Neuroactive steroids and their methods of use

A compound of Formula II:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• m is 0, 1, 2, or 3;
• m1 is of 0, 1, or 2;
• n is 1 or 2;
• n1 is 0, 1, 2, 3, 4 or 5;
• q is independently 0, 1, 2, or 3;
• r is independently 0, 1 or 2;
• s is independently 0, 1 or 2;
• t is independently 0, 1, 2 or 3;
• u is independently 1 or 2;
• X is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —SRA1, —N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA1)2, —SC(═O)RA2, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —NHC(═O)RA1, —NHC(═O)ORA1, —NHC(═O)SRA1, —NHC(═O)N(RA1)2, —OS(═O)2RA2, —OS(═O)2ORA1, —S S(═O)2RA2, —S—S(═O)2ORA1, —S(═O)RA2, —SO2RA2, or —S(═O)2ORA1, wherein each instance of RA1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• and each instance of RA2 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• Z is each independently selected from —CR23R24—, —NR23— or —O—;
• A is CR17 or N, wherein R17 is selected from the group consisting of a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a hydroxyl group, an amino group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, a substituted or unsubstituted alkyl group, a halogen, a hydroxyl group, a substituted or unsubstituted amino group, an oxo group, a nitro group, a cyano group, an alkenyl group, an alkynyl group, an alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group;
• A is C when is a double bond;
• R5 and one of R6a or R6b is absent when is a double bond;
• R3, R2a, R2b, R4a, R4b, R5, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R18, R19, R20a, or R20b are each independently selected from the group consisting of a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, an alkoxy group, a halogenated alkoxy group, a halogen, an amino group, a mercapto group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, —(CH2)n1R23, —(CH2)n1OR23, —(CH2)n1SR23, —(CH2)n1C(O)R23, —(CH2)n1C(O)OR23, —(CH2)n1S(O)m1R23, —(CH2)n1NR23R24, —(CH2)n1C(O)NR23R24, —(CH2)n1NR23C(O)R24 or —(CH2)n1NR23S(O)m1R24, wherein the alkyl group, the haloalkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• or any two adjacent or non-adjacent groups of R3, R2a, R2b, R4a, R4b, R5, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R18, R19, R20a, or R20b may form a cycloalkyl group, a heteroalkyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• or R15a and R15b, or R16a and R16b are joined to form an oxo (═O) group;
• or one of R15a or R15b, and one of R16a or R16b are absent so as to form a double bond;
• and
• R22, R23, R24, R25, and R26 are each independently selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a hydroxyl group, an amino group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from a deuterium atom, a substituted or unsubstituted alkyl group, a halogen, a hydroxyl group, a substituted or unsubstituted amino group, an oxo group, a nitro group, a cyano group, an alkenyl group, an alkynyl group, an alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group,
• provided that:
• when m is 0 and Z is —CH2—, either R15a or R15b is not H.

A compound of Formula III:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• m is 0, 1, 2, or 3;
• m1 is 0, 1, or 2;
• n is 1 or 2;
• n1 is 0, 1, 2, 3, 4 or 5;
• q is independently 0, 1, 2, or 3;
• r is independently 0, 1 or 2;
• s is independently 0, 1 or 2;
• t is independently 0, 1, 2 or 3;
• u is independently 1 or 2;
• X is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —SRA1, —N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA1)2, —SC(═O)RA2, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —NHC(═O)RA1, —NHC(═O)ORA1, —NHC(═O)SRA1, —NHC(═O)N(RA1)2, —OS(═O)2RA2, —OS(═O)2ORA1, —S—S(═O)2RA2, —S—S(═O)2ORA1, —S(═O)RA2, —SO2RA2, or —S(═O)2ORA1, wherein each instance of RA1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• and each instance of RA is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• Z is each independently selected from —CR23R24—, —NR23—, or —O—;
• W is each independently selected from —S(CH2)n1—,
• A is CR17 or N, wherein R17 is selected from the group consisting of a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a hydroxyl group, an amino group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, a substituted or unsubstituted alkyl group, a halogen, a hydroxyl group, a substituted or unsubstituted amino group, an oxo group, a nitro group, a cyano group, an alkenyl group, an alkynyl group, an alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group;
• A is C when is a double bond;
• R5 and one of R6a or R6b is absent when is a double bond;
• R3, R2a, R2b, R4a, R4b, R5, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R18, R19, R20a, or R20b are each independently selected from the group consisting of a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, an alkoxy group, a halogenated alkoxy group, a halogen, an amino group, a mercapto group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, —(CH2)n1R23, —(CH2)n1OR23, —(CH2)n1SR23, —(CH2)n1C(O)R23, —(CH2)n1C(O)OR23, —(CH2)n1S(O)m1R23, —(CH2)n1NR23R24, —(CH2)n1C(O)NR23R24, —(CH2)n1NR23C(O)R24, or —(CH2)n1NR23S(O)m1R24, wherein the alkyl group, the haloalkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• or any two adjacent or non-adjacent groups of R3, R2a, R2b, R4a, R4b, R5, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R18, R19, R20a, or R20b may form a cycloalkyl group, a heteroalkyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• and
• R22, R23, R24, R25, and R26 are each independently selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a hydroxyl group, an amino group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from a deuterium atom, a substituted or unsubstituted alkyl group, a halogen, a hydroxyl group, a substituted or unsubstituted amino group, an oxo group, a nitro group, a cyano group, an alkenyl group, an alkynyl group, an alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group;
• provided that:
• when m is 0;
• Z is —CH2—;
• W is
• n1 is 0;
• and
• either R15a or R15b is not H.

