Compounds which inhibit beta-secretase activity and methods of use thereof

A compound represented by the following structural formula:

• (Y-ZkA1
• wherein:
• Y is a carrier molecule;
• Z is a bond, —OP(O)−2O—, —C(O)OR33—, —C(O)NHR33—, —S(O)2NHR33—, substituted or unsubstituted aliphatic, or substituted or unsubstituted heteroalkylene;
• R33 is a bond or an alkylene;
• k is 0 or an integer from 1 to 5;
• and
• A1 is a moiety represented by the following structural formula:
• or optical isomers, diastereomers, or pharmaceutically acceptable salts of A1 wherein:
• X is —C(O)—, —S(O)n—, or —NH—C(O)—;
• n is 1 or 2;
• m is 0, 1, 2, 3, 4, or 5;
• j is 0 or 1;
• P1 is a substituted or unsubstituted aliphatic, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted alkylsulfanylalkyl;
• P1′, and P2′ are each, independently, a substituted or unsubstituted aliphatic, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted heterocycle, or substituted or unsubstituted heterocycloalkyl;
• R1 is a substituted or unsubstituted aliphatic, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocyclooxy, substituted or unsubstituted heterocycloalkoxy, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroaralkyl, substituted or unsubstituted heteroaralkoxy, or —NR5R6;
• or R1, together with X, is a peptide or Y-Z-;
• R4 is H, or substituted or unsubstituted aliphatic;
• R2 and R3 are each, independently, H, a substituted or unsubstituted aliphatic, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heteroaralkyl;
• or one of R2 and R3, together with the nitrogen to which it is attached, is a peptide or a Y-Z-;
• or R2 and R3, together with the nitrogen to which they are attached, form a substituted or unsubstituted heterocycle or substituted or unsubstituted heteroaryl;
• R5 and R6 are each, independently, H, substituted or unsubstituted aliphatic, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroaralkyl;
• R34 is H, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;
• and
• P2 is —C(R35)(R36)—S(O)t-L-R12, wherein
• t is 0, 1, or 2,
• L is a bond, —C(O)—, -L1-O—, —C(O)NH—, —NH—, —C(O)O—, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene, wherein L1 is a bond, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene, and
• R12 is hydrogen, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• and
• R35 and R36 are each, independently hydrogen, halogen, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,
• wherein if t is 1 or 2, then L is a bond, -L1-O—, —NH—, substituted or unsubstituted alkylene, or substituted or unsubstituted heteroalkylene.