19-nor neuroactive steroids and methods of use thereof

A method for treating a CNS-related disorder related to GABA-modulation in a human subject in need thereof, comprising administering to the human subject a therapeutically effective amount of

• (a) a compound of Formula (III)
• or a pharmaceutically acceptable salt thereof, wherein:
• represents a single or double bond;
• R1 is substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, or substituted or unsubstituted C3-6 carbocyclyl;
• R2 is hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, or substituted or unsubstituted C3-6 carbocyclyl, or —ORA2, wherein RA2 is hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, or substituted or unsubstituted C3-6 carbocyclyl;
• R3a is hydrogen or —ORA3, wherein RA3 is hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, or substituted or unsubstituted C3-6 carbocyclyl, and R3b is hydrogen;
• or R3a and R3b are joined to form an oxo (═O) group;
• each instance of R4a and R4b is independently hydrogen, substituted or unsubstituted C1-6 alkyl, alkoxy, halogen, or —ORA4, wherein RA4 is hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, or substituted or unsubstituted C3-6 carbocyclyl, provided if the between C5 and C6 is a single bond, then the hydrogen at C5 is in the alpha or beta configuration;
• and provided if the between C5 and C6 is a double bond, R4b is absent;
• each instance of R5 is independently halogen, —NO2, —CN, —ORGA, —N(RGA)2, —C(═O)RGA, —C(═O)ORGA, —OC(═O)RGA, —OC(═O)ORGA, —C(═O)N(RGA)2, —N(RGA)C(═O)RGA, —OC(═O)N(RGA)2, —N(RGA)C(═O)ORGA, —S(═O)2RGA, —S(═O)2ORGA, —OS(═O)2RGA, —S(═O)2N(RGA)2, or —N(RGA)S(═O)2RGA;
• substituted or unsubstituted C3-4 carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, or optionally two RGA are taken with the intervening atoms to form a substituted or unsubstituted 3- to 4-membered carbocyclic or heterocyclic ring;
• each instance of RGA is independently hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted C3-6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two RGA groups are taken with the intervening atoms to form a substituted or unsubstituted carbocyclic or heterocyclic ring;
• and
• e is 1, 2, 3, 4, or 5;
• or
• (b) a pharmaceutical composition comprising a compound of Formula (III) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.