A compound of Formula IV-A or IV-B:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• m is 0, 1, 2, or 3;
• m1 is of 0, 1, or 2;
• n is 1 or 2;
• n1 is 0, 1, 2, 3, 4 or 5;
• p is 0, 1, 2, 3 or 4;
• q is independently 0, 1, 2, or 3;
• r is independently 0, 1 or 2;
• s is independently 0, 1 or 2;
• t is independently 0, 1, 2 or 3;
• u is independently 1 or 2;
• X is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —SRA1, —N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA1)2, —SC(═O)RA2, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —NHC(═O)RA1, —NHC(═O)ORA1, —NHC(═O)SRA1, —NHC(═O)N(RA1)2, —OS(═O)2RA2, —OS(═O)2ORA1, —S—S(═O)2RA2, —S—S(═O)2ORA1, —S(═O)RA2, —SO2RA2, or —S(═O)2ORA1, wherein each instance of RA1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• and each instance of RA2 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• Z is each independently selected from —CR23R24—, —NR23— or —O—;
• W is each independently selected from —S(CH2)n1—,
• Y is —C(R23)2— or —O—;
• RD is each independently selected from the group consisting of a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, an alkoxy group, a halogenated alkoxy group, a halogen, an amino group, a mercapto group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, —(CH2)n1R23, —(CH2)n1OR23, —(CH2)n1SR23, —(CH2)n1C(O)R23, —(CH2)n1C(O)OR23, —(CH2)n1S(O)m1R23, —(CH2)n1S(O)(NR23)R24, —(CH2)n1NR23R24, —(CH2)n1C(O)NR23R24, —(CH2)n1NR23C(O)R24 or —(CH2)n1NR23S(O)m1R24, wherein the alkyl group, the haloalkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, a heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• R5 and one of R6a or R6b is absent when is a double bond;
• R3, R2a, R2b, R4a, R4b, R5, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R18, R19, R20a, or R20b are each independently selected from the group consisting of a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, an alkoxy group, a halogenated alkoxy group, a halogen, an amino group, a mercapto group, a nitro group, a hydroxyl group, a cyano group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, —(CH2)n1R23, —(CH2)n1OR23, —(CH2)n1SR23, —(CH2)n1C(O)R23, —(CH2)n1C(O)OR23, —(CH2)n1S(O)m1R23, —(CH2)n1NR23R24, —(CH2)n1C(O)NR23R24, —(CH2)n1NR23C(O)R24 or —(CH2)n1NR23S(O)m1R24, wherein the alkyl group, the haloalkyl group, the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• or any two adjacent or non-adjacent groups of R3, R2a, R2b, R4a, R4b, R5, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R18, R19, R20a, or R20b may form a cycloalkyl group, a heteroalkyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclic group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from the group consisting of a deuterium atom, an alkyl group, a halogen, an amino group, a mercapto group, an oxo group, a nitro group, a cyano group, a hydroxyl group, an alkenyl group, an alkynyl group, an alkoxy group, a halogenated alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, —(CH2)n1R25, —(CH2)n1OR25, —(CH2)n1SR25, —(CH2)n1C(O)R25, —(CH2)n1C(O)OR25, —(CH2)n1S(O)m1R25, —(CH2)n1NR25R26, —(CH2)n1C(O)NR25R26, —(CH2)n1C(O)NHR25, —(CH2)n1NR25C(O)R26, and —(CH2)n1NR25S(O)m1R26;
• or R15a and R15b, or R16a and R16b are joined to form an oxo (═O) group;
• or one of R15a or R15b, and one of R16a or R16b are absent so as to form a double bond;
• and
• R22, R23, R24, R25, and R26 are each independently selected from a hydrogen atom, a deuterium atom, an alkyl group, a deuterated alkyl group, a hydroxyl group, an amino group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are optionally further substituted by one or more of the substituent groups selected from a deuterium atom, a substituted or unsubstituted alkyl group, a halogen, a hydroxyl group, a substituted or unsubstituted amino group, an oxo group, a nitro group, a cyano group, an alkenyl group, an alkynyl group, an alkoxy group, a hydroxyalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group.

