Compositions and methods for treating CNS disorders

Abstract

To provide compositions and methods for treating CNS disorders.SOLUTION: Provided herein are compounds of Formula (I-X) in the figure or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions comprising the compounds, and methods of using the compounds, e.g., in treatment of CNS-related disorders. Provided herein are compounds designed, e.g., to act as GABAA receptor modulators. In some embodiments, such compounds are envisioned to be useful as therapeutic agents for treating a CNS-related disorder (e.g., a disorder described herein, such as postpartum depression or major depressive disorder).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 by reference in their entirety herein. [Background technology]

[0002] 2. Background of the Invention Brain excitability is defined as the level of alertness of an animal, which is a continuum ranging from coma to convulsions, and is controlled by various neurotransmitters. In general, 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 inside of the cell being negative with respect to the outside of the cell. The electrical potential (voltage) is determined by the flow of ions (K + , 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, it causes a change in potential 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 the 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 effect on brain excitability is 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 effect on overall brain excitability. GABA controls the excitability of individual neurons by controlling the conductance of chloride ions across the neuronal membrane. By interacting with recognition sites on the GRC, GABA promotes the flow of chloride ions into the cell down the electrochemical gradient of the GRC. An intracellular increase in the level of this anion causes hyperpolarization of the transmembrane potential, making the neuron less sensitive to excitatory inputs (i.e., the neuron is less excitable). In other words, the higher the concentration of chloride ions in the neuron, the lower the brain's level of excitability and arousal.

[0004] It is well established that the GRC is involved in mediating anxiety, seizure activity and sedation. Thus, GABA and drugs that act like GABA or enhance the action of GABA (e.g., therapeutically useful barbiturates and benzodiazepines (BZ), 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 separate 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 occur endogenously. 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 alter 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 regulators 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, N.C. 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, N.L. et al., J Pharmacol. Exp. Ther. 241:346-353 (1987) Summary of the Invention [Means for solving the problem]

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

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

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

[0010] or a pharma- ceutically acceptable salt thereof.

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

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

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

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

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

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

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

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

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

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

[0021] In some embodiments, the present specification provides a compound of formula (III-II): [ka] or a pharma- ceutically acceptable salt thereof.

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

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

[0024] In some embodiments, the compound of formula (III-I) or (III-II) has the formula (III-Ie): [ka] or a pharma- ceutically acceptable salt thereof.

