Macrocyclic beta-secretase inhibitors

A compound having the structural formula

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is
• R2 is —N(R5)C(O)R4—;
• R3 is arylene, heteroarylene, heterocyclylene or cycloalkylene;
• R4 is arylene, heteroarylene, heterocyclylene or cycloalkylene;
• R5 is hydrogen, alkyl, aryl, heteroaryl or cycloalkyl;
• R6 and R7 (when present) are independently selected from hydrogen, —OH, alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aralkoxy, heteroaralkoxy and alkoxy, with the proviso that when R6 and R7 are —OH, aralkoxy, heteroaralkoxy and alkoxy, R6 and R7 are not attached to a ring carbon adjacent to a ring nitrogen;
• R8 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, —C(O)R9, —C(O)OR12, —S(O)R9, —S(O2)R9 or —CN;
• with the proviso that when Y is O, R8 cannot be —C(O)R9, —C(O)OR12, —S(O)R9, —S(O2)R9 or —CN;
• R9 is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, alkenyl, alkynyl or —N(R10)(R11);
• R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocyclyl, aralkyl, heteroaralkyl, heterocyclylalkyl, alkenyl and alkynyl;
• or R10 and R11 together with the nitrogen to which they are attached, form a 3-7 membered heterocyclyl ring;
• R12 is alkyl, cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, alkenyl or alkynyl;
• X is O, S, C(R5), or NH;
• Y is O, or (H,H);
• m is 1, 2, or 3;
• n is 0, 1, 2, or 3;
• and
• o is 0, 1, 2, or 3;
• wherein each alkyl is optionally substituted with 1 to 3 moieties selected from the group consisting of halo, aryl, cycloalkyl, cyano, hydroxy, alkoxy, alkylthio, amino, —NH(alkyl), —NH(cycloalkyl), —N(alkyl)2, carboxy and —C(O)O-alkyl;
• and
• wherein each arylene, heteroarylene, heterocyclyl, heterocyclylalkyl, heterocyclylene, cycloalkylene, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocyclyl, aralkyl, heteroaralkyl, aralkoxy or heteroaralkoxy is optionally substituted with 1 to 4 moieties selected from the group consisting of —CF3, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkylaryl, heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl, alkylheteroaryl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, cycloalkyl, heterocyclyl, —C(═N—CN)—NH2, —C(═NH)—NH2, —C(═NH)—NH(alkyl), Y1Y2N—, Y1Y2N-alkyl-, Y1Y2NC(O)—, Y1Y2NSO2— and —SO2NY1Y2, wherein Y1 and Y2 can be the same or different and are independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, and aralkyl, with the proviso that cycloalkylene and heterocyclylene can be substituted with ═O.