Inhibitors Of Beta-Secretase

A compound represented by the following Structural Formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is —H, (C1-C6)alkyl, aryl(C1-C6)alkyl, or heteroaryl(C1-C6)alkyl;
• each R2 is independently selected from a) —H, —F, —Cl, —Br, and —CN, and b) (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, aryl, heteroaryl, phenoxy, or benzyloxy, each optionally substituted with 1 to 3 substituents selected from the group consisting of —F, —Cl, —Br, —CN, —OR5, —NR6R7, —S(O)iR5, —NR11S(═O)iR5, —C(═O)OR5, —C(═O)NR12R13, —NR11C(═O)R5, —C(═S)NR12R13, —C(═O)R5, (C1-C6)alkyl, (C3-C8)cycloalkyl, (C2-C6)alkenyl, halo(C1-C6)alkyl, (C1-C3)alkylsulfonylaminoalkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, (C1-C3)alkylcarbonylamino(C1-C6)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C6)alkoxy(C1-C3)alkyl, aryl and heteroaryl;
• each R3 and R4 are independently —H, -halogen, —CN, —NO2, —OR5, —NR6R7, —S(O)iR5, —C(═O)OR5, —C(═O)NR12R13, —C(═O)R5, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, aryl, or heteroaryl, wherein each (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C8)cycloalkyl, aryl, or heteroaryl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F, —Cl, —Br, —CN, —OR5, —NR6R7, —S(O)iR5, —NR11S(═O)iR5, —C(═O)OR5, —C(═O)NR12R13, —NR11C(═O)R5, —C(═S)NR12R13, —C(═O)R5, (C1-C6)alkyl, (C2-C6)alkenyl, halo(C1-C6)alkyl, (C1-C3)alkylsulfonylaminoalkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, (C1-C3)alkylcarbonylamino(C1-C6)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C6)alkoxy(C1-C3)alkyl, an aryl group, and a heteroaryl group;
• X is —O—, —S—, —SO—, —SO2—, —CH2O— or —OCH2—;
• each Y is independently —C(R8R9)—;
• W is —N(R14)—, —S—, —O—;
• Z is —C(═O)—, —C(═S)—, —C(═NR15)—, —O—, —C(═O)C(R16R17)—, —C(═S)C(R16R17)—, —C(═NR15)C(R16R17)—, —N(R18)—, —(CR16R17)m— or —O—(CR16R17)—;
• R5 is —H, (C1-C6)alkyl, halo(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C3)alkoxy(C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, (C3-C7) cycloheteroalkyl, aryl, heteroaryl or benzyl, each of which is optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F, —Cl, —Br, —CN, (C1-C6)alkyl, halo(C1-C6)alkyl, and (C1-C3)alkoxy(C1-C6)alkyl;
• each R6 and R7 are independently selected from —H, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C8) cycloalkyl, and (C3-C8)cycloalkyl(C1-C6)alkyl, each optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F, —Br, —CN, (C1-C6)alkyl, halo(C1-C6)alkyl and (C1-C3)alkoxy(C1-C6)alkyl;
• R8 is selected from hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C14) cycloalkyl, (C3-C13)cycloheteroalkyl, aryl or heteroaryl, each optionally substituted with 1 to 4 substituents independently selected from the group consisting of —F, —Cl, —Br, —CN, —OR5, —NR6R7, —S(O)iR5, —NR11S(═O)iR5, —C(═O)OR5, —C(═O)NR12R13, —NR11C(═O)R5, —C(═S)NR12R13, —C(═O)R5, (C1-C6)alkyl, (C2-C6)alkenyl, halo(C1-C6)alkyl, (C1-C3)alkylsulfonylaminoalkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, (C1-C3)alkylcarbonylamino(C1-C6)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C6)alkoxy(C1-C3)alkyl, aryl, heteroaryl, (C3-C8)cycloalkyl and (C3-C7)cycloheteroalkyl;
• R9— is selected from —H, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkynyl, (C3-C14)cycloalkyl, (C3-C13)cycloheteroalkyl, aryl or heteroaryl, each optionally substituted with 1 to 4 substituents independently selected from the group consisting of —F, —Cl, —Br, —CN, —OR5, —NR6R7, —S(O)iR5, —NR11S(═O)iR5, —C(═O)OR5, —C(═O)NR12R13, —NR11C(═O)R5, —C(═S)NR12R13, —C(O)R5, (C1-C6)alkyl, (C2-C6)alkenyl, halo(C1-C6)alkyl, (C1-C3)alkylsulfonylaminoalkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, (C1-C3)alkylcarbonylamino(C1-C6)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C6)alkoxy(C1-C3)alkyl, aryl, heteroaryl, (C3-C8)cycloalkyl and (C3-C7)cycloheteroalkyl;
• or
• R8 and R9, together with the carbon to which they are attached, form ring A, which is a 3-14 membered monocyclic, 9-14 membered bicyclic or 9-14 membered polycyclic ring, wherein ring A is optionally substituted with 1 to 4 substituents independently selected from the group consisting of —F, —Cl, —Br, —CN, —OR5, —NR6R7, —S(O)iR5, —NR11S(═O)iR5, —C(═O)OR5, —C(═O)NR12R13, —NR11C(═O)R5, —C(═S)NR12R13, —C(═O)R5, (C1-C6)alkyl, (C2-C6)alkenyl, halo(C1-C6)alkyl, (C1-C3)alkylsulfonylaminoalkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, (C1-C3)alkylcarbonylamino(C1-C6)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C6)alkoxy(C1-C3)alkyl, aryl and heteroaryl;
• R11 is —H, (C1-C6)alkyl or halo(C1-C6)alkyl;
• each R12 and R13 are independently —H, (C1-C6)alkyl, (C1-C3)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, amino(C1-C6)alkyl, (C1-C3)alkylamino(C1-C6)alkyl, or di(C1-C3)alkylamino(C1-C6)alkyl;
• or R12 and R13, together with the nitrogen to which they are attached, form a 3-8 membered ring optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F, —Cl, —Br, —CN, —OR5, —NR6R7, —S(O)iR5, —NR11S(═O)iR5, —C(═O)OR5, —C(═O)NR12R13, —NR11C(═O)R5, —C(═S)NR12R13, —C(═O)R5, (C1-C6)alkyl, (C2-C6)alkenyl, halo(C1-C6)alkyl, (C1-C3)alkylsulfonylaminoalkyl, hydroxy(C1-C6)alkyl, cyano(C1-C6)alkyl, (C1-C3)alkylcarbonylamino(C1-C6)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy and (C1-C6)alkoxy(C1-C3)alkyl, wherein the 3-8 membered ring optionally contains 1 to 3 additional heteroatoms, which are independently selected from O, N and S, wherein when the additional heteroatom is nitrogen, the nitrogens is substituted with —H, (C1-C3)alkyl or halo(C1-C3)alkyl, and when the additional heteroatom is sulfur, the sulfurs is optionally mono or di-oxygenated;
• R14 is —H, (C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C8)cycloalkyl, cycloheteroalkyl(C1-C3)alkyl, (C3-C8)cycloalkyl(C1-C3)alkyl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, each optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F, —Br, —CN, (C1-C6)alkyl, halo(C1-C6)alkyl and (C1-C3)alkoxy;
• R15 is —H or (C1-C6)alkyl;
• R16 and R17 are each independently —H or (C1-C3)alkyl;
• R18 is —H or (C1-C3)alkyl;
• i is 0, 1 or 2;
• p is 1 or 2;
• m is 1 or 2;
• and
• n is 1 or 2.