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

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

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

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

[0029] In some embodiments, a method of treating a CNS-related disorder in a subject in need thereof includes administering to the subject an effective amount of a compound described herein or a pharmaceutical formulation thereof. The method of claim 1, further comprising administering to the patient a therapeutically 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 pharma- ceutically 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 pharma- ceutically acceptable salt thereof, and a pharma- ceutically 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, GABAA These compounds act as GABA modulators, which affect the GABA receptor in 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 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 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 pharma- ceutically acceptable salt thereof, In formula (IX), p is 0, 1, or 2; R 19is 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) 2 R X2 , -OS(=O) 2 OR X1 , -SS(=O) 2 R X2 , -SS(=O) 2 OR X1 , -S(=O)R X2 , -SO 2 R X2 , or -S(=O) 2 OR 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, R 11b is hydrogen; or R 11a and R 11b together form an oxo (=O) group; R 6a and R 6b Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Al or a pharma- ceutically 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 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 pharma- ceutically acceptable salt thereof, In formula (II), R 3a , R 2a , R6a , R 6b , R 11a , R 11b is as defined in item 1; R m , R n , and R x Each occurrence of is independently hydrogen, halogen, -NO 2 , -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) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(R GA ) 2 , -N(R GA )S(=O) 2 R 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 a 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 C2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, substituted or is 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 pharma- ceutically acceptable salt thereof, wherein the groups, taken together with intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring. (Item 9) R 3a is optionally substituted with alkoxy or 1 to 2 halo groups (e.g., fluoro). 1~6 is alkyl, R m , R n , and R x At least one of is a halogen (e.g., -F, -Cl, -Br), -NO 2 , -CN, -OR GA , -N(R GA ) 2 , -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(O)R GA For example, -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(R GA ) 2 , substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 , -CH 2 CH 3 , haloalkyl, e.g., -CF 3 ), 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] The compound according to any one of items 1 to 9, selected from the compounds represented by the following formula: (Item 11) Formula (IIB): [ka] The compound according to any one of items 1 to 9, selected from the compounds represented by the following formula: (Item 12) R 3a But non-substituted C 1~6 The compound according to any one of items 1 to 11, wherein the compound 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 C optionally substituted with 1 or 2 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 3a But -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CH 2 OCH 2 CH 3 , or -CH 2 OCH 3 15. The compound according to any one of items 1 to 14, wherein (Item 16) R 3a But -CH 3 16. The compound according to any one of items 1 to 15, (Item 17) R 2a -OH, -OCH 3 , -OCH2 CH 3 , -OCH 2 CH 2 CH 3 , -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , substituted or unsubstituted cyclopropyl, fluoro, or chloro. (Item 18) R 2a But -CH 3 or -OCH 3 18. The compound according to any one of items 1 to 17, (Item 19) R 2a But, -OCH 3 19. The compound according to any one of items 1 to 18, wherein (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 n is 0 or 1; and n is 1 or 2; and n is 2 or 3. The compound according to any one of items 1 to 20, wherein both 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 The compound according to any one of items 1 to 23, wherein all of are hydrogen. (Item 25) R m , R n , and Rx At least one of the following is substituted or unsubstituted C 1~2 Alkyl (e.g., -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , halogen, -SR GA , -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , or -S(=O) 2 N(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 At least one of the following 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) 2 R GA , -S(=O) 2 OR GA , or -S(=O) 2 N(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) 2 R GA The compound according to any one of items 1 to 27, (Item 29) R GA But -CH 3 29. The compound according to any one of items 1 to 28, wherein (Item 30) R m and 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), -NO 2 , -CN, -OR GA , -N(R GA ) 2 , -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(R GA ) 2 , substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 , -CH 2 CH 3 , haloalkyl, e.g., -CF 3 ), 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) 2 R GA , -S(=O) 2 OR GA , or -S(=O) 2 N(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 halogens (e.g., -F, -Cl, -Br), -NO 2 , -CN, or substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 , -CH 2 CH 3 , haloalkyl, e.g., -CF 3 ), 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 , R 6a , and R 6b is hydrogen. (Item 35) R 2a , R 11a , R 11b , R 6a , R 6b , R m , R n , and R x 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 At least four of the following are hydrogen: (Item 37) R 2a , R 11a , R 11b , R 6a , R 6b , R m , R n , and R x The compound according to any one of items 1 to 36, wherein at least five of are hydrogen. (Item 38) R n halogens (e.g., -F, -Cl, -Br), -NO 2 , -CN, -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(=O)R GA , -S(=O) 2 R GA , substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 , -CH 2 CH 3 , haloalkyl, e.g., -CF 3 ), 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, -SR GA , -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , or -S(=O) 2 N(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 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 Alkyl (e.g., haloalkyl, e.g., -CF 3 , -CHF 2 , -CH 2 F), or alkoxy. Item 1. The compound according to item 1. (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 pharma- ceutically acceptable salt thereof, and a pharma- ceutically 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, a pharma- ceutically acceptable salt or a pharma-ceutically 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 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, 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 pharma- ceutically 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 C 2 ~C 6 Alkyl, substituted or unsubstituted C 2 ~C 6 Alkenyl, or substituted or unsubstituted C 2 ~C 6 is alkynyl; R 5is hydrogen or methyl, or [ka] If 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 form an oxo (=O) group; 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, -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 , -SS(=O) 2 R A2 , -SS(=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, 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 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, 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 , -NH 2 , -N(R D1 ) 2 , or -NRD1 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(RA1 ) 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 , -SS(=O) 2 R A2 , -SS(=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, a sulfur protecting group when attached to a sulfur atom, a nitrogen protecting group when attached to a nitrogen atom, -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: [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 pharma- ceutically acceptable salt thereof. (Item 49) 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, 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 49. The compound according to item 48, which is 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, 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 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, 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 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 48-55, 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 48-56, 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) 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 58. The compound according to any one of items 48 to 57, wherein is unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 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) 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) 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 n is 0 or 1; and n is 1 or 2. The compound according to any one of items 48 to 65, wherein both are hydrogen. (Item 67) R 11a or R 11b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 68) R 11a or R 11b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 68. The compound according to any one of items 48 to 67, wherein the aryl group is alkoxyhalo, or -OH. (Item 69) R 11aor R 11b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 ,or- CH(CH 3 ) 2 The compound according to any one of items 48 to 68, wherein (Item 70) R 11a and R 11b can be taken together to form oxo. (Item 71) R 7a or R 7b 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 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 n is 0 or 1. The compound according to any one of items 48 to 71, wherein both of are hydrogen. (Item 73) R 7a and R 7b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 74) R 7a and R 7beach independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 74. The compound according to any one of items 48 to 73, wherein the aryl group is alkoxyhalo, or -OH. (Item 75) R 7a or R 7b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 48 to 74, wherein (Item 76) R 5 is hydrogen at the cis position relative to C19. (Item 77) R 5 is a hydrogen atom in the trans position relative 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) R 3 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 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 The compound according to any one of items 48 to 86, wherein is hydrogen. (Item 88) R 3 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 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 But substitution C 2 ~C 6 The compound according to any one of items 48 to 91, wherein the compound is alkyl. (Item 93) R 19 But non-substituted C 2 ~C 6 The compound according to any one of items 48 to 92, wherein R is alkyl. (Item 94) R 19 But substitution C2 ~C 6 The compound according to any one of items 48 to 93, which is alkenyl. (Item 95) R 19 But non-substituted C 2 ~C 6 The compound according to any one of items 48 to 94, wherein the compound is alkenyl. (Item 96) R 19 But substitution C 2 ~C 6 The compound according to any one of items 48 to 95, which is alkynyl. (Item 97) R 19 But non-substituted C 2 ~C 6 The compound according to any one of items 48 to 96, which is 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 The compound according to any one of items 48 to 100, wherein both of are hydrogen. (Item 102) R 6a is halo or alkyl, R 6b The compound according to any one of items 48 to 101, wherein is hydrogen. (Item 103) R 6aand R 6b and n is 0, 1 or 2; and n is 1 or 2; and n is 2 or 3; and n is 3 or 4; (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 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 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 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 , -NH 2 , 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 107) R12a and R 12b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 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 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 each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 101. The compound according to any one of items 48 to 109, wherein the aryl group is alkoxyhalo, or -OH. (Item 111) R 12a and R 12b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 48 to 110, wherein (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 are each independently hydrogen or substituted or unsubstituted alkyl; The compound according to any one of items 48 to 113, (Item 115) R 17b is 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. The compound according to any one of items 48 to 115, (Item 117) R 1 but, [ka] 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(RGA )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 Al Quinyl, 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- to 4-membered carbocyclic or heterocyclic ring; Here, 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 Here, R 20 Each occurrence of is independently a 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 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- to 4-membered carbocyclic or heterocyclic ring; Here, R GA Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6Alkyl, 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) has the formula (II-Ia): [ka] 49. The compound according to item 48, which is a compound of formula (I) or a pharma- ceutically acceptable salt thereof. (Item 120) The compound of formula (II-I) is represented by the formula (II-Ib) [ka] 49. The compound according to item 48, which is a compound of formula (I) or a pharma- ceutically acceptable salt thereof. (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 represented by the 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 pharma- ceutically 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 pharma- ceutically acceptable salt thereof, wherein the groups together with intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring. (Item 124) The compound of formula (II-I) has the 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 heterocyclyl or heteroaryl ring; 49. The compound according to item 48, or a pharma- ceutically acceptable salt thereof. (Item 125) The compound of formula (II-I) is represented by the formula (II-Ih): [ka] is a compound of In formula (II-Ih), R 35each is independently halogen, alkyl, hydroxyl, or cyano; r is 0, 1, 2, or 3; 49. The compound according to item 48, or a pharma- ceutically acceptable salt thereof. (Item 126) The compound of formula (II-I) is represented by the 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 heterocyclyl or heteroaryl ring; 49. The compound according to item 48, or a pharma- ceutically acceptable salt thereof. (Item 127) A pharmaceutical composition comprising the compound according to any one of items 48 to 126 or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable excipient. (Item 128) 13. 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 pharma- ceutically 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 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. (Item 130) 130. The method of claim 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 130. The method of item 129, wherein the major depressive disorder is moderate major depressive disorder. (Item 134) Item 130. The method of item 129, wherein the major depressive disorder is severe major depressive disorder. (Item 135) Formula (III-I): [ka] or a pharma- ceutically acceptable salt thereof, In formula (III-I), n is 0, 1, or 2; R 3ais 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 C 2 ~C 6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted C 2 ~C 6 alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; R 5 is hydrogen or methyl, or [ka] If 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 form an oxo (=O) group; 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, -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 , -SS(=O) 2 R A2 , -SS(=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, 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 is a 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 , -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, 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 pharma- ceutically acceptable salt thereof. (Item 136) Formula (III-II): [ka] or a pharma- ceutically 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, C 1 ~C 6 Substituted alkyl, C 2 ~C 6 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 If is hydrogen, R 18 is a substitution C 1 ~C 6 Alkyl, unsubstituted C 3 ~C 6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, where R 18 When is a substituted methyl, the methyl is preferably a halo GEN, -CN, -NO 2 ,-SO 2 H, -SO 3 H, -OR aa , -ON(R bb ) 2 , -N(R bb ) 2 , -C(=O)R aa , -C(O)H, -CO 2 H, carbocyclyl, heterocyclyl, aryl, or heteroaryl, where R aa Each occurrence of is independently 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3-14 membered heterocyclyl, C 6~14 aryl, and 5- to 14-membered heteroaryl, or two R aa the groups taken together 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 , -CO 2 R aa , -SO 2 R aa , or -C(=NR cc ) OR aa or a pharma- ceutically acceptable salt thereof. (Item 137) R 3a is not trifluoromethyl. (Item 138) R 18 But halogen, cyano, -CO 2 H, or alkyl substituted with phenyl. (Item 139) R 2a and R 2b 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 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 , -NH 2 , or -N(R D1 ) 2 where R D1 140. 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 , -NH 2 , -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. (Item 142) R 2a and R 2b and n is 0 or 1; and n is 1 or 2. 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 each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 144. The compound according to any one of items 135 to 143, wherein the aryl group is alkoxyhalo, or -OH. (Item 145) R 2a and R 2b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2The compound according to any one of items 135 to 144, wherein (Item 146) R 18 is substituted or unsubstituted C 2 ~C 6 146. The compound according to any one of items 135 to 145, wherein the compound is alkyl. (Item 147) R 18 But substitution C 2 ~C 6 147. The compound according to any one of items 135 to 146, wherein the compound is alkyl. (Item 148) R 18 But non-substituted C 2 ~C 6 The compound according to any one of items 135 to 147, wherein the compound is alkyl. (Item 149) R 18 The compound according to any one of items 135 to 148, wherein is substituted propyl. (Item 150) R 18 The compound according to any one of items 135 to 149, wherein is a substituted butyl. (Item 151) R 1a or R 1b 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 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 , -NH 2 , 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. (Item 153) R 1a or R 1b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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. (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 1beach independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 156. The compound according to any one of items 135 to 155, which is alkoxyhalo, or -OH. (Item 157) R 1a or R 1b each independently represents -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 135 to 156, wherein (Item 158) R 4a or R 4b 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 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, -ORD1 , -OC(=O)R D1 , -NH 2 , 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 160) R 4a and R 4b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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. (Item 161) R 4a and R 4b and n is 0 or 1. The compound according to any one of items 135 to 160, wherein both 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 each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1~C 6 163. The compound according to any one of items 135 to 162, wherein the aryl group is alkoxyhalo, or -OH. (Item 164) R 4a and R 4b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 135 to 163, wherein (Item 165) R 11a or R 11b 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 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 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 , -NH 2 , or -N(R D1 ) 2 where R D1166. The compound according to any one of items 135-165, 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 , -NH 2 , -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 11b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 170) R 11a or R 11b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 169. The compound according to any one of items 135 to 169, wherein the aryl group is alkoxyhalo, or -OH. (Item 171) R11a or R 11b each independently represents -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 135 to 170, wherein (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 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 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 174) R 7a or R 7b 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)RD1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 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 175) R 7a and R 7b and (b) are hydrogen. Compound. (Item 176) R 7a and R 7b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 177) R 7a and R 7b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 177. The compound according to any one of items 135 to 176, which is alkoxyhalo, or -OH. (Item 178) R 7a or R 7b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 135 to 177, wherein (Item 179) R5 is hydrogen cis to C19. (Item 180) R 5 is a hydrogen atom trans to C19. (Item 181) R 5 is methyl in the cis position relative to the C19 position. (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) 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 substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. (Item 187) R 3a is substituted or unsubstituted alkyl. (Item 188) R 3a The compound according to any one of items 136 to 187, wherein is hydrogen. (Item 189) R 3a The compound according to any one of items 135 to 188, wherein is substituted alkyl. (Item 190) R 3a The compound according to any one of items 135 to 189, wherein is unsubstituted alkyl. (Item 191) R 3a is methyl. (Item 192) R 3a But -CH 2 The compound according to any one of items 135 to 191, wherein OMe is OMe. (Item 193) R 3a But -CH 2 The compound according to any one of items 135 to 192, wherein OEt. (Item 194) R 19 The compound according to any one of items 135 to 193, wherein is ethyl. (Item 195) R 19 The compound according to any one of items 135 to 194, wherein 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 But substitution C 2 ~C 6 The compound according to any one of items 135 to 197, wherein the compound is alkyl. (Item 199) R 19 But non-substituted C 2 ~C 6 The compound according to any one of items 135 to 198, wherein the compound is alkyl. (Item 200) R 19 But substitution C 2 ~C 6 The compound according to any one of items 135 to 199, which is alkenyl. (Item 201) R 19But non-substituted C 2 ~C 6 The compound according to any one of items 135 to 200, which is alkenyl. (Item 202) R 19 But substitution C 2 ~C 6 The compound according to any one of items 135 to 201, which is 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, R 6b The compound according to any one of items 135 to 205, wherein 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 12bare 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 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 Each occurrence is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted aryl ... The compound according to any one of items 135 to 208, wherein the aryl is 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 , -NH 2 , 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. (Item 211) R 12a and R 12b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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. (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 12b is each independently hydrogen or substituted or unsubstituted alkyl. (Item 214) R 12a and R 12b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 The compound according to any one of items 135 to 213, wherein the alkoxyhalo is -OH. (Item 215) R 12a and R 12b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 135 to 214, wherein (Item 216) R 12a and R 12b 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 is 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 Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -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) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2N(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, 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 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; 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 Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -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) 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, 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 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; 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 R16b 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 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 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 , -NH 2 , 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. (Item 225) R 16a and R 16b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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. (Item 226) R 16a and R 16b 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 each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 The compound according to any one of items 135 to 227, wherein the alkoxyhalo is -OH. (Item 229) R 16a and R 16b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 The compound according to any one of items 135 to 228, wherein (Item 230) R 18 But -CH(CH 3 ) 2 The compound according to any one of items 135 to 229, wherein (Item 231) R 18 The compound according to any one of items 135 to 230, wherein is substituted alkyl. (Item 232) The alkyl is -OCH 3 , -CH 2 CN, or -OCH(CH 3 ) 2 232. The compound according to item 231, wherein said compound is substituted with (Item 233) R 18 is propyl, butyl, t-butyl, or isopropyl, or ethyl. (Item 234) The compound of formula (III-I) is represented by the formula (III-Ia) [ka] 137. The compound according to item 135 or 136, which is a compound of formula (I) or a pharma- ceutically acceptable salt thereof. (Item 235) The compound of formula (III-I) is represented by the formula (III-Ib) [ka] 137. The compound according to item 135 or 136, which is a compound of formula (I) or a pharma- ceutically acceptable salt thereof. (Item 236) The compound of formula (III-I) is represented by the 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 32 137. The compound according to item 135 or 136, or a pharma- ceutically 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 pharma- ceutically 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 represented by the formula (III-Ih) [ka] is a compound of In formula (III-Ih), R 35 each is independently halogen, alkyl, hydroxyl, or cyano; r is 0, 1, 2, or 3; 137. The compound according to item 135 or 136, or a pharma- ceutically acceptable salt thereof. (Item 239) The compound of formula (III-I) is represented by the 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 heterocyclyl or heteroaryl ring; 137. The compound according to item 135 or 136, or a pharma- ceutically acceptable salt thereof. (Item 240) A pharmaceutical composition comprising a compound according to any one of items 135 to 239 or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically 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 pharma- ceutically 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 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. (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 PREFERRED EMBODIMENTS

