Prodrugs of Neurosteroid Analogs and Uses Thereof

A compound of Formula I or a pharmaceutically acceptable salt, hydrate, or hydrated salt thereof,

• wherein the dotted lines, on each occurrence, independently represent a pair of shared electrons or are void;
• wherein n is 0 or 1;
• wherein:
• (1) X is OH or NR1R2,
• Y is O or NR3,
• RA, RB, RC, RD, RE, and RF are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, carboxyl, carbonate, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, acyl, sulfinyl, sulfonyl, sulfonate, sulfonamide, amide, optionally Si-substituted silyl, ester, thioester, carbonate ester, and carbamate, and
• R1, R2, and R3 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, with the proviso that at least one of R1 and R2 is hydrogen;
• (2) X is NR1R2,
• Y is O or NR3,
• R1 joins RC or RE to form a 4-7 membered, optionally substituted heterocycle,
• R2 is hydrogen,
• RA, RB, RC, RD, RE, and RF, on each occurrence when not joined by R1 to form the heterocycle, are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, carboxyl, carbonate, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, acyl, sulfinyl, sulfonyl, sulfonate, sulfonamide, amide, optionally Si-substituted silyl, ester, thioester, carbonate ester, and carbamate, and
• R3 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
• or
• (3) X is OH or NR1R2,
• Y is NR3,
• R3 joins RA to form a 4-7 membered, optionally substituted heterocycle,
• RB, RC, RD, RE, and RF are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, carboxyl, carbonate, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, acyl, sulfinyl, sulfonyl, sulfonate, sulfonamide, amide, optionally Si-substituted silyl, ester, thioester, carbonate ester, and carbamate, and
• R1 and R2 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, with the proviso that at least one of R1 and R2 is hydrogen;
• wherein Z is ═O, —OR4, ═N(OR5), or
• wherein T, U, V, and W are independently O or S;
• wherein R4 and R5 are independently selected from the group consisting of hydrogen, acyl, ester, thioester, and amide;
• wherein R6 and R7 are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, carboxyl, carbonate, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, acyl, sulfinyl, sulfonyl, sulfonate, sulfonamide, amide, optionally Si-substituted silyl, ester, thioester, carbonate ester, and carbamate;
• wherein R8 and R9 are independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl;
• and
• wherein Formula I is not: