dioxide ring;

Ar 1 and Ar 2 independently represent phenyl or heteroaryl, either of which bears 0-3 substituents independently selected from halogen, CN, NO 2 , CF 3 , CHF 2 , OH, OCF 3 , CHO, CH═NOH, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 2-6 acyl, C 2-6 alkenyl and C 1-4 alkyl which optionally bears a substituent selected from halogen, CN, NO 2 , CF 3 , OH and C 1-4 alkoxy;

aryl at every occurrence thereof refers to phenyl or heteroaryl which optionally bear up to 3 substituents selected from halogen, CN, NO 2 , CF 3 , OCF 3 , OR 3 , COR 3 , CO 2 R 3 , OCOR 4 , N(R 5 ) 2 , CON(R 5 ) 2 and optionally-substituted C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl or C 2-6 alkenyloxy wherein the substituent is selected from halogen, CN, CF 3 , phenyl, OR 3 , CO 2 R 3 , OCOR 4 , N(R 5 ) 2 and CON(R 5 ) 2 ; and

C-heterocyclyl and N-heterocyclyl at every occurrence thereof refer respectively to a heterocyclic ring system bonded through carbon or nitrogen, said ring system being non-aromatic and comprising up to 10 atoms, at least one of which is O, N or S, and optionally bearing up to 3 substituents selected from oxo, halogen, CN, NO 2 , CF 3 , OCF 3 , OR 3 , COR 3 , CO 2 R 3 , OCOR 4 , OSO 2 R 4 , N(R 5 ) 2 , CON(R 5 ) 2 and optionally-substituted phenyl, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl or C 2-6 alkenyloxy wherein the substituent is selected from halogen, CN, CF 3 , OR 3 , CO 2 R 3 , OCOR 4 , N(R 5 ) 2 and CON(R 5 ) 2 ;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein Ar 1 is 6-trifluoromethyl-3-pyridyl, 4-chlorophenyl or 4-trifluoromethylphenyl and Ar 2 is 2,5-difluorophenyl.

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

wherein X represents N or CH;

R 6 represents H, F, Cl, Br, CN, CF 3 , CH═CH 2 or CH 3 ;

R 7 represents F, Cl, Br, CN, CH 3 or CH 2 OH; and

R 1 is as defined in claim 1 ;

or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 3 wherein R 1 is CF 3 .

5. The compound according to claim 4 which is trifluoromethanesulfonic acid, N-[4-(2,5-difluorophenyl)-4-(6-trifluoromethyl-pyridine-3-sulfonyl)-cyclohexyl]-amide or a pharmaceutically acceptable salt thereof.

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

7. A method of treatment of a subject suffering from or prone to a condition associated with the deposition of β-amyloid which comprises administering to the subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

8. The method according to claim 7 wherein the condition is Alzheimer's disease.

9. A process for preparing a compound according to claim 1 in which R 2 is H comprising reacting a sulfinylchloride R 1 SOCl or a sulfonyl chloride R 1 SO 2 Cl or a sulfonic anhydride (R 1 SO 2 ) 2 O with an amine of formula III:

wherein R 1 , Ar 1 and Ar 2 are as defined in claim 1 .