[0034] Detailed Description of Specific Embodiments of the Invention As generally described herein, the present invention relates to a method for treating, e.g., a GABA A Provided are compounds designed to act as receptor modulators. In certain embodiments, it is envisioned that such compounds are 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] Definitions of certain functional groups and chemical terms are detailed below. Chemical elements are identified according to the Periodic Table of the Elements (CAS version, Handbook of Chemistry and Physics, 75th Edition, inside cover), and certain functional groups are generally defined as set forth therein. Additionally, general rules of organic chemistry, as well as certain functional moieties and reactivities, are described in detail 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, 1999; York,2001;Larock,Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd ed., 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., Univ. 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., enantiomeric excess). In other words, the "S" form of a compound is substantially free of the "R" form of the compound and is therefore enantiomeric in excess of the "R" form. The term "enantiomerically pure" or "pure enantiomer" means 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 weights are based on the total weight of all enantiomers or stereoisomers of the compound.

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

[0039] The term "diastereomerically pure" means that a compound contains 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 of a single diastereomer. Diastereomeric Purity and Enantiomeric Purity Methods for determining diastereomeric purity are well known in the art. Diastereomeric purity can be determined by any analytical method capable of quantitatively distinguishing 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 order of the atoms or in the arrangement of the atoms in space are referred to as "isomers". Isomers that differ in the arrangement of the 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 represented by the R and S ordering rules of Cahn and Prelog, or by the way the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., (+) or (-)-isomers, respectively). Chiral compounds can exist either as 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" is C 1 , C 2 , C 3 , C 4 , C 5 , C 6 , 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 , C3~4 , C 4~6 , C 4~5 , and C 5~6 is intended to include 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 linear 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"). 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 one carbon atom ("C 1 In some embodiments, an alkyl group has 2 to 6 carbon atoms ("C 2~6 "Alkyl"). C 1~6Examples of alkyl groups include methyl (C 1 ), ethyl (C 2 ), n-propyl (C 3 ), isopropyl (C 3 ), n-Butyl (C 4 ), tert-Butyl (C 4 ), sec-Butyl (C 4 ), iso-butyl (C 4 ), n-pentyl (C 5 ), 3-pentanyl (C 5 ),a Mill (C 5 ), neopentyl (C 5 ), 3-methyl-2-butanyl (C 5 ), tertiary amyl (C 5 ) and n-hexyl (C 6 Further examples of alkyl groups include n-heptyl (C 7 ), n-octyl (C 8 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, 1-5 substituents, 1-3 substituents, or 1 substituent ("substituted alkyl"). In certain embodiments, an alkyl group is an unsubstituted C 1~10 Alkyl (e.g., -CH 3 In certain embodiments, the alkyl group is a substituted C 1~10 Alkyl. A common abbreviation for alkyl is Me(-CH 3 ), Et(-CH 2 CH 3 ), iPr(-CH(CH 3 ) 2 ), nPr(-CH 2 CH 2 CH 3 ), n-Bu(-CH 2 CH 2 CH 2 CH 3 ), or i-Bu(-CH 2 CH(CH 3 ) 2 ) are mentioned.