A compound of Formula V:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• m is 0, 1, 2, or 3;
• n is 1 or 2;
• q is independently 0, 1, 2, or 3;
• r is independently 0, 1 or 2;
• s is independently 0, 1 or 2;
• t is independently 0, 1, 2 or 3;
• u is independently 1 or 2;
• X is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —SRA1, —N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)SRA1, —OC(═O)N(RA1)2, —SC(═O)RA2, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —NHC(═O)RA1, —NHC(═O)ORA1, —NHC(═O)SRA1, —NHC(═O)N(RA1)2, —OS(═O)2RA2, —OS(═O)2ORA1, —S—S(═O)2RA2, —S—S(═O)2ORA1, —S(═O)RA2, —SO2RA2, or —S(═O)2ORA1 wherein each instance of RA1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a sulfur protecting group when attached to a sulfur atom, or a nitrogen protecting group when attached to a nitrogen atom;
• and each instance of RA2 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R5 is hydrogen or methyl, or when is a double bond, R5 and one of R6a or R6b is absent;
• R19 is hydrogen or substituted or unsubstituted alkyl;
• R18 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
• R3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each of R6a and R6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
• or R6a and R6b are joined to form an oxo (═O) group;
• and
• each of R2a, R2b, R4a, R4b, R11a, R11b, R16a, or R16b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkynyl, —ORD1, —OC(═O)RD1, —NH2, —N(RD1)2, or —NRD1C(═O)RD1, wherein each instance of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two RD1 groups are joined to form an substituted or unsubstituted heterocyclic ring;
• or any one of R2a and R2b, or R4a and R4b, or R11a and R11b, or R16a and R16b are joined to form an oxo (═O) group;
• provided that:
• q, s, r, u, and t are not simultaneously 1.

A compound of Formula VI:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• m is 0, 1, 2, 3, or 4;
• n is 0, 1, 2, 3, or 4;
• provided that when m is 0, n is not 0 or 1;
• X is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each of R1a, R1b, R2a, R2b, R4a, R4b, R7a, R7b, R11a, R11b, R12a, R12b, R15a, R15b, R16a, and R16b is independently hydrogen, halogen, cyano, —NO2, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —N(RA1)2, —SRA1, —C(═O)RA1, —C(═O)ORA1, —C(═O)SRA1, —C(═O)N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, —OC(═O)N(RA1)2, —OC(═O)SRA1, —OS(═O)2RA1, —OS(═O)2ORA1, —OS(═O)2N(RA1)2, —N(RA1)C(═O)RA1, —N(RA1)C(═NRA1)RA1, —N(RA1)C(═O)ORA1, —N(RA1)C(═O)N(RA1)2, —N(RA1)C(═NRA1) N(RA1)2, —N(RA1)S(═O)2RA1, —N(RA1)S(═O)2ORA1, —N(RA1)S(═O)2N(RA1)2, —SC(═O)RA1, —SC(═O)ORA1, —SC(═O)SRA1, —SC(═O)N(RA1)2, —S(═O)2RA1, —S(═O)2ORA1, or —S(═O)2N(RA1)2, wherein each instance of RA1 is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, or substituted or unsubstituted 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 a sulfur protecting group when attached to sulfur;
• or R11a and R11b are joined to form an oxo (═O) group;
• or R12a and R12b are joined to form an oxo (═O) group;
• or R15a and R15b are joined to form an oxo (═O) group;
• or R16a and R16b are joined to form an oxo (═O) group;
• or R4a and R4b are joined to form an oxo (═O) group;
• or R7a and R7b are joined to form an oxo (═O) group;
• or R2a and R2b are joined to form an oxo (═O) group;
• or R1a and R1b are joined to form an oxo (═O) group;
• R3 is hydrogen, substituted or unsubstituted alkyl;
• R5 is hydrogen or methyl;
• each of R6a and R6b is independently hydrogen, halogen, cyano, —NO2, —OH, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
• or R6a and R6b are joined to form an oxo (═O) group;
• R18 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;
• R19 is hydrogen or substituted or unsubstituted alkyl;
• and R20a, R20b, R23a, or R23b are each independently selected from the group consisting of a hydrogen atom, an alkyl group, a halogenated alkyl group, an alkoxy group, a halogenated alkoxy group.