Compositions and methods for the treatment of CNS disorders

Abstract

To provide compositions and methods for treating CNS disorders.SOLUTION: Provided herein are compounds of Formula (II-I) in the figure and pharmaceutically acceptable salts thereof. In Formula (II-I), : t is 1, 2 or 3; n is 0, 1 or 2; R19 is substituted or unsubstituted C2-C6 alkyl, substituted or unsubstituted C2-C6 alkenyl, or substituted or unsubstituted C2-C6 alkynyl.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Application No. 62 / 734,718 (filed September 21, 2018), U.S. Application No. 62 / 722,781 (filed August 24, 2018), U.S. Application No. 62 / 620,095 (filed January 22, 2018), U.S. Application No. 62 / 611,983 (filed December 29, 2017), and U.S. Application No. 62 / 610,069 (filed December 22, 2017), the contents of each of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Background of the Invention Brain excitability, defined as the level of alertness of an animal on a continuum ranging from coma to seizures, is controlled by various neurotransmitters. Generally, neurotransmitters are involved in controlling the conductance of ions across the neuronal membrane. At rest, the neuronal membrane has an electrical potential (or membrane voltage) of approximately -70 mV, with the interior of the cell being negative relative to the exterior. The electrical potential (voltage) is determined by the conductance of ions (K) across the neuronal semipermeable membrane. + , Na + , Cl - Neurotransmitters are stored in presynaptic vesicles and are released under the influence of a neuronal action potential. When released into the synaptic cleft, a change in potential occurs from -70 mV to -50 mV. This action is due to the Na + It is mediated by postsynaptic nicotinic receptors stimulated by acetylcholine, which increases membrane permeability to ions. The reduced membrane potential stimulates neuronal excitability in the form of postsynaptic action potentials.

[0003] In the case of the GABA receptor complex (GRC), its effects on brain excitability are mediated by the neurotransmitter gamma-aminobutyric acid (GABA). Because up to 40% of neurons in the brain utilize GABA as a neurotransmitter, GABA exerts a profound influence on global brain excitability. GABA controls the excitability of individual neurons by regulating chloride ion conductance across neuronal membranes. By interacting with recognition sites on GRCs, GABA promotes the flow of chloride ions into the cell down the GRC's electrochemical gradient. Elevated intracellular levels of this anion cause hyperpolarization of the transmembrane potential, reducing the neuron's sensitivity to excitatory inputs (i.e., reducing neuronal excitability). In other words, the higher the chloride ion concentration within neurons, the lower the brain's excitability and arousal levels.

[0004] The GRC has been well documented to be involved in mediating anxiety, seizure activity, and sedation. Thus, GABA and drugs that act like or potentiate the actions of GABA (e.g., therapeutically useful barbiturates and benzodiazepines (BZs), e.g., Valium®) exert their therapeutically useful effects by interacting with specific regulatory sites on the GRC. Accumulating evidence now suggests that the GRC contains distinct sites for neuroactive steroids in addition to the benzodiazepine and barbiturate binding sites. See, e.g., Lan, NC et al., Neurochem. Res. (1991) 16:347-356.

[0005] Neuroactive steroids can be endogenously produced. The most potent endogenous neuroactive steroids are 3α-hydroxy-5-reduced pregnan-20-one and 3α-21-dihydroxy-5-reduced pregnan-20-one (metabolites of the hormonal steroids progesterone and deoxycorticosterone, respectively). The ability of these steroid metabolites to change brain excitability was recognized in 1986 (Majewska, MD et al., Science 232:1004-1007 (1986); Harrison, NL et al., J Pharmacol. Exp. Ther. 241:346-353 (1987)). There is a need for new and improved compounds that act as modulators of brain excitability and as agents for the prevention and treatment of CNS-related diseases. The compounds, compositions and methods described herein are directed to this end. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Lan, NC et al., Neurochem. Res. (1991) 16:347-356 [Non-patent document 2] Majewska, MD et al., Science 232:1004-1007(1986) [Non-patent document 3] Harrison, NL et al., J Pharmacol. Exp. Ther. 241:346-353 (1987) Summary of the Invention [Means for solving the problem]

[0007] For example, provided herein are compounds designed to act as GABA modulators. In some embodiments, it is contemplated that such compounds are useful as therapeutic agents for treating CNS-related disorders.

[0008] As used herein, compounds of formula (IX): [ka]

[0009] or a pharmaceutically acceptable salt thereof. Also provided herein is a compound of formula (II): [ka]

[0010] or a pharmaceutically acceptable salt thereof.

[0011] In some embodiments, the present specification provides a compound of formula (II-I): [ka] or a pharmaceutically acceptable salt thereof.

[0012] In some embodiments, the compound of formula (II-I) has formula (II-Ia): [ka] or a pharmaceutically acceptable salt thereof.

[0013] In some embodiments, the compound of formula (II-I) has the formula (II-Ib): [ka] or a pharmaceutically acceptable salt thereof.

[0014] In some embodiments, the compound of formula (II-I) has the formula [ka] or a pharmaceutically acceptable salt thereof.

[0015] In some embodiments, the compound of formula (II-I) has the formula [ka] or a pharmaceutically acceptable salt thereof.

[0016] In some embodiments, the compound of formula (II-I) has the formula [ka] or a pharmaceutically acceptable salt thereof.

[0017] In some embodiments, the compound of formula (II-I) has the formula [ka] or a pharmaceutically acceptable salt thereof.

[0018] In some embodiments, the compound of formula (II-I) has the formula [ka] or a pharmaceutically acceptable salt thereof.

[0019] In some embodiments, the compound of formula (II-I) has the formula [ka] or a pharmaceutically acceptable salt thereof.

[0020] In some embodiments, the present specification provides a compound of formula (III-I): [ka] or a pharmaceutically acceptable salt thereof.

[0021] In some embodiments, the present disclosure provides compounds of formula (III-II): [ka] or a pharmaceutically acceptable salt thereof.

[0022] In some embodiments, the compound of formula (III-I) or (III-II) is a compound of formula (II I-Ia) [ka] or a pharmaceutically acceptable salt thereof.

[0023] In some embodiments, the compound of formula (III-I) or (III-II) is a compound of formula (II I-Ib) [ka] or a pharmaceutically acceptable salt thereof.

[0024] In some embodiments, the compound of formula (III-I) or (III-II) is a compound of formula (II No) [ka] or a pharmaceutically acceptable salt thereof.

[0025] In some embodiments, the compound of formula (III-I) or (III-II) is a compound of formula (II I-Ig) [ka] or a pharmaceutically acceptable salt thereof.

[0026] In some embodiments, the compound of formula (III-I) or (III-II) has the formula (III-Ih): [ka] or a pharmaceutically acceptable salt thereof.

[0027] In some embodiments, the compound of formula (III-I) or (III-II) is a compound of formula (II I-Ii), [ka] or a pharmaceutically acceptable salt thereof.

[0028] In some embodiments, the pharmaceutical composition comprises a compound described herein or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0029] In some embodiments, a method for treating a CNS-related disorder in a subject in need thereof comprises administering to the subject an effective amount of a compound described herein or a pharmaceutically acceptable salt thereof. In some embodiments, the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a memory and / or cognition disorder, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. In some embodiments, the CNS-related disorder is depression. In some embodiments, the CNS-related disorder is postpartum depression. In some embodiments, the CNS-related disorder is major depressive disorder. In some embodiments, the major depressive disorder is moderate major depressive disorder. In some embodiments, the major depressive disorder is severe major depressive disorder.

[0030] In some embodiments, the compound is selected from the group consisting of the compounds identified in Table I-1, Table II-1, or Table III-1 herein.

[0031] In one aspect, provided herein are pharmaceutically acceptable salts of the compounds described herein (e.g., compounds of formula (IX, II, II-I, III-I, or III-II)).

[0032] In one aspect, provided herein is a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In certain embodiments, the compound of the invention is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the compound of the invention is provided in a therapeutically effective amount. In certain embodiments, the compound of the invention is provided in a prophylactically effective amount.

[0033] The compounds of the invention as described herein may, in certain embodiments, be used to treat, for example, GABA A These compounds act as GABA modulators, affecting the GABA receptor in either a positive or negative manner. A They are predicted to have central nervous system (CNS) activity as regulators of CNS excitability as mediated by their ability to modulate receptors. Thus, in another aspect, a method of treating a CNS-related disorder in a subject in need thereof is provided, comprising administering to the subject an effective amount of a compound of the present invention. In certain embodiments, the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a memory and / or cognitive disorder, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. In certain embodiments, the CNS-related disorder is depression. In certain embodiments, the CNS-related disorder is postpartum depression. In certain embodiments, the CNS-related disorder is major depressive disorder. In certain embodiments, the major depressive disorder is moderate major depressive disorder. In certain embodiments, the major depressive disorder is severe major depressive disorder. In certain embodiments, the compound is administered orally, subcutaneously, intravenously, or intramuscularly. In certain embodiments, the compound is administered orally. In certain embodiments, the compound is administered chronically. In certain embodiments, the compound is administered continuously, for example, by continuous intravenous infusion. In an embodiment of the present invention, for example, the following items are provided: (Item 1) Formula (IX): [ka] or a pharmaceutically acceptable salt thereof, In formula (IX), p is 0, 1, or 2; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 1is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -SR X1 , -N(R X1 )2, -OC(=O)R X1 , -OC(=O)OR X1 , -OC(=O)SR X1 , -OC(=O)N(R X1 )2, -SC(=O)R X2 , -SC(=O)OR X1 , -SC(=O)SR X1 , -SC(=O)N(R X1 )2, -NHC(=O)R X1 , -NHC(=O)OR X1 , -NHC(=O)SR X1 , -NHC(=O)N(R X1 )2, -OS(=O)2R X2 , -OS(=O)2OR X1 , -SS(=O)2R X2 , -SS(=O)2OR X1 , -S(=O)R X2 , -SO2R X2 , or -S(=O)2OR X1 where R X1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, or two R X1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R X2 each occurrence 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; R 3a is a substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 is a carbocyclyl; R 2a is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, or -OR A2 where R A2 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 is a carbocyclyl; R 11a is hydrogen or -OR A3 where R A3 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 carbocyclyl, and R 11b is hydrogen; or R 11a and R 11b together to form an oxo (=O) group; R 6a and R 6b Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 or a pharmaceutically acceptable salt thereof. (Item 2) R 19 is hydrogen. (Item 3) R 19 is methyl. (Item 4) R 1 is substituted or unsubstituted alkyl. (Item 5) R 1 is a substituted or unsubstituted heteroaryl. (Item 6) R 1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl contains at least one nitrogen atom. (Item 7) R 1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is bicyclic. (Item 8) Formula (II): [ka] or a pharmaceutically acceptable salt thereof, In formula (II), R 3a , R 2a , R 6a , R 6b , R 11a , R 11b is as defined in item 1; R m , R n , and R x Each occurrence of independently represents hydrogen, halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA)C(=O)OR GA , -N(R GA )C(=O)N(R GA )2, -SR GA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl (e.g., haloalkyl), substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 carbocyclyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA A compound, or a pharmaceutically acceptable salt thereof, wherein the groups, together with intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring. (Item 9) R 3a optionally substituted with alkoxy or 1 to 2 halo groups (e.g., fluoro); 1~6 alkyl, and R m , R n , and R x At least one of is a halogen (e.g., -F, -Cl, -Br), -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA, -SR GA , -S(O)R GA , e.g., -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, substituted or unsubstituted C 1~6 alkyl (e.g., -CH3, -CH2CH3, haloalkyl, e.g., -CF3), where R GA is a substituted or unsubstituted C 1~2 9. The compound according to any one of items 1 to 8, wherein R is alkyl. (Item 10) Formula (IIA): [ka] 10. The compound according to any one of items 1 to 9, selected from the compounds: (Item 11) Formula (IIB): [ka] 10. The compound according to any one of items 1 to 9, selected from the compounds: (Item 12) R 3a But unsubstituted C 1~6 12. The compound according to any one of items 1 to 11, wherein R is alkyl. (Item 13) R 3a C optionally substituted with alkoxy 1~6 13. The compound according to any one of items 1 to 12, wherein R is alkyl. (Item 14) R 3a optionally substituted with one or two halo (e.g., fluoro) 1~6 14. The compound according to any one of items 1 to 13, wherein R is alkyl. (Item 15) R 3a15. The compound according to any one of items 1 to 14, wherein is -CH3, -CH2CH3, -CH2F, -CHF2, -CH2OCH2CH3, or -CH2OCH3. (Item 16) R 3a 16. The compound according to any one of items 1 to 15, wherein is —CH 3 . (Item 17) R 2a 17. The compound according to any one of items 1 to 16, wherein is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. (Item 18) R 2a 18. The compound according to any one of items 1 to 17, wherein is —CH 3 or —OCH 3 . (Item 19) R 2a 19. The compound according to any one of items 1 to 18, wherein is —OCH 3 . (Item 20) R 2a 20. The compound according to any one of items 1 to 19, wherein is hydrogen. (Item 21) R 11a and R 11b and (b) are hydrogen. (Item 22) R m , R n , and R x 22. The compound according to any one of items 1 to 21, wherein at least one of is hydrogen. (Item 23) R m , R n , and R x 23. The compound according to any one of items 1 to 22, wherein at least two of are hydrogen. (Item 24) R m , R n , and R x 24. The compound according to any one of items 1 to 23, wherein all of are hydrogen. (Item 25) R m , R n , and R x At least one of the following is substituted or unsubstituted C 1~2 Alkyl (e.g., -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, halogen, -SR GA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , or -S(=O)2N(R GA )2, where R GA is a substituted or unsubstituted C 1~2 25. The compound according to any one of items 1 to 24, wherein R is alkyl. (Item 26) R m , R n , and R x 26. The compound according to any one of items 1 to 25, wherein at least one of is —CN. (Item 27) R m , R n , and R x At least one of the following is -SR GA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , or -S(=O)2N(R GA )2, where R GA is substituted or unsubstituted C 1~2 27. The compound according to any one of items 1 to 26, wherein R is alkyl. (Item 28) R m , R n , and R x At least one of the following is -S(=O)2R GA 28. The compound according to any one of items 1 to 27, wherein (Item 29) R GA 29. The compound according to any one of items 1 to 28, wherein is —CH 3 . (Item 30) R mand R x 30. The compound according to any one of items 1 to 29, wherein is hydrogen. (Item 31) R n halogens (e.g., -F, -Cl, -Br), -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, substituted or unsubstituted C 1~6 alkyl (e.g., -CH3, -CH2CH3, haloalkyl, e.g., -CF3), where R GA is a substituted or unsubstituted C 1~2 31. The compound according to any one of items 1 to 30, wherein R is alkyl. (Item 32) R n But, -SR GA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , or -S(=O)2N(R GA )2, where R GA is a substituted or unsubstituted C 1-2 32. The compound according to any one of items 1 to 31, wherein R is alkyl. (Item 33) R n is a halogen (e.g., -F, -Cl, -Br), -NO2, -CN, or substituted or unsubstituted C 1~6 alkyl (e.g., -CH3, -CH2CH3, haloalkyl, e.g., -CF3), where R GA is a substituted or unsubstituted C 1~2 33. The compound according to any one of items 1 to 32, wherein R is alkyl. (Item 34) R 2a , R 11a , R 11b , R6a , and R 6b 34. The compound according to any one of items 1 to 33, wherein is hydrogen. (Item 35) R 2a , R 11a , R 11b , R 6a , R 6b , R m , R n , and R x 35. The compound according to any one of items 1 to 34, wherein at least three of are hydrogen. (Item 36) R 2a , R 11a , R 11b , R 6a , R 6b , R m , R n , and R x 36. The compound according to any one of items 1 to 35, wherein at least four of are hydrogen. (Item 37) R 2a , R 11a , R 11b , R 6a , R 6b , R m , R n , and R x 37. The compound according to any one of items 1 to 36, wherein at least five of are hydrogen. (Item 38) R n is halogen (e.g., -F, -Cl, -Br), -NO2, -CN, -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(=O)R GA , -S(=O)2R GA , substituted or unsubstituted C 1~6 alkyl (e.g., -CH3, -CH2CH3, haloalkyl, e.g., -CF3), where R GA is a substituted or unsubstituted C 1~2 38. The compound according to any one of items 1 to 37, wherein R is alkyl. (Item 39) R n But, -SRGA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , or -S(=O)2N(R GA )2, where R GA is a substituted or unsubstituted C 1-2 39. The compound according to any one of items 1 to 38, wherein R is alkyl. (Item 40) R n 40. The compound according to any one of items 1 to 39, wherein is —CN. (Item 41) R 3a is substituted or unsubstituted C 1~6 41. The compound according to any one of items 1 to 40, wherein the alkyl (e.g., haloalkyl, e.g., -CF3, -CHF2, -CH2F) or alkoxy. (Item 42) The compound is selected from the group consisting of: [ka] The compound according to item 1, selected from the group consisting of: (Item 43) A pharmaceutical composition comprising a compound according to any one of the preceding paragraphs or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. (Item 44) 44. A method for treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound, pharmaceutically acceptable salt or pharmaceutically acceptable composition according to any one of items 1 to 43. (Item 45) 45. The method of item 44, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a disorder of memory and / or cognition, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, or tinnitus. (Item 46) 45. The method of claim 44, wherein the compound is administered orally, subcutaneously, intravenously, or intramuscularly. (Item 47) 45. The method of claim 44, wherein the compound is administered chronically. (Item 48) Formula (II-I): [ka] or a pharmaceutically acceptable salt thereof, In formula (II-I), t is 1, 2, or 3; n is 0, 1, or 2; R 19 is a substituted or unsubstituted C2-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, or a substituted or unsubstituted C2-C6 alkynyl; R 5 is hydrogen or methyl, or [ka] is a double bond, R 5 does not exist; R 3 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; R 6a and R 6b each is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R 6a and R 6b together to form an oxo (=O) group; R 1is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 )2, -N(R A1 ), -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 )2, -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 )2, -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 )2, -OS(=O)2R A2 , -OS(=O)2OR A1 , -SS(=O)2R A2 , -SS(=O)2OR A1 , -S(=O)R A2 , -SO2R A2 , or -S(=O)2OR A1 where R A1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, or two R A1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R A2is 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; R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , or R 17b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 each occurrence 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, or 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 R D1 groups taken together form a substituted or unsubstituted heterocyclic ring; or R 2a and R 2b , R 4a and R 4b , R 7a and R 7b , R 11a and R 11b , and R 12a and R 12b any one of these taken together form an oxo (=O) group; R 15a , R 15b , R 16a , and R 16beach independently represents hydrogen, halogen, cyano, hydroxyl, 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, -OR A1 , -SR A1 , -N(R A1 )2, -N(R A1 ),-CN(R A1 )2, -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 )2, -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 )2,-NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 )2, -OS(=O)2R A2 , -OS(=O)2OR A1 , -SS(=O)2R A2 , -SS(=O)2OR A1 , -S(=O)R A2 , -SO2R A2 , or -S(=O)2OR A1 where R A1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, -SOR A2 , -C(O)R A2 or two R A1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; RA2 is 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; where: [ka] represents a single bond or a double bond, and when a double bond is present in ring B, R 6a or R 6b is absent, or a pharmaceutically acceptable salt thereof. (Item 49) The compound according to item 48, wherein R2a and R2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -ORD1, -OC(=O)RD1, -NH2, -N(RD1)2, or -NRD1C(=O)RD1, wherein each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 50) The compound according to item 48 or 49, wherein R2a and R2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -ORD1, -OC(=O)RD1, -NH2, or -N(RD1)2, wherein each occurrence of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 51) The compound according to any one of items 48 to 50, wherein R2a and R2b are each independently hydrogen, substituted or unsubstituted alkyl, -ORD1, -OC(=O)RD1, -NH2, -N(RD1)2, or -NRD1C(=O)RD1, wherein each occurrence of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 52) 52. The compound according to any one of items 48 to 51, wherein both R2a and R2b are hydrogen. (Item 53) 53. The compound according to any one of items 48 to 52, wherein R2a and R2b are each independently hydrogen or substituted or unsubstituted alkyl. (Item 54) 54. The compound according to any one of items 48-53, wherein each of R2a and R2b is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 55) 55. The compound according to any one of items 48 to 54, wherein R2a and R2b are -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 56) 56. The compound according to any one of items 48 to 55, wherein R4a and R4b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -ORD1, -OC(=O)RD1, -NH2, -N(RD1)2, or -NRD1C(=O)RD1, where each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 57) 57. The compound according to any one of items 48 to 56, wherein R4a and R4b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -ORD1, -OC(=O)RD1, -NH2, or -N(RD1)2, where each occurrence of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 58) The compound according to any one of items 48 to 57, wherein R4a and R4b are each independently hydrogen, substituted or unsubstituted alkyl, -ORD1, -OC(=O)RD1, -NH2, -N(RD1)2, or -NRD1C(=O)RD1, where each occurrence of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 59) 59. The compound according to any one of items 48 to 58, wherein both R4a and R4b are hydrogen. (Item 60) 59. The compound according to any one of items 48 to 59, wherein R4a and R4b are each independently hydrogen or substituted or unsubstituted alkyl. (Item 61) 61. The compound according to any one of items 48-60, wherein each of R4a and R4b is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 62) 62. The compound according to any one of items 48 to 61, wherein R4a and R4b are -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 63) 63. The compound according to any one of items 48 to 62, wherein R11a or R11b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -ORD1, -OC(=O)RD1, -NH2, -N(RD1)2, or -NRD1C(=O)RD1, where each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 64) 64. The compound according to any one of items 48 to 63, wherein R11a or R11b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -ORD1, -OC(=O)RD1, -NH2, or -N(RD1)2, where each occurrence of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 65) The compound according to any one of items 48 to 64, wherein R11a or R11b is each independently hydrogen, substituted or unsubstituted alkyl, -ORD1, -OC(=O)RD1, -NH2, -N(RD1)2, or -NRD1C(=O)RD1, where each occurrence of RD1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 66) R 11a or R 11b and (66) are hydrogen. (Item 67) R 11a or R 11bis each independently hydrogen or substituted or unsubstituted alkyl. (Item 68) R 11a or R 11b 68. The compound according to any one of items 48 to 67, wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 69) R 11a or R 11b 69. The compound according to any one of items 48 to 68, wherein is —CH 3 , —CH 2 CH 3 , —OH, —OCH 3 , or —CH(CH 3 ) 2 . (Item 70) R 11a and R 11b can be taken together to form oxo. (Item 71) R 7a or R 7b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 71. The compound according to any one of items 48-70, wherein each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 72) R 7a and R 7b and (b) are hydrogen. (Item 73) R7a and R 7b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 74) R 7a and R 7b 74. The compound according to any one of items 48 to 73, wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 75) R 7a or R 7b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 76) R 5 is a hydrogen atom cis to C19. (Item 77) R 5 is a hydrogen atom trans to C19. (Item 78) R 5 is methyl cis to C19. (Item 79) R 5 is methyl in the trans position relative to the C19 position. (Item 80) 80. The compound according to any one of items 48 to 79, wherein t is 1. (Item 81) 81. The compound according to any one of items 48 to 80, wherein t is 2. (Item 82) 82. The compound according to any one of items 48 to 81, wherein n is 1. (Item 83) 83. The compound according to any one of items 48 to 82, wherein n is 2. (Item 84) R3 84. The compound according to any one of items 48 to 83, wherein is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. (Item 85) R 3 85. The compound according to any one of items 48 to 84, wherein is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 86) R 3 86. The compound according to any one of items 48 to 85, wherein is substituted or unsubstituted alkyl. (Item 87) R 3 87. The compound according to any one of items 48 to 86, wherein is hydrogen. (Item 88) R 3 88. The compound according to any one of items 48 to 87, wherein is substituted alkyl. (Item 89) R 3 89. The compound according to any one of items 48 to 88, wherein is unsubstituted alkyl. (Item 90) R 3 89. The compound according to any one of items 48 to 89, wherein is methyl. (Item 91) R 19 The compound according to any one of items 48 to 90, wherein is ethyl. (Item 92) R 19 is a substituted C2-C6 alkyl. (Item 93) R 19 is unsubstituted C2-C6 alkyl. (Item 94) R 19 is substituted C2-C6 alkenyl. (Item 95) R19 is unsubstituted C2-C6 alkenyl. (Item 96) R 19 is a substituted C2-C6 alkynyl. (Item 97) R 19 is unsubstituted C2-C6 alkynyl. (Item 98) R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. (Item 99) R 6a and R 6b is independently hydrogen or substituted alkyl. (Item 100) R 6a and R 6b is independently hydrogen or unsubstituted alkyl. (Item 101) R 6a and R 6b and (b) are hydrogen. (Item 102) R 6a is halo or alkyl, and R 6b is hydrogen. (Item 103) R 6a and R 6b and n is 0 or 1. The compound according to any one of items 48 to 102, wherein both of are halo. (Item 104) R 6a and R 6b The compound according to any one of items 48 to 103, wherein both of are alkyl. (Item 105) R 12a and R 12b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 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, or substituted or unsubstituted heteroaryl. (Item 106) R 12a and R 12b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 106. The compound according to any one of items 48 to 105, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 107) R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1107. The compound according to any one of items 48-106, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 108) R 12a and R 12b The compound according to any one of items 48 to 107, wherein both of are hydrogen. (Item 109) R 12a and R 12b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 110) R 12a and R 12b 109. The compound according to any one of items 48 to 109, wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 111) R 12a and R 12b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 112) R 12a and R 12b The compound according to any one of items 48 to 111, wherein both of are hydrogen. (Item 113) R 12a and R 12b The compound according to any one of items 48 to 112, wherein together form oxo. (Item 114) R 12a and R 12b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 115) R 17bis fluorine, hydroxyl, methyl, or hydrogen, said hydrogen optionally being replaced by deuterium. (Item 116) R 1 is 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. (Item 117) R 1 but, [ka] and where R 20 Each occurrence of independently represents hydrogen, halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -OC(=O)R GA , -OC(=O)OR GA , -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, C 5~10substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 117. The compound according to any one of items 48 to 116, wherein e is 0, 1, 2, 3, 4, or 5; and n is 1, 2, 3, 4, or 5. (Item 118) R 1 but, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -OC(=O)R GA , -OC(=O)OR GA , -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2RGA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA ;Substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, C 5~10 substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 18. The compound according to any one of items 48 to 117, wherein e is 0, 1, 2, 3, 4, or 5; and n is 1, 2, 3, 4, or 5. (Item 119) The compound of formula (II-I) may be represented by formula (II-Ia): [ka] 49. The compound according to item 48, wherein the compound is: (Item 120) The compound of formula (II-I) is of formula (II-Ib) [ka] 49. The compound according to item 48, wherein the compound is: (Item 121) The compound of formula (II-I) is represented by the formula (II-Ic): [ka] 49. The compound according to item 48, which is a compound of formula: (Item 122) The compound of formula (II-I) is of formula (II-Ie) [ka] is a compound of In formula (II-Ie), m is 0, 1, 2, or 3; p is 0, 1, or 3; R 32 49. The compound according to item 48, or a pharmaceutically acceptable salt thereof, wherein each of is independently halogen, alkyl, hydroxyl, or cyano. (Item 123) The compound of formula (II-I) is represented by the formula (II-Ig): [ka] is a compound of In formula (II-Ig), u is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA)2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA 49. The compound according to item 48, or a pharmaceutically acceptable salt thereof, wherein the groups together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring. (Item 124) The compound of formula (II-I) is of formula (II-Iga) [ka] is a compound of In formula (II-Iga), u is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6carbocyclyl, 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 R GA the groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring; 49. The compound according to item 48 or a pharmaceutically acceptable salt thereof. (Item 125) The compound of formula (II-I) is of formula (II-Ih) [ka] is a compound of In formula (II-Ih), R 35 each is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2, or 3; 49. The compound according to item 48 or a pharmaceutically acceptable salt thereof. (Item 126) The compound of formula (II-I) is of formula (II-Ii) [ka] is a compound of In formula (II-Ii), s is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GAEach occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring; 49. The compound according to item 48 or a pharmaceutically acceptable salt thereof. (Item 127) A pharmaceutical composition comprising the compound according to any one of items 48 to 126 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. (Item 128) 127. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound according to any one of items 48 to 127, or a pharmaceutically acceptable salt thereof. (Item 129) 129. The method of item 128, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a disorder of memory and / or cognition, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. (Item 130) Item 129. The method of item 129, wherein the CNS-related disorder is depression. (Item 131) 130. The method of claim 129, wherein the CNS-related disorder is postpartum depression. (Item 132) 130. The method of item 129, wherein the CNS-related disorder is major depressive disorder. (Item 133) Item 129. The method of item 129, wherein the major depressive disorder is moderate major depressive disorder. (Item 134) Item 129. The method of item 129, wherein the major depressive disorder is severe major depressive disorder. (Item 135) Formula (III-I): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-I), n is 0, 1, or 2; R 3a is 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; R 18 is a substituted alkyl or unsubstituted C2-C6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted C2-C6 alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; R 5 is hydrogen or methyl, or [ka] is a double bond, R 5 does not exist; R 6a and R 6b each is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R 6a and R 6b together to form an oxo (=O) group; R 1is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 )2, -N(R A1 ), -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 )2, -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 )2, -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 )2, -OS(=O)2R A2 , -OS(=O)2OR A1 , -SS(=O)2R A2 , -SS(=O)2OR A1 , -S(=O)R A2 , -SO2R A2 , or -S(=O)2OR A1 where R A1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, or two R A1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R A2is 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; R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , or R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 ,-OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 each occurrence 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, or 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 R D1 groups taken together form a substituted or unsubstituted heterocyclic ring; or R 2a and R 2b , R 4a and R 4b , R 7a and R 7b , R 11a and R 11b , and R 12a and R 12b any one of these taken together form an oxo (=O) group; where: [ka] represents a single bond or a double bond, and when a double bond is present in ring B, R 6a or R 6b is absent, or a pharmaceutically acceptable salt thereof. (Item 136) Formula (III-II): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-II), Variable group R 18 ,n,R 5 , R 1 , R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , and R 16b is as defined in formula III-I of item 1; R 3a 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; R 19 is hydrogen, C1-C6 substituted alkyl, C2-C6 unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; However, n is 0 and R 1is methyl and R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , and R 16b is hydrogen, R 18 is a substituted C1-C6 alkyl, an unsubstituted C3-C6 alkyl, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkynyl, where R 18 is a substituted methyl, the methyl is not a halogen, -CN, -NO2, -SO2H, -SO3H, -OR aa , -ON(R bb )2, -N(R bb )2, -C(=O)R aa , —C(O)H, —COH, carbocyclyl, heterocyclyl, aryl, or heteroaryl, where R aa Each occurrence of independently, C 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl, and 5- to 14-membered heteroaryl, or two R aa groups taken together to form a 3- to 14-membered heterocyclyl ring or a 5- to 14-membered heteroaryl ring; R bb Each occurrence of is independently hydrogen, -OH, -OR aa , -N(R cc )2, -CN, -C(=O)R aa , -C(=O)N(R cc )2, -CO2R aa , -SO2R aa , or -C(=NR cc ) OR aaor a pharmaceutically acceptable salt thereof. (Item 137) R 3a is not trifluoromethyl. (Item 138) R 18 138. The compound according to any one of items 135 to 137, wherein is alkyl substituted with halogen, cyano, —CO2H, or phenyl. (Item 139) R 2a and R 2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 139. The compound according to any one of items 135-138, wherein each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 140) R 2a and R 2b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 139. The compound according to any one of items 135-139, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 141) R 2a and R 2b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 141. The compound according to any one of items 135-140, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 142) R 2a and R 2b and n is 0 or 1. The compound according to any one of items 135 to 141, wherein both are hydrogen. (Item 143) R 2a and R 2b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 144) R 2a and R 2b wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 145) R 2a and R 2b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 146) R 18 is a substituted or unsubstituted C2-C6 alkyl. (Item 147) R 18 is a substituted C2-C6 alkyl. (Item 148) R 18 is unsubstituted C2-C6 alkyl. (Item 149) R 18 149. The compound according to any one of items 135 to 148, wherein is substituted propyl. (Item 150) R 18 149. The compound according to any one of items 135 to 149, wherein is substituted butyl. (Item 151) R 1a or R 1b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 151. The compound according to any one of items 135-150, wherein each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 152) R 1a or R 1b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1152. The compound according to any one of items 135-151, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 153) R 1a or R 1b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 153. The compound according to any one of items 135-152, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 154) R 1a or R 1b is each independently hydrogen. (Item 155) R 1a or R 1b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 156) R 1a or R 1b wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 157) R 1a or R 1b is each independently -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 158) R 4a or R 4b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 158. The compound according to any one of items 135-157, wherein each occurrence 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, or substituted or unsubstituted heteroaryl. (Item 159) R 4a and R 4b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 159. The compound according to any one of items 135-158, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 160) R 4a and R 4b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1159. The compound according to any one of items 135 to 159, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 161) R 4a and R 4b and (b) are hydrogen. (Item 162) R 4a and R 4b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 163) R 4a and R 4b wherein each is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 164) R 4a and R 4b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 165) R 11a or R 11b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1is 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, or substituted or unsubstituted heteroaryl. (Item 166) R 11a or R 11b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 166. The compound according to any one of items 135 to 165, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 167) R 11a or R 11b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 167. The compound according to any one of items 135-166, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 168) R 11a or R 11b is each independently hydrogen. (Item 169) R 11a or R 11bis each independently hydrogen or substituted or unsubstituted alkyl. (Item 170) R 11a or R 11b wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 171) R 11a or R 11b is each independently -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 172) R 15a or R 15b is each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl. (Item 173) R 15a or R 15b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 173. The compound according to any one of items 135-172, wherein each occurrence of 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, or substituted or unsubstituted heteroaryl. (Item 174) R7a or R 7b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 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, or substituted or unsubstituted heteroaryl. (Item 175) R 7a and R 7b The compound according to any one of items 135 to 174, wherein both are hydrogen. (Item 176) R 7a and R 7b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 177) R 7a and R 7b 177. The compound according to any one of items 135-176, wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. (Item 178) R 7a or R 7b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 179) R 5 is a hydrogen atom cis to C19. (Item 180) R 5 is a hydrogen atom trans to C19. (Item 181) R 5 is methyl cis to C19. (Item 182) R 5 is methyl in the trans position relative to the C19 position. (Item 183) The compound according to any one of items 135 to 182, wherein n is 1 or n is 0. (Item 184) 184. The compound according to any one of items 135 to 183, wherein n is 2. (Item 185) R 3a is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. (Item 186) R 3a is a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl. (Item 187) R 3a is substituted or unsubstituted alkyl. (Item 188) R 3a is hydrogen. (Item 189) R 3a The compound according to any one of items 135 to 188, wherein is substituted alkyl. (Item 190) R 3aThe compound according to any one of items 135 to 189, wherein is unsubstituted alkyl. (Item 191) R 3a is methyl. (Item 192) R 3a The compound according to any one of Items 135 to 191, wherein is -CH2OMe. (Item 193) R 3a The compound according to any one of Items 135 to 192, wherein is —CH2OEt. (Item 194) R 19 The compound according to any one of items 135 to 193, wherein is ethyl. (Item 195) R 19 is hydrogen. (Item 196) R 19 The compound according to any one of items 135 to 195, wherein is substituted alkyl. (Item 197) R 19 The compound according to any one of items 135 to 196, wherein is unsubstituted alkyl. (Item 198) R 19 is a substituted C2-C6 alkyl. (Item 199) R 19 is unsubstituted C2-C6 alkyl. (Item 200) R 19 is substituted C2-C6 alkenyl. (Item 201) R 19 is unsubstituted C2-C6 alkenyl. (Item 202) R 19 is a substituted C2-C6 alkynyl. (Item 203) R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. (Item 204) R 6a and R 6b is independently hydrogen or substituted alkyl. (Item 205) R 6a and R 6b The compound according to any one of items 135 to 204, wherein both of are hydrogen. (Item 206) R 6a is halo or alkyl, and R 6b is hydrogen. (Item 207) R 6a and R 6b The compound according to any one of items 135 to 206, wherein both of are halo. (Item 208) R 6a and R 6b The compound according to any one of items 135 to 207, wherein both are alkyl. (Item 209) R 12a and R 12b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1is 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, or substituted or unsubstituted heteroaryl. (Item 210) R 12a and R 12b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 211) R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 211. The compound according to any one of items 135 to 210, wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 212) R 12a and R 12b The compound according to any one of items 135 to 211, wherein both of are hydrogen. (Item 213) R 12a and R 12bis each independently hydrogen or substituted or unsubstituted alkyl. (Item 214) R 12a and R 12b wherein each is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or -OH. (Item 215) R 12a and R 12b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 216) R 12a and R 12b and n is 0 or 1. The compound according to any one of items 135 to 215, wherein both are hydrogen. (Item 217) R 12a and R 12b The compound according to any one of items 135 to 216, wherein together form oxo. (Item 218) R 12a and R 12b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 219) R 12a and R 12b are each H. (Item 220) R 1 is 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. (Item 221) R 1 but, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 221. The compound according to any one of items 135 to 220, wherein e is 0, 1, 2, 3, 4, or 5. (Item 222) R 1 but, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA ;Substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 222. The compound according to any one of items 135 to 221, wherein e is 0, 1, 2, 3, 4, or 5. (Item 223) R 16a and R 16b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 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, or substituted or unsubstituted heteroaryl. (Item 224) R 16a and R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1wherein each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 225) R 16a and R 16b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 226) R 16a and R 16b and n is 0 or 1. The compound according to any one of items 135 to 225, wherein both are hydrogen. (Item 227) R 16a and R 16b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 228) R 16a and R 16b wherein each of is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or -OH. (Item 229) R 16a and R 16b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. (Item 230) R18 The compound according to any one of items 135 to 229, wherein is —CH(CH 3 ) 2 . (Item 231) R 18 The compound according to any one of items 135 to 230, wherein is substituted alkyl. (Item 232) 232. The compound according to item 231, wherein the alkyl is substituted with -OCH3, -CH2CN, or -OCH(CH3)2. (Item 233) R 18 is propyl, butyl, t-butyl, or isopropyl, or ethyl. (Item 234) The compound of formula (III-I) is of formula (III-Ia) [ka] 137. The compound according to item 135 or 136, which is a compound of formula (I) or a pharmaceutically acceptable salt thereof. (Item 235) The compound of formula (III-I) is of formula (III-Ib) [ka] 137. The compound according to item 135 or 136, which is a compound of formula (I) or a pharmaceutically acceptable salt thereof. (Item 236) The compound of formula (III-I) is of formula (III-Ie) [ka] is a compound of In formula (III-Ie), m is 0, 1, 2, or 3; p is 0, 1, 2 or 3; R 32137. The compound according to item 135 or 136, or a pharmaceutically acceptable salt thereof, wherein each of is independently halogen, alkyl, hydroxyl, or cyano. (Item 237) The compound of formula (III-I) is represented by the formula (III-Ig) [ka] is a compound of In formula (III-Ig), u is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA 137. The compound according to item 135 or 136, or a pharmaceutically acceptable salt thereof, wherein the groups together with intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring. (Item 238) The compound of formula (III-I) is of formula (III-Ih) [ka] is a compound of In formula (III-Ih), R 35 each is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2, or 3; 137. The compound according to item 135 or 136, or a pharmaceutically acceptable salt thereof. (Item 239) The compound of formula (III-I) is of formula (III-Ii) [ka] is a compound of In formula (III-Ii), s is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring; 137. The compound according to item 135 or 136, or a pharmaceutically acceptable salt thereof. (Item 240) A pharmaceutical composition comprising a compound according to any one of items 135 to 239 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. (Item 241) 240. A method of treating a CNS-related disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound according to any one of items 135 to 240, or a pharmaceutically acceptable salt thereof. (Item 242) 242. The method of claim 241, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a disorder of memory and / or cognition, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. (Item 243) 242. The method of claim 241, wherein the CNS-related disorder is depression. (Item 244) 242. The method of claim 241, wherein the CNS-related disorder is postpartum depression. (Item 245) 242. The method of claim 241, wherein the CNS-related disorder is major depressive disorder. (Item 246) 242. The method of claim 241, wherein the major depressive disorder is moderate major depressive disorder. (Item 247) 242. The method of claim 241, wherein the major depressive disorder is severe major depressive disorder. DETAILED DESCRIPTION OF THE INVENTION