[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 methylene (-CH 2 -), ethylene (-CH 2 CH 2 -), propylene (-CH 2 CH 2 CH 2 -), butylene (-CH 2 CH 2 CH 2 CH 2 -), pentylene (-CH 2 CH 2 CH 2 CH 2 CH 2 -), and hexylene (-CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 Exemplary substituted alkylene groups, e.g., substituted with one or more alkyl (methyl) groups, include, but are not limited to, substituted methylene (-CH(CH 3 )-, (-C(CH 3 ) 2 -), substituted ethylene (-CH(CH 3 )CH 2 -, -CH 2 CH(CH 3 )-, -C(CH 3 ) 2 CH 2 -, -CH 2 C(CH 3 ) 2 -), substituted propylene (-CH(CH 3 )CH 2 CH 2 -, -CH 2 CH(CH 3 )CH 2 -, -CH 2 CH 2 CH(CH 3 )-, -C(CH 3 ) 2 CH 2 CH2 -, -CH 2 C(CH 3 ) 2 CH 2 - and -CH 2 CH 2 C(CH 3 ) 2 -), 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. The alkylene group can be substituted or unsubstituted with one or more substituents described herein.

[0046] "Alkenyl" refers to the radical of a straight-chain 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, the alkenyl does not contain any triple bonds. In some embodiments, the alkenyl group has 2 to 10 carbon atoms ("C 2~10 In some embodiments, an alkenyl group has 2 to 9 carbon atoms ("C 2~9 In some embodiments, the alkenyl group has 2 to 8 carbon atoms ("C 2~8 In some embodiments, the 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, the alkenyl group has 2 to 3 carbon atoms ("C 2~3In some embodiments, the alkenyl group has two carbon atoms ("C 2 The one or more carbon-carbon double bonds can be internal (e.g., 2-butenyl) or terminal (e.g., 1-butenyl). 2~4 Examples of alkenyl groups include ethenyl (C 2 ), 1-propenyl (C 3 ), 2-propenyl (C 3 ), 1-butenyl (C 4 ), 2-butenyl (C 4 ), butadienyl (C 4 ) etc. 2~6 Examples of alkenyl groups include the above-mentioned C 2~4 Alkenyl groups, as well as pentenyl ( C 5 ), pentadienyl (C 5 ), hexenyl (C 6 Further examples of alkenyl include heptenyl (C 7 ), octenyl (C 8 ), octatrienyl (C 8 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., 1-5 substituents, 1-3 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 2~20In certain embodiments, an alkenyl does not contain any double bonds. In some embodiments, an alkynyl group has 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, the alkynyl group has 2 to 3 carbon atoms ("C 2~3 In some embodiments, the alkynyl group has two carbon atoms ("C 2 The one or more carbon-carbon triple bonds can be internal (e.g., 2-butynyl) or terminal (e.g., 1-butynyl). 2~4 Examples of alkynyl groups include ethynyl (C 2 ), 1-propynyl (C 3 ), 2-propynyl (C 3 ), 1-butynyl (C 4 ), 2-butynyl (C 4 ) but are not limited to these. 2~6 Examples of alkenyl groups include the above-mentioned C 2~4 Alkynyl groups, as well as pentynyl (C 5 ), Hexynyl (C 6 Further examples of alkynyl include heptynyl (C 7 ), Octynyl (C 8Unless 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, 1-5 substituents, 1-3 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, further comprising 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, the heteroalkyl group is , saturated groups having 1 to 7 carbon atoms and 1, 2, 3, or 4 heteroatoms ("hetero C 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 one carbon atom and one heteroatom ("heteroC 1 In some embodiments, a 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 heteroalkyl group. 1~10 It is an 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 six ring carbon atoms ("C 6 aryl"; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms ("C 10Aryl"; for example, 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 with one or more carbocyclyl or heterocyclyl groups, where the attachment 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.In particular, 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 halo, C 1 ~C 8 Alkyl, C 1 ~C 8 Haloalkyl, cyano, hydroxy, C 1 ~C 8 Substituted with one or more groups selected from alkoxy and amino.

[0051] Representative examples of substituted aryl include: [ka] Here, R 56 and R 57 can be hydrogen, and R 56 and R 57 At least one of each independently represents C 1 ~C 8 Alkyl, C 1 ~C 8 Haloalkyl, 4-10 membered heterocyclyl, alkanoyl, C 1 ~C 8 Alkoxy, heteroaryloxy, alkylamino, arylamino, heteroarylamino, NR 58 COR 59 , N.R. 58 SOR 59 , N.R. 58 SO 2 R 59 , COO alkyl, COO aryl, CONR 58 R 59 ,CONR 58 OR 59 , N.R. 58 R 59 , S.O. 2 NR 58 R 59 , S-alkyl, SO alkyl, SO 2 Alkyl, S aryl, SO aryl, SO 2 aryl; or R 56 and R 57 may be linked to form a cyclic ring (saturated or unsaturated) of 5 to 8 atoms, optionally including one or more heteroatoms selected from the group N, O or S. 60 and R 61 are independently hydrogen, C 1 ~C 8 Alkyl, C 1 ~C 4 Haloalkyl, C 3 ~C 10 Cycloalkyl, 4-10 membered heterocyclyl, C 6 ~C 10Aryl, Substituted C 6 ~C 10 It is aryl, 5- to 10-membered heteroaryl or substituted 5- to 10-membered heteroaryl.

[0052] "Fused aryl" refers to an aryl which 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 5-10 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 1-4 ring heteroatoms are provided in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl"). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment may be a carbon or nitrogen atom, as permitted by valence. Heteroaryl bicyclic ring systems may 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, and 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 with one or more aryl groups, where the point of attachment can be on either the aryl ring or the heteroaryl ring, and in such cases the number of ring members refers to the number of ring members in the fused (aryl / heteroaryl) ring system. For 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, the heteroaryl group is a 5-10 membered aromatic ring system in which ring carbon atoms and 1-4 ring heteroatoms are provided in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl"). In some embodiments, the heteroaryl group is a 5-8 membered aromatic ring system in which ring carbon atoms and 1-4 ring heteroatoms are provided in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heteroaryl"). In some embodiments, the heteroaryl group is a 5-8 membered aromatic ring system in which ring carbon atoms and 1-4 ring heteroatoms are provided in the aromatic ring system, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heteroaryl"). Provided in the system are 5-6 membered aromatic ring systems, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heteroaryl"). In some embodiments, the 5-6 membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 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, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5-14 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, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzoisothiazolyl, 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 heteroaryl include those of the formula: [ka] where each Z is carbonyl, N, NR65 , O and S; R 65 are independently hydrogen, C 1 ~C 8 Alkyl, C 3 ~C 10 Cycloalkyl, 4-10 membered heterocyclyl, C 6 ~C 10 aryl and 5-10 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 The carbocyclyl group is cyclopropyl (C 3 ), cyclopropenyl (C 3 ), cyclobutyl (C 4 ), cyclobutenyl (C 4 ), cyclopentyl (C 5 ), cyclopentenyl (C 5 ), cyclohexyl (C 6 ), cyclohexenyl (C 6 ), cyclohexadienyl (C 6 ) and the like. Exemplary C 3~8 The carbocyclyl group is the above-mentioned C 3~6 Carbocyclyl groups, as well as cycloheptyl (C 7 ), cycloheptenyl (C 7 ), cycloheptadienyl (C 7 ), cycloheptatrienyl (C7 ), cyclooctyl (C 8 ), cyclooctenyl (C 8 ), bicyclo[2.2.1]heptanyl (C 7 ), bicyclo[2.2.2]octanyl (C 8 ) and the like. Exemplary C 3~10 The carbocyclyl group is the above-mentioned C 3~8 Carbocyclyl groups, as well as cyclononyl (C 9 ), cyclononenyl (C 9 ), cyclodecyl (C 10 ), cyclodecenyl (C 10 ), octahydro-1H-indenyl (C 9 ), 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 includes fused, bridged, or spiro ring systems (e.g., bicyclic systems ("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, and 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 ("C3~10 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 ("C 5~10 "Cycloalkyl"). C 5~6 Examples of cycloalkyl groups include cyclopentyl (C 5 ) and cyclohexyl (C 5 ) are listed. C 3~6 Examples of cycloalkyl groups include the above-mentioned C 5~6 Cycloalkyl groups, as well as cyclopropyl (C 3 ) and cyclobutyl (C 4 ) are listed. C 3~8 Examples of cycloalkyl groups include the above-mentioned C 3~6 Cycloalkyl groups, as well as cycloheptyl (C 7 ) and cyclooctyl (C 8 Unless otherwise specified, each occurrence of a cycloalkyl group is independently unsubstituted ("unsubstituted cycloalkyl") or substituted ("substituted cycloalkyl") with one or more substituents. 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 1-4 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 may be at a carbon or nitrogen atom, when valence permits. Heterocyclyl groups may be monocyclic ring systems ("monocyclic heterocyclyl") or fused, bridged, or spiro ring systems, such as bicyclic systems ("bicyclic heterocyclyl"), and may be saturated or partially unsaturated. Heterocyclyl bicyclic ring systems may 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 with 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 with one or more aryl or heteroaryl groups, where the point of attachment is on the heterocyclyl ring, in which case 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 3-10 membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3-10 membered heterocyclyl.

