Prodrugs of GABA analogs, compositions and uses thereof

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• n is 1;
• X is O or NR16;
• Y is O or S;
• R1 is selected from the group consisting of hydrogen, R24C(O)—, R25OC(O)—, R24C(S)—, R25OC(S)—, R25SC(O)—, R25SC(S)—, (R9O)(R10O)P(O)—, R25S—,
• m is 0 or 1;
• W is O or NR17;
• R2 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, acylamino, substituted acylamino, alkylamino, substituted alkylamino, alkylsulfinyl, substituted alkylsulfinyl, alkylsulfonyl, substituted alkylsulfonyl, alkylthio, substituted alkylthio, alkoxycarbonyl, substituted alkoxycarbonyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, aryloxy, substituted aryloxy, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, dialkylamino, substituted dialkylamino, halo, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heteroalkyloxy, substituted heteroalkyloxy, heteroaryloxy and substituted heteroaryloxy or optionally, R2 and R16 together with the atoms to which they are bonded form a C3-C10 cycloheteroalkyl or substituted C3-C10 cycloheteroalkyl ring;
• R3 and R6 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl;
• R4 and R5 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, acyl, substituted acyl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroarylalkyl and substituted heteroarylalkyl or optionally, R4 and R5 together with the carbon atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl or bridged cycloalkyl ring;
• R8 and R12 are independently selected from the group consisting of hydrogen, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl, or optionally R8 and R12 together with the carbon atoms to which they are bonded form a cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl or substituted C3-C10 cycloheteroalkyl ring;
• R11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, acyl, substituted acyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cyano, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, alkoxycarbonyl, substituted alkoxycarbonyl, cycloheteroalkyloxycarbonyl, substituted cycloheteroalkyloxycarbonyl, aryloxycarbonyl, substituted aryloxycarbonyl, heteroaryloxycarbonyl, substituted heteroaryloxycarbonyl and nitro;
• R7, R9, R10, R15, R16 and R17 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl;
• R13 and R14 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloalkoxycarbonyl, substituted cycloalkoxycarbonyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl or optionally, R13 and R14 together with the carbon atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl or substituted C3-C10 cycloheteroalkyl ring;
• R24 is selected from the group consisting of hydrogen, acyl, substituted acyl, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl;
• and
• R25 is selected from the group consisting of acyl, substituted acyl, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl;
• and
• with the provisos that:
• when R3 and R6 are both hydrogen, then R4 and R5 are neither both hydrogen nor both C1 to C10 alkyl;
• when X is NR16, then R1 is not hydrogen;
• when R1 is R25OC(O)—, then R25 is not R26C(O)CR13R14, wherein R26 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl;
• when X is NH, R3, R5 and R6 are each hydrogen, and R4 is cyclohexyl, then R2 is not arylalkyl,
• wherein each substituent is independently selected from —Z, —R29, —O−, ═O, —OR29, —SR29, —S−, ═S, —NR29R30, ═NR29, —CZ3, —CF3, —CN, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)2O−, —S(O)2OH, —S(O)2R29, —OS(O2)O−, —OS(O)2R29, —P(O)(O−)2, —P(O)(OR29)(O−), —OP(O)(OR29)(OR30), —C(O)R29, —C(S)R29, —C(O)OR29, —C(O)NR29R30, —C(O)O−, —C(S)OR29, —NR31C(O)NR29R30, —NR31C(S)NR29R30, —NR31C(NR29)R29R30, —C(NR29)NR29R30, where each Z is independently a halogen;
• each R29 and R30 are independently hydrogen, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, —NR31R32, —C(O)R31 or —S(O)2R31 or optionally R29 and R30 together with the atom to which they are both bonded form a C3-C10 cycloheteroalkyl ring or substituted C3-C10 cycloheteroalkyl ring;
• and R31 and R32 are independently hydrogen, alkyl, substituted alkyl, C6-C20 aryl, substituted C6-C20 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, C3-C10 cycloheteroalkyl, substituted C3-C10 cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, C5-20heteroaryl, substituted C5-20heteroaryl, heteroarylalkyl and substituted heteroarylalkyl,
• wherein each C5-20 heteroaryl is derived from a member of the group selected from thiophene, pyrrole, benzothiophene, benzofuran, indole, pyridine, quinoline, imidazole, oxazole and pyrazine;
• and
• wherein each C3-C10 cycloheteroalkyl is independently derived from a member of the group consisting of epoxides, imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidine, and quinuclidine.