[0034] Detailed Description of Specific Embodiments of the Invention As generally described herein, the present invention provides a method for treating GABA- ACompounds designed to act as receptor modulators are provided. In certain embodiments, such compounds are expected to be useful as therapeutic agents for treating CNS-related disorders (e.g., disorders described herein, e.g., depression, such as postpartum depression or major depressive disorder). definition chemical definition

[0035] The definitions of specific functional groups and chemical terms are explained in detail below.Chemical elements are identified according to the Periodic Table of Elements (CAS version, Handbook of Chemistry and Physics, 75th edition, inside cover), and specific functional groups are generally defined as described therein.In addition, the general rules of organic chemistry and specific functional moieties and reactivity are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd edition, Cambridge University Press, Cambridge, 1987.

[0036] Isomers (e.g., stereoisomers) can be isolated from mixtures by methods known to those skilled in the art, including chiral high-pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric synthesis. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions p. 268 (EL Eliel, ed., University of Notre Dame Press, Notre Dame, IN 1972). The present invention further includes the compounds described herein as individual isomers substantially free of other isomers, and alternatively as mixtures of various isomers.

[0037] As used herein, a pure enantiomer compound is substantially free of other enantiomers or stereoisomers of a compound (i.e., in enantiomeric excess). In other words, the "S" form of a compound is substantially free of the "R" form of the compound and is thus in enantiomeric excess of the "R" form. The terms "enantiomerically pure" or "pure enantiomer" mean that a compound contains more than 75%, more than 80%, more than 85%, more than 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than 95%, more than 96%, more than 97%, more than 98%, more than 98.5%, more than 99%, more than 99.2%, more than 99.5%, more than 99.6%, more than 99.7%, more than 99.8%, or more than 99.9% by weight of an enantiomer. In certain embodiments, the weight is based on the total weight of all enantiomers or stereoisomers of the compound.

[0038] In the compositions provided herein, enantiomerically pure compounds may be present together with other active or inactive ingredients. For example, a pharmaceutical composition containing an enantiomerically pure R-position / center / carbon compound may contain, for example, about 90% excipients and about 10% enantiomerically pure R-compounds. In certain embodiments, the enantiomerically pure R-compounds in such compositions may contain, for example, at least about 95% by weight of the R-compound and at most about 5% by weight of the S-compound, relative to the total weight of the compound. For example, a pharmaceutical composition containing an enantiomerically pure S-compound may contain, for example, about 90% excipients and about 10% of the enantiomerically pure S-compounds. In certain embodiments, the enantiomerically pure S-compounds in such compositions may contain, for example, at least about 95% by weight of the S-compound and at most about 5% by weight of the R-compound, relative to the total weight of the compound. In certain embodiments, the active ingredient may be formulated with a small amount of excipients or carriers, or may be formulated without excipients or carriers.

[0039] The term "diastereomerically pure" means that a compound is greater than 75% by weight, greater than 80% by weight, greater than 85% by weight, greater than 90% by weight, greater than 91% by weight, greater than 92% by weight, greater than 93% by weight, greater than 94% by weight, greater than 95% by weight, greater than 96% by weight, greater than 97% by weight, greater than 98% by weight, greater than 98.5% by weight, greater than 99% by weight, greater than 99.2% by weight, greater than 99.5% by weight, greater than 99.6% by weight. , greater than 99.7% by weight, greater than 99.8% by weight, or greater than 99.9% by weight It is meant to include a single diastereomer. Methods for determining diastereomeric purity and enantiomeric purity are well known in the art. Diastereomeric purity can be determined by any analytical method that can quantitatively distinguish between a compound and its diastereomer, such as high performance liquid chromatography (HPLC).

[0040] "Stereoisomers": It should also be understood that compounds that have the same molecular formula but differ in the nature or bonding sequence of their atoms or in the arrangement of their atoms in space are referred to as "isomers." Isomers that differ in the arrangement of their atoms in space are referred to as "stereoisomers." Stereoisomers that are not mirror images of each other are referred to as "diastereomers," and those that are non-superimposable mirror images of each other are referred to as "enantiomers." For example, if a compound has an asymmetric center, it is bonded to four different groups, and a set of enantiomers is possible. Enantiomers can be characterized by the absolute configuration of the asymmetric center and described by the R and S ordering rules of Cahn and Prelog, or by the way the molecule rotates the plane of polarized light and can be dextrorotatory or levorotatory (i.e., respectively). Chiral compounds are designated as (+) or (-)-isomers. Chiral compounds can exist as either individual enantiomers or as mixtures thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture."

[0041] The articles "a" and "an" may be used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an analogue" means one analogue or more than one analogue.

[0042] When a range of values ​​is listed, it is intended to encompass each value and subrange within the range. For example, "C 1~6 "Alkyl" refers to C1, C2, C3, C4, C5, C6, C 1~6 , C 1~5 , C 1~4 , C 1~3 , C 1~2 , C 2~6 , C 2~5 , C 2~4 , C 2~3 , C 3~6 , C 3~5 , C 3~4 , C 4~6 , C 4~5 , and C 5~6is intended to encompass alkyl of the formula:

[0043] The following terms are intended to have the meanings provided below and are useful in understanding the specification and the intended scope of the invention.

[0044] "Alkyl" means the radical of a straight-chain or branched saturated hydrocarbon group having 1 to 20 carbon atoms ("C 1~20 In some embodiments, an alkyl group has 1 to 12 carbon atoms ("C 1~12 In some embodiments, an alkyl group has 1 to 10 carbon atoms ("C 1~10 In some embodiments, an alkyl group has 1 to 9 carbon atoms ("C 1~9 In some embodiments, an alkyl group has 1 to 8 carbon atoms ("C 1~8 In some embodiments, an alkyl group has 1 to 7 carbon atoms ("C 1~7 In some embodiments, an alkyl group has 1 to 6 carbon atoms (also referred to herein as "lower alkyl" or "C 1~6 In some embodiments, an alkyl group has 1 to 5 carbon atoms ("C 1~5 In some embodiments, an alkyl group has 1 to 4 carbon atoms ("C 1~4 In some embodiments, an alkyl group has 1 to 3 carbon atoms ("C 1~3 In some embodiments, an alkyl group has 1 to 2 carbon atoms ("C 1~2 In some embodiments, the alkyl group has 1 carbon atom ("C alkyl"). In some embodiments, the alkyl group has 2 to 6 carbon atoms ("C 2~6 alkyl). C 1~6Examples of alkyl groups include methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), iso-butyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), and n-hexyl (C6). Further examples of alkyl groups include n-heptyl (C7), n-octyl (C8), and the like. Unless otherwise specified, each occurrence of an alkyl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted alkyl") or substituted with one or more substituents; for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkyl"). In certain embodiments, an alkyl group is an unsubstituted C 1~10 In certain embodiments, the alkyl group is a substituted C 1~10 Common abbreviations for alkyl include Me(-CH), Et(-CHCH), iPr(-CH(CH)), nPr(-CHCHCH), n-Bu(-CHCHCHCHCH), or i-Bu(-CHCH(CH)).

[0045] "Alkylene" refers to an alkyl group in which two hydrogens have been removed to produce a divalent radical, which can be substituted or unsubstituted. Unsubstituted alkylene groups include, but are not limited to, methylene (-CH-), ethylene (-CHCH-), propylene (-CHCHCH-), butylene (-CHCHCHCHCH-), pentylene (-CHCHCHCHCHCH-), and hexylene (-CHCHCHCHCHCHCH-). Exemplary substituted alkylene groups, e.g., substituted with one or more alkyl (methyl) groups, include, but are not limited to, substituted methylene (-CH(CH)-, (-C(CH)-), substituted ethylene (-CH(CH)CH-, -CHCH(CH)-, -C(CH)CH-, -CHC(CH)-), substituted propylene (-CH(CH)CHCH-, -CHCH(CH)CH-, -CHCHCH(CH)CH-, -CHCHCH(CH)-, -C(CH)CHCH-, -CHC(CH)CH-, and -CHCHC(CH)-), and the like. When a range or number of carbons is given for a particular alkylene group, it is understood that the range or number refers to the range or number of carbons in a divalent linear carbon chain. An alkylene group can be substituted or unsubstituted with one or more substituents described herein.

[0046] "Alkenyl" refers to the radical of a straight- or branched-chain hydrocarbon group having 2 to 20 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 carbon-carbon double bonds), and optionally one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 carbon-carbon triple bonds) ("C 2~20 In certain embodiments, alkenyl does not contain any triple bonds. In some embodiments, alkenyl groups have 2 to 10 carbon atoms ("C 2~10 In some embodiments, an alkenyl group has 2 to 9 carbon atoms ("C 2~9In some embodiments, an alkenyl group has 2 to 8 carbon atoms ("C 2~8 In some embodiments, an alkenyl group has 2 to 7 carbon atoms ("C 2~7 In some embodiments, an alkenyl group has 2 to 6 carbon atoms ("C 2~6 In some embodiments, an alkenyl group has 2 to 5 carbon atoms ("C 2~5 In some embodiments, an alkenyl group has 2 to 4 carbon atoms ("C 2~4 In some embodiments, an alkenyl group has 2 to 3 carbon atoms ("C 2~3 In some embodiments, an alkenyl group has two carbon atoms ("C2 alkenyl"). The one or more carbon-carbon double bonds can be internal (e.g., 2-butenyl) or terminal (e.g., 1-butenyl). C 2~4 Examples of alkenyl groups include ethenyl (C2), 1-propenyl (C3), 2-propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like. 2~6 Examples of alkenyl groups include the above-mentioned C 2~4 Alkenyl groups include pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Further examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Unless otherwise specified, each occurrence of an alkenyl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted alkenyl") or substituted with one or more substituents, e.g., 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkenyl"). In certain embodiments, an alkenyl group is an unsubstituted C 2~10 In certain embodiments, the alkenyl group is a substituted C 2~10 It is alkenyl.