[0060] In some embodiments, a heterocyclyl group is a 5-10 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("5-10 membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5-8 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heterocyclyl"). In some embodiments, a heterocyclyl group is a 5-6 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, where each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heterocyclyl"). In some embodiments, a 5-6 membered hetero A cyclyl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, a 5- to 6-membered heterocyclyl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, a 5- to 6-membered heterocyclyl has one 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. C 6Exemplary 5-membered heterocyclyl groups (also referred to herein as 5,6-bicyclic heterocyclic rings) fused to an aryl ring include, but are not limited to, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, etc. 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, etc.

[0062] A "nitrogen-containing heterocyclyl" group refers to a 4-7 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). Particular 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 with a nitrogen, oxygen, or sulfur heteroatom. Hetero can apply to any of the hydrocarbyl groups listed 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 This 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 aryl ... "Alkanoyl" refers to an alkyl group consisting of R, ... 20 is an acyl group, which is a group other than hydrogen. Representative acyl groups are formyl (-CHO), acetyl (-C(=O)CH 3 ), cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl (-C(=O)Ph), benzylcarbonyl (-C(=O)CH 2 Ph), --C(O)-C 1 -C 8 Alkyl, -C(O)-(CH 2 ) t (C 6 -C 10 aryl), -C(O)-(CH 2 ) t (5-10 membered heteroaryl), -C(O)-(CH 2 ) t (C 3 -C 10 Cycloalkyl) and -C(O)-(CH 2 ) t (4-10 membered heterocyclyl) (t is an integer from 0 to 4). 21 is a halo or hydroxy substituted C 1 ~C 8 Alkyl; or C 3 ~C 10 Cycloalkyl, 4-10 membered heterocyclyl, C 6 ~C 10 Aryl, arylalkyl, 5-10 membered heteroaryl or heteroarylalkyl, each of which is an unsubstituted C 1 ~C 4 Alkyl, halo, unsubstituted C 1 ~C 4 Alkoxy, unsubstituted C 1 ~C 4 Haloalkyl, unsubstituted C 1 ~C 4 Hydroxyalkyl or unsubstituted C 1 ~C 4 substituted with haloalkoxy or hydroxy.

[0065] "Alkoxy" means -OR 29 The 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, C 6 ~C 10 Aryl, aryloxy, carboxyl, cyano, C 3 ~C 10 Cycloalkyl, 4-10 membered heterocyclyl, halogen, 5-10 membered heteroaryl, hydroxyl, nitro, thioalkoxy, thioaryloxy, thiol, alkyl-S(O)-, aryl-S(O)-, alkyl-S(O) 2 - and aryl-S(O) 2 -, for example, 1 to 5 substituents, particularly 1 to 3 substituents, and particularly 1 substituent selected from the group consisting of: -. Exemplary "substituted alkoxy" groups include -O-(CH 2 ) t (C 6 ~C 10 Aryl), -O-(CH 2 ) t (5-10 membered heteroaryl), -O-(CH 2 ) t (C 3 ~C 10 Cycloalkyl) and -O-(CH 2 ) t(4-10 membered heterocyclyl), where t is an integer from 0 to 4, and any aryl, heteroaryl, cycloalkyl or heterocyclyl group present may itself be an unsubstituted C 1 ~C 4 Alkyl, halo, unsubstituted C 1 ~C 4 Alkoxy, unsubstituted C 1 ~C 4 Haloalkyl, unsubstituted C 1 ~C 4 Hydroxyalkyl or unsubstituted C 1 ~C 4 A particularly exemplary "substituted alkoxy" group is -OCF 3 , -OCH 2 CF 3 , -OCH 2 Ph, -OCH 2 -Cyclopropyl, -OCH 2 CH 2 OH and -OCH 2 CH 2 NMe 2 It is.

[0067] "Amino" means -NH 2 It refers to radicals.

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

[0069] "Substituted amino" refers to a group of the formula -N(R 38 ) 2 where R 38 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, substituted or unsubstituted heteroaryl, or an amino-protected group, where R 38 At least one of R is not hydrogen. 38 are independently hydrogen, C 1 ~C8 Alkyl, C 3 ~C 8 Alkenyl, C 3 ~C 8 Alkynyl, C 6 ~C 10 Aryl, 5-10 membered heteroaryl, 4-10 membered heterocyclyl or C 3 ~C 10 Cycloalkyl; or halo or hydroxy substituted C 1 ~C 8 Alkyl; halo or hydroxy substituted C 3 ~C 8 Alkenyl; C substituted with halo or hydroxy 3 ~C 8 Alkynyl, or -(CH 2 ) t (C 6 ~C 10 Aryl), -(CH 2 ) t (5-10 membered heteroaryl), -(CH 2 ) t (C 3 ~C 10 Cycloalkyl) or -(CH 2 ) t (4-10 membered heterocyclyl), where t is an integer from 0 to 8, each of which is selected from unsubstituted C 1 ~C 4 Alkyl, halo, unsubstituted C 1 ~C 4 Alkoxy, unsubstituted C 1 ~C 4 Haloalkyl, unsubstituted C 1 ~C 4 Hydroxyalkyl or unsubstituted C 1 ~C 4 or both R are substituted by haloalkoxy or hydroxy; 38 The groups taken together form an alkylene group.

[0070] Exemplary "substituted amino" groups include -NR 39 -C 1 ~C 8 Alkyl, -NR 39 -(CH2 ) t (C 6 ~C 10 Aryl), -NR 39 -(CH 2 ) t (5-10 membered heteroaryl), -NR 39 -(CH 2 ) t (C 3 ~C 10 Cycloalkyl) and -NR 39 -(CH 2 ) t (4-10 membered heterocyclyl), where t is an integer from 0 to 4, e.g., 1 or 2, and each R 39 are independently H or C 1 ~C 8 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 an unsubstituted C 1 ~C 4 Alkyl, halo, unsubstituted C 1 ~C 4 Alkoxy, unsubstituted C 1 ~C 4 Haloalkyl, unsubstituted C 1 ~C 4 Hydroxyalkyl or unsubstituted C 1 ~C 4 It may be substituted by 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 includes both mono- and di-substituted amino groups.

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

[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. Exemplary 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" means -NO 2 It refers to radicals.

[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., 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, or a "substituted" or "unsubstituted" heteroaryl group). 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 spontaneously undergo transformation (e.g., by rearrangement, cyclization, elimination, or other reaction). Unless otherwise indicated, 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 are the same or different at each position. The term "substituted" is intended to include substitution with all permissible substituents of organic compounds, any of the substituents described herein that form a stable compound. The present invention contemplates any and all such combinations to arrive at a stable compound. For purposes of the present 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 thus form a stable moiety.

