Alkenyl-substituted spirocyclic sulfamides as inhibitors of gamma-secretase

1. A compound of formula I:

wherein R 4 is selected from:

X represents H, halogen, CN or methyl;

R 1 represents H or C 1-4 alkyl which is optionally substituted with OH or C 1-4 alkoxy;

R 2 and R 3 together with the nitrogen to which they are mutually attached complete a monocyclic heterocyclic ring system of 5-10 ring atoms selected from C, N, O and S, said ring system optionally having an additional benzene or heteroaryl ring fused thereto, said heterocyclic system and optional fused ring bearing 0-3 substituents independently selected from halogen, oxo, NO 2 , CN, R 12 , Ar, ArCH 2 O, ArO, ArOCH 2 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ;

and when R 1 completes a ring with R 2 , R 3 represents H, C 1-6 alkyl, C 2-6 acyl, C 2-6 alkenyl or benzyl;

m is 0 or 1, with the proviso that when m is 1 neither R 2 nor R 3 is H and R 3 is not acyl, and that m is 1 when X and R 1 are both H;

R 11 represents H or R 12 ;

R 12 represents C 1-6 alkyl which optionally bears up to 3 halogen substituents or one substituent selected from CN, OH, C 1-4 alkoxy and C 1-4 alkoxycarbonyl;

R 14 represents H or C 1-6 alkyl, C 3-7 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl or benzyl, any of which optionally bear up to 3 halogen substituents or one substituent selected from CN, NO 2 , OH, C 1-4 alkoxy, CO 2 H, C 1-4 alkoxycarbonyl, C 2-6 acyl, C 2-6 acyloxy amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 2-6 acylamino, carbamoyl, C 1-4 alkylcarbamoyl and di(C 1-4 alkyl)carbamoyl; and

Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF 3 , NO 2 , CN, OCF 3 , C 1-6 alkyl and C 1-6 alkoxy; or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 wherein R 14 is 2,2,2-trifluoroethyl, X is F, CN or methyl, and R 1 is H.

4. A compound according to claim 1 wherein m is 1 and X and R 1 are both H.

5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutical carrier.

6. A method of treatment of Alzheimer's disease comprising administering to that subject an effective amount of a compound according to claim 1 .