[0047] "Alkynyl" refers to the radical of a straight-chain or branched-chain hydrocarbon group having 2 to 20 carbon atoms, one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 carbon-carbon triple bonds), and optionally one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 carbon-carbon double bonds) ("C 2~20 In certain embodiments, alkenyl does not contain any double bonds. In some embodiments, alkynyl groups have 2 to 10 carbon atoms ("C 2~10 In some embodiments, an alkynyl group has 2 to 9 carbon atoms ("C 2~9 In some embodiments, an alkynyl group has 2 to 8 carbon atoms ("C 2~8 In some embodiments, an alkynyl group has 2 to 7 carbon atoms ("C 2~7 In some embodiments, an alkynyl group has 2 to 6 carbon atoms ("C 2~6 In some embodiments, an alkynyl group has 2 to 5 carbon atoms ("C 2~5 In some embodiments, an alkynyl group has 2 to 4 carbon atoms ("C 2~4 In some embodiments, an alkynyl group has 2 to 3 carbon atoms ("C 2~3 In some embodiments, an alkynyl group has two carbon atoms ("C2 alkynyl"). The one or more carbon-carbon triple bonds can be internal (e.g., 2-butynyl) or terminal (e.g., 1-butynyl). C 2~4 Examples of alkynyl groups include, but are not limited to, ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2-butynyl (C4), and the like. 2~6 Examples of alkenyl groups include the above-mentioned C 2~4Alkynyl groups include pentynyl (C5), hexynyl (C6), and the like. Further examples of alkynyl include heptynyl (C7), octynyl (C8), and the like. Unless otherwise specified, each occurrence of an alkynyl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted alkynyl") or substituted with one or more substituents; for example, 1 to 5 substituents, 1 to 3 substituents, or 1 substituent ("substituted alkynyl"). In certain embodiments, an alkynyl group is an unsubstituted C 2~10 In certain embodiments, the alkynyl group is a substituted C 2~10 It is alkynyl.

[0048] The term "heteroalkyl," as used herein, refers to an alkyl group, as defined herein, that further comprises one or more (e.g., 1, 2, 3, or 4) heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus) in the parent chain, where the one or more heteroatoms are inserted between adjacent carbon atoms in the parent carbon chain and / or where one or more heteroatoms are inserted between a carbon atom and the parent molecule (i.e., between the points of attachment). In certain embodiments, a heteroalkyl group refers to a saturated group having 1 to 10 carbon atoms and 1, 2, 3, or 4 heteroatoms ("heteroC 1~10 In some embodiments, a heteroalkyl group refers to a saturated group having 1 to 9 carbon atoms and 1, 2, 3, or 4 heteroatoms ("heteroC 1~9 In some embodiments, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1, 2, 3, or 4 heteroatoms ("heteroC 1~8 In some embodiments, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1, 2, 3, or 4 heteroatoms ("heteroC 1~7 In some embodiments, a heteroalkyl group is a group having 1 to 6 carbon atoms and 1, 2, or 3 heteroatoms ("heteroC 1~6In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms ("heteroC 1~5 In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms ("heteroC 1~4 In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom ("heteroC 1~3 In some embodiments, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom ("heteroC 1~2 In some embodiments, the heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom ("heteroC1 alkyl"). In some embodiments, the heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms ("heteroC 2~6 Unless otherwise specified, each occurrence of a heteroalkyl group is independently unsubstituted ("unsubstituted heteroalkyl") or substituted with one or more substituents ("substituted heteroalkyl"). In certain embodiments, a heteroalkyl group is an unsubstituted heteroC 1~10 In certain embodiments, the heteroalkyl group is a substituted heteroC 1~10 It is alkyl.

[0049] "Aryl" refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic arrangement) having 6 to 14 ring carbon atoms and 0 heteroatoms provided in the aromatic ring system ("C 6~14 In some embodiments, an aryl group has 6 ring carbon atoms ("C aryl"; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms ("C 10Aryl"; e.g., naphthyl, such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring carbon atoms ("C 14 "Aryl"; e.g., anthracyl). "Aryl" also includes ring systems in which an aryl ring, as defined above, is fused to one or more carbocyclyl or heterocyclyl groups, where the bonding radical or point of attachment is on the aryl ring, and in such cases the number of carbon atoms continues to refer to the number of carbon atoms in the aryl ring system. Typical aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, and trinaphthalene.Particularly, aryl groups include phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Unless otherwise specified, each occurrence of an aryl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted aryl") or substituted with one or more substituents ("substituted aryl"). In certain embodiments, an aryl group is an unsubstituted C 6~14 In certain embodiments, the aryl group is a substituted C 6~14 It is aryl.

[0050] In certain embodiments, the aryl group is substituted with one or more groups selected from halo, C1-C8 alkyl, C1-C8 haloalkyl, cyano, hydroxy, C1-C8 alkoxy, and amino.

[0051] Representative examples of substituted aryl include: [ka] where R 56 and R 57 can be hydrogen, and R 56 and R 57 At least one of the following is independently selected from C1-C8 alkyl, C1-C8 haloalkyl, 4- to 10-membered heterocyclyl, alkanoyl, C1-C8 alkoxy, heteroaryloxy, alkylamino, arylamino, heteroarylamino, NR 58 COR 59 , N.R. 58 SOR 59 , N.R. 58 SO2R 59 , COO alkyl, COO aryl, CONR 58 R 59 ,CONR 58 OR 59 , N.R. 58 R 59 , SO2NR 58 R 59 , S-alkyl, SO alkyl, SO alkyl, S aryl, SO aryl, SO aryl; or R 56 and R 57 may be linked to form a cyclic ring (saturated or unsaturated) of 5 to 8 atoms (optionally containing one or more heteroatoms selected from the group N, O, or S). R 60 and R 61 are independently hydrogen, C1-C8 alkyl, C1-C4 haloalkyl, C3-C 10 Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 Aryl, substituted C6-C 10 It is aryl, 5- to 10-membered heteroaryl or substituted 5- to 10-membered heteroaryl.

[0052] "Fused aryl" refers to an aryl that shares two ring carbons with a second aryl or heteroaryl ring, or a carbocyclyl or heterocyclyl ring.

[0053] "Heteroaryl" refers to a radical of a 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 π-electrons shared in a cyclic arrangement) in which ring carbon atoms and 1 to 4 ring heteroatoms are provided in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 10-membered heteroaryl"). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, if valence allows. Heteroaryl bicyclic ring systems can contain one or more heteroatoms in one or both rings. "Heteroaryl" includes ring systems in which a heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups, where the point of attachment is on the heteroaryl ring; in such cases, the number of ring members continues to refer to the number of ring members in the heteroaryl ring system. "Heteroaryl" also includes ring systems in which a heteroaryl ring, as defined above, is fused to one or more aryl groups, wherein the point of attachment can be on either the aryl ring or the heteroaryl ring; in such cases, the number of ring members refers to the number of ring members in the fused (aryl / heteroaryl) ring system. In bicyclic heteroaryl groups in which one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, etc.), the point of attachment can be on either ring, i.e., on the ring with a heteroatom (e.g., 2-indolyl) or on the ring without a heteroatom (e.g., 5-indolyl).

[0054] In some embodiments, heteroaryl groups are 5- to 10-membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 10-membered heteroaryl"). In some embodiments, heteroaryl groups are 5- to 8-membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 8-membered heteroaryl"). In some embodiments, heteroaryl groups are 5- to 6-membered aromatic ring systems having ring carbon atoms and 1-4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5- to 6-membered heteroaryl"). In some embodiments, 5- to 6-membered heteroaryls have 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, a 5- to 6-membered heteroaryl has 1 to 2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, a 5- to 6-membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each occurrence of a heteroaryl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted heteroaryl") or substituted with one or more substituents ("substituted heteroaryl"). In certain embodiments, a heteroaryl group is an unsubstituted 5- to 14-membered heteroaryl. In certain embodiments, a heteroaryl group is a substituted 5- to 14-membered heteroaryl.

[0055] Exemplary 5-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, but are not limited to, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, but are not limited to, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, but are not limited to, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, but are not limited to, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, but are not limited to, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, but are not limited to, triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing one heteroatom include, but are not limited to, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6-bicyclic heteroaryl groups include, but are not limited to, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzisothiazolyl, benzothiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include, but are not limited to, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.

[0056] Representative examples of heteroaryls include those of the formula: [ka] where each Z is a carbonyl, N, NR 65 , O and S; R 65 are independently hydrogen, C1-C8 alkyl, C3-C 10 Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 aryl and 5- to 10-membered heteroaryl.

[0057] "Carbocyclyl" or "carbocyclic" means a ring system having 3 to 10 ring carbon atoms ("C 3~10 In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms ("C 3~8 In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms ("C 3~6 In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms ("C 3~6 In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms ("C 5~10 carbocyclyl). Exemplary C 3~6 Carbocyclyl groups include, but are not limited to, cyclopropyl (C), cyclopropenyl (C), cyclobutyl (C), cyclobutenyl (C), cyclopentyl (C), cyclopentenyl (C), cyclohexyl (C), cyclohexenyl (C), cyclohexadienyl (C), and the like. 3~8 The carbocyclyl group includes the above-mentioned C 3~6 Examples include, but are not limited to, carbocyclyl groups, as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptanyl (C7), bicyclo[2.2.2]octanyl (C8), and the like. 3~10 The carbocyclyl group includes the above-mentioned C 3~8Carbocyclyl groups, as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C 10 ), spiro[4.5]decanyl (C 10 ) and the like. As the foregoing examples are illustrated, in certain embodiments, a carbocyclyl group is monocyclic ("monocyclic carbocyclyl") or contains a fused, bridged, or spiro ring system (e.g., a bicyclic system ("bicyclic carbocyclyl")), which may be saturated or partially unsaturated. "Carbocyclyl" also includes ring systems in which a carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, where the point of attachment is on the carbocyclyl ring; in such cases, the number of carbons continues to refer to the number of carbons in the carbocyclyl ring system. Unless otherwise specified, each occurrence of a carbocyclyl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted carbocyclyl") or substituted with one or more substituents ("substituted carbocyclyl"). In certain embodiments, a carbocyclyl group is an unsubstituted C 3~10 In certain embodiments, the carbocyclyl group is a substituted C 3~10 It is a carbocyclyl.

[0058] In some embodiments, "carbocyclyl" refers to a monocyclic saturated carbocyclyl group having 3 to 10 ring carbon atoms ("C 3~10 In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms ("C 3~8 In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C 3~6 In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms ("C 5~6 In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms ("C5~10 Cycloalkyl). C 5~6 Examples of cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C5). 3~6 Examples of cycloalkyl groups include the above-mentioned C 5~6 Cycloalkyl groups include cyclopropyl (C3) and cyclobutyl (C4). 3~8 Examples of cycloalkyl groups include the above-mentioned C 3~6 Cycloalkyl groups include cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise specified, each occurrence of a cycloalkyl group is independently unsubstituted ("unsubstituted cycloalkyl") or substituted with one or more substituents ("substituted cycloalkyl"). In certain embodiments, a cycloalkyl group is an unsubstituted C 3~10 In certain embodiments, the cycloalkyl group is a substituted C 3~10 It is cycloalkyl.

[0059] "Heterocyclyl" or "heterocyclic" refers to the radical of a 3- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3- to 10-membered heterocyclyl"). In heterocyclyl groups containing one or more nitrogen atoms, the point of attachment can be at a carbon or nitrogen atom, when valence allows. Heterocyclyl groups can be monocyclic ring systems ("monocyclic heterocyclyl") or fused, bridged, or spiro ring systems (e.g., bicyclic systems ("bicyclic heterocyclyl")), and can be saturated or partially unsaturated. Heterocyclyl bicyclic ring systems can contain one or more heteroatoms in one or both rings. "Heterocyclyl" also includes ring systems in which a heterocyclyl ring, as defined above, is fused to one or more carbocyclyl groups, where the point of attachment is on the carbocyclyl or heterocyclyl ring, or on a ring system in which a heterocyclyl ring, as defined above, is fused to one or more aryl or heteroaryl groups, where the point of attachment is on the heterocyclyl ring; in such cases, the number of ring members continues to refer to the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each occurrence of heterocyclyl is independently optionally substituted, i.e., unsubstituted ("unsubstituted heterocyclyl") or substituted with one or more substituents ("substituted heterocyclyl"). In certain embodiments, the heterocyclyl group is an unsubstituted 3- to 10-membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3- to 10-membered heterocyclyl.

[0060] In some embodiments, a heterocyclyl group is a 5- to 10-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon (a "5- to 10-membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5- to 8-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur (a "5- to 8-membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5- to 6-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur (a "5- to 6-membered heterocyclyl"). In some embodiments, a 5- to 6-membered heterocyclyl has 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5- to 6-membered heterocyclyl has 1 to 2 ring heteroatoms selected from nitrogen, oxygen, and sulfur, In some embodiments, the 5- to 6-membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur.

[0061] Exemplary 3-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azirdinyl, oxiranyl, and thiorenyl. Exemplary 4-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing one heteroatom include, but are not limited to, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5-membered heterocyclyl groups containing three heteroatoms include, but are not limited to, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing one heteroatom include, but are not limited to, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, but are not limited to, triazinanyl. Exemplary 7-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclyl groups containing one heteroatom include, but are not limited to, azocanyl, oxecanyl, and thiocanyl. Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,6-bicyclic heterocyclic rings) fused to a C6 aryl ring include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like.Exemplary 6-membered heterocyclyl groups (also referred to herein as 6,6-bicyclic heterocyclic rings) fused to an aryl ring include, but are not limited to, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like.

[0062] A "nitrogen-containing heterocyclyl" group refers to a 4- to 7-membered non-aromatic cyclic group containing at least one nitrogen atom, such as, but not limited to, morpholine, piperidine (e.g., 2-piperidinyl, 3-piperidinyl, and 4-piperidinyl), pyrrolidine (e.g., 2-pyrrolidinyl and 3-pyrrolidinyl), azetidine, pyrrolidone, imidazoline, imidazolidinone, 2-pyrazoline, pyrazolidine, piperazine, and N-alkylpiperazines (such as N-methylpiperazine). Specific examples include azetidine, piperidone, and piperazone.

[0063] "Hetero," when used to describe a compound or a group present on a compound, means that one or more carbon atoms in the compound or group are replaced by a nitrogen, oxygen, or sulfur heteroatom. Hetero can apply to any of the hydrocarbyl groups described above (e.g., alkyl having 1 to 5, especially 1 to 3, heteroatoms, e.g., heteroalkyl; cycloalkyl, e.g., heterocyclyl; aryl, e.g., heteroaryl; and cycloalkenyl, e.g., cycloheteroalkenyl).

[0064] "Acyl" means -C(O)R 20 refers to the radical, where R 20 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, as defined herein. "Alkanoyl" refers to a group in which R 20is an acyl group where the aryl group is a group other than hydrogen. Representative acyl groups include formyl (-CHO), acetyl (-C(=O)CH3), cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl (-C(=O)Ph), benzylcarbonyl (-C(=O)CH2Ph), --C(O)-C1-C8 alkyl, and -C(O)-(CH2). t (C6-C 10 aryl), -C(O)-(CH2) t (5-10 membered heteroaryl), -C(O)-(CH2) t (C3-C 10 cycloalkyl) and -C(O)-(CH2) t (4- to 10-membered heterocyclyl) (t is an integer from 0 to 4). 21 is C1-C8 alkyl substituted with halo or hydroxy; or C3-C 10 Cycloalkyl, 4-10 membered heterocyclyl, C6-C 10 Aryl, arylalkyl, 5-10 membered heteroaryl or heteroarylalkyl (each of which is substituted with unsubstituted C1-C4 alkyl, halo, unsubstituted C1-C4 alkoxy, unsubstituted C1-C4 haloalkyl, unsubstituted C1-C4 hydroxyalkyl or unsubstituted C1-C4 haloalkoxy or hydroxy).

[0065] "Alkoxy" means -OR 29 refers to the group, where R 29 is 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. Particular alkoxy groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy. Particular alkoxy groups are lower alkoxy, i.e., having 1 to 6 carbon atoms. Further particular alkoxy groups have 1 to 4 carbon atoms.

[0066] In certain embodiments, R 29 is amino, substituted amino, C6-C 10 Aryl, aryloxy, carboxyl, cyano, C3-C 10 The "substituted alkoxy" group is a group having one or more substituents, for example, 1 to 5 substituents, particularly 1 to 3 substituents, and particularly 1 substituent, selected from the group consisting of cycloalkyl, 4- to 10-membered heterocyclyl, halogen, 5- to 10-membered heteroaryl, hydroxyl, nitro, thioalkoxy, thioaryloxy, thiol, alkyl-S(O)-, aryl-S(O)-, alkyl-S(O)2-, and aryl-S(O)2-. Exemplary "substituted alkoxy" groups include -O-(CH2) t (C6~C 10 aryl), -O-(CH2) t (5-10 membered heteroaryl), -O-(CH2) t (C3~C 10 cycloalkyl) and -O-(CH2) t (4-10 membered heterocyclyl), where t is an integer from 0 to 4, and any aryl, heteroaryl, cycloalkyl, or heterocyclyl group present can itself be substituted by unsubstituted C1-C4 alkyl, halo, unsubstituted C1-C4 alkoxy, unsubstituted C1-C4 haloalkyl, unsubstituted C1-C4 hydroxyalkyl, or unsubstituted C1-C4 haloalkoxy or hydroxy. Particularly exemplary "substituted alkoxy" groups are -OCF3, -OCH2CF3, -OCH2Ph, -OCH2-cyclopropyl, -OCH2CH2OH, and -OCH2CH2NMe2.

[0067] "Amino" refers to the -NH2 radical.

[0068] An "oxo group" refers to -C(=O)-.

[0069] "Substituted amino" refers to a group of the formula -N(R 38 )2, where R 38is 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, or an amino protecting group, wherein R 38 At least one of R is not hydrogen. 38 are independently hydrogen, C1-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C6-C 10 Aryl, 5- to 10-membered heteroaryl, 4- to 10-membered heterocyclyl or C3-C 10 cycloalkyl; or C1-C8 alkyl substituted with halo or hydroxy; C3-C8 alkenyl substituted with halo or hydroxy; C3-C8 alkynyl substituted with halo or hydroxy, or -(CH2) t (C6~C 10 aryl), -(CH2) t (5-10 membered heteroaryl), -(CH2) t (C3~C 10 cycloalkyl) or -(CH2) t (4-10 membered heterocyclyl), where t is an integer from 0 to 8, each of which is substituted by unsubstituted C1-C4 alkyl, halo, unsubstituted C1-C4 alkoxy, unsubstituted C1-C4 haloalkyl, unsubstituted C1-C4 hydroxyalkyl, or unsubstituted C1-C4 haloalkoxy or hydroxy; or both R 38 The groups taken together form an alkylene group.

[0070] Exemplary "substituted amino" groups include -NR 39 -C1-C8 alkyl, -NR 39 -(CH2) t (C6~C 10 aryl), -NR 39 -(CH2) t (5-10 membered heteroaryl), -NR 39 -(CH2) t (C3~C 10 cycloalkyl) and -NR39 -(CH2) t (4-10 membered heterocyclyl), where t is an integer from 0 to 4, e.g., 1 or 2, and each R 39 independently represent H or C1-C8 alkyl; any alkyl group present may itself be substituted by halo, substituted or unsubstituted amino, or hydroxy; any aryl, heteroaryl, cycloalkyl, or heterocyclyl group present may itself be substituted by unsubstituted C1-C4 alkyl, halo, unsubstituted C1-C4 alkoxy, unsubstituted C1-C4 haloalkyl, unsubstituted C1-C4 hydroxyalkyl, or unsubstituted C1-C4 haloalkoxy or hydroxy. For the avoidance of doubt, the term "substituted amino" includes alkylamino, substituted alkylamino, alkylarylamino, substituted alkylarylamino, arylamino, substituted arylamino, dialkylamino, and substituted dialkylamino groups, as defined below. Substituted amino encompasses both mono- and di-substituted amino groups.

[0071] "Carboxy" refers to the radical --C(O)OH.

[0072] "Cyano" refers to the -CN radical.

[0073] "Halo" or "halogen" refers to fluoro (F), chloro (Cl), bromo (Br), and iodo (I). In certain embodiments, a halo group is either fluoro or chloro.

[0074] "Haloalkyl" refers to an alkyl radical in which the alkyl group is substituted with one or more halogens. Typical haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, fluoromethyl, chloromethyl, dichloromethyl, dibromoethyl, tribromomethyl, tetrafluoroethyl, and the like.

[0075] "Hydroxy" refers to the radical --OH.

[0076] "Nitro" refers to the -NO2 radical.

[0077] "Thioketo" refers to the =S group.

[0078] As defined herein, alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted (e.g., "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 groups). In general, the term "substituted," whether preceded by the term "optionally" or not, means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom) is replaced with an acceptable substituent, e.g., a substituent that, when substituted, gives rise to a stable compound, e.g., a compound that does not undergo spontaneous transformation (e.g., by rearrangement, cyclization, elimination, or other reaction). Unless otherwise specified, a "substituted" group has a substituent at one or more substitutable positions of the group, and when two or more positions in any given structure are substituted, the substituents may be the same or different at each position. The term "substituted" is intended to include substitution with all permissible substituents of organic compounds, any substituents described herein that result in a stable compound. The present invention contemplates any and all such combinations to arrive at a stable compound. For purposes of this invention, heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituents, as described herein, that satisfy the valence of the heteroatom and thereby form a stable moiety.

