Cyclohexyl sulphones
View Patent ↗Novel sulphones of formula I are disclosed: The compounds modulate the processing of amyloid precursor protein by gamma-secretase, and hence are useful in the treatment or prevention of Alzheimer's disease.
1. A compound of formula I:
wherein:
m is 0 or 1;
Z represents CON(R 2a ) 2 ;
R 1b represents H, C 1-4 alkyl or OH;
R 1c represents H or C 1-4 alkyl;
with the proviso that when m is 1, R 1b and R 1c do not both represent C 1-4 alkyl;
Ar 1 represents C 6-10 aryl which bears 0-3 substituents independently selected from halogen, CF 3 , OH, OCF 3 , C 1-4 alkoxy or C 1-4 alkyl which optionally bears a substituent selected from halogen, CF 3 , OH and C 1-4 alkoxy;
Ar 2 represents C 6-10 aryl which bears 0-3 substituents independently selected from halogen, CF 3 , OH, OCF 3 , C 1-4 alkoxy or C 1-4 alkyl which optionally bears a substituent selected from halogen, CF 3 , OH and C 1-4 alkoxy;
R 2a represents H, C 1-6 alkyl, or C 2-6 alkenyl, wherein said alkyl or alkenyl optionally bears a substituent selected from halogen, CF 3 , or OR 2b ;
R 2b represents H, C 1-6 alkyl, or C 2-6 alkenyl, wherein said alkyl or alkenyl optionally bears a substituent selected from halogen, CF 3 , OH, or C 1-4 alkoxy;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 wherein Ar 1 is selected from phenyl groups substituted in the 4-position with halogen, methyl or trifluoromethyl, and phenyl groups substituted in the 3- and 4-positions by halogen.
3. A compound according to claim 1 wherein Ar 2 is selected from phenyl groups substituted in the 2- and 5-positions by halogen.
4. A compound according to claim 1 wherein m is 0, Ar 1 represents 4-chlorophenyl, Ar 2 represents 2,5-difluorophenyl, R 1c represents H and Z represents CONH 2 .
5. A compound according to claim 1 wherein m is 0, Ar 1 represents 4-trifluoromethylphenyl, Ar 2 represents 2,5-difluorophenyl, R 1c represents H and Z represents CONH 2 .
6. A compound according to claim 1 wherein m is 0, Ar 1 represents 4-chlorophenyl, Ar 2 represents 2,5-difluorophenyl, R 1c represents H and Z represents CONHCH 2 CH 3 .
7. A pharmaceutical composition comprising a compound of formula I as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
8. A method of treatment of Alzheimer's disease which comprises administering to a subject suffering from Alzheimer's disease an effective amount of a compound of formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof.