Pak inhibitors for the treatment of fragile x syndrome

A compound having the structure of Formula IV, or a pharmaceutically acceptable salt or N-oxide thereof:

• wherein:
• R1 is H, or substituted or unsubstituted alkyl;
• R2 is alkyl substituted with —OH, —OMe, —SH, —SMe, or halogen;
• R3 is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted amino, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl;
• R4 is substituted or unsubstituted 6-membered monocyclic heteroaryl ring attached to the phenyl ring via a carbon atom of R4, substituted or unsubstituted bicyclic heteroaryl ring attached to the phenyl ring via a carbon atom of R4, or substituted or unsubstituted heterocycloalkyl attached to the phenyl ring via a carbon atom of R4;
• each R5 is independently halogen, —CN, —NO2, —OH, —OCF3, —OCH2F, —OCF2H, —CF3, —SR8, —NR10S(═O)2R9, —S(═O)2N(R10)2, —S(═O)R9, —S(═O)2R9, —C(═O)R9, —OC(═O)R9, —CO2R10, —N(R10)2, —C(═O)N(R10)2, —NR10C(═O)R10, —NR10C(═O)OR10, —NR10C(═O)N(R10)2, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted heteroalkyl, or substituted or unsubstituted heterocycloalkyl;
• or substituted or unsubstituted cycloalkyl;
• or substituted or unsubstituted aryl;
• or substituted or unsubstituted heteroaryl;
• each R8 is independently H or R9;
• each R9 is independently substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each R10 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• or two R10, together with the atoms to which they are attached form a heterocycle;
• and
• s is 0-4.

A method for treating Fragile X syndrome in an individual in need thereof, comprising administering to the subject a therapeutically effective amount of a compound having the structure of Formula I, Formula II, or Formula III, or a pharmaceutically acceptable salt or N-oxide thereof:

• wherein:
• ring T is an aryl or heteroaryl ring;
• R1 is H, or substituted or unsubstituted alkyl;
• R2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aralkoxy, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkylalkyl, spiro-cycloakyl-heterocycloalkyl, -alkylene-S(═O)R9, -alkylene-S(═O)2R9, —S(═O)2R9;
• R3 is H, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted amino, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted heterocycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted heteroarylalkyl;
• R4 is substituted or unsubstituted heteroaryl attached to ring T or the phenyl ring via a carbon atom of R4, or substituted or unsubstituted heterocycloalkyl attached to ring T or the phenyl ring via a carbon atom of R4;
• each R5 is independently halogen, —CN, —NO2, —OH, —OCF3, —OCH2F, —OCF2H, —CF3, —NR10S(═O)2R9, —S(═O)2N(R10)2, —S(═O)R9, —S(═O)2R9, —C(═O)R9, —OC(═O)R9, —CO2R10, —N(R10)2, —C(═O)N(R10)2, —NR10C(═O)R10, —NR10C(═O)OR10, —NR10C(═O)N(R10)2, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted heteroalkyl, or substituted or unsubstituted heterocycloalkyl;
• or substituted or unsubstituted cycloalkyl;
• or substituted or unsubstituted aryl;
• or substituted or unsubstituted heteroaryl;
• each R8 is independently H or R9;
• each R9 is independently substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each R10 is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• or two R10, together with the atoms to which they are attached form a heterocycle;
• and
• s is 0-4.