[0079] Exemplary carbon atom substituents include halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR aa , -ON(R bb )2, -N(R bb )2, -N(R bb )3 + X - , -N(OR cc )R bb , -SH, -SR aa , -SSR cc , -C(=O)R aa , -CO2H, -CHO, -C(OR cc )2, -CO2R aa , -OC(=O)R aa , -OCO2R aa , -C(=O)N(R bb )2, -OC(=O)N(R bb )2, -NR bb C(=O)R aa , -NR bb CO2R aa , -NR bb C(=O)N(R bb )2, -C(=NR bb )R aa , -C(=NR bb ) OR aa , -OC(=NR bb )R aa , -OC(=NR bb ) OR aa , -C(=NR bb )N(R bb )2, -OC(=NR bb )N(R bb )2, -NR bb C(=NR bb )N(R bb )2, -C(=O)NR bb SO2R aa , -NR bb SO2R aa , -SO2N(R bb )2, -SO2R aa , -SO2OR aa , -OSO2R aa , -S(=O)R aa , -OS(=O)R aa , -Si(R aa)3, -OSi(R aa )3-C(=S)N(R bb )2, -C(=O)SR aa , -C(=S)SR aa , -SC(=S)SR aa , -SC(=O)SR aa , -OC(=O)SR aa , -SC(=O)OR aa , -SC(=O)R aa , -P(=O)2R aa , -OP(=O)2R aa , -P(=O)(R aa )2, -OP(=O)(R aa )2, -OP(=O)(OR cc )2, -P(=O)2N(R bb )2, -OP(=O)2N(R bb )2, -P(=O)(NR bb )2, -OP(=O)(NR bb )2, -NR bb P(=O)(OR cc )2, -NR bb P(=O)(NR bb )2, -P(R cc )2, -P(R cc )3, -OP(R cc )2, -OP(R cc )3, -B(R aa )2, -B(OR cc )2, -BR aa (OR cc ), C 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl and 5- to 14-membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd or two geminal hydrogens on the carbon atom are substituted with groups =O, =S, =NN(R bb )2, =NNR bbC(=O)R aa , =NNR bb C(=O)OR aa , =NNR bb S(=O)2R aa , =NR bb or =NOR cc Replaced by;

[0080] R aa Each occurrence of C 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl and 5- to 14-membered heteroaryl, or two R aa groups linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd substituted with a group;

[0081] R bb Each occurrence of is independently hydrogen, -OH, -OR aa , -N(R cc )2, -CN, -C(=O)R aa , -C(=O)N(R cc )2, -CO2R aa , -SO2R aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc )2, -SO2N(R cc )2, -SO2R cc , -SO2OR cc , -SOR aa , -C(=S)N(R cc )2, -C(=O)SR cc , -C(=S)SR cc , -P(=O)2R aa , -P(=O)(R aa )2, -P(=O)2N(Rcc )2, -P(=O)(NR cc )2, C 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl and 5- to 14-membered heteroaryl, or two R bb groups linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd substituted with a group;

[0082] R cc Each occurrence of is independently hydrogen, C 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl and 5- to 14-membered heteroaryl, or two R cc groups linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd substituted with a group;

[0083] R dd Each occurrence of is independently a halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OR ee , -ON(R ff )2, -N(R ff )2, -N(R ff )3 + X - , -N(OR ee )R ff , -SH, -SR ee , -SSRee , -C(=O)R ee , -CO2H, -CO2R ee , -OC(=O)R ee , -OCO2R ee , -C(=O)N(R ff )2, -OC(=O)N(R ff )2, -NR ff C(=O)R ee , -NR ff CO2R ee , -NR ff C(=O)N(R ff )2, -C(=NR ff ) OR ee , -OC(=NR ff )R ee , -OC(=NR ff ) OR ee , -C(=NR ff )N(R ff )2, -OC(=NR ff )N(R ff )2, -NR ff C(=NR ff )N(R ff )2, -NR ff SO2R ee , -SO2N(R ff )2, -SO2R ee , -SO2OR ee , -OSO2R ee , -S(=O)R ee , -Si(R ee )3, -OSi(R ee )3, -C(=S)N(R ff )2, -C(=O)SR ee , -C(=S)SR ee , -SC(=S)SR ee , -P(=O)2R ee , -P(=O)(R ee )2, -OP(=O)(R ee )2, -OP(=O)(OR ee )2, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclyl, 3-10 membered heterocyclyl, C 6~10aryl, and 5- to 10-membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently selected from 0, 1, 2, 3, 4, or 5 R gg substituted with a group or two geminal R dd The substituents may be taken together to form =O or =S;

[0084] R ee Each occurrence of C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclyl, C 6~10 aryl, 3- to 10-membered heterocyclyl, and 3- to 10-membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently selected from 0, 1, 2, 3, 4, or 5 R gg substituted with a group;

[0085] R ff Each occurrence of is independently hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclyl, 3-10 membered heterocyclyl, C 6~10 aryl and 5- to 10-membered heteroaryl, or two R ff groups linked to form a 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R gg substituted with a group;

[0086] R gg Each occurrence of is independently a halogen, -CN, -NO2, -N3, -SO2H, -SO3H, -OH, -OC 1~6 Alkyl, -ON(C1~6 alkyl)2, -N(C 1~6 alkyl)2, -N(C 1~6 alkyl)3 + X - , -NH(C 1~6 alkyl)2 + X - , -NH2(C 1~6 alkyl) + X - , -NH3 + X - , -N(OC 1~6 Alkyl)(C 1~6 alkyl), -N(OH)(C 1~6 alkyl), -NH(OH), -SH, -SC 1~6 Alkyl, -SS(C 1~6 alkyl), -C(=O)(C 1~6 alkyl), -CO2H, -CO2(C 1~6 alkyl), -OC(=O)(C 1~6 alkyl), -OCO2(C 1~6 alkyl), -C(=O)NH2, -C(=O)N(C 1~6 alkyl)2, -OC(=O)NH(C 1~6 alkyl), -NHC(=O)(C 1~6 alkyl), -N(C 1~6 alkyl)C(=O)(C 1~6 alkyl), -NHCO2(C 1~6 alkyl), -NHC(=O)N(C 1~6 alkyl)2, -NHC(=O)NH(C 1~6 alkyl), -NHC(=O)NH2, -C(=NH)O(C 1~6 alkyl), -OC(=NH)(C 1~6 alkyl), -OC(=NH)OC 1~6 Alkyl, -C(=NH)N(C 1~6 alkyl)2, -C(=NH)NH(C 1~6 alkyl), -C(=NH)NH2, -OC(=NH)N(C 1~6 alkyl)2, -OC(NH)NH(C 1~6 alkyl), -OC(NH)NH2, -NHC(NH)N(C 1~6 alkyl)2, -NHC(=NH)NH2, -NHSO2(C1~6 alkyl), -SO2N(C 1~6 alkyl)2, -SO2NH(C 1~6 alkyl), -SO2NH2, -SO2C 1~6 Alkyl, -SO2OC 1~6 Alkyl, -OSO2C 1~6 Alkyl, -SOC 1~6 Alkyl, -Si(C 1~6 alkyl)3, -OSi(C 1~6 alkyl)3-C(=S)N(C 1~6 alkyl)2, C(=S)NH(C 1~6 alkyl), C(=S)NH2, -C(=O)S(C 1~6 alkyl), -C(=S)SC 1~6 Alkyl, -SC(=S)SC 1~6 Alkyl, -P(=O)2(C 1~6 alkyl), -P(=O)(C 1~6 alkyl)2, -OP(=O)(C 1~6 alkyl)2, -OP(=O)(OC 1~6 Alkyl)2, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclyl, C 6~10 aryl, 3- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, or two geminal R gg The substituents may be taken together to form =O or =S; where X - is the counter ion.

[0087] A "counterion" or "anionic counterion" is a negatively charged group that associates with a cationic quaternary amino group to maintain electroneutrality. Exemplary counterions include halide ions (e.g., F - , Cl - , Br - , I - ), NO3 - , ClO4 - , O.H. - , H2PO4 - , HSO4 -, sulfonate ions (e.g., methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, benzenesulfonate, 10-camphorsulfonate, naphthalene-2-sulfonate, naphthalene-1-sulfonic acid-5-sulfonate, ethane-1-sulfonic acid-2-sulfonate, etc.) and carboxylate ions (e.g., acetate, ethanoate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, etc.).

[0088] These and other exemplary substituents are described in detail in the detailed description and claims. It is not intended that the present invention be limited in any way by the exemplary recitation of substituents above.

[0089] Other Definitions As used herein, the term "modulation" refers to the A "Modulators" (e.g., modulator compounds) refer to the inhibition or potentiation of receptor function, e.g., GABA receptors. A It can be an agonist, partial agonist, antagonist, or partial antagonist of the receptor.

[0090] "Pharmaceutically acceptable" means approved or approvable by a regulatory authority of a federal or state government, or a corresponding authority in a country other than the United States, or listed in the United States Pharmacopoeia or other generally recognized pharmacopoeia for use in animals (more specifically, humans).

[0091] "Pharmaceutically acceptable salts" refers to salts of compounds of the present invention that are pharmaceutically acceptable and that possess the desired pharmacological activity of the parent compound. In particular, such salts are non-toxic and can be inorganic or organic acid addition salts and inorganic or organic base addition salts. Specifically, such salts include (1) salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or salts formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphor or (2) salts formed when an acidic proton present in the parent compound is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or when coordinated with an organic base, e.g., ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, etc. Salts further include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, etc.; and, if the compound contains a basic functional group, salts of non-toxic organic or inorganic acids, e.g., hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalate, etc. The term "pharmaceutically acceptable cation" refers to an acceptable cationic counterion of an acidic functional group. Such cations are exemplified by sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium cations, and the like.See, for example, Berge et al., J. Pharm. Sci. (1977) 66(1):1-79.

[0092] The term "prodrug" is intended to include therapeutically inactive compounds that are converted into therapeutically active agents of the present invention under physiological conditions. One method for creating a prodrug is to design a selected moiety that is hydrolyzed or cleaved at the targeted in vivo site of action under physiological conditions to release the desired molecule, which then exerts its therapeutic effect. In certain embodiments, the prodrug is converted by enzymatic activity in the subject.

[0093] In some embodiments, the compound of Formula (IX, II, II-I, III-I, or III-II) is a prodrug, wherein the prodrug contains a cleavable moiety on the C3 hydroxy as shown in Formula (IX, II, II-I, III-I, or III-II). "Tautomers" refer to interchangeable forms of a particular compound structure and vary in the displacement of hydrogen atoms and electrons. Thus, two structures may be in equilibrium through the shift of π electrons and atoms (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. Another example of tautomerism is the acid and nitro forms of phenylnitromethane, which are similarly formed in the presence of acid or base. Tautomers may be relevant to achieving optimal chemical reactivity and biological activity of a compound of interest.

[0094] "Subjects" to which administration is contemplated include, but are not limited to, humans (i.e., male or female of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or elderly adults)) and / or non-human animals, e.g., mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys), cows, pigs, horses, sheep, goats, rodents, cats, and / or dogs). In certain embodiments, the subject is a human. In certain embodiments, the subject is a non-human animal.

[0095] In certain embodiments, the substituent present on the oxygen atom is an oxygen protecting group (also referred to as a hydroxyl protecting group). Oxygen protecting groups include -R aa , -N(R bb )2, -C(=O)SR aa , -C(=O)R aa , -CO2R aa , -C(=O)N(R bb )2, -C(=NR bb )R aa , -C(=NR bb ) OR aa , -C(=NR bb )N(R bb )2, -S(=O)R aa , -SO2R aa , -Si(R aa )3, -P(R cc )2, -P(R cc )3, -P(=O)2R aa , -P(=O)(R aa )2, -P(=O)(OR cc )2, -P(=O)2N(R bb )2, and -P(=O)(NR bb )2(where R aa , R bb , and R cc Oxygen protecting groups include, but are not limited to, aryl, aryl, aryl- ... rd edition, John Wiley & Sons, 1999, which is incorporated herein by reference.

[0096] Exemplary oxygen protecting groups include, but are not limited to, methyl, methoxylmethyl (MOM), 2-methoxyethoxymethyl (MEM), benzyl (Bn), triisopropylsilyl (TIPS), t-butyldimethylsilyl (TBDMS), t-butylmethoxyphenylsilyl (TBMPS), methanesulfonate (mesylate), and tosylate (Ts).

[0097] In certain embodiments, the substituent present on the sulfur atom is a sulfur protecting group (also referred to as a thiol protecting group). Sulfur protecting groups include -R aa , -N(R bb )2, -C(=O)SR aa , -C(=O)R aa , -CO2R aa , -C(=O)N(R bb )2, -C(=NR bb )R aa , -C(=NR bb ) OR aa , -C(=NR bb )N(R bb )2, -S(=O)R aa , -SO2R aa , -Si(R aa )3, -P(R cc )2, -P(R cc )3, -P(=O)2R aa , -P(=O)(R aa )2, -P(=O)(OR cc )2, -P(=O)2N(R bb )2, and -P(=O)(NR bb ) 2, where R aa , R bb , and R cc is as defined herein. Sulfur protecting groups are well known in the art and are described in Protecting Groups in Organic Synthesis, T.W. Greene and P.G.M. Buts, 3 rd edition, John Wiley & Sons, 1999, which is incorporated herein by reference.

[0098] In certain embodiments, the substituent present on the nitrogen atom is an amino protecting group (also referred to herein as a nitrogen protecting group). Amino protecting groups include -OH, -OR aa , -N(R cc )2, -C(=O)R aa , -C(=O)OR aa , -C(=O)N(R cc )2, -S(=O)2R aa , -C(=NR cc )R aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc )2, -SO2N(R cc )2, -SO2R cc , -SO2OR cc , -SOR aa , -C(=S)N(R cc )2, -C(=O)SR cc , -C(=S)SR cc , C 1~10 Alkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl, and 5- to 14-membered heteroaryl groups, where each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd group, where R aa , R bb , R cc , and R dd is as defined herein. Amino protecting groups are well known in the art and are described in Protecting Groups in Organic Synthesis, T.W. Greene and P.G.M. Buts, 3 rd edition, John Wiley & Sons, 1999, which is incorporated herein by reference.

[0099] Exemplary amino protecting groups include amide groups (e.g., —C(═O)R aa ) (including, but not limited to, formamide and acetamide); carbamate groups (e.g., —C(═O)OR aa ) (including, but not limited to, 9-fluorenylmethylcarbamate (Fmoc), t-butylcarbamate (BOC), and benzylcarbamate (Cbz); sulfonamide groups (e.g., —S(═O)R aa ) (including but not limited to p-toluenesulfonamide (Ts), methanesulfonamide (Ms), and N-[2-(trimethylsilyl)ethoxy]methylamine (SEM)).

[0100] Disease, disorder, and condition are used interchangeably herein.

[0101] As used herein, unless otherwise specified, the terms "treat," "treating," and "treatment" contemplate actions taken while a subject is suffering from a particular disease, disorder, or condition to reduce the severity of the disease, disorder, or condition, or to delay or slow the progression of the disease, disorder, or condition. Generally, an "effective amount" of a compound refers to an amount sufficient to elicit a desired biological response, e.g., to treat a CNS-related disorder, and is sufficient to induce anesthesia or sedation. As will be appreciated by those skilled in the art, the effective amount of a compound of the present invention may vary depending on factors such as the desired biological goal, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, weight, health, and condition of the subject.

[0102] As used herein, unless otherwise specified, a "therapeutically effective amount" of a compound is an amount sufficient to provide a therapeutic benefit in the treatment of a disease, disorder, or condition, or to delay or minimize one or more symptoms associated with the disease, disorder, or condition. A therapeutically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other therapies, that provides a therapeutic benefit in the treatment of the disease, disorder, or condition. The term "therapeutically effective amount" can encompass an amount that improves overall treatment, an amount that reduces or avoids the symptoms or causes of a disease or condition, or an amount that enhances the therapeutic efficacy of another therapeutic agent.

[0103] In an alternative embodiment, the present invention contemplates administering a compound of the present invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable composition thereof, as a preventative measure before a subject is affected by a particular disease, disorder, or condition. As used herein, unless otherwise specified, a "prophylactically effective amount" of a compound is an amount sufficient to prevent a disease, disorder, or condition, or one or more symptoms associated with the disease, disorder, or condition, or to prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, that provides a prophylactic benefit in the prevention of the disease, disorder, or condition. The term "prophylactically effective amount" can encompass an amount that improves overall prevention or an amount that enhances the prophylactic efficacy of another prophylactic agent.

[0104] As used herein, an "episodic dosing regimen" refers to a dosing regimen in which a compound of Formula (IX, II, II-I, III-I, or III-II) or a composition comprising a compound of Formula (IX, II, II-I, III-I, or III-II) is administered to a subject for a limited period of time corresponding to a diagnosis of a disorder or a symptom thereof (e.g., a diagnosis or symptom of an episode of depression, major depressive disorder, bipolar depression, anxiety, or postpartum depression). In some embodiments, the major depressive disorder is moderate major depressive disorder. In some embodiments, the major depressive disorder is severe major depressive disorder. In some embodiments, the compound is formulated as individual dosage units (each unit comprising a compound of Formula (IX, II, II-I, III-I, or III-II) and one or more suitable pharmaceutical excipients). In some embodiments, the duration of an episodic dosing regimen is several weeks (e.g., about 8 weeks). In contrast to chronic administration as defined herein, episodic dosing of a compound is administered for a limited period of time (e.g., about 2 weeks to about 8 weeks) corresponding to a diagnosis of a disorder (e.g., depression or symptoms thereof). In some embodiments, episodic dosing is administered once daily for several weeks (e.g., about 2 weeks to about 6 weeks). In one embodiment, the duration of episodic dosing is 2 weeks. In some embodiments, more than one episodic dosing regimen (e.g., two or more episodic regimens over the course of the subject's lifetime) is administered to the subject. Compound

[0105] It should be recognized that the formulas set forth herein may refer to specific carbon atoms (C17, C3, C19, etc.) These references are based on the carbon atom positions according to the steroid nomenclature known and used in the industry as follows: [ka] . For example, C17 refers to the 17th carbon, and C3 refers to the 3rd carbon.

[0106] As described herein, in one aspect, the present invention provides a compound of formula (IX): [ka] or a pharmaceutically acceptable salt thereof, In formula (IX), p is 0, 1, or 2; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 1 is a 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, -SR X1 , -N(R X1 )2, -OC(=O)R X1 , -OC(=O)OR X1 , -OC(=O)SR X1 , -OC(=O)N(R X1 )2, -SC(=O)R X2 , -SC(=O)OR X1 , -SC(=O)SR X1 , -SC(=O)N(R X1 )2, -NHC(=O)R X1 , -NHC(=O)OR X1 , -NHC(=O)SR X1 , -NHC(=O)N(R X1 )2, -OS(=O)2R X2 , -OS(=O)2OR X1 , -SS(=O)2R X2 , -SS(=O)2OR X1 , -S(=O)R X2 , -SO2R X2 , or -S(=O)2OR X1 where R X1each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, or two R X1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R X2 each occurrence 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; R 3a is a substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 is a carbocyclyl; R 2a is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, or -OR A2 where R A2 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 is a carbocyclyl; R 11a is hydrogen or -OR A3 where R A3 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 carbocyclyl, and R 11b is hydrogen; or R 11a and R 11b together to form an oxo (=O) group; R 6a and R 6b Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, or halogen.

[0107] It should be recognized that the stereochemistry of C17 can be depicted in either of the following equivalent ways: [ka] .

[0108] In certain embodiments, R 19 is hydrogen in compounds of formula (IX); in certain embodiments, R 19 is methyl in the compound of formula (IX).

[0109] In certain embodiments, R 1 is a substituted or unsubstituted alkyl in compounds of formula (IX).

[0110] In certain embodiments, R 1 is a substituted or unsubstituted heteroaryl in compounds of formula (IX).

[0111] In certain embodiments, R 1 is a substituted or unsubstituted heteroaryl, wherein said heteroaryl contains at least one nitrogen atom in the compound of formula (IX).

[0112] In certain embodiments, R 1is a substituted or unsubstituted heteroaryl, wherein said heteroaryl is bicyclic in compounds of formula (IX).

[0113] In one aspect, the present invention provides a compound of formula (II): [ka] and pharmaceutically acceptable salts thereof, In formula (II), R 3a is a substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 Carbocyclyl; R 2a is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, or -OR A2 where R A2 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 Carbocyclyl; R 11a is hydrogen or -OR A3 where R A3 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 carbocyclyl, and R 11b is hydrogen; or R 11a and R 11btogether form an oxo (=O) group; R 6a and R 6b Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, or halogen; R m , R n , and R x Each occurrence of independently represents hydrogen, halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -N(R GA )C(=O)N(R GA )2, -SR GA , -S(O)R GA , e.g., -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 carbocyclyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6carbocyclyl, 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 R GA Compounds and pharmaceutically acceptable salts thereof are provided in which the groups, together with intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

[0114] In certain embodiments, R in the 19-nor C3,3-disubstituted C21-pyrazolyl of formula (II) 3a is a C optionally substituted with alkoxy or 1 to 2 halo groups (e.g., fluoro). 1~6 alkyl or R m , R n , and R x At least one of is a halogen (e.g., -F, -Cl, -Br), -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, substituted or unsubstituted C 1~6 alkyl (e.g., -CH3, -CH2CH3, haloalkyl, e.g., -CF3), where R GA is a substituted or unsubstituted C 1~2 It is alkyl.

[0115] Based on the foregoing, it is understood that steroids of formula (II) include 3,3-disubstituted 19-nor compounds and pharmaceutically acceptable salts thereof, wherein the A / B ring system of the compound is cis (as provided in formula (IIA)), and wherein the A / B ring system of the compound is trans (as provided in formula (IIB)): [ka] . R of formula (IX) or formula (I-1) 3a base

[0116] As generally defined herein, R 3a is a substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 It is a carbocyclyl.

[0117] In certain embodiments, R 3a is a substituted or unsubstituted C 1~6 Alkyl, e.g., substituted or unsubstituted C 1~2 Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C 3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 An exemplary R is alkyl. 3a C 1~6 Alkyl groups include substituted or unsubstituted methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), iso-butyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), n-hexyl (C6), C substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more fluoro groups. 1~6 alkyl (e.g., -CF3, -CH2F, -CHF2, difluoroethyl, and 2,2,2-trifluoro-1,1-dimethyl-ethyl), C substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more chloro groups 1~6C substituted with alkyl (e.g., -CH2Cl, -CHCl2), and alkoxy groups 1~6 Examples of alkyl include, but are not limited to, alkyl (e.g., -CH2OCH3 and -CH2OCH2CH3). In certain embodiments, R 3a is a substitution C 1~6 alkyl (e.g., R 3a is haloalkyl, alkoxyalkyl, or aminoalkyl). In certain embodiments, R 3a is Me, Et, n-Pr, n-Bu, i-Bu, fluoromethyl, chloromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, difluoroethyl, 2,2,2-trifluoro-1,1-dimethyl-ethyl, methoxymethyl, methoxyethyl, or ethoxymethyl.

[0118] In certain embodiments, R 3a is the unsubstituted C 1~3 alkyl (e.g., R 3a is -CH3, -CH2CH3, or -CH2CH2CH3).

[0119] In certain embodiments, R 3a is a C substituted with one or more fluorine atoms 1~6 alkyl (e.g., R 3a is —CHF, —CHF, or —CF). In certain embodiments, R 3a C is substituted with one or two fluorine atoms 1~6 alkyl (e.g., R 3a is -CH2F or -CHF2).

[0120] In certain embodiments, R 3a is one or more -OR A1 C substituted with a group 1~6 alkyl, where R A1 is hydrogen or substituted or unsubstituted alkyl. In certain embodiments, R 3a is -CH2ORA1 For example, where R A1 is, for example, an R of formula -CHOH, -CHOCH, -CHOCHCH, or -CHOCHCHCH 3a hydrogen, -CH3, -CH2CH3, or -CH2CH2CH3 to give the group.

[0121] In certain embodiments, R 3a is a substituted or unsubstituted C 2~6 Alkenyl, for example, substituted or unsubstituted C 2~3 Alkenyl, substituted or unsubstituted C 3~4 Alkenyl, substituted or unsubstituted C 4~5 Alkenyl, or substituted or unsubstituted C 5~6 alkenyl. In certain embodiments, R 3a is ethenyl (C2), propenyl (C3), or butenyl (C4) that is unsubstituted or substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxyl. In certain embodiments, R 3a is ethenyl, propenyl, or butenyl that is unsubstituted or substituted with alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxy. In certain embodiments, R 3a is ethenyl.

[0122] In certain embodiments, R 3a is a substituted or unsubstituted C 2~6 Alkynyl, for example, substituted or unsubstituted C 2~3 Alkynyl, substituted or unsubstituted C 3~4 Alkynyl, substituted or unsubstituted C 4~5 Alkynyl, or substituted or unsubstituted C 5~6 In certain embodiments, R 3ais ethynyl, propynyl, or butynyl that is unsubstituted or substituted with alkyl, halo, haloalkyl (e.g., CF), alkoxyalkyl, cycloalkyl (e.g., cyclopropyl or cyclobutyl), or hydroxyl. In certain embodiments, R 3a is selected from the group consisting of trifluoroethynyl, cyclopropylethynyl, cyclobutylethynyl, and propynyl, fluoropropynyl, and chloroethynyl. 3a is ethynyl (C2), propynyl (C3), or butynyl (C4) that is unsubstituted or substituted with one or more substituents selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl. In certain embodiments, R 3a is ethynyl (C2), propynyl (C3), or butynyl (C4) substituted with a substituted phenyl. In certain embodiments, the phenyl substituent is further substituted with one or more substituents selected from the group consisting of halo, alkyl, trifluoroalkyl, alkoxy, acyl, amino, or amido. In certain embodiments, R 3a is ethynyl (C2), propynyl (C3), or butynyl (C4) substituted with substituted or unsubstituted pyrrolyl, imidazolyl, pyrazolyl, oxazoyl, thiazolyl, isoxazoyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxadiazolyl, thiadiazolyl, or tetrazolyl.

[0123] In certain embodiments, R 3a is ethynyl, propynyl, or butynyl that is unsubstituted or substituted with alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxyl. In certain embodiments, R 3a is ethynyl or propynyl substituted with substituted or unsubstituted aryl. In certain embodiments, R 3ais ethynyl or propynyl that is unsubstituted or substituted with phenyl that is substituted with halo, alkyl, alkoxy, haloalkyl, trihaloalkyl, or acyl. 3a is ethynyl or propynyl substituted with substituted or unsubstituted carbocyclyl. In certain embodiments, R 11a is ethynyl or propynyl substituted with substituted or unsubstituted cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 3a is ethynyl or propynyl substituted with substituted or unsubstituted heteroaryl. In certain embodiments, R 3a is substituted or unsubstituted pyridinyl, or ethynyl or propynyl substituted with pyrimidinyl. In certain embodiments, R 3a is ethynyl or propynyl substituted with substituted or unsubstituted pyrrolyl, imidazolyl, pyrazolyl, oxazoyl, thiazolyl, isoxazoyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl. In certain embodiments, R 3a is ethynyl or propynyl substituted with substituted or unsubstituted heterocyclyl. In certain embodiments, R 3a is ethynyl or propynyl substituted with substituted or unsubstituted pyrrolidinyl, piperidinyl, piperazinyl, or mopholinyl. 3a is propynyl or butynyl substituted with hydroxyl or alkoxy. In certain embodiments, R 3a is propynyl or butynyl substituted with methoxy or ethoxy. In certain embodiments, R 3a is ethynyl or propynyl substituted with chloro. In certain embodiments, R 3a is ethynyl or propynyl substituted with trifluoromethyl.

[0124] In certain embodiments, R 3a is a substituted or unsubstituted C 3~6 Carbocyclyl, e.g., substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted C 4~5 Carbocyclyl, or substituted or unsubstituted C 5~6 In certain embodiments, R 3a is substituted or unsubstituted cyclopropyl or substituted or unsubstituted cyclobutyl. The group R of formula (IX) or formula (I-1) 2a , R 11a , R 11b , R 6a , and R 6b

[0125] As generally defined herein, R 2a is hydrogen, halogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 Carbocyclyl, or -OR A2 where R A2 is hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 It is a carbocyclyl.

