Cyclohexyl sulphone derivatives as gamma-secretase inhibitors

A compound of formula I:

• wherein
• X represents SCN, SR1, S(O)R1, (CRaRb)mSO2R1, SO2N(R2)2, SO2NHCOR1, SO2NHN(R2)2, OSO2N(R2)2, OS(O)N(R2)2, OSO2NHCOR1, COR4, NHCOR1, NHCO2R1, NHCON(R2)2, NHSO2R1 or NHSO2N(R2)2;
• m is 0 or 1
• Ra represents H or C1-4alkyl;
• Rb represents H, C1-4alkyl, CO2H, C1-4alkoxycarbonyl or C1-4alkylsulphonyl;
• or Rb may combine with R1 to form a 5- or 6-membered ring;
• L represents a bond, ═CH— or —(CHRa)n—;
• with the proviso that L does not represent a bond when X represents NHCOR1, NHCO2R1 or NHSO2R1;
• and with the proviso that if L represents ═CH—, X represents SO2R1 or COR4;
• n is 1, 2 or 3;
• R1 represents CF3 or C1-6alkyl, C2-6alkenyl, C3-9cycloalkyl or C3-6cycloalkylC1-6alkyl, any of which may bear up to 2 substituents selected from halogen, CN, CF3, OR3, COR3, CO2R3, OCOR3a, SO2R3a, N(R5)2, and CON(R5)2,
• or R1 represents aryl, arylC1-6alkyl, C-heterocyclyl or C-heterocyclylC1-6alkyl;
• or R1 may combine with Rb to form a 5- or 6-membered ring;
• each R2 independently represents H, C1-6alkoxy, or C1-6alkyl, C2-6alkenyl, C3-9cycloalkyl or C3-6cycloalkylC1-6alkyl, any of which may bear up to 2 substituents selected from halogen, CN, CF3, OR3, COR3, CO2R3, OCOR3a, and CON(R5)2;
• or aryl, arylC1-6alkyl, C-heterocyclyl or C-heterocyclylC1-6alkyl;
• or two R2 groups together with a nitrogen atom to which they are mutually attached complete an N-heterocyclyl group;
• R3 represents H, C1-4alkyl, phenyl or heteroaryl;
• R3a represents C1-4alkyl, phenyl or heteroaryl;
• R4 represents (CRaRb)SO2R1, pyridine N-oxide, or phenyl or heteroaryl which bear a substituent selected from CO2H, methylenedioxy, difluoromethylenedioxy, COR3, C-heterocyclyl, C1-4alkylsulphonyl and substituted C1-6alkyl, C1-6alkoxy, C2-6alkenyl or C2-6alkenyloxy wherein the substituent is selected from halogen, CN, CF3, OR3, CO2R3, OCOR3a, N(R5)2 and CON(R5)2;
• R5 represents H or C1-4alkyl, or two R5 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;
• Ar1 and Ar2 independently represent phenyl or heteroaryl, either of which bears 0–3 substituents independently selected from halogen, CN, NO2, CF3, CHF2, OH, OCF3, CHO, CH═NOH, C1-4alkoxy, C1-4alkoxycarbonyl, C2-6acyl, C2-6alkenyl and C1-4alkyl which optionally bears a substituent selected from halogen, CN, NO2, CF3, OH and C1-4alkoxy;
• aryl at every occurrence thereof refers to phenyl or heteroaryl which optionally bear up to 3 substituents selected from halogen, CN, NO2, CF3, OCF3, OR3, COR3, CO2R3, OCOR3a, N(R5)2, CON(R5)2 and optionally-substituted C1-6alkyl, C1-6alkoxy, C2-6alkenyl or C2-6alkenyloxy wherein the substituent is selected from halogen, CN, CF3, phenyl, OR3, CO2R3, OCOR3a, N(R5)2 and CON(R5)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, NO2, CF3, OCF3, OR3, COR3, CO2R3, OCOR3a, OSO2R3a, N(R5)2, CON(R5)2 and optionally-substituted phenyl, C1-6alkyl, C1-6alkoxy, C2-6alkenyl or C2-6alkenyloxy wherein the substituent is selected from halogen, CN, CF3, OR3, CO2R3, OCOR3a, N(R5)2 and CON(R5)2;
• or a pharmaceutically acceptable salt thereof.