[0079] Exemplary carbon atom substituents include halogen, -CN, -NO 2 , -N 3 , -SO 2 H, -SO 3 H, -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 、-CO 2 H、-CHO、-C(OR cc ) 2 、-CO 2 R aa 、-OC(=O)R aa 、-OCO 2 R aa 、-C(=O)N(R bb ) 2 、-OC(=O)N(R bb ) 2 、-NR bb C(=O)R aa 、-NR bb CO 2 R 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 SO 2 R aa 、-NR bb SO 2 R aa 、-SO 2 N(R bb ) 2 、-SO 2 R aa 、-SO 2 OR aa 、-OSO 2 Raa 、-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) 2 R aa 、-OP(=O) 2 R aa 、-P(=O)(R aa ) 2 、-OP(=O)(R aa ) 2 、-OP(=O)(OR cc ) 2 、-P(=O) 2 N(R bb ) 2 、-OP(=O) 2 N(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, 3-14 membered heterocyclyl, C 6~14 aryl and 5-14 membered heteroaryl, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd or the two geminal hydrogens on the carbon atom are replaced by groups =O, =S, =NN(R bb ) 2 , =NNR bb C(=O)R aa , =NNR bb C(=O)OR aa , =NNR bb S(=O) 2 R aa , =NR bb OR =NOR cc Replaced by;

[0080] R aa Each occurrence of is independently 1~10 Alkyl, C 1~10 Haloalkyl, C 2~ 10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3-14 membered heterocyclyl, C 6~14 aryl and 5- to 14-membered heteroaryl, or two R aa groups linked together form a 3- to 14-membered heterocyclyl or a 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently represents 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(Rcc ) 2 , -CN, -C(=O)R aa , -C(=O)N(R cc ) 2 , -CO 2 R aa , -SO 2 R aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc ) 2 , -SO 2 N(R cc ) 2 , -SO 2 R cc , -SO 2 OR cc , -SOR aa , -C(=S)N(R cc ) 2 , -C(=O)SR cc , -C(=S)SR cc , -P(=O) 2 R aa , -P(=O)(R aa ) 2 , -P(=O) 2 N(R cc ) 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, 3-14 membered heterocyclyl, C 6~14 aryl and 5- to 14-membered heteroaryl, or two R bb groups linked together form a 3- to 14-membered heterocyclyl or a 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently represents 0, 1, 2, 3, 4, or 5 R dd substituted with a group;

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

[0083] R dd Each occurrence of is independently a halogen, -CN, -NO 2 , -N 3 , -SO 2 H, -SO 3 H, -OH, -OR ee , -ON(R ff ) 2 , -N(R ff ) 2 , -N(R ff ) 3 + X - , -N(OR ee )R ff , -SH, -SR ee , -SSR ee , -C(=O)R ee , -CO 2 H, -CO 2 R ee , -OC(=O)R ee , -OCO 2 R ee , -C(=O)N(R ff ) 2 , -OC(=O)N(R ff ) 2 , -NR ff C(=O)R ee , -NR ff CO 2 R ee , -NR ff C(=O)N(R ff ) 2 , -C(=NRff ) 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 SO 2 R ee , -SO 2 N(R ff ) 2 , -SO 2 R ee , -SO 2 OR ee , -OSO 2 R 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) 2 R 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, where 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 is independently 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 3~10 Carbocyclyl, C 6~10 Aryl, 3~ 10-membered heterocyclyl and 3-10-membered heteroaryl, where 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 5-10 membered heteroaryl, or two R ff groups linked together form a 3- to 14-membered heterocyclyl or a 5- to 14-membered heteroaryl ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently represents 0, 1, 2, 3, 4, or 5 R gg substituted with a group;

[0086] R gg Each occurrence of is independently a halogen, -CN, -NO 2 , -N 3 , -SO2 H, -SO 3 H, -OH, -OC 1~6 Alkyl, -ON(C 1~6 Alkyl) 2 , -N(C 1~6 Alkyl) 2 , -N(C 1~6 Alkyl) 3 + X - , -NH(C 1~6 Alkyl) 2 + X - , -NH 2 (C 1~6 Alkyl) + X - , -NH 3 + 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), -CO 2 H, -CO 2 (C 1~6 alkyl), -OC(=O)(C 1~6 Alkyl), -OCO 2 (C 1~6 alkyl), -C(=O)NH 2 , -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), -NHCO 2 (C 1~6 alkyl), -NHC(=O)N(C 1~6 Alkyl) 2 , -NHC(=O)NH(C 1~6 alkyl), -NHC(=O)NH 2 , -C(=NH)O(C 1~6 alkyl), -OC(=NH)(C 1~6alkyl), -OC(=NH)OC 1~6 Alkyl, -C(=NH)N(C 1~6 Alkyl) 2 , -C(=NH)NH(C 1~6 alkyl), -C(=NH)NH 2 , -OC(=NH)N(C 1~6 Alkyl) 2 , -OC(NH)NH(C 1~6 alkyl), -OC(NH)NH 2 , -NHC(NH)N(C 1~6 Alkyl) 2 , -NHC(=NH)NH 2 , -NHSO 2 (C 1~6 Alkyl), -SO 2 N(C 1~6 Alkyl) 2 , -SO 2 NH(C 1~6 Alkyl), -SO 2 NH 2 , -SO 2 C 1~6 Alkyl, -SO 2 O.C. 1~6 Alkyl, -OSO 2 C 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)NH 2 , -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 , C1~6 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 electrical neutrality. Exemplary counterions include halide ions (e.g., F - , Cl - , Br - , I - ), NO 3 - , ClO 4 - , O.H. - , H 2 PO 4 - , HSO 4 - , 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, etc.). Examples of tartrates include glycerate, lactate, tartrate, and glycolate.

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

[0089] Other Definitions As used herein, the term "modulation" refers to the A The term "modulator" refers to the inhibition or potentiation of receptor function. 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, and more specifically, in humans.

[0091] "Pharmaceutically acceptable salts" refers to salts of the compounds of the present invention that are pharma- ceutically 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, and the like; 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-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, and the like. or (2) salts formed when an acidic proton present in the parent compound is replaced with a metal ion, such as an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base, such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, etc. Salts further include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, etc.; and, where the compound contains a basic functional group, salts of non-toxic organic or inorganic acids, such as hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalate, etc. The term "pharmacologically 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, e.g., 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 to the therapeutically active agents of the present invention under physiological conditions. One method of making prodrugs is to design selected moieties that are 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, prodrugs are converted by the enzyme activity of the subject.

[0093] In some embodiments, the compound of formula (IX, II, II-I, III-I or III-II ) are prodrugs, where the prodrugs contain a cleavable moiety on the C3 hydroxy as shown in formula (IX, II, II-I, III-I or III-II). "Tautomers" refer to compounds of a particular compound structure in interchangeable form and with varying displacement of hydrogen atoms and electrons. Thus, two structures may be in equilibrium with the movement 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 obtaining 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 , -CO 2 R 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 , -SO 2 R aa , -Si(R aa ) 3 , -P(R cc ) 2 , -P(R cc ) 3 , -P(=O) 2 R aa , -P(=O)(R aa ) 2 , -P(=O)(OR cc ) 2 , -P(=O) 2 N(R bb ) 2 , and -P(=O)(NR bb ) 2 (where R aa , R bb , and R cc (wherein is as defined herein). Oxygen protecting groups are well known in the art and are described in Protecting Groups in Organic Synthesis, TW Greene and PG M Huts, 3 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 , -CO 2 R 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 , -SO 2 R aa , -Si(R aa ) 3 , -P(R cc ) 2 , -P(R cc ) 3 , -P(=O) 2 R aa , -P(=O)(R aa ) 2 , -P(=O)(OR cc ) 2 , -P(=O) 2 N(R bb ) 2 , and -P(=O)(NR bb ) 2 Wherein R aa , R bb , and R ccis as defined herein. Sulfur protecting groups are well known in the art and Groups in Organic Synthesis,TWGreene and PGMWuts,3 rd edition, John Wiley & Sons, 1999, which is incorporated herein by reference. Can be obtained.