[0126] In certain embodiments, R 2a is hydrogen. In certain embodiments, R 2a is halogen, for example, fluoro, chloro, bromo, or iodo. In certain embodiments, R 2a is fluoro or chloro. In certain embodiments, R 2a is a substituted or unsubstituted C 1~6 Alkyl, e.g., substituted or unsubstituted C 1~2Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C 3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 For example, in some embodiments, R 2a is halo (e.g., bromo, chloro, fluoro (i.e., R of the formula -CHF, -CHF, -CF) 2a To obtain the group)) or -OR A2 C, substituted as needed 1~6 In certain embodiments, R A2 is -CH3, -CH2CH3, or -CH2CH2CH3 (i.e., R of formula -OH, -OCH3, -OCH2CH3, or -OCH2CH2CH3 2a In certain embodiments, R 2a is a substituted or unsubstituted C 2~6 alkenyl, and in certain embodiments, R 2a is a substituted or unsubstituted C 2~6 Alkynyl, for example, substituted or unsubstituted C 2~3 Alkynyl, substituted or unsubstituted C 3~4 Alkynyl, substituted or unsubstituted C 4~5 Alkynyl, or substituted or unsubstituted C 5~6 In certain embodiments, R 2a is a substituted or unsubstituted C 3~6 Carbocyclyl, e.g., substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted C 4~5 Carbocyclyl, or substituted or unsubstituted C 5~6 In certain embodiments, R 2a is substituted or unsubstituted cyclopropyl or substituted or unsubstituted cyclobutyl. 2a is -CH3, -CH2CH3, -CH2CH2CH3, or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OR A2 In certain embodiments, RA2 is hydrogen. In certain embodiments, R A2 is a substituted or unsubstituted alkyl, for example, a substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 1~2 Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C 3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 In certain embodiments, R A2 is hydrogen, -CH3, -CH2CH3, or -CH2CH2CH3 (i.e., R of formula -OH, -OCH3, -OCH2CH3, or -OCH2CH2CH3) 2a In certain embodiments, R 2a is a non-hydrogen substituent in the alpha configuration. In certain embodiments, R 2a is a non-hydrogen substituent in the β configuration.

[0127] As generally defined herein, R 11a is hydrogen or -OR A3 where R A3 is hydrogen or substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 carbocyclyl, and R 11b is hydrogen; or R 11a and R 11b together form an oxo (=O) group.

[0128] In certain embodiments, R 11a and R 11b Both are hydrogen.

[0129] In certain embodiments, R 11a and R 11b together form an oxo (=O) group.

[0130] In certain embodiments, R 11a -OR A3 and R 11b is hydrogen. In certain embodiments, R 11a -OR A3 and R 11a is in the α or β configuration. 11a -OR A3 and R 11a is in the alpha configuration. 11a -OR A3 and R 11a is in the β configuration. A3 is hydrogen. In certain embodiments, R A3 is a substituted or unsubstituted C 1~6 Alkyl, e.g., substituted or unsubstituted C 1~2 Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C 3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 In certain embodiments, R A3 is hydrogen, -CH3, -CH2CH3, or -CH2CH2CH3 (i.e., R of formula -OH, -OCH3, -OCH2CH3, or -OCH2CH2CH3) 11a (To obtain the base).

[0131] As generally defined herein, R 6a and R 6b Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, or halogen. The p group of formula (IX)

[0132] In some embodiments, p is 0, 1, or 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. R in formula (I-1) m , R n, and R x base

[0133] As generally defined herein, R m , R n , and R x Each occurrence of independently represents hydrogen, halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -N(R GA )C(=O)N(R GA )2, -SR GA , -S(O)R GA , e.g., -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 It is a carbocyclyl, or a substituted or unsubstituted 3- to 6-membered heterocyclyl.

[0134] Additionally, as generally defined herein, R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 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 R GA The groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring. In certain embodiments, R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl (e.g., substituted or unsubstituted C 1~2 Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C 3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 alkyl), substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. GA Each occurrence of is hydrogen, —CH 3 , —CH 2 CH 3 , or substituted or unsubstituted phenyl.

[0135] In certain embodiments, R m , R n , and R x At least one of R is hydrogen. m , R n , and R x At least two of R are hydrogen. m , R n , and R x All of are hydrogen to give an unsubstituted pyrazolyl.

[0136] In certain embodiments, R m , R n , and R x At least one of R is a non-hydrogen substituent. m , R n , and R x"Non-hydrogen substituent" is R m , R n , and R x is not hydrogen, but halogen, -NO2, -CN, -CF3, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -SR GA , -S(O)R GA , e.g., -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA ;Substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 It means either one of carbocyclyl or substituted or unsubstituted 3- to 6-membered heterocyclyl.

[0137] In certain embodiments, R m , R n , and R x At least one of R is halogen, e.g., fluoro, bromo, iodo, or chloro. m , R n , and R x One of R is halogen. mis halogen, e.g., fluoro, bromo, iodo, or chloro. In certain embodiments, R n is halogen, e.g., fluoro, bromo, iodo, or chloro. In certain embodiments, R x is halogen, for example, fluoro, bromo, iodo, or chloro.

[0138] In certain embodiments, R m , R n , and R x At least one of R is -NO. m , R n , and R x In certain embodiments, one of R m is —NO. In certain embodiments, R n is —NO. In certain embodiments, R x is -NO2.

[0139] In certain embodiments, R m , R n , and R x At least one of R is -CN. m , R n , and R x In certain embodiments, one of R m is -CN. In certain embodiments, R n is -CN. In certain embodiments, R x is -CN.

[0140] In certain embodiments, R m , R n , and R x At least one of -OR GA For example, where R GA is hydrogen or substituted or unsubstituted C 1~6 alkyl (e.g., —CH or —CF). In certain embodiments, R m , R n , and Rx One of the is -OR GA , for example, —OH, —OCH, or —OCF. In certain embodiments, R m -OR GA , for example, —OH, —OCH, or —OCF. In certain embodiments, R n -OR GA In certain embodiments, R x -OR GA , for example, -OH, -OCH3, or -OCF3.

[0141] In certain embodiments, R m , R n , and R x At least one of -N(R GA )2, for example, where R GA is hydrogen or substituted or unsubstituted C 1~6 alkyl (e.g., —CH or —CF). In certain embodiments, R m , R n , and R x One of the is -N(R GA )2, for example, -NH2, -NHCH3, or -N(CH3)2. In certain embodiments, R m is -N(R GA )2, for example, -NH2, -NHCH3, or -N(CH3)2. In certain embodiments, R n is -N(R GA )2, for example, -NH2, -NHCH3, or -N(CH3)2. In certain embodiments, R x is -N(R GA )2, for example, -NH2, -NHCH3, or -N(CH3)2.

[0142] In certain embodiments, R m , R n , and R x At least one of the following is -C(=O)R GA , -C(=O)OR GA , or -C(=O)N(R GA )2, for example, where RGA is hydrogen or substituted or unsubstituted C 1~6 alkyl (e.g., —CH or —CF). In certain embodiments, R m , R n , and R x One of them is -C(=O)R GA , for example, —CHO, —C(═O)CH, or —C(═O)CHCH. In certain embodiments, R m is -C(=O)R GA , for example, —CHO, —C(═O)CH, or —C(═O)CHCH. In certain embodiments, R n is -C(=O)R GA , for example, —CHO, —C(═O)CH, or —C(═O)CHCH. In certain embodiments, R x is -C(=O)R GA , for example, —CHO, —C(═O)CH, or —C(═O)CHCH. In certain embodiments, R m , R n , and R x One of them is -C(=O)OR GA , for example, —C(═O)OH, —C(═O)OCH, or —C(═O)OCHCH. In certain embodiments, R m is -C(=O)OR GA , for example, —C(═O)OH, —C(═O)OCH, or —C(═O)OCHCH. In certain embodiments, R n is -C(=O)OR GA , for example, —C(═O)OH, —C(═O)OCH, or —C(═O)OCHCH. In certain embodiments, R x is -C(=O)OR GA , for example, —C(═O)OH, —C(═O)OCH, or —C(═O)OCHCH. In certain embodiments, R m , R n , and R x One of the is -C(=O)N(R GA)2, for example, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2. In certain embodiments, R m is -C(=O)N(R GA )2, for example, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2. In certain embodiments, R n is -C(=O)N(R GA )2, for example, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2. In certain embodiments, R x is -C(=O)N(R GA )2, for example, -C(=O)NH2, -C(=O)NHCH3, or -C(=O)N(CH3)2.

[0143] In certain embodiments, R m , R n , and R x At least one of the following is -OC(=O)R GA , -OC(=O)OR GA , or -OC(=O)N(R GA )2, for example, where R GA is hydrogen or substituted or unsubstituted C 1~6 alkyl (e.g., —CH or —CF). In certain embodiments, R m , R n , and R x One of them is -OC(=O)R GA , for example, —OC(═O)CH. In certain embodiments, R m is -OC(=O)R GA , for example, —OC(═O)CH. In certain embodiments, R n is -OC(=O)R GA , for example, —OC(═O)CH. In certain embodiments, R x is -OC(=O)R GA , for example, —OC(═O)CH. In certain embodiments, R m , R n , and R x One of them is -OC(=O)OR GA, for example, —OC(═O)OCH. In certain embodiments, R m is -OC(=O)OR GA , for example, —OC(═O)OCH. In certain embodiments, R n is -OC(=O)OR GA , for example, —OC(═O)OCH. In certain embodiments, R x is -OC(=O)OR GA , for example, —OC(═O)OCH. In certain embodiments, R m , R n , and R x One of them is -OC(=O)N(R GA )2, for example, -OC(=O)NHCH3 or -OC(=O)N(CH3)2. In certain embodiments, R m is -OC(=O)N(R GA )2, for example, -OC(=O)NHCH3 or -OC(=O)N(CH3)2. In certain embodiments, R n is -OC(=O)N(R GA )2, for example, -OC(=O)NHCH3 or -OC(=O)N(CH3)2. In certain embodiments, R x is -OC(=O)N(R GA )2, for example, -OC(=O)NHCH3 or -OC(=O)N(CH3)2.

[0144] In certain embodiments, R m , R n , and R x At least one of -N(R GA )C(=O)R GA , -N(R GA )C(=O)OR GA , or -N(R GA )C(=O)N(R GA )2, for example, where R GA is hydrogen or substituted or unsubstituted C 1~6 alkyl (e.g., —CH or —CF). In certain embodiments, R m , R n , and R xOne of the is -N(R GA )C(=O)R GA , for example, —NHC(═O)CH. In certain embodiments, R m is -N(R GA )C(=O)R GA , for example, —NHC(═O)CH. In certain embodiments, R n is -N(R GA )C(=O)R GA , for example, —NHC(═O)CH. In certain embodiments, R x is -N(R GA )C(=O)R GA , for example, —NHC(═O)CH. In certain embodiments, R m , R n , and R x One of the is -N(R GA )C(=O)OR GA , for example, —NHC(═O)OCH. In certain embodiments, R m is -N(R GA )C(=O)OR GA , for example, —NHC(═O)OCH. In certain embodiments, R n is -N(R GA )C(=O)OR GA , for example, —NHC(═O)OCH. In certain embodiments, R x is -N(R GA )C(=O)OR GA , for example, —NHC(═O)OCH. In certain embodiments, R m , R n , and R x One of the is -N(R GA )C(=O)N(R GA )2, for example, -NHC(=O)NH2 or -NHC(=O)N(CH3)2. In certain embodiments, R m is -N(R GA )C(=O)N(R GA )2, for example, -NHC(=O)NH2 or -NHC(=O)N(CH3)2. In certain embodiments, R n is -N(R GA)C(=O)N(R GA )2, for example, -NHC(=O)NH2 or -NHC(=O)N(CH3)2. In certain embodiments, R x is -N(R GA )C(=O)N(R GA )2, for example, -NHC(=O)NH2 or -NHC(=O)N(CH3)2.

[0145] In certain embodiments, R m , R n , and R x At least one of the following is -SR GA , -S(O)R GA , e.g., -S(=O)R GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA For example, where R GA is hydrogen, substituted or unsubstituted C 1~6 alkyl (e.g., —CH or —CF), substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. In certain embodiments, R m , R n , and R x One of them is -SR GA , for example, -SCH, or -S-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m , R n , and R x One of them is -S(O)R GA , e.g., -S(=O)R GA , for example, —S(═O)CH, —S(═O)CF, or —S(═O)-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m , R n , and R x One of them is -S(=O)2R GA, for example, —S(═O)2CH3, —S(═O)2CF3, or —S(═O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m -SR GA , e.g., -SCH3, -SCF3; -S(O)R GA , e.g., -S(=O)R GA , for example, -S(=O)CH3, -S(=O)CF3; -S(=O)2R GA , for example, —S(═O)2CH3, —S(═O)2CF3, or —S(═O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n -SR GA , e.g., -SCH3, -SCF3; -S(O)R GA , e.g., -S(=O)R GA , for example, -S(=O)CH3, -S(=O)CF3; -S(=O)2R GA , for example, —S(═O)2CH3, —S(═O)2CF3, or —S(═O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x -SR GA , e.g., -SCH3, -SCF3; -S(O)R GA , e.g., -S(=O)R GA , for example, -S(=O)CH3, -S(=O)CF3; -S(=O)2R GA , for example, —S(═O)2CH3, —S(═O)2CF3, or —S(═O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m , R n , and R x One of them is -S(=O)2OR GA In certain embodiments, R m is -S(=O)2OR GA, for example, —S(═O)2OCH3, —S(═O)2OCF3, or —S(═O)2Oaryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n is -S(=O)2OR GA , for example, —S(═O)2OCH3, —S(═O)2OCF3, or —S(═O)2Oaryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x is -S(=O)2OR GA , for example, —S(═O)2OCH3, —S(═O)2OCF3, or —S(═O)2Oaryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m , R n , and R x One of them is -OS(=O)2R GA In certain embodiments, R m is -OS(=O)2R GA , for example, —OS(═O)CH, —OS(═O)CF, or —OS(═O)-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n is -OS(=O)2R GA , for example, —OS(═O)CH, —OS(═O)CF, or —OS(═O)-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x is -OS(=O)2R GA , for example, —OS(═O)CH, —OS(═O)CF, or —OS(═O)-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m , R n , and R x One of the is -S(=O)2N(R GA )2. In certain embodiments, R m is -S(=O)2N(R GA)2, for example, -S(=O)2NHCH3, -S(=O)2NHCF3, or -S(=O)2-NH-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n is -S(=O)2N(R GA )2, for example, -S(=O)2NHCH3, -S(=O)2NHCF3, or -S(=O)2-NH-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x is -S(=O)2N(R GA )2, for example, -S(=O)2NHCH3, -S(=O)2NHCF3, or -S(=O)2-NH-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m , R n , and R x One of the is -N(R GA )S(=O)2R GA In certain embodiments, R m is -N(R GA )S(=O)2R GA , for example, —NHS(═O)2CH3, —NHS(═O)2CF3, or —NHS(═O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n is -N(R GA )S(=O)2R GA , for example, —NHS(═O)2CH3, —NHS(═O)2CF3, or —NHS(═O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x is -N(R GA )S(=O)2R GA , for example, -NHS(=O)2CH3, -NHS(=O)2CF3, or -NHS(=O)2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl.

[0146] In certain embodiments, Rm , R n , and R x At least one of the following is a substituted or unsubstituted C 1~6 Alkyl, e.g., substituted or unsubstituted C 1~2 Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C 3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 An exemplary C 1~6 Alkyl groups include substituted or unsubstituted methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), iso-butyl (C4), n-pentyl (C5), 3-pentanyl (C5), amyl (C5), neopentyl (C5), 3-methyl-2-butanyl (C5), tertiary amyl (C5), n-hexyl (C6), C substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more fluoro groups. 1~6 alkyl (e.g., -CF3, -CH2F, -CHF2, difluoroethyl, and 2,2,2-trifluoro-1,1-dimethyl-ethyl), C substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more chloro groups 1~6 C substituted with alkyl (e.g., -CH2Cl, -CHCl2), and alkoxy groups 1~6 Examples of alkyl include, but are not limited to, alkyl (e.g., -CH2OCH3 and -CH2OCH2CH3). In certain embodiments, R m , R n , and R x At least one of the substitutions C 1~6 alkyl (e.g., R m , R n , and R x At least one of R is haloalkyl, alkoxyalkyl, or aminoalkyl. m , R n , and R xAt least one of is Me, Et, n-Pr, n-Bu, i-Bu, fluoromethyl, chloromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, difluoroethyl, 2,2,2-trifluoro-1,1-dimethyl-ethyl, methoxymethyl, methoxyethyl, or ethoxymethyl.

[0147] In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 2~6 Alkenyl (e.g., substituted or unsubstituted C 2~3 Alkenyl, substituted or unsubstituted C 3~4 Alkenyl, substituted or unsubstituted C 4~5 Alkenyl, or substituted or unsubstituted C 5~6 alkenyl). In certain embodiments, R m , R n , and R x At least one of R is ethenyl (C2), propenyl (C3), or butenyl (C4) that is unsubstituted or substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxyl. m , R n , and R x At least one of is ethenyl, propenyl, or butenyl that is unsubstituted or substituted with alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxy.

[0148] In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 2~6 Alkynyl, for example, substituted or unsubstituted C 2~3 Alkynyl, substituted or unsubstituted C 3~4 Alkynyl, substituted or unsubstituted C 4~5 Alkynyl, or substituted or unsubstituted C 5~6 In certain embodiments, Rm , R n , and R x At least one of is ethynyl, propynyl, or butynyl that is unsubstituted or substituted with alkyl, halo, haloalkyl (e.g., CF), alkoxyalkyl, cycloalkyl (e.g., cyclopropyl or cyclobutyl), or hydroxyl.

[0149] In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 3~6 Carbocyclyl, e.g., substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted C 4~5 Carbocyclyl, or substituted or unsubstituted C 5~6 In certain embodiments, R m , R n , and R x At least one of is substituted or unsubstituted cyclopropyl or substituted or unsubstituted cyclobutyl.

[0150] In certain embodiments, R m , R n , and R x At least one of is a substituted or unsubstituted 3- to 6-membered heterocyclyl, for example, a substituted or unsubstituted 3- to 4-membered heterocyclyl, a substituted or unsubstituted 4- to 5-membered heterocyclyl, or a substituted or unsubstituted 5- to 6-membered heterocyclyl.

[0151] In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GAis a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3).

[0152] Exemplary R as a Non-Hydrogen Substituent m , R n , and R x are contemplated herein.

[0153] For example, in certain embodiments, the formula [ka] The C21-pyrazolyl of the formula is a monosubstituted pyrazolyl ring of the formula: [ka] (In the formula, R m , R n , and R x are each a non-hydrogen substituent as defined herein).

[0154] In certain embodiments, the formula [ka] The C21-pyrazolyl of the formula is a disubstituted pyrazolyl ring of the formula: [ka] (In the formula, R m , R n , and R x are each a non-hydrogen substituent as defined herein).

[0155] In certain embodiments, the formula [ka] The C21-pyrazolyl is a trisubstituted pyrazolyl ring, where R m , R n, and R x Each of is a non-hydrogen substituent as defined herein.

[0156] For example, R 2a is a hydrogen or non-hydrogen alpha substituent, in certain embodiments, of formula (II-A1) or (II-B1): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3a is —CH, —CHCH, —CHF, —CHF, —CF, —CHOCH, or substituted or unsubstituted cyclopropyl. 2a is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. 11a and R 11b and R are hydrogen. 11a and R 11b together form =O (oxo). In certain embodiments where Ring B contains a C5-C6 double bond, R 6a is hydrogen, fluoro, —CH, or —CF. In certain embodiments where Ring B does not contain a C-C double bond, R 6a and R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b are —CH or —CF. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a is a non-hydrogen substituent, and R 6bis hydrogen. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0157] R 2a is hydrogen or a non-hydrogen β-substituent, in certain embodiments, of formula (II-A2) or (II-B2): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3a is —CH, —CHCH, —CHF, —CHF, —CF, —CHOCH, or substituted or unsubstituted cyclopropyl. 2a is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. 11a and R 11b and R are hydrogen. 11a and R 11b together form =O (oxo). In certain embodiments where Ring B contains a C5-C6 double bond, R 6ais hydrogen, fluoro, —CH, or —CF. In certain embodiments where Ring B does not contain a C-C double bond, R 6a and R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b are —CH or —CF. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a is a non-hydrogen substituent, and R 6b is hydrogen. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0158] R 11a is a hydrogen or non-hydrogen alpha substituent, and R 11b In certain embodiments, where R is hydrogen, the compound of formula (II-A3) or (II-B3): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3ais —CH, —CHCH, —CHF, —CHF, —CF, —CHOCH, or substituted or unsubstituted cyclopropyl. 2a is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. 2a is a non-hydrogen substituent in the alpha configuration. In certain embodiments, R 2a is a non-hydrogen substituent in the β configuration. In certain embodiments where Ring B contains a C5-C6 double bond, R 6a is hydrogen, fluoro, —CH, or —CF. In certain embodiments where Ring B does not contain a C-C double bond, R 6a and R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b are —CH or —CF. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a is a non-hydrogen substituent, and R 6b is hydrogen. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m , Rn , and R x Each occurrence of is hydrogen.

[0159] R 11a is a hydrogen or non-hydrogen β-substituent, and R 11b In certain embodiments, where R is hydrogen, the compound of formula (II-A4) or (II-B4): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3a is —CH, —CHCH, —CHF, —CHF, —CF, —CHOCH, or substituted or unsubstituted cyclopropyl. 2a is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. 2a is a non-hydrogen substituent in the alpha configuration. In certain embodiments, R 2a is a non-hydrogen substituent in the β configuration. In certain embodiments where Ring B contains a C5-C6 double bond, R 6a is hydrogen, fluoro, —CH, or —CF. In certain embodiments where Ring B does not contain a C-C double bond, R 6a and R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b are —CH or —CF. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a is a non-hydrogen substituent, and R 6bis hydrogen. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0160] R 11a and R 11b taken together to form an oxo group, in certain embodiments, formula (II-A5) or (II-B5): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3a is —CH, —CHCH, —CHF, —CHF, —CF, —CHOCH, or substituted or unsubstituted cyclopropyl. 2a is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. 2a is a non-hydrogen substituent in the alpha configuration. In certain embodiments, R 2a is a non-hydrogen substituent in the β configuration. In certain embodiments where Ring B contains a C5-C6 double bond, R 6ais hydrogen, fluoro, —CH, or —CF. In certain embodiments where Ring B does not contain a C-C double bond, R 6a and R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b are —CH or —CF. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a is a non-hydrogen substituent, and R 6b is hydrogen. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0161] R 6a In certain embodiments, where is a non-hydrogen substituent, formula (II-A6) or (II-B6): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3ais —CH, —CHCH, —CHF, —CHF, —CF, —CHOCH, or substituted or unsubstituted cyclopropyl. 2a is -OH, -OCH3, -OCH2CH3, -OCH2CH2CH3, -CH3, -CH2CH3, -CH2CH2CH3, substituted or unsubstituted cyclopropyl, fluoro, or chloro. 2a is a non-hydrogen substituent in the alpha configuration. In certain embodiments, R 2a is a non-hydrogen substituent in the β configuration. In certain embodiments, R 11a and R 11b and R are hydrogen. 11a and R 11b together form =O (oxo). In certain embodiments, R 6a is fluoro, -CH3, or -CF3, and R 6b is hydrogen. In certain embodiments, R 6b is fluoro, -CH3, or -CF3, and R 6a is hydrogen. In certain embodiments, R 6a and R 6b and R are —CH or —CF. In certain embodiments, R 6a and R 6b and R are both fluoro. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m, R n , and R x Each occurrence of is hydrogen.

[0162] In certain embodiments, the compound of formula (II-A7) or (II-B7): [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, R 3a is -CH3, -CH2CH3, -CH2F, -CHF2, -CF3, -CH2OCH3, or substituted or unsubstituted cyclopropyl. In certain embodiments, the C21-pyrazolyl ring is a monosubstituted pyrazolyl. In certain embodiments, the C21-pyrazolyl ring is a disubstituted pyrazolyl. In certain embodiments, R m , R n , and R x At least one of the following is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3, -CF3), -CO2R GA , -C(=O)R GA , -CN, -NO2, or halogen, where R GA is a substituted or unsubstituted C 1~2 In certain embodiments, the C21-pyrazolyl ring is unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0163] In some embodiments, the compound is: [Table 1-1] [Table 1-2] [Table 1-3]

[0164]

[0165] In some embodiments, a compound of formula (II-I): [ka] or a pharmaceutically acceptable salt thereof, In formula (II-I), t is 1, 2, or 3; n is 0, 1, or 2; R 19 is a substituted or unsubstituted C2-C6 alkyl, a substituted or unsubstituted C2-C6 alkenyl, or a substituted or unsubstituted C2-C6 alkynyl; R 5 is hydrogen or methyl, or [ka] is a double bond, R 5 does not exist; R 3 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; R 6a and R 6b each is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R 6a and R 6b together to form an oxo (=O) group; R 1 is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR A1 , -SRA1 , -N(R A1 )2, -N(R A1 ), -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 )2, -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 )2, -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 )2, -OS(=O)2R A2 , -OS(=O)2OR A1 , -SS(=O)2R A2 , -SS(=O)2OR A1 , -S(=O)R A2 , -SO2R A2 , or -S(=O)2OR A1 where R A1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, or two R A1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R A2 is 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; R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R11a , R 11b , R 12a , R 12b , or R 17b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 each occurrence 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, or 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 R D1 groups taken together form a substituted or unsubstituted heterocyclic ring; or R 2a and R 2b , R 4a and R 4b , R 7a and R 7b , R 11a and R 11b , and R 12a and R 12b any one of these taken together form an oxo (=O) group; R 15a , R 15b , R 16a , and R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, 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, -OR A1 , -SR A1 , -N(R A1 )2, -N(R A1 ), -CN(R A1)2, -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 )2, -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 )2, -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 )2, -OS(=O)2R A2 , -OS(=O)2OR A1 , -SS(=O)2R A2 , -SS(=O)2OR A1 , -S(=O)R A2 , -SO2R A2 , or -S(=O)2OR A1 where R A1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, -SOR A2 , -C(O)R A2 or two R A1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R A2 is 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; where: [ka] represents a single bond or a double bond, and when a double bond is present in ring B, R 6a or R 6b One of the two and R 5 does not exist.

