Benzodiazepine derivatives as inhibitors of gamma secretase

A compound of formula I:

• 23
• wherein
• n is 0-3;
• each Rx independently represents halogen, —CN, —NO2, C1-6alkoxy, polyfluoroC1-6alkyl, —OH or C1-4alkoxy;
• X represents O, S or N—Ra where Ra together with R1 completes a fused imidazole or 4,5-dihydroimidazole ring;
• Y represents —CH2—, —CH(OH)—, —CH(CH3)—, —CH2O—, —O— or —S;
• R1 represents H, C1-6alkyl, C3-8cycloalkyl, C2-6alkenyl, C2-6alkynyl or polyfluoroC1-6alkyl, said alkyl, cycloalkyl, alkenyl and alkynyl groups being optionally substituted by halogen, —CN, —NO2, aryl, heteroaryl, —COR6, —CO2R6, —CON(R6)2, —OCOR7, —NR6COR7, —NR6SO2R7, —SO3R6, —SO2N(R6)2, —OR6, —SR6 or —N(R6)2;
• or when X is N—Ra, R1 together with Ra completes a fused imidazole or 4,5-dihydroimidazole ring;
• R2 and R2a each represents hydrogen, or R2 and R2a together complete a fused lactam ring of 4-7 members;
• R3 represents aryl, heteroaryl, C1-6alkyl, polyfluoroC1-6alkyl, C3-8cycloalkyl or C3-8cycloalkylC1-6alkyl;
• each R6 independently represents H, polyfluoroC1-6alkyl, or C1-6alkyl which is optionally substituted with halogen, —CN, —NO2, —OH, —SH, —NH2, phenyl, C1-4alkoxy, C1-4alkylthio, C1-4alkylamino, di(C1-4alkyl)amino, —CO2H, —CO2C1-4alkyl, —CONH2, —CONHC1-4alkyl or —CON(C1-4alkyl)2;
• or two R6 groups attached to a single nitrogen atom may complete a heterocyclic ring of from 3 to 12 members including the said nitrogen, the remaining atoms being selected from C, N, O and S, and the ring optionally bearing up to 3 substituents independently selected from C1-6alkyl, polyfluoroC1-6alkyl, C2-7acyl, —OH and —CONH2;
• R7 represents R6 that is other than H;
• “aryl” refers to phenyl which is optionally fused to a 5-7 membered saturated or unsaturated ring which may be carbocyclic or may comprise up to 3 heteroatoms selected from nitrogen, oxygen and sulphur, and which may be oxo-substituted, said phenyl and optional fused ring together bearing 0-3 substituents independently selected from C1-6alkyl [which is optionally substituted with halogen, —CN, —NO2, —OH, —SH, —NH2, C1-4alkoxy, C1-4alkylthio, C1-4alkylamino, di(C1-4alkyl)amino, —CO2H. —CO2C1-4alkyl, —CONH2, —CONHC1-4alkyl or —CON(C1-4alkyl)2], polyfluoroC1-6alkyl, halogen, —CN, —NO2, heteroaryl, —COR6, —CO2R6, —CON(R6)2, —OCOR7, —NR6COR7, —NR6SO2R7, —SO3R6, —SO2N(R6)2, —OR6, —SR6 and —N(R6)2;
• “heteroaryl” refers to a heteroaromatic ring of 5 or 6 members, at least one member being nitrogen, oxygen or sulphur and the remainder carbon, said ring optionally being fused to a 5-7 membered saturated or unsaturated ring which may be carbocyclic or may comprise up to 3 heteroatoms selected from nitrogen, oxygen and sulphur, and which may be oxo-substituted heteroaromatic ring and optional fused ring together bearing 0-3 substituents independently selected from C1-6alkyl [which is optionally substituted with halogen, —CN, —NO2, —OH, —SH, —NH2, C1-4alkoxy, C1-4alkylthio, C1-4alkylamino, di(C1-4alkyl)amino, —CO2H, —CO2C1-4alkyl, —CONH2, —CONHC1-4alkyl or —CON(C1-4alkyl)2], polyfluoroC1-6alkyl, halogen, —CN, —NO2, phenyl, —COR6, —CO2R6, —CON(R6)2, —OCOR7, —NR6COR7, —NR6SO2R7, —SO3R6, —SO2N(R6)2, —OR6, SR6 and —N(R6)2;
• or a pharmaceutically acceptable salt thereof.