[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) 2 R aa , -C(=NR cc )R aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc ) 2 , -SO 2 N(R cc ) 2 , -SO 2 R cc , -SO 2 OR 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, 3-14 membered heterocyclyl, C 6~14aryl, 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. Huts, 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-fluorenylmethyl carbamate (Fmoc), t-butyl carbamate (BOC), and benzyl carbamate (Cbz); sulfonamide groups (e.g., -S(=O) 2 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. In general, 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 the 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 include 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 provides a method for determining whether a subject suffers from a particular disease, disorder, or condition. The administration of the compound of the present invention or its pharmacologic acceptable salt or pharmacologic acceptable composition is intended as a prophylaxis against the disease.As used herein, unless otherwise specified, the "prophylactically effective amount" of a compound is an amount sufficient to prevent a disease, disorder or condition, or one or more symptoms related to the disease, disorder or condition, or to prevent its recurrence.The prophylactically effective amount of a compound means the 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 include an amount that improves overall prophylaxis, or an amount that enhances the prophylactic efficacy of another prophylactic agent.

[0104] As used herein, an "episodic dosing regimen" is 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 a moderate major depressive disorder. In some embodiments, the major depressive disorder is a 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 the 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) in response to a diagnosis of a disorder (e.g., depression or symptoms thereof). In some embodiments, episodic dosing is administered once a day 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 subject's lifetime) is administered to the subject. Compound

[0105] It should be recognized that the formulas depicted herein may refer to specific carbon atoms (C17, C3, C19, etc.). These references are based on the position of the carbon atoms 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 pharma- ceutically 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) 2 R X2 , -OS(=O) 2 OR X1 , -SS(=O) 2 R X2 , -SS(=O) 2 OR X1 , -S(=O)R X2 , -SO 2 R X2 , or -S(=O) 2 OR X1where 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 C2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 Carbocyclyl, R 11b is hydrogen; or R 11a and R 11b together form an oxo (=O) group; R 6a and R 6b Each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 It is 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 the compound 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 the compound of formula (IX).

[0110] In certain embodiments, R 1 is a substituted or unsubstitued heteroaryl in the compound 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 represented by formula (II): [ka] and pharma-ceutically 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, 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 is independently hydrogen, halogen, -NO 2 , -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 For example, -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(R GA ) 2 , -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 3~6 carbocyclyl, or substituted or unsubstituted 3- to 6-membered heterocyclyl; 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 Compounds and pharma- ceutically acceptable salts thereof are provided in which the radicals, 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 optionally substituted with alkoxy or 1-2 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), -NO 2 , -CN, -OR GA , -N(R GA ) 2 , -C(=O)R GA , -C(=O)OR GA , -SR GA , -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(R GA ) 2 , substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 , -CH 2 CH 3 , haloalkyl, e.g., -CF3 ), where R GA is a substituted or unsubstituted C 1~2 It is an alkyl.

[0115] Based on the foregoing, it is understood that steroids of formula (II) include 3,3-disubstituted 19-nor compounds and pharma- ceutically 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 an alkyl group. 3a C 1~6 The alkyl group may be substituted or unsubstituted methyl (C1), ethyl (C 2 ), n-propyl (C 3 ), isopropyl (C 3 ), n-Butyl (C 4 ), tert-Butyl (C 4 ), sec-Butyl (C 4), iso-butyl (C 4 ), n-pentyl (C 5 ), 3-pentanyl (C 5 ), Amyl (C 5 ), neopentyl (C 5 ), 3-methyl-2-butanyl (C 5 ), tertiary amyl (C 5 ), n-hexyl (C 6 ), C substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more fluoro groups 1~6 Alkyl (e.g., -CF 3 , -CH 2 F, -CHF 2 , 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 Alkyl (e.g., -CH 2 Cl, -CHCl 2 ), and C substituted with an alkoxy group 1~6 Alkyl (e.g., -CH 2 OCH 3 and -CH 2 OCH 2 CH 3 In certain embodiments, R 3a is a substitution C 1~6 is 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 unsubstituted C 1~3 is alkyl (e.g., R 3a is -CH 3 , -CH2 CH 3 , or -CH 2 CH 2 CH 3 (It is.)

[0119] In certain embodiments, R 3a is C substituted with one or more fluorine atoms 1~6 is alkyl (e.g., R 3a is -CH 2 F, -CHF 2 ,or -CF 3 In certain embodiments, R 3a is C substituted with one or two fluorine atoms 1~6 is alkyl (e.g., R 3a is -CH 2 F or -CHF 2 (It is.)

[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 -CH 2 OR A1 For example, where R A1 For example, the formula -CH 2 OH, -CH 2 OCH 3 , -CH 2 OCH 2 CH 3 , or -CH 2 OCH 2 CH 2 CH 3 R 3a Hydrogen to obtain the group, -CH 3 , -CH 2 CH 3 , or -CH 2 CH 2 CH 3 It is.

[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 (C ) which is unsubstituted or substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxyl; 2 ), propenyl (C 3 ), or butenyl (C 4 In certain embodiments, R 3a is ethenyl, propenyl, or butenyl, which 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 3a is unsubstituted or is alkyl, halo, haloalkyl (e.g., CF 3 ), alkoxyalkyl, cycloalkyl (e.g., cyclopropyl or cyclobutyl), or ethynyl, propynyl, or butynyl substituted with hydroxyl. 3ais selected from the group consisting of trifluoroethynyl, cyclopropylethynyl, cyclobutylethynyl, and propynyl, fluoropropynyl, and chloroethynyl. 3a is ethynyl (C ) which 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. 2 ), Propynyl (C 3 ), or butynyl (C 4 In certain embodiments, R 3a is an ethynyl substituted with a substituted phenyl (C 2 ), Propynyl (C 3 ), or butynyl (C 4 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. 3a is an ethynyl (C ) substituted with substituted or unsubstituted pyrrolyl, imidazolyl, pyrazolyl, oxazoyl, thiazolyl, isoxazoyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxadiazolyl, thiadiazolyl, or tetrazolyl; 2 ), Propynyl (C 3 ), or butynyl (C 4 ).

[0123] In certain embodiments, R 3a is ethynyl, propynyl, or butynyl, 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 3a is unsubstituted or is selected from the group consisting of halo, alkyl, alkoxy, haloalkyl, trihaloalkyl, and or phenyl substituted with 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. In certain embodiments, R 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. In certain embodiments, R 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, R3a 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, e.g., 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 1~2 Alkyl, substituted or unsubstituted C 2~3 Alkyl, substituted or unsubstituted C3~4 Alkyl, substituted or unsubstituted C 4~5 Alkyl, or substituted or unsubstituted C 5~6 For example, in some embodiments, R 2a is a halo (e.g., bromo, chloro, fluoro (i.e., a group of the formula -CH 2 F, -CHF 2 , -CF 3 R 2a To obtain the group)) or -OR A2 with C being substituted as necessary 1~6 In certain embodiments, R A2 is -CH 3 , -CH 2 CH 3 or -CH 2 CH 2 CH 3 (i.e., the formula -OH, -OCH 3 , -OCH 2 CH 3 , or -OCH 2 CH 2 CH 3 R 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, e.g. 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 2ais substituted or unsubstituted cyclopropyl or substituted or unsubstituted cyclobutyl. In certain embodiments, R 2a is -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OR A2 In certain embodiments, R A2 is hydrogen. In certain embodiments, R A2 is a substituted or unsubstituted alkyl, e.g., 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, -CH 3 , -CH 2 CH 3 , or -CH 2 CH 2 CH 3 (i.e., the formula -OH, -OCH 3 , -OCH 2 CH 3 , or -OCH 2 CH 2 CH 3 R 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 C2~6 Alkenyl, substituted or unsubstituted C 2~6 Alkynyl, or substituted or unsubstituted C 3~6 carbocyclyl, 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 In certain embodiments, R 11a -OR A3 and R 11a In certain embodiments, R 11a -OR A3 and R 11a In certain embodiments, R 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, -CH 3 , -CH 2 CH3 , or -CH 2 CH 2 CH 3 (i.e., the formula -OH, -OCH 3 , -OCH 2 CH 3 , or -OCH 2 CH 2 CH 3 R 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 It is 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 basis

[0133] As generally defined herein, R m , R n , and R x Each existence is independent Hydrogen, halogens, -NO 2 , -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 For example, -S(=O)R GA , -S(=O) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(R GA ) 2 , -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 3~6 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 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 certain embodiments, R GA Each occurrence of is independently hydrogen, 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 alkyl), substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. In certain embodiments, R 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 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 A "non-hydrogen substituent" is R m , R n , and R x is not hydrogen, but a halogen, -NO 2 , -CN, -CF 3 , -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 For example, -S(=O)R 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 3~6 It means any 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. In certain embodiments, R m , R n , and R x is halogen. In certain embodiments, R m is halogen, e.g., fluoro, bromo, iodo, or chloro. In certain embodiments, R n is halogen, for example fluoro, bromo, iodo, or chloro. In the embodiment, 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 -NO 2 In certain embodiments, R m , R n , and R x One of them is -NO 2 In certain embodiments, R m -NO 2 In certain embodiments, R n -NO 2 In certain embodiments, R x -NO 2 It is.