[0166] It should be recognized that the stereochemistry of C17 can be depicted in any of the following equivalent ways: [ka] . R in formula (II-I) 2a and R 2b base

[0167] In some situations, R 2a and R 2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0168] In some situations, R 2a and R 2b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0169] In some situations, R 2a and R 2b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0170] In some situations, R 2a and R 2b are both hydrogen.

[0171] In some embodiments, R 2a and R 2b is each independently hydrogen or substituted or unsubstituted alkyl.

[0172] In some embodiments, R 2a and R 2b each independently is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0173] In some embodiments, R 2a and R 2b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (II-I) 4a and R 4b base

[0174] In some situations, R4a and R 4b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0175] In some situations, R 4a and R 4b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0176] In some situations, R 4a and R 4b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0177] In some situations, R 4a and R 4b and R are hydrogen. 16a and R 16b is each independently hydrogen or substituted or unsubstituted alkyl.

[0178] In some situations, R 4a and R 4b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. 4a and R 4b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. 11a and R 11b

[0179] In some embodiments, R 11a and R 11b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0180] In some further embodiments, R 11a and R 11b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0181] In some situations, R 11a and R 11b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 11a and R 11b are both hydrogen.

[0182] In some situations, R 11a and R 11b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 11a and R 11b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0183] In some situations, R 11a and R 11b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2.

[0184] In some embodiments, R 11a and R 11b together to form oxo (=O). R in formula (II-I) 15a and R 15b base

[0185] In some situations, R 15a and R 15b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0186] In some embodiments, R 15a and R 15b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0187] In some embodiments, R 15a and R 15bare each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0188] In some further embodiments, R 15a and R 15b are both hydrogen.

[0189] In some situations, R 15a and R 15b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 15a and R 15b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. 15a and R 15b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (II-I) 16a and R 16b base

[0190] In some situations, R 16a and R 16b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0191] In some embodiments, R 16a and R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0192] In some embodiments, R 16a and R 16b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0193] In some further embodiments, R 16a and R 16b are both hydrogen.

[0194] In some situations, R 16a and R 16b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R16a and R 16b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0195] In some situations, R 16a and R 16b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (II-I) 7a and R 7b base

[0196] In some embodiments, R 7a and R 7b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 each occurrence 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, or substituted or unsubstituted heteroaryl, or R 7a and R 7b When either of these is taken together, it forms an oxo (=O).

[0197] In some further embodiments, R 7a and R 7b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0198] In some situations, R 7a and R 7b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0199] In some situations, R 7a and R 7b All of the is hydrogen.

[0200] In some situations, R 7a and R 7b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 7a and R 7b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0201] In some situations, R 7a and R 7b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2.

[0202] In some embodiments, R 7a and R 7b When either of these is taken together, it forms an oxo (=O). R in formula (II-I) 5 base

[0203] In some situations, R 5 is a hydrogen cis to C19. In some other aspects, R 5 is a hydrogen trans to C19. 5 is a methyl cis to C19. In some further embodiments, R 5 is a methyl in the trans position relative to C19. R in formula (II-I) 3 base

[0204] In some embodiments, R 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

[0205] In some embodiments, R 3 is a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0206] In some embodiments, R 3 is a substituted or unsubstituted alkyl.

[0207] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a substituted alkyl (e.g., —CHOMe or —CHOEt, etc.). In some embodiments, R 3 is unsubstituted alkyl. In some embodiments, R 3 is methyl. R in formula (II-I) 19 base

[0208] In some situations, R 19 is C2-C6 alkyl. In some aspects, R 19 is a deuterium-substituted C2-C6 alkyl.

[0209] In some embodiments, R19 is a substituted C2-C6 alkyl. In some embodiments, R 19 is an unsubstituted C2-C6 alkyl.

[0210] In some embodiments, R 19 is a substituted C-C alkenyl. 19 is unsubstituted C2-C6 alkenyl.

[0211] In some embodiments, R 19 is a substituted C2-C6 alkynyl. 19 is unsubstituted C2-C6 alkynyl.

[0212] In some situations, R 19 is ethyl. R in formula (II-I) 6a and R 6b base

[0213] In some embodiments, R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

[0214] In some situations, R 6a and R 6b are independently hydrogen or substituted or unsubstituted alkyl.

[0215] In some situations, R 6a and R 6b are independently hydrogen or substituted alkyl. In some embodiments, R 6a and R 6b is independently hydrogen or unsubstituted alkyl.

[0216] In some situations, R 6a and R 6b and R are hydrogen. 6a is halo or alkyl, and R 6bis hydrogen. In some embodiments, R 6a and R 6b Both are halos.

[0217] In some situations, R 6a and R 6b are both alkyl.

[0218] In some embodiments, R 6a and R 6b together form an oxo group. R in formula (II-I) 12a and R 12b base

[0219] In some embodiments, R 12a and R 12b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0220] In some situations, R 12a and R 12b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0221] In some embodiments, R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0222] In some embodiments, R 12a and R 12b are both hydrogen.

[0223] In some further embodiments, R 12a and R 12b is each independently hydrogen or substituted or unsubstituted alkyl.

[0224] In some embodiments, R 12a and R 12b together form an oxo group (=O). R in formula (II-I) 17b base

[0225] In some embodiments, R 17b is fluorine, hydroxyl, methyl, or hydrogen. In some further embodiments, R 17b The hydrogen in is replaced with deuterium. t and n in formula (II-I)

[0226] In some embodiments, t is 1. In some other embodiments, t is 2. In some other embodiments, t is 3.

[0227] In some embodiments, n is 1. In some other embodiments, n is 2. R in formula (II-I) 1 base

[0228] In some embodiments, R 1 is 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.

[0229] In some embodiments, R 1 teeth, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, C 5~10 substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; e is 0, 1, 2, 3, 4, or 5; or n is 0, 1, 2, 3, 4, or 5.

[0230] In some embodiments, R 1 teeth, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA)2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, C 5~10 substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; e is 0, 1, 2, 3, 4, or 5; and n is 0, 1, 2, 3, 4, or 5.

[0231] In some embodiments, R 1is a substituted carbocyclyl, substituted heterocyclyl, substituted aryl, or substituted heteroaryl, where each substituted carbocyclyl, substituted heterocyclyl, substituted aryl, or substituted heteroaryl is independently substituted with an unsubstituted or substituted carbocyclyl, unsubstituted or substituted heterocyclyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl.

[0232] In some embodiments, the compound of formula (II-I) has the formula (II-Ia): [ka] or a pharmaceutically acceptable salt thereof.

[0233] In some embodiments, the compound of formula (II-I) has the formula (II-Ib): [ka] or a pharmaceutically acceptable salt thereof.

[0234] In some embodiments, the compound of formula (II-I) has the formula (II-Ic): [ka] or a pharmaceutically acceptable salt thereof.

[0235] In some embodiments, the compound of formula (II-I) has the formula (II-Ie): [ka] or a pharmaceutically acceptable salt thereof, In formula (II-Ie), m is 0, 1, 2, or 3; p is 0, 1, or 3; R 32 Each of is independently halogen, alkyl, hydroxyl, or cyano.

[0236] In some embodiments, the compound of formula (II-I) has the formula (II-Ig): [ka] or a pharmaceutically acceptable salt thereof, In formula (II-Ig), u is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA The groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

[0237] In some embodiments, the compound of formula (II-I) has the formula (II-Iga) [ka] or a pharmaceutically acceptable salt thereof, In formula (II-Ii), u is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA The groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

[0238] In some embodiments, the compound of formula (II-I) has the formula (II-Ih): [ka] or a pharmaceutically acceptable salt thereof, In formula (II-Ih), R 35 is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2, or 3.

[0239] In some embodiments, the compound of formula (II-I) has the formula (II-Ii): [ka] or a pharmaceutically acceptable salt thereof, In formula (II-Ii), s is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA The groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

[0240] In some embodiments, the compound is selected from the group consisting of the compounds identified in Table II-1 below: [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] compound

[0241] In some embodiments, a compound of formula (III-I): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-I), n is 0, 1, or 2; R 3a is 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; R 18is a substituted alkyl or unsubstituted C2-C6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted C2-C6 alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; R 5 is hydrogen or methyl, or [ka] is a double bond, R 5 does not exist; R 6a and R 6b each is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R 6a and R 6b together to form an oxo (=O) group; R 1 is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 )2, -N(R A1 ), -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 )2, -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 )2, -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 )2, -OS(=O)2RA2 , -OS(=O)2OR A1 , -SS(=O)2R A2 , -SS(=O)2OR A1 , -S(=O)R A2 , -SO2R A2 , or -S(=O)2OR A1 where R A1 each occurrence 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, a nitrogen protecting group when attached to a nitrogen atom, or two R A1 groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R A2 is 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; R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , or R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 ,-OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where RD1 each occurrence 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, or 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 R D1 groups taken together form a substituted or unsubstituted heterocyclic ring; or R 2a and R 2b , R 4a and R 4b , R 7a and R 7b , R 11a and R 11b , and R 12a and R 12b any one of these taken together form an oxo (=O) group; where: [ka] represents a single bond or a double bond, and when a double bond is present in ring B, R 6a or R 6b One of them does not exist.

[0242] In some embodiments, a compound of formula (III-II): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-II), Variable group R 18 ,n,R 5 , R 1 , R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b, R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , and R 16b is as defined in formula III-I above; R 3a 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; R 19 is hydrogen, C1-C6 substituted alkyl, C2-C6 unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; However, n is 0 and R 1 is methyl and R 1a , R 1b , R 2a , R 2b , R 4a , R 4b , R 6a , R 6b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , and R 16b is hydrogen, R 18 is a substituted C1-C6 alkyl, an unsubstituted C3-C6 alkyl, a substituted or unsubstituted alkenyl, or a substituted or unsubstituted alkynyl, where R 18 is a substituted methyl, the methyl is not a halogen, -CN, -NO2, -SO2H, -SO3H, -OR aa , -ON(R bb )2, -N(R bb )2, -C(=O)R aa , —C(O)H, —COH, carbocyclyl, heterocyclyl, aryl, or heteroaryl, where R aa Each occurrence of independently, C1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3- to 14-membered heterocyclyl, C 6~14 aryl, and 5- to 14-membered heteroaryl, or two R aa groups taken together to form a 3- to 14-membered heterocyclyl ring or a 5- to 14-membered heteroaryl ring; R bb Each occurrence of is independently hydrogen, -OH, -OR aa , -N(R cc )2, -CN, -C(=O)R aa , -C(=O)N(R cc )2, -CO2R aa , -SO2R aa , or -C(=NR cc ) OR aa is selected from. R in formula (III-I) and formula (III-II) 18 base

[0243] In some situations, R 18 is alkyl substituted with halogen, cyano, —COH, or phenyl.

[0244] In some embodiments, R 18 is a substituted or unsubstituted C2-C6 alkyl.

[0245] In some embodiments, R 18 is -CH(CH3)2.

[0246] In some embodiments, R 18 is a substituted alkyl. In some embodiments, the alkyl is substituted with —OCH 3 , —CH 2 CN, or —OCH(CH 3 ) 2 .

[0247] In some embodiments, R 18 is propyl, butyl, t-butyl, or isopropyl, or ethyl. R in formula (III-I) and formula (III-II)1a and R 1b base

[0248] In some situations, R 1a and R 1b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0249] In some situations, R 1a and R 1b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0250] In some situations, R 1a and R 1b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0251] In some situations, R 1a and R 1b are both hydrogen.

[0252] In some embodiments, R 1a and R 1b is each independently hydrogen or substituted or unsubstituted alkyl.

[0253] In some embodiments, R 1a and R 1b are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. 1a and R 1b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (III-I) and formula (III-II) 2a and R 2b base

[0254] In some situations, R 2a and R 2b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0255] In some situations, R 2a and R 2b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0256] In some situations, R 2a and R 2b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0257] In some situations, R 2a and R 2b are both hydrogen.

[0258] In some embodiments, R 2a and R 2b is each independently hydrogen or substituted or unsubstituted alkyl.

[0259] In some embodiments, R 2a and R 2b each independently is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0260] In some embodiments, R 2a and R 2b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (III-I) and formula (III-II) 4a and R 4b base

[0261] In some situations, R 4a and R 4b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0262] In some situations, R 4a and R 4b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0263] In some situations, R 4a and R 4b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0264] In some situations, R 4a and R 4b and R are hydrogen. 16a and R 16b is each independently hydrogen or substituted or unsubstituted alkyl.

[0265] In some situations, R 4a and R 4b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. 4a and R 4b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (III-I) and formula (III-II) 11a and R 11b base

[0266] In some embodiments, R 11a and R 11bare each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0267] In some further embodiments, R 11a and R 11b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0268] In some situations, R 11a and R 11b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 11a and R 11b are both hydrogen.

[0269] In some situations, R 11a and R 11b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 11a and R 11b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0270] In some situations, R 11a and R 11b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2.

[0271] In some embodiments, R 11a and R 11b together to form oxo (=O). R in formula (III-I) and formula (III-II) 15a and R 15b base

[0272] In some situations, R 15a and R 15b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0273] In some embodiments, R 15a and R 15b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0274] In some embodiments, R 15a and R 15b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0275] In some further embodiments, R 15a and R 15b are both hydrogen.

[0276] In some situations, R 15a and R 15b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R15a and R 15b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH. 15a and R 15b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (III-I) and formula (III-II) 16a and R 16b base

[0277] In some situations, R 16a and R 16b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0278] In some embodiments, R 16a and R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0279] In some embodiments, R 16a and R 16b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0280] In some further embodiments, R 16a and R 16b are both hydrogen.

[0281] In some situations, R 16a and R 16b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 16a and R 16b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0282] In some situations, R 16a and R 16b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2. R in formula (III-I) and formula (III-II) 7a and R 7b base

[0283] In some embodiments, R 7a and R 7b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1, -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 each occurrence 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, or substituted or unsubstituted heteroaryl, or R 7a and R 7b When either of these is taken together, it forms an oxo (=O).

[0284] In some further embodiments, R 7a and R 7b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0285] In some situations, R 7a and R 7b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0286] In some situations, R7a and R 7b All of the is hydrogen.

[0287] In some situations, R 7a and R 7b are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 7a and R 7b are independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkoxyhalo, or —OH.

[0288] In some situations, R 7a and R 7b is -CH3, -CH2CH3, -OH, -OCH3, or -CH(CH3)2.

[0289] In some embodiments, R 7a and R 7b When either of these is taken together, it forms an oxo (=O). R in formula (III-I) and formula (III-II) 5 base

[0290] In some situations, R 5 is a hydrogen cis to C19. In some other aspects, R 5 is a hydrogen trans to C19. 5 is a methyl cis to C19. In some further embodiments, R 5 is a methyl in the trans position relative to C19. R in formula (III-I) and formula (III-II) 3a base

[0291] In some embodiments, R 3a is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

[0292] In some embodiments, R 3ais a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl.

[0293] In some embodiments, R 3a is a substituted or unsubstituted alkyl.

[0294] In some embodiments, R 3a is hydrogen. In some embodiments, R 3a is a substituted alkyl (e.g., —CHOMe or —CHOEt, etc.). In some embodiments, R 3a is unsubstituted alkyl. In some embodiments, R 3a is methyl.

[0295] In some situations, R 3a is not trifluoromethyl. R in formula (III-I) and formula (III-II) 19 base

[0296] In some situations, R 19 is substituted alkyl. In some aspects, R 19 is an unsubstituted alkyl.

[0297] In some situations, R 19 is C2-C6 alkyl. In some embodiments, R 19 is hydrogen. In some aspects, R 19 is a deuterium-substituted C2-C6 alkyl.

[0298] In some embodiments, R 19 is a substituted C2-C6 alkyl. In some embodiments, R 19 is an unsubstituted C2-C6 alkyl.

[0299] In some embodiments, R 19 is a substituted C-C alkenyl. 19 is unsubstituted C2-C6 alkenyl.

[0300] In some embodiments, R 19 is a substituted C2-C6 alkynyl. 19 is unsubstituted C2-C6 alkynyl.

[0301] In some situations, R 19 is ethyl. R in formula (III-I) and formula (III-II) 6a and R 6b base

[0302] In some embodiments, R 6a and R 6b is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

[0303] In some situations, R 6a and R 6b are independently hydrogen or substituted or unsubstituted alkyl.

[0304] In some situations, R 6a and R 6b are independently hydrogen or substituted alkyl. In some embodiments, R 6a and R 6b is independently hydrogen or unsubstituted alkyl.

[0305] In some situations, R 6a and R 6b and R are hydrogen. 6a is halo or alkyl, and R 6b is hydrogen. In some embodiments, R 6a and R 6b Both are halos.

[0306] In some situations, R 6a and R 6b are both alkyl.

[0307] In some embodiments, R 6a and R 6b together form an oxo group. R in formula (III-I) and formula (III-II) 12a and R 12b base

[0308] In some embodiments, R 12a and R 12b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of 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, or substituted or unsubstituted heteroaryl.

[0309] In some situations, R 12a and R 12b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH2, or -N(R D1 )2, where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0310] In some embodiments, R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1, -OC(=O)R D1 , -NH2, -N(R D1 )2, or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0311] In some embodiments, R 12a and R 12b are both hydrogen.

[0312] In some further embodiments, R 12a and R 12b is each independently hydrogen or substituted or unsubstituted alkyl.

[0313] In some embodiments, R 12a and R 12b together form an oxo group (=O). Group n of formula (III-I) and formula (III-II)

[0314] In some embodiments, n is 1. In some other embodiments, n is 2.

[0315] In some embodiments, n is 0. In some embodiments, n is 1. In some other embodiments, n is 2. R in formula (III-I) and formula (III-II) 1 base

[0316] In some embodiments, R 1 is 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.

[0317] In some embodiments, R1 teeth, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6carbocyclyl, 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; e is 0, 1, 2, 3, 4, or 5.

[0318] In some embodiments, R 1 teeth, [ka] and where R 20 Each occurrence of independently represents a halogen, -NO2, -CN, -OR GA , -N(R GA )2, -C(=O)R GA , -C(=O)OR GA , -OC(=O)R GA , -OC(=O)OR GA , -C(=O)N(R GA )2, -N(R GA )C(=O)R GA , -OC(=O)N(R GA )2, -N(R GA )C(=O)OR GA , -S(=O)2R GA , -S(=O)2OR GA , -OS(=O)2R GA , -S(=O)2N(R GA )2, or -N(R GA )S(=O)2R GA , substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, or optionally two R GA together with the intervening atoms form a substituted or unsubstituted 3- or 4-membered carbocyclic or heterocyclic ring; where R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; e is 0, 1, 2, 3, 4, or 5.

[0319] In some embodiments, the compound of formula (III-I) or (III-II) has the formula (III-Ia), [ka] or a pharmaceutically acceptable salt thereof.

[0320] In some embodiments, the compound of formula (III-I) or (III-II) has the formula (III-Ib) [ka] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound of formula (III-I) or (III-II) is a compound of formula (III-Ie): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-Ie), m is 0, 1, 2, or 3; p is 0, 1, 2, or 3; R 32is independently halogen, alkyl, hydroxyl, or cyano. In some embodiments, the compound of Formula (III-I) or (III-II) has the formula (III-Ig): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-Ig), u is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA The groups taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring. In some embodiments, the compound of formula (III-I) or (III-II) has formula (III-Ih): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-Ih), R 35 is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2, or 3. In some embodiments, the compound of Formula (III-I) or (III-II) has the formula (III-Ii): [ka] or a pharmaceutically acceptable salt thereof, In formula (III-Ii), s is 0, 1, or 2; each X is independently -C(R N )-, -C(R N )2-, -O-, -S-, -N-, or N(R N )-, where R N are independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O)OR GA , -C(=O)N(R GA )2, -S(=O)2R GA , or -S(=O)2N(R GA )2; R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, substituted or unsubstituted C 2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or unsubstituted C 3~6 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 R GA The groups, taken together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

[0321] In some embodiments, the compound is selected from the group consisting of the compounds identified in Table III-1 herein: [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4]

[0322] In one aspect, provided herein are pharmaceutically acceptable salts of the compounds described herein (e.g., compounds of Formula (IX, II, II-I, III-1, or III-2)).

[0323] In one aspect, provided herein is a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0324] In certain embodiments, the compounds of the invention are provided in a pharmaceutical composition in an effective amount. In certain embodiments, the compounds of the invention are provided in a therapeutically effective amount.

[0325] The compounds of the invention described herein may, in certain embodiments, be used to treat, for example, GABA A GAB acts on receptors in a positive or negative manner A Such compounds act as modulators of GABA. A They are predicted to have central nervous system (CNS) activity as regulators of CNS excitability as mediated by their ability to modulate receptors.

[0326] Therefore, in another aspect, a method for treating a CNS-related disorder in a subject in need thereof is provided, comprising administering to the subject an effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof. In certain embodiments, the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a memory and / or cognitive disorder, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. In certain embodiments, the CNS-related disorder is depression. In certain embodiments, the CNS-related disorder is postpartum depression. In certain embodiments, the CNS-related disorder is major depressive disorder. In certain embodiments, the major depressive disorder is moderate major depressive disorder. In certain embodiments, the major depressive disorder is severe major depressive disorder. In certain embodiments, the compound is administered orally, subcutaneously, intravenously, or intramuscularly. In certain embodiments, the compound is administered orally. In certain embodiments, the compound is administered chronically. In certain embodiments, the compound is administered continuously, for example, by continuous intravenous infusion.

[0327] Exemplary compounds of the invention can be synthesized from the following known starting materials using methods known to those skilled in the art or certain references. In one aspect, provided herein are pharmaceutically acceptable salts of the compounds described herein (e.g., compounds of Formula (IX, II, II-I, III-I, or III-II)). Alternative Embodiments

[0328] In alternative embodiments, the compounds described herein may also contain one or more isotopic substitutions. For example, hydrogen may be: 2 H (D or deuterium) or 3 H (T or tritium); carbon can be, for example, 13 C or 14 C; oxygen can be, for example, 18 O; nitrogen can be, for example,15 N, etc. In other embodiments, a specific isotope (e.g., 3 H, 13 C. 14 C. 18 O or 15 N) can represent at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or at least 99.9% of the total isotopic abundance of the element occupying a particular site on the compound. Pharmaceutical Compositions

[0329] In one aspect, provided herein is a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In certain embodiments, the compound of the present invention is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the compound of the present invention is provided in a therapeutically effective amount.

[0330] In certain embodiments, the pharmaceutical composition comprises an effective amount of the active ingredient. In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the active ingredient.

[0331] The pharmaceutical compositions provided herein can be administered by a variety of routes, including, but not limited to, oral (enteral), parenteral (by injection), rectal, transdermal, intradermal, intrathecal, subcutaneous (SC), intravenous (IV), intramuscular (IM), and intranasal administration.

[0332] Generally, the compounds provided herein are administered in an effective amount. The amount of the compound actually administered is typically determined by a physician in light of the relevant circumstances (including the condition being treated, the selected route of administration, the actual compound being administered, the age, weight and response of the individual patient, the severity of the patient's symptoms, etc.).

[0333] When used to prevent the occurrence of CNS disorders, the compounds provided herein can typically be administered to subjects at risk of developing the condition at the dosage levels described above, under the advice and supervision of a physician. Subjects at risk of developing a particular condition generally include subjects with a family history of the condition, or subjects identified by genetic testing or screening as being particularly susceptible to developing the condition.

[0334] The pharmaceutical compositions provided herein can also be administered chronically ("chronic administration"). Chronic administration refers to administration of a compound or pharmaceutical composition thereof over an extended period of time, e.g., 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or can be continued indefinitely, e.g., for the remainder of the subject's life. In certain embodiments, chronic administration is intended to provide a constant level of the compound in the blood, e.g., within the therapeutic window, for an extended period of time.

[0335] The pharmaceutical compositions of the present invention can also be delivered using various dosing methods. For example, in certain embodiments, the pharmaceutical composition can be given as a bolus, for example, to raise the concentration of the compound in the blood to an effective level. The placement of the bolus dose depends on the systemic level of the active ingredient desired throughout the body; for example, an intramuscular or subcutaneous bolus dose allows for a slow release of the active ingredient, while a bolus delivered directly into a vein (e.g., via IV infusion) allows for a faster delivery, which quickly raises the concentration of the active ingredient in the blood to an effective level. In other embodiments, the pharmaceutical composition can be administered as a continuous infusion, for example, via IV infusion, to maintain a steady-state concentration of the active ingredient in the subject's body. Furthermore, in still other embodiments, the pharmaceutical composition can be administered initially as a bolus dose, followed by continuous infusion. Compositions for oral administration can take the form of bulk liquid solutions or suspensions or bulk powders. However, more commonly, the compositions are provided in unit dosage forms to facilitate accurate dosing. The term "unit dosage form" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined amount of active ingredient calculated to produce a desired therapeutic effect, together with suitable pharmaceutical excipients. Typical unit dosage forms include pre-measured, pre-filled ampoules or syringes of liquid compositions, or pills, tablets, capsules, and the like in the case of solid compositions. In such compositions, the compound is usually a minor component (about 0.1 to about 50% by weight, or preferably about 1 to about 40% by weight), with the remainder being various vehicles or excipients and processing aids useful in forming the desired dosage form.

[0336] For oral administration, a typical regimen is 1 to 5 times, particularly 2 to 4 times, and typically 3 times per day. Using these dosing patterns, each dose provides about 0.01 to about 20 mg / kg of a compound provided herein, with preferred doses being about 0.1 to about 10 mg / kg, particularly about 1 to about 5 mg / kg.

[0337] Transdermal doses are generally selected to provide blood levels similar to or lower than those achieved using injection doses, and generally range from about 0.01% to about 20% by weight, preferably from about 0.1% to about 20% by weight, preferably from about 0.1% to about 10% by weight, and more preferably from about 0.5% to about 15% by weight.

[0338] Injectable dose levels range from about 0.1 mg / kg / hour to at least 20 mg / kg / hour, all over a period of about 1 to about 120 hours, particularly 24 to 96 hours. A preloading bolus of about 0.1 mg / kg to about 10 mg / kg or more may also be administered to achieve adequate steady-state levels. The maximum total dose is not expected to exceed about 5 g / day for a 40-80 kg human patient.

[0339] Liquid forms suitable for oral administration may include a suitable aqueous or nonaqueous vehicle with buffers, suspending and dispensing agents, colorants, flavors, etc. Solid forms may include, for example, any of the following ingredients, or compounds of a similar nature: binders (e.g., microcrystalline cellulose, gum tragacanth, or gelatin); excipients (e.g., starch or lactose); disintegrating agents (e.g., alginic acid, Primogel, or corn starch); lubricants (e.g., magnesium stearate); glidants (e.g., colloidal silicon dioxide); sweetening agents (e.g., sucrose or saccharin); or flavoring agents (e.g., peppermint, methyl salicylate, or orange flavor).

[0340] Injectable compositions are typically based on injectable sterile saline or phosphate-buffered saline or other injectable excipients known in the art. Conventionally, the active compound in such compositions is typically a minor component, often about 0.05-10% by weight, with the remainder being the injectable excipient, etc.

[0341] Transdermal compositions are typically formulated as topical ointments or creams containing active ingredient(s).When formulated as an ointment, active ingredient is typically mixed with a paraffin ointment base or a water-miscible ointment base.Alternatively, active ingredient can be formulated as a cream, for example, containing an oil-in-water cream base.Such transdermal formulations are well known in the art and generally contain additional ingredients that enhance the skin penetration or stability of active ingredient or formulation.All such known transdermal formulations and ingredients are included within the scope provided herein.

[0342] The compounds provided herein can also be administered by a transdermal device. Accordingly, transdermal administration can be accomplished using a patch either of the reservoir or porous membrane type or of a solid matrix variety.

[0343] The components described above for orally administrable, injectable, or topically administrable compositions are merely representative. Other materials, processing techniques, and the like are set forth in Part 8 of Remington's Pharmaceutical Sciences, 17th Edition, 1985, Mack Publishing Company, Easton, Pennsylvania, which is incorporated herein by reference.

[0344] The compounds of this invention can also be administered in sustained release forms or from sustained release drug delivery systems. A description of representative sustained release materials can be found in Remington's Pharmaceutical Sciences.

[0345] The present invention also relates to pharmaceutically acceptable acid addition salts of the compounds of the present invention. Acids that can be used to prepare pharmaceutically acceptable salts are those that form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions (e.g., hydrochloride, hydroiodide, hydrobromide, nitrate, sulfate, bisulfate, phosphate, acetate, lactate, citrate, tartrate, succinate, maleate, fumarate, benzoate, para-toluenesulfonate, etc.).

[0346] In another aspect, the present invention provides pharmaceutical compositions (eg, compositions suitable for injection, such as intravenous (IV) administration) comprising a compound of the present invention and a pharmaceutically acceptable excipient.

[0347] Pharmaceutically acceptable excipients include any and all diluents or other liquid vehicles suitable for the particular dosage form desired, e.g., injection, dispersing or suspending aids, surfactants, isotonic agents, preservatives, lubricants, etc. General considerations in the formulation and / or manufacture of pharmaceutical compositions can be found, for example, in Remington's Pharmaceutical Sciences, 16th Edition, E.W. Martin (Mack Publishing Co., Easton, Pa., 1980), and Remington: The Science and Practice of Pharmacy, 21st Edition (Lippincott Williams & Wilkins, 2005).

[0348] For example, injectable preparations, such as sterile injectable aqueous suspensions, can be formulated by known techniques using suitable dispersing or wetting agents and suspending agents. Exemplary excipients that can be used include, but are not limited to, water, sterile saline or phosphate-buffered saline, or Ringer's solution.

[0349] In certain embodiments, the pharmaceutical composition further comprises a cyclodextrin derivative. The most common cyclodextrins are α-, β-, and γ-cyclodextrins, which consist of six, seven, and eight α-1,4-linked glucose units, respectively, optionally containing one or more substituents on the attached sugar moiety, including, but not limited to, substituted or unsubstituted methylation, hydroxyalkylation, acylation, and sulfoalkyl ether substitution. In certain embodiments, the cyclodextrin is a sulfoalkyl ether β-cyclodextrin, e.g., sulfobutyl ether β-cyclodextrin, also known as CAPTISOL®. See, e.g., U.S. Patent No. 5,376,645. In certain embodiments, the composition comprises hexapropyl-β-cyclodextrin. In more specific embodiments, the composition comprises hexapropyl-β-cyclodextrin (10-50% in water).

[0350] Injectable compositions can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

[0351] Generally, the compounds provided herein are administered in an effective amount. The amount of the compound actually administered is typically determined by a physician in light of the relevant circumstances (including the condition being treated, the selected administration route, the actual compound being administered, the age, weight, response, and severity of the patient's symptoms, etc.).

[0352] The compositions are provided in unit dosage forms to facilitate accurate dosing. The term "unit dosage form" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined amount of active ingredient calculated to produce a desired therapeutic effect, together with suitable pharmaceutical excipients. Typical unit dosage forms include pre-measured, pre-filled ampoules or syringes of liquid compositions. In such compositions, the compound is usually a minor component (about 0.1 to about 50% by weight, or preferably about 1 to about 40% by weight), with the remainder being various vehicles or carriers and processing aids useful for forming the desired dosage form.

[0353] The compounds provided herein can be administered as a single active agent or can be administered in combination with other active agents.In one aspect, the present invention provides a combination of the compounds of the present invention with another pharmacologically active agent.The administration of the combination can be carried out by any technique that is clear to those skilled in the art, including, for example, separate administration, sequential administration, simultaneous administration and alternating administration.

[0354] Although the description of pharmaceutical compositions provided herein is primarily directed to pharmaceutical compositions suitable for administration to humans, those skilled in the art will understand that such compositions are generally suitable for administration to all types of animals. Modifications of pharmaceutical compositions suitable for administration to humans to make them suitable for administration to a variety of animals are well understood, and veterinary pharmacologists of ordinary skill can design and / or perform such modifications with routine experimentation. General considerations in the formulation and / or manufacture of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy, 21st Edition, Lippincott Williams & Wilkins, 2005.

[0355] In one aspect, a kit is provided that includes a composition (eg, a solid composition) that includes a compound of Formula (IX, II, II-I, III-I, or III-II).

[0356] Methods of Use and Treatment In certain aspects, it is contemplated that the compounds described herein (e.g., compounds of Formula (IX, II, II-I, III-I, or III-II)) are useful as therapeutic agents for treating a CNS-related disorder (e.g., a sleep disorder, a mood disorder (e.g., depression), a schizophrenia spectrum disorder, a seizure disorder, epileptogenesis, a disorder of memory and / or cognition, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, or tinnitus) in a subject in need thereof (e.g., a subject with Rett syndrome, Fragile X syndrome, or Angelman syndrome). Exemplary CNS conditions associated with GABA modulation include sleep disorders [e.g., insomnia], mood disorders [e.g., depression (e.g., major depressive disorder (MDD)), dysthymic disorder (e.g., minor depression), bipolar disorder (e.g., Type I and / or Type II), anxiety disorders (e.g., generalized anxiety disorder (GAD), social anxiety disorder), stress, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD))], schizophrenia spectrum disorders [e.g., schizophrenia, schizoaffective disorder], seizure disorders [e.g., epilepsy (e.g., status epilepticus (SE)), seizures], memory and / or cognition disorders [e.g., attention disorders (e.g., attention deficit hyperactivity disorder (ADHD))], dementia (e.g., Alzheimer's disease, Lewis body type dementia, dementia, vascular dementia], movement disorders (e.g., Huntington's disease, Parkinson's disease), personality disorders (e.g., antisocial personality disorder, obsessive-compulsive personality disorder), autism spectrum disorders (ASD) (e.g., autism, a host of causes of autism such as synaptophathy (e.g., Rett syndrome, Fragile X syndrome, Angelman syndrome)), pain (e.g., neuropathic pain, injury-related pain syndrome, acute pain, chronic pain), traumatic brain injury (TBI), vascular disease (e.g., stroke, ischemia, vascular malformation), substance abuse disorders and / or withdrawal syndromes (e.g., opiate, cocaine, and / or alcohol addiction), and tinnitus.

[0357] In certain embodiments, the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a memory and / or cognitive disorder, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. In certain embodiments, the CNS-related disorder is depression. In certain embodiments, the CNS-related disorder is postpartum depression. In certain embodiments, the CNS-related disorder is major depressive disorder. In certain embodiments, the major depressive disorder is moderate major depressive disorder. In certain embodiments, the major depressive disorder is severe major depressive disorder.

[0358] In one aspect, a method of reducing or preventing seizure activity in a subject is provided, comprising administering to a subject in need of such treatment an effective amount of a compound of the invention. In some embodiments, the method reduces or prevents epileptogenesis.

[0359] In yet another aspect, the present invention provides a combination of the compound of the present invention with another pharmacologically active agent.The compound provided herein can be administered as a single active agent or can be administered in combination with other agents.The administration of the combination can proceed by any technique that is clear to those skilled in the art, including, for example, separate administration, sequential administration, simultaneous administration, and alternating administration.

[0360] In another aspect, there is provided a method of treating or preventing brain excitation in a subject susceptible to or afflicted with a condition associated with brain excitation, comprising administering to the subject an effective amount of a compound of the invention.

[0361] In yet another aspect, there is provided a method of treating or preventing stress or anxiety in a subject, comprising administering to a subject in need of such treatment an effective amount of a compound of the invention or a composition thereof.

[0362] In yet another aspect, there is provided a method of alleviating or preventing insomnia in a subject, comprising administering to a subject in need of such treatment an effective amount of a compound of the invention or a composition thereof.

[0363] In yet another aspect, there is provided a method for inducing sleep and substantially maintaining the level of REM sleep seen in normal sleep, without inducing substantial rebound insomnia, comprising administering an effective amount of a compound of the invention.

[0364] In yet another aspect, there is provided a method of alleviating or preventing premenstrual syndrome (PMS) or postpartum depression (PND) in a subject, comprising administering to a subject in need of such treatment an effective amount of a compound of the invention.

[0365] In yet another aspect, there is provided a method of treating or preventing a mood disorder in a subject, comprising administering to a subject in need of such treatment an effective amount of a compound of the invention. In certain embodiments, the mood disorder is depression.

[0366] In yet another aspect, a method for treating cognitive enhancement or memory impairment is provided by administering a therapeutically effective amount of the compound of the present invention to a subject.In certain embodiments, the disorder is Alzheimer's disease.In certain embodiments, the disorder is Rett syndrome.

[0367] In yet another aspect, there is provided a method of treating an attention disorder by administering to a subject a therapeutically effective amount of a compound of the invention. In certain embodiments, the attention disorder is ADHD.

[0368] In certain embodiments, the compound is administered chronically to the subject. In certain embodiments, the compound is administered orally, subcutaneously, intramuscularly, or intravenously to the subject.

[0369] Neuroendocrine Disorders and Dysfunctions Methods that can be used to treat neuroendocrine disorders and dysfunctions are provided herein. As used herein, "neuroendocrine disorder" or "neuroendocrine dysfunction" refers to various conditions caused by an imbalance in the body's hormone production, which is directly related to the brain. Neuroendocrine disorders involve the interaction between the nervous system and the endocrine system. The hypothalamus and pituitary gland are two areas of the brain that control hormone production, so damage to the hypothalamus or pituitary gland, for example, due to traumatic brain injury, can affect hormone production and other neuroendocrine functions of the brain. In some embodiments, the neuroendocrine disorder or dysfunction is associated with a women's health disorder or condition (e.g., a women's health disorder or condition described herein). In some embodiments, the neuroendocrine disorder or dysfunction associated with a women's health disorder or condition is polycystic ovary syndrome.

[0370] Symptoms of neuroendocrine disorders include, but are not limited to, behavioral, emotional, and sleep-related symptoms, symptoms related to reproductive function, and physical symptoms, including, but not limited to, fatigue, poor memory, anxiety, depression, weight gain or loss, emotional lability, lack of concentration, difficulty paying attention, loss of lipids, infertility, amenorrhea, loss of muscle mass, increased abdominal body fat, low blood pressure, low heart rate, hair loss, anemia, constipation, cold intolerance, and dry skin.

[0371] Neurodegenerative diseases and disorders Methods that can be used to treat neurodegenerative diseases and disorders are provided herein.The term "neurodegenerative disease" includes diseases and disorders associated with the progressive loss of neuronal structure or function, or the death of neurons.Neurodegenerative diseases and disorders include Alzheimer's disease (including associated symptoms of mild, moderate, or severe cognitive impairment); amyotrophic lateral sclerosis (ALS); anoxic and ischemic damage; ataxia and seizures (including for the treatment and prevention, and for the prevention of seizures caused by schizoaffective disorder or drugs used to treat schizophrenia); benign amnesia; cerebral edema; cerebellar ataxia (including McLeod neuroacanthocytosis syndrome (MLS)); closed head injury; coma; contusion injury (e.g., spinal cord injury and head injury); dementia (including multi-infarct dementia and senile dementia); disorders of consciousness; Down's syndrome; Drug-induced or pharmaceutical-induced tremor tremors (e.g., psycholeptic-induced acute akathisia, acute ataxia, tremor tremors or tardive dyskinesia, neuroleptic malignant syndrome, or drug-induced postural tremor); epilepsy; fragile X syndrome; Gilles de la Tourette syndrome; head trauma; hearing impairment and hearing loss; Huntington's disease; Lennox syndrome; levodopa-induced dyskinesia; mental retardation; movement disorders including akinesia and akinesia (rigidity) syndromes (including brainstem neurocalcification, corticobasal degeneration, multiple system atrophy, tremor tremors-ALS dementia complex, Parkinson's disease, postencephalitic tremor tremors, and progressive supranuclear palsy);Muscle spasms and disorders associated with muscle spasticity or weakness (chorea (e.g., benign hereditary chorea, drug-induced chorea, hemiballismus, Huntington's disease, neuroacanthocytosis, Sydenham's chorea, and symptomatic chorea), dyskinesias (including tics such as complex tics, simple tics, and symptomatic tics), myoclonus (including generalized myoclonus and focal cyloclonus), tremor (e.g., resting tremor, postural tremor, and intention tremor) and ataxias (axial ataxia, dystonic writer's cramp, hemiplegic ataxia, paroxysmal ataxia, and focal ataxias (e.g., blepharospasm, oromandibular dystonia) Neurodegenerative diseases include, but are not limited to, neuronal damage (including eye damage, ocular retinopathy or macular degeneration); stroke, thromboembolic stroke, hemorrhagic stroke, cerebral ischemia, cerebral vasospasm, hypoglycemia, amnesia, hypoxia, anoxia, perinatal asphyxia and neurotoxicity after cardiac arrest; Parkinson's disease; seizures; status epilepticus; stroke; tinnitus; renal tubular sclerosis, and neurodegeneration induced by viral infection (such as those caused by acquired immunodeficiency syndrome (AIDS) and encephalopathy). Neurodegenerative diseases also include, but are not limited to, stroke, thromboembolic stroke, hemorrhagic stroke, cerebral ischemia, cerebral vasospasm, hypoglycemia, amnesia, hypoxia, anoxia, perinatal asphyxia and neurotoxicity after cardiac arrest. Methods of treating or preventing neurodegenerative diseases also include treating or preventing the loss of neuronal function that is characteristic of neurodegenerative disorders.

[0372] Mood disorders Also provided herein are methods for treating mood disorders, such as clinical depression, postpartum depression or postpartum depression, perinatal depression, atypical depression, melancholic depression, psychogenic major depression, catatonic depression, seasonal affective disorder, dysthymia, dual depression, depressive personality disorder, recurrent brief depression, minor depressive disorder, bipolar disorder or manic-depressive disorder, depression caused by a chronic medical condition, treatment-resistant depression, refractory depression, suicide, suicidal ideation, or suicidal behavior. In some embodiments, the methods described herein provide a therapeutic effect for subjects suffering from depression (e.g., moderate or severe depression). In some embodiments, the mood disorder is associated with a disease or disorder described herein (e.g., neuroendocrine diseases and disorders, neurodegenerative diseases and disorders (e.g., epilepsy), movement disorders, tremors (e.g., Parkinson's disease), women's health disorders or conditions).

[0373] Clinical depression, also known as major depression, major depressive disorder (MDD), unipolar depression, unipolar disorder, and recurrent depression, refers to a mental disorder characterized by a pervasive and persistent low mood accompanied by low self-esteem and a loss of interest or pleasure in normally enjoyable activities. Some people with clinical depression have difficulty sleeping, become thin, and generally feel agitated and irritable. Clinical depression affects how individuals feel, think, and behave, and can lead to a variety of emotional and physical problems. Individuals with clinical depression may have difficulty performing daily activities and may feel as if life is not worth living.

[0374] Perinatal depression refers to depression during pregnancy. Symptoms include irritability, crying, agitation, difficulty sleeping, extreme fatigue (emotional and / or physical), changes in appetite, difficulty concentrating, increased anxiety and / or worry, feelings of separation from the infant and / or fetus, and loss of interest in previously enjoyable activities.

[0375] Postpartum depression (PND), also known as postpartum depression (PPD), refers to a type of clinical depression that women suffer from after giving birth.Symptoms may include sadness, fatigue, changes in sleep and eating habits, decreased sexual desire, crying episodes, anxiety and irritability.In some embodiments, PND is treatment-resistant depression (for example, treatment-resistant depression as described herein).In some embodiments, PND is treatment-refractory depression (for example, treatment-refractory depression as described herein).

[0376] In some embodiments, the subject with PND also experiences depression or symptoms of depression during pregnancy.This depression is herein referred to as perinatal depression.In some embodiments, the subject who experiences perinatal depression has a high risk of experiencing PND.

[0377] Atypical depression (AD) is characterized by mood reactivity (e.g., paradoxical anhedonia) and aggressiveness, significant weight gain, or increased appetite. Patients with AD may also have significant social impairment as a result of excessive sleep or somnolence (hypersomnia), a feeling of heaviness in the limbs, and hypersensitivity to perceived interpersonal rejection.

[0378] Melancholic depression is characterized by loss of pleasure in most or all activities (anhedonia), unresponsiveness to pleasurable stimuli, a depressed mood that is more pronounced than a mood of sadness or loss, excessive weight loss, or excessive feelings of guilt.

[0379] Psychotic major depression (PMD) or psychotic depression refers to a major depressive episode, particularly one of a melancholic nature, in which an individual experiences psychotic symptoms such as delusions and hallucinations.

[0380] Catatonic depression refers to major depression accompanied by disturbances in motor behavior and other symptoms. Individuals may become mute and stuporous, become immobile, or exhibit aimless or bizarre movements.

[0381] Seasonal affective disorder (SAD) refers to a type of seasonal depression in which an individual has a seasonal pattern of depressive episodes that begin occurring in the fall or winter.

[0382] Dysthymia refers to a condition related to unipolar depression in which the same physical and cognitive problems are evident, although they tend to be less severe and last longer (e.g., at least 2 years).

[0383] Dual depression refers to a severely depressed mood (dysthymia) lasting at least two years and interrupted by periods of major depression.

[0384] Depressive personality disorder (DPD) refers to a personality disorder with depressive features.

[0385] Recurrent Brief Depression (RBD) refers to a condition in which an individual has depressive episodes approximately once per month, with each episode lasting two weeks or less, typically less than two to three days.

[0386] Minor depressive disorder or minor depression refers to depression in which at least two symptoms are present for two weeks.

[0387] Bipolar disorder or manic-depressive disorder causes extreme mood swings, including high affect (mania or hypomania) and low affect (depression). During manic periods, individuals may feel or act unusually happy, energetic, or irritable. They often make thoughtless decisions with little regard for consequences. They usually have a decreased need for sleep. During depressive periods, individuals may cry uncontrollably, make less eye contact with others, and have a negative outlook on life. The risk of suicide for people with this disorder is high—more than 6% over a 20-year period—and 30–40% will engage in self-harm. Other mental health problems, such as anxiety disorders and substance use disorders, commonly coexist with bipolar disorder.

[0388] Chronic condition-induced depression refers to depression caused by a chronic medical condition such as cancer or chronic pain, chemotherapy, or chronic stress.

[0389] Treatment-resistant depression refers to the state that individuals are treated for depression but their symptoms do not improve.For example, antidepressants or psychological counseling (psychotherapy) do not alleviate the depressive symptoms of individuals with treatment-resistant depression.In some cases, individuals with treatment-resistant depression improve their symptoms, but then return.Treatment-resistant depression occurs in patients with depression that is resistant to standard pharmacological treatments, including tricyclic antidepressants, MAOIs, SSRIs, and double and triple uptake inhibitors, and / or anxiolytics, and non-pharmacological treatments (for example, psychotherapy, electroconvulsive therapy, vagus nerve stimulation and / or transcranial magnetic stimulation).

[0390] Postoperative depression refers to a state of depression following a surgical procedure (e.g., as a result of facing death). For example, an individual may experience persistent feelings of sadness or emptiness, loss of pleasure or interest in hobbies and activities that they normally enjoy, or persistent feelings of worthlessness or hopelessness.

[0391] A mood disorder associated with a female health condition or disorder refers to a mood disorder (e.g., depression) that is associated with (e.g., caused by) a female health condition or disorder (e.g., those described herein).

[0392] Suicidal tendencies, ideation, and behavior refer to an individual's tendency to commit suicide. Suicidal ideation involves thoughts about or an abnormal obsession with suicide. The spectrum of suicidal ideation varies widely, from fleeting thoughts to extensive thinking, detailed plans, role-playing, and abortive attempts. Symptoms may include talking about suicide, obtaining the means to commit suicide, withdrawing from social contacts, preoccupation with death, feeling trapped or hopeless about a situation, increased alcohol or drug use, engaging in risky or self-destructive behavior, and saying goodbye to people as if they will never see each other again.

[0393] Symptoms of depression include persistent anxious or sad feelings, helpless feelings, hopelessness, pessimism, worthlessness, low energy, restlessness, difficulty sleeping, insomnia, irritability, fatigue, motor challenges, loss of interest in pleasurable activities or hobbies, poor concentration, low energy, low self-esteem, lack of positive thoughts or plans, excessive sleep, overeating, loss of appetite, insomnia, self-harm, thoughts of suicide and suicide attempts.The presence, severity, frequency and duration of symptoms may vary from case to case.Depression symptoms and their alleviation can be confirmed by a doctor or psychologist (for example, mental status examination).

[0394] In some embodiments, the method includes monitoring the subject using known depression scales, such as the Hamilton Depression (HAM-D) scale, Clinical Global Impression (CGI) and Montgomery-Asberg Depression Rating Scale (MADRS). In some embodiments, the therapeutic effect can be measured by the reduction of the Hamilton Depression (HAM-D) total score exhibited by the subject. The reduction of the HAM-D total score can occur within 4, 3, 2 or 1 day; or within 96, 84, 72, 60, 48, 24, 20, 16, 12, 10, 8 hours or less. The therapeutic effect can be evaluated over a specific treatment period. For example, therapeutic efficacy can be measured by a reduction in HAM-D total score from baseline after administration of a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I or III-II)) (e.g., 12, 24, or 48 hours after administration; or 24, 48, 72, or 96 hours or more after administration; or 1 day, 2 days, 14 days, 21 days, or 28 days; or 1 week, 2 weeks, 3 weeks, or 4 weeks; or 1 month, 2 months, 6 months, or 10 months; or 1 year, 2 years, or over a lifetime).

[0395] In some embodiments, the subject has a mild depressive disorder, e.g., a mild major depressive disorder. In some embodiments, the subject has a moderate depressive disorder, e.g., a moderate major depressive disorder. In some embodiments, the subject has a severe depressive disorder, e.g., a severe major depressive disorder. In some embodiments, the subject has a very severe depressive disorder, e.g., a very severe major depressive disorder. In some embodiments, the subject's baseline HAM-D total score (i.e., before treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II))) is at least 24. In some embodiments, the subject's baseline HAM-D total score is at least 18. In some embodiments, the subject's baseline HAM-D total score is between 14 and 18, including 14 and 18. In some embodiments, the subject's baseline HAM-D total score is between 19 and 22, including 19 and 22. In some embodiments, the subject's HAM-D total score before treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) is greater than or equal to 23. In some embodiments, the baseline score is at least 10, 15, or 20. In some embodiments, the subject's HAM-D total score after treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) is about 0 to 10 (e.g., less than 10; 0 to 10, 0 to 6, 0 to 4, 0 to 3, 0 to 2, or 1.8). In some embodiments, the subject's HAM-D total score after treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) is less than 10, 7, 5, or 3.In some embodiments, the reduction in HAM-D total score is from a baseline score of about 20-30 (e.g., 22-28, 23-27, 24-27, 25-27, 26-27) to a HAM-D total score of about 0-10 (e.g., less than 10; 0-10, 0-6, 0-4, 0-3, 0-2, or 1.8) after treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)). In some embodiments, the reduction in HAM-D total score from baseline HAM-D total score after treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) is at least 1, 2, 3, 4, 5, 7, 10, 25, 40, 50, or 100-fold. In some embodiments, the reduction in HAM-D total score from baseline after treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) is at least 50% (e.g., 60%, 70%, 80%, or 90%). In some embodiments, the therapeutic effect is measured as a reduction in HAM-D total score after treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)) (e.g., 12, 24, 48 hours; or 24, 48, 72, 96 hours or more; or 1 day, 2 days, 14 days or more after administration) of at least 10, 15, or 20 points compared to baseline HAM-D total score.

[0396] In some embodiments, the method for treating a depressive disorder, e.g., major depressive disorder, provides a therapeutic effect (e.g., as measured by a decrease in the Hamilton Rating Scale for Depression (HAM-D) score) within 14, 10, 4, 3, 2, or 1 day, or within 24, 20, 16, 12, 10, or 8 hours or less. In some embodiments, the method for treating a depressive disorder, e.g., major depressive disorder, provides a therapeutic effect (e.g., as determined by a statistically significant decrease in the HAM-D score) within 1 or 2 days of treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)). In some embodiments, the method for treating a depressive disorder, e.g., major depressive disorder, provides a therapeutic effect (e.g., as determined by a statistically significant decrease in the HAM-D score) within a period of less than or equal to 14 days from the start of treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)). In some embodiments, the method for treating a depressive disorder, e.g., major depressive disorder, provides a therapeutic effect (e.g., as determined by a statistically significant reduction in HAM-D total score) within a period of less than or equal to 21 days from the initiation of treatment with a compound described herein (e.g., a compound of Formula (IX, II, II-I, III-I, or III-II)). In some embodiments, the method for treating a depressive disorder, e.g., major depressive disorder, provides a thera...

Claims

1. Formula (II-I): 【Chemistry 121】 or a pharma- ceutically acceptable salt thereof, In formula (II-I), t is 1, 2, or 3; n is 0, 1, or 2; R １９ is unsubstituted C ２ ~C ６ Alkyl, substituted or unsubstituted C ２ ~C ６ Alkenyl, or substituted or unsubstituted C ２ ~C ６ alkynyl; R ５ is hydrogen, or 【Chemistry 122】 is a double bond, R ５ does not exist; R ３ 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; R ６ａ and R ６ｂ each is hydrogen; R １ is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR Ａ１ , -SR Ａ１ , -N(R Ａ１ ) ２ , -N(R Ａ１ ), -OC(=O)R Ａ１ , -OC(=O)OR Ａ１ , -OC(=O)SR Ａ１ , -OC(=O)N(R Ａ１ ) ２ , -SC(=O)R Ａ２ , -SC(=O)OR Ａ１ , -SC(=O)SR Ａ１ , -SC(=O)N(R Ａ１ ) ２ , -NHC(=O)R Ａ１ , -NHC(=O)OR Ａ１ , -NHC(=O)SR Ａ１ , -NHC(=O)N(R Ａ１ ) ２ , -OS(=O) ２ R Ａ２ , -OS(=O) ２ OR Ａ１ , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ where R Ａ１ each occurrence 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, where said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate, a nitrogen protecting group when attached to a nitrogen atom, where said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine, or two R Ａ１ groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R Ａ２ is 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; R ２ａ , R ２ｂ , R ４ａ , R ４ｂ , R ７ａ , R ７ｂ , R １１ａ , R １１ｂ , R １２ａ , R １２ｂ , and R １７ｂ each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ each occurrence 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, or substituted or unsubstituted heteroaryl; an oxygen protecting group when attached to an oxygen atom, wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate; a nitrogen protecting group when attached to a nitrogen atom, wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine; Ｄ１ groups taken together form a substituted or unsubstituted heterocyclic ring; or R ２ａ and R ２ｂ , R ４ａ and R ４ｂ , and R ７ａ and R ７ｂ any one of these taken together form an oxo (=O) group; R １５ａ , R １５ｂ , R １６ａ , and R １６ｂ each independently represents hydrogen, halogen, cyano, hydroxyl, 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, -OR Ａ１ , -SR Ａ１ , -N(R Ａ１ ) ２ , -N(R Ａ１ ), -OC(=O)R Ａ１ , -OC(=O)OR Ａ１ , -OC(=O)SR Ａ１ , -OC(=O)N(R Ａ１ ) ２ , -SC(=O)R Ａ２ , -SC(=O)OR Ａ１ , -SC(=O)SR Ａ１ , -SC(=O)N(R Ａ１ ) ２ ,-NHC(=O)R Ａ１ , -NHC(=O)OR Ａ１ , -NHC(=O)SR Ａ１ , -NHC(=O)N(R Ａ１ ) ２ , -OS(=O) ２ R Ａ２ , -OS(=O) ２ OR Ａ１ , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ where R Ａ１ each occurrence 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 (wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate), a nitrogen protecting group when attached to a nitrogen atom (wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine), -SO ２ R Ａ２ , -C(O)R Ａ２ or two R Ａ１ groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R Ａ２ is 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; Where: 【Chemistry 123】 represents a single bond or a double bond, and when a double bond is present in ring B, R ６ａ Or R ６ｂ is absent, or a pharma- ceutically acceptable salt thereof.

2. R ２ａ and R ２ｂ Each of is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

3. R ２ａ and R ２ｂ each independently represents hydrogen, —OH, substituted or unsubstituted C １ ~C ６ Alkoxy, or substituted or unsubstituted C １ ~C ６ 3. The compound or a pharma- ceutically acceptable salt of claim 1 or 2, wherein: R is an alkyl group;

4. R ２ａ and R ２ｂ each independently represents hydrogen, —OH, —CH ３ , -CH ２ CH ３ , -OCH ３ , or -CH(CH ３ ) ２ 4. The compound according to any one of claims 1 to 3, or a pharma- ceutically acceptable salt thereof.

5. R ４ａ and R ４ｂ Each of is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ or a pharma- ceutically acceptable salt thereof according to any one of claims 1 to 4, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

6. R ４ａ and R ４ｂ each independently represents hydrogen, —OH, substituted or unsubstituted C １ ~C ６ Alkoxy, or substituted or unsubstituted C １ ~C ６ 6. The compound or a pharma- ceutically acceptable salt according to any one of claims 1 to 5, wherein: R is an alkyl group;

7. R ４ａ and R ４ｂ each independently represents hydrogen, —OH, —CH ３ , -CH ２ CH ３ , -OCH ３ , or -CH(CH ３ ) ２ 7. The compound according to any one of claims 1 to 6, or a pharma- ceutically acceptable salt thereof, wherein:

8. R １１ａ and R １１ｂ Each of is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ or a pharma- ceutically acceptable salt thereof according to any one of claims 1 to 7, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

9. R １１ａ and R １１ｂ each independently represents hydrogen, —OH, substituted or unsubstituted C １ ~C ６ Alkoxy, or substituted or unsubstituted C １ ~C ６ 9. The compound or a pharma- ceutically acceptable salt of any one of claims 1 to 8, wherein: R is alkyl.

10. R １１ａ and R １１ｂ each independently represents hydrogen, —OH, —CH ３ , -CH ２ CH ３ , -OCH ３ , or -CH(CH ３ ) ２ 10. The compound according to any one of claims 1 to 9, or a pharma- ceutically acceptable salt thereof.

11. R ７ａ and R ７ｂ Each of is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ or a pharma- ceutically acceptable salt thereof. The compound of any one of claims 1 to 10, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

12. R ７ａ and R ７ｂ each independently represents hydrogen, —OH, substituted or unsubstituted C １ ~C ６ Alkoxy, or substituted or unsubstituted C １ ~C ６ 12. The compound or a pharma- ceutically acceptable salt of any one of claims 1 to 11, wherein: R is alkyl.

13. R ７ａ and R ７ｂ each independently represents hydrogen, —OH, —CH ３ , -CH ２ CH ３ , -OCH ３ , or -CH(CH ３ ) ２ 13. The compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof, wherein:

14. R ５ 14. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 13, wherein is hydrogen cis to C19.

15. R ５ 14. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 13, wherein is hydrogen trans to C19.

16. 16. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 15, wherein t is 1 or 2.

17. 17. The compound or pharma- ceutically acceptable salt according to any one of claims 1 to 16, wherein n is 1 or 2.

18. R ３ is hydrogen, substituted or unsubstituted C １～６ 18. The compound or a pharma- ceutically acceptable salt of any one of claims 1 to 17, Which is alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

19. R ３ is hydrogen or a substituted or unsubstituted C １～６ 19. The compound or a pharma- ceutically acceptable salt of any one of claims 1 to 18, wherein: R is alkyl;

20. R ３ 20. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 19, wherein is hydrogen or unsubstituted methyl.

21. R １９ is unsubstituted C ２ ~C ６ 21. The compound or a pharma- ceutically acceptable salt of any one of claims 1 to 20, wherein: R is alkyl.

22. R １９ 22. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 21, wherein is unsubstituted ethyl.

23. R １２ａ and R １２ｂ Each of is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ 23. The compound of any one of claims 1 to 22, or a pharma- ceutically acceptable salt thereof, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

24. R １２ａ and R １２ｂ each independently represents hydrogen, —OH, substituted or unsubstituted C １ ~C ６ Alkoxy, or substituted or unsubstituted C １ ~C ６ 24. The compound or a pharma- ceutically acceptable salt of any one of claims 1 to 23, wherein: R is alkyl;

25. R １２ａ and R １２ｂ each independently represents hydrogen, —OH, —CH ３ , -CH ２ CH ３ , -OCH ３ , or -CH(CH ３ ) ２ 25. The compound according to any one of claims 1 to 24, or a pharma- ceutically acceptable salt thereof, wherein:

26. R １７ｂ 26. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 25, wherein is fluorine, hydroxyl, methyl, or hydrogen, said hydrogen optionally being replaced by deuterium.

27. R １ or a pharma- ceutically acceptable salt thereof. The compound of any one of claims 1 to 26, wherein is 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.

28. R １ but, 【Chemistry 124】 and Here, R ２０ Each occurrence of is independently hydrogen, halogen, -NO ２ , -CN, -OR ＧＡ , -N(R ＧＡ ) ２ , -C(=O)R ＧＡ , -C(=O)OR ＧＡ , -C(=O)N(R ＧＡ ) ２ , -OC(=O)R ＧＡ , -OC(=O)OR ＧＡ , -N(R ＧＡ ) C(=O)R ＧＡ , -OC(=O)N(R ＧＡ ) ２ , -N(R ＧＡ ) C(=O)OR ＧＡ , -S(=O) ２ R ＧＡ , -S(=O) ２ OR ＧＡ , -OS(=O) ２ R ＧＡ , -S(=O) ２ N (R ＧＡ ) ２ , or -N(R ＧＡ ) S(=O) ２ R ＧＡ , substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C ３～４ Carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, C ６～１０ substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, or optionally two R ＧＡ together with the intervening atoms form a substituted or unsubstituted 3- to 4-membered carbocyclic or heterocyclic ring; Here, R ＧＡ Each occurrence is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C ３～６ 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, wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate, a nitrogen protecting group when attached to nitrogen, wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine, or two R ＧＡ the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 28. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 27, wherein e is 0, 1, 2, 3, 4, or 5; and n is 1, 2, 3, 4, or 5.

29. The compound of formula (II-I) has the formula (II-Ia): 【Chemistry 126】 or a pharma- ceutically acceptable salt thereof, In formula (II-Ia), n is 0, 1, or 2; R ５ is hydrogen or methyl, or 【Chemistry 122】 is a double bond, R ５ does not exist; R ３ 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; R ６ａ and R ６ｂ each is hydrogen; R １ is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR Ａ１ , -SR Ａ１ , -N(R Ａ１ ) ２ , -OC(=O)R Ａ１ , -OC(=O)OR Ａ１ , -OC(=O)SR Ａ１ , -OC(=O)N(R Ａ１ ) ２ , -SC(=O)R Ａ２ , -SC(=O)OR Ａ１ , -SC(=O)SR Ａ１ , -SC(=O)N(R Ａ１ ) ２ , -NHC(=O)R Ａ１ , -NHC(=O)OR Ａ１ , -NHC(=O)SR Ａ１ , -NHC(=O)N(R Ａ１ ) ２ , -OS(=O) ２ R Ａ２ , -OS(=O) ２ OR Ａ１ , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ where R Ａ１ each occurrence 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, where said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate, a nitrogen protecting group when attached to a nitrogen atom, where said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine, or two R Ａ１ groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R Ａ２ is 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; R １２ａ and R １２ｂ each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ each occurrence 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, or substituted or unsubstituted heteroaryl; an oxygen protecting group when attached to an oxygen atom, wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate; a nitrogen protecting group when attached to a nitrogen atom, wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine; Ｄ１ the groups taken together form a substituted or unsubstituted heterocyclic ring; R １６ａ and R １６ｂ each independently represents hydrogen, halogen, cyano, hydroxyl, 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, -OR Ａ１ , -SR Ａ１ , -N(R Ａ１ ) ２ , -N(R Ａ１ ), -CN(R Ａ１ ) ２ , -C(O)R Ａ１ , -OC(=O)R Ａ１ , -OC(=O)OR Ａ１ , -OC(=O)SR Ａ１ , -OC(=O)N(R Ａ１ ) ２ , -SC(=O)R Ａ２ , -SC(=O)OR Ａ１ , -SC(=O)SR Ａ１ , -SC(=O)N(R Ａ１ ) ２ , -NHC(=O)R Ａ１ , -NHC(=O)OR Ａ１ , -NHC(=O)SR Ａ１ , -NHC(=O)N(R Ａ１ ) ２ , -OS(=O) ２ R Ａ２ , -OS(=O) ２ OR Ａ１ , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ where R Ａ１ each occurrence 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 (wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate), a nitrogen protecting group when attached to a nitrogen atom (wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine), -SO ２ R Ａ２ , -C(O)R Ａ２ or two R Ａ１ groups taken together form a substituted or unsubstituted heterocyclic or heteroaryl ring; R Ａ２ is 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; Where: 【Chemistry 123】 represents a single or double bond, 【Chemistry 123-1】 is a double bond, R ６ａ Or R ６ｂ One of them does not exist, 2. The compound of claim 1 or a pharma- ceutically acceptable salt thereof. 【Request 30】 【Chemical 123-3】 is a single bond, R ５ 30. The compound or pharma- ceutically acceptable salt of claim 29, wherein is hydrogen cis to C19. 【Request 31】 【Chemical 123-5】 is a single bond, R ５ 30. The compound or pharma- ceutically acceptable salt of claim 29, wherein is hydrogen trans to C19.

32. R ３ 32. The compound or pharma- ceutically acceptable salt of any one of claims 29 to 31, wherein is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

33. R ３ is a substituted or unsubstituted C １～６ 33. The compound or a pharma- ceutically acceptable salt of any one of claims 29 to 32, wherein: R is alkyl.

34. R ３ But substitution C １～６ 34. The compound or a pharma- ceutically acceptable salt of any one of claims 29 to 33, wherein: R is alkyl.

35. R ３ 35. The compound or pharma- ceutically acceptable salt of any one of claims 29 to 34, wherein is methyl, methoxymethyl or ethoxymethyl.

36. R １２ａ and R １２ｂ each independently represents hydrogen, substituted or unsubstituted C １～６ 36. The compound or pharma- ceutically acceptable salt of any one of claims 29 to 35, wherein: R is alkyl; or -OH.

37. R １２ａ and R １２ｂ Each of １～６ 37. The compound or a pharma- ceutically acceptable salt of any one of claims 29 to 36, wherein: R is alkyl.

38. R １２ａ and R １２ｂ 38. The compound or pharma- ceutically acceptable salt of any one of claims 29 to 37, wherein each of is hydrogen.

39. R １６ａ and R １６ｂ Each of is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, -OR Ｄ１ , -OC(=O)R Ｄ１ , -NH ２ , -N(R Ｄ１ ) ２ or -NR Ｄ１ C(=O)R Ｄ１ where R Ｄ１ 39. The compound or pharma- ceutically acceptable salt of any one of claims 29-38, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

40. R １６ａ and R １６ｂ Each of the is independently hydrogen, or substituted or unsubstituted C １～６ 40. The compound or a pharma- ceutically acceptable salt of any one of claims 29 to 39, wherein: R is alkyl.

41. R １６ａ and R １６ｂ Each of １～６ 41. The compound or a pharma- ceutically acceptable salt of any one of claims 29 to 40, wherein: R is alkyl.

42. R １６ａ and R １６ｂ 42. The compound or pharma- ceutically acceptable salt of any one of claims 29 to 41, wherein each of is hydrogen.

43. n is 0 or 1, R １ But -N(R Ａ１ ) ２ , -OR Ａ１ , substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a pharma- ceutically acceptable salt thereof.

44. R １ but, 【Chemistry 124-1】 and Here, R ２０ Each occurrence of is independently hydrogen, halogen, -NO ２ , -CN, -OR ＧＡ , -N(R ＧＡ ) ２ , -C(=O)R ＧＡ , -C(=O)OR ＧＡ , -C(=O)N(R ＧＡ ) ２ , -OC(=O)R ＧＡ , -OC(=O)OR ＧＡ , -N(R ＧＡ ) C(=O)R ＧＡ , -OC(=O)N(R ＧＡ ) ２ , -N(R ＧＡ ) C(=O)OR ＧＡ , -S(=O) ２ R ＧＡ , -S(=O) ２ OR ＧＡ , -OS(=O) ２ R ＧＡ , -S(=O) ２ N (R ＧＡ ) ２ , or -N(R ＧＡ ) S(=O) ２ R ＧＡ , substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C ３～４ Carbocyclyl, substituted or unsubstituted 3- to 4-membered heterocyclyl, C ６～１０ substituted or unsubstituted aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, or optionally two R ＧＡ together with the intervening atoms form a substituted or unsubstituted 3- to 4-membered carbocyclic or heterocyclic ring; Here, R ＧＡ Each occurrence is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C ３～６ 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, wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate, a nitrogen protecting group when attached to nitrogen, wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine, or two R ＧＡ the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 44. The compound or pharma- ceutically acceptable salt of claim 43, wherein e is 0, 1, 2, 3, 4, or 5; and n is 1, 2, 3, 4, or 5.

45. The compound of formula (II-Ia) is represented by the formula (II-Ib) or the formula (II-Ic) 【Chemistry 127】 30. The compound or pharma- ceutically acceptable salt of claim 29, which is the compound or a pharma- ceutically acceptable salt thereof:

46. The compound of formula (II-Ia) is represented by the formula (II-Ie) 【Chemistry 129】 or a pharma- ceutically acceptable salt thereof, In formula (II-Ie), m is 0, 1, 2, or 3; p is 0, 1, or 3; R ３２ 30. The compound or pharma- ceutically acceptable salt of claim 29, wherein each of is independently halogen, alkyl, hydroxyl, or cyano.

47. The compound of formula (II-Ia) has the formula (II-Ig) 【Chemistry 130】 or a pharma- ceutically acceptable salt thereof, In formula (II-Ig), u is 0, 1, or 2; Each X is independently -C(R Ｎ ) -, -C(R Ｎ ) ２ -, -S-, -N-, or N(R Ｎ ) - and Each R Ｎ are independently hydrogen, substituted or unsubstituted C １～６ Alkyl, C(=O)R ＧＡ , -C(=O)OR ＧＡ , -C(=O)N(R ＧＡ ) ２ , -S(=O) ２ R ＧＡ Or -S(=O) ２ N (R ＧＡ ) ２ and Each R ＧＡ are independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C ３～６ 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, wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate, a nitrogen protecting group when attached to nitrogen, wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine, or two R ＧＡ the radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring, or a pharma- ceutically acceptable salt thereof; 30. The compound of claim 29 or a pharma- ceutically acceptable salt thereof.

48. The compound of formula (II-Ia) is represented by the formula (II-Ii) 【Chemistry 133】 or a pharma- ceutically acceptable salt thereof, In formula (II-Ii), s is 0, 1, or 2; R 5 is hydrogen or methyl; or 【Chemistry 148】 is a double bond, then R 5 is absent; R 3 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 R 6a and R 6b is hydrogen; Each X is independently -C(R Ｎ ) -, -C(R Ｎ ) ２ -, -O-, -S-, -N-, or N(R Ｎ )-, and each R Ｎ are independently hydrogen, substituted or unsubstituted C １～６ Alkyl, C(=O)R ＧＡ , -C(=O)OR ＧＡ , -C(=O)N(R ＧＡ ) ２ , -S(=O) ２ R ＧＡ Or -S(=O) ２ N (R ＧＡ ) ２ and each R ＧＡ are independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ２～６ Alkenyl, substituted or unsubstituted C ２～６ Alkynyl, substituted or unsubstituted C ３～６ 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, wherein said oxygen protecting group is methyl, methoxymethyl, 2-methoxyethoxymethyl, benzyl, triisopropylsilyl, t-butyldimethylsilyl, t-butylmethoxyphenylsilyl, methanesulfonate, or tosylate, a nitrogen protecting group when attached to nitrogen, wherein said nitrogen protecting group is formamide, acetamide, 9-fluorenylmethylcarbamate, t-butylcarbamate, benzylcarbamate, p-toluenesulfonamide, methanesulfonamide, or N-[2-(trimethylsilyl)ethoxy]methylamine, or two R ＧＡ the radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring; or a pharma- ceutically acceptable salt thereof.

30. The compound of claim 29 or a pharma- ceutically acceptable salt thereof.

49. 【Chemical 146-1】 【Chemistry 146-2】 【Chemistry 146-3】 【Chemistry 146-4】 【Chemistry 146-5】 【Chemistry 146-6】 【Chemistry 146-7】 【Chemistry 146-8】 【Chemistry 146-9】 【Chemistry 146-10】 【Chemistry 146-11】 【Chemistry 146-12】 or a pharma- ceutically acceptable salt thereof.

50. The compound comprising: 【Chemistry 149】 【Chemistry 150】 【Chemistry 151】 【Chemistry 152】 【Chemistry 153】 【Chemistry 154】 50. The compound of claim 49, selected from:

51. The compound comprising: 【Chemistry 155】 【Chemistry 156】 【Chemistry 157】 【Chemistry 158】 【Chemistry 159】 50. The compound of claim 49, or a pharma- ceutically acceptable salt thereof, selected from:

52. The compound comprising: 【Chemistry 160】 【Chemistry 161】 50. The compound of claim 49, selected from:

53. 53. A pharmaceutical composition comprising a compound or a pharma- ceutically acceptable salt according to any one of claims 1 to 52, and a pharma- ceutically acceptable excipient.

54. 53. A composition comprising a compound or a pharma- ceutically acceptable salt according to any one of claims 1 to 52 for therapeutically treating a CNS-related disorder in a subject in need thereof.

55. 55. The composition of claim 54, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a memory and / or cognition disorder, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus.

56. 55. The composition of claim 54, wherein the CNS-related disorder is depression.

57. 57. The composition of claim 56, wherein the depression is postpartum depression.

58. 55. The composition of claim 54, wherein the CNS-related disorder is major depressive disorder.

59. 59. The composition of claim 58, wherein the major depressive disorder is moderate major depressive disorder.

60. 59. The composition of claim 58, wherein the major depressive disorder is severe major depressive disorder.

61. 55. The composition of claim 54, wherein the CNS-related disorder is stroke.

62. 55. The composition of claim 54, wherein the CNS-related disorder is tremor.

63. 63. The composition of claim 62, wherein the tremor is essential tremor.

64. The composition according to any one of claims 54 to 63, which is administered orally.

65. The composition according to any one of claims 54 to 64, characterized in that it is administered for a long period of time.

66. 53. A composition comprising a compound or a pharma- ceutically acceptable salt according to any one of claims 1 to 52 for inducing anesthesia and / or sedation in a subject in need thereof.

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