[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 is -OR GA For example, where R GA is hydrogen or substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 Or -CF 3 In certain embodiments, R m , R n , and R x One of them is -OR GA , e.g., -OH, -OCH 3 , or -OCF 3 In certain embodiments, Rm -OR GA , e.g., -OH, -OCH 3 , or -OCF 3 In certain embodiments, R n -OR GA In certain embodiments, R x -OR GA , e.g., -OH, -OCH 3 , or -OCF 3 It is.

[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 3 Or -CF 3 In certain embodiments, R m , R n , and R x One of the following is -N(R GA ) 2 , e.g., -NH 2 , -NHCH 3 , or -N(CH 3 ) 2 In certain embodiments, R m is -N(R GA ) 2 , e.g., -NH 2 , -NHCH 3 , or -N(CH 3 ) 2 In certain embodiments, R n is -N(R GA ) 2 , e.g., -NH 2 , -NHCH 3 , or -N(CH 3 ) 2 In certain embodiments, R x is -N(R GA ) 2 , e.g., -NH 2, -NHCH 3 , or -N(CH 3 ) 2 It is.

[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 R GA is hydrogen or substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 Or -CF 3 In certain embodiments, R m , R n , and R x One of them is -C(=O)R GA For example, -CHO, -C(=O)CH 3 , or -C(=O)CH 2 CH 3 In certain embodiments, R m is -C(=O)R GA For example, -CHO, -C(=O)CH 3 , or -C(=O)CH 2 CH 3 In certain embodiments, R n is -C(=O)R GA For example, -CHO, -C(=O)CH 3 , or -C(=O)CH 2 CH 3 In certain embodiments, R x is -C(=O)R GA For example, -CHO, -C(=O)CH 3 , or -C(=O)CH 2 CH 3 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 3, or -C(=O)OCH 2 CH 3 In certain embodiments, R m is -C(=O)OR GA For example, -C(=O)OH, -C(=O)OCH 3 , or -C(=O)OCH 2 CH 3 In certain embodiments, R n is -C(=O)OR GA For example, -C(=O)OH, -C(=O)OCH 3 , or -C(=O)OCH 2 CH 3 In certain embodiments, R x is -C(=O)OR GA For example, -C(=O)OH, -C(=O)OCH 3 , or -C(=O)OCH 2 CH 3 In certain embodiments, R m , R n , and R x One of them is -C(=O)N(R GA ) 2 For example, -C(=O)NH 2 , -C(=O)NHCH 3 , or -C(=O)N(CH 3 ) 2 In certain embodiments, R m is -C(=O)N(R GA ) 2 For example, -C(=O)NH 2 , -C(=O)NHCH 3 , or -C(=O)N(CH 3 ) 2 In certain embodiments, R n is -C(=O)N(R GA ) 2 For example, -C(=O)NH 2 , -C(=O)NHCH 3 , or -C(=O)N(CH 3 ) 2 In certain embodiments, R x is -C(=O)N(RGA ) 2 For example, -C(=O)NH 2 , -C(=O)NHCH 3 , or -C(=O)N(CH 3 ) 2 It is.

[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 3 Or -CF 3 In certain embodiments, R m , R n , and R x One of them is -OC(=O)R GA For example, -OC(=O)CH 3 In certain embodiments, R m is -OC(=O)R GA For example, -OC(=O)CH 3 In certain embodiments, R n is -OC(=O)R GA For example, -OC(=O)CH 3 In certain embodiments, R x is -OC(=O)R GA For example, -OC(=O)CH 3 In certain embodiments, R m , R n , and R x One of them is -OC(=O)OR GA For example, -OC(=O)OCH 3 In certain embodiments, R m is -OC(=O)OR GA For example, -OC(=O)OCH 3 In certain embodiments, R nis -OC(=O)OR GA For example, -OC(=O)OCH 3 In certain embodiments, R x is -OC(=O)OR GA For example, -OC(=O)OCH 3 In certain embodiments, R m , R n , and R x One of them is -OC(=O)N(R GA ) 2 For example, -OC(=O)NHCH 3 or -OC(=O)N(CH 3 ) 2 In certain embodiments, R m is -OC(=O)N(R GA ) 2 For example, -OC(=O)NHCH 3 or -OC(=O)N(CH 3 ) 2 In certain embodiments, R n is -OC(=O)N(R GA ) 2 For example, -OC(=O)NHCH 3 or -OC(=O)N(CH 3 ) 2 In certain embodiments, R x is -OC(=O)N(R GA ) 2 For example, -OC(=O)NHCH 3 or -OC(=O)N(CH 3 ) 2 It is.

[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 GAis hydrogen or substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 Or -CF 3 In certain embodiments, R m , R n , and R x One of them is -N(R GA )C(=O)R GA For example, -NHC(=O)CH 3 In certain embodiments, R m is -N(R GA )C(=O)R GA For example, -NHC(=O)CH 3 In certain embodiments, R n is -N(R GA )C(=O)R GA For example, -NHC(=O)CH 3 In certain embodiments, R x is -N(R GA )C(=O)R GA For example, -NHC(=O)CH 3 In certain embodiments, R m , R n , and R x One of them is -N(R GA )C(=O)OR GA For example, -NHC(=O)OCH 3 In certain embodiments, R m is -N(R GA )C(=O)OR GA For example, -NHC(=O)OCH 3 In certain embodiments, R n is -N(R GA )C(=O)OR GA For example, -NHC(=O)OCH 3 In certain embodiments, R x is -N(R GA )C(=O)OR GA For example, -NHC(=O)OCH 3 In certain embodiments, R m , R n , and R xOne of them is -N(R GA )C(=O)N(R GA ) 2 For example, -NHC(=O)NH 2 or -NHC(=O)N(CH 3 ) 2 In certain embodiments, R m is -N(R GA )C(=O)N(R GA ) 2 For example, -NHC(=O)NH 2 or -NHC(=O)N(CH 3 ) 2 In certain embodiments, R n is -N(R GA )C(=O)N(R GA ) 2 For example, -NHC(=O)NH 2 or -NHC(=O)N(CH 3 ) 2 In certain embodiments, R x is -N(R GA )C(=O)N(R GA ) 2 For example, -NHC(=O)NH 2 or -NHC(=O)N(CH 3 ) 2 It is.

[0145] In certain embodiments, R m , R n , and R x At least one of the following is -SR GA , -S(O)R GA For example, -S(=O)R 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 For example, where RGA is hydrogen, substituted or unsubstituted C 1~6 Alkyl (e.g., -CH 3 Or -CF 3 ), 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 , e.g., -SCH 3 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 For example, -S(=O)R GA For example, -S(=O)CH 3 , -S(=O)CF 3 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) 2 R GA For example, -S(=O) 2 CH 3 , -S(=O) 2 CF 3 , or -S(=O) 2 -aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R m -SR GA , e.g., -SCH 3 , -SCF 3 ;-S(O)R GA For example, -S(=O)R GA For example, -S(=O)CH 3 , -S(=O)CF 3 ;-S(=O) 2 R GA For example, -S(=O) 2 CH 3 , -S(=O) 2 CF3 , or -S(=O) 2 -aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n -SR GA , e.g., -SCH 3 , -SCF 3 ;-S(O)R GA For example, -S(=O)R GA For example, -S(=O)CH 3 , -S(=O)CF 3 ;-S(=O) 2 R GA For example, -S(=O) 2 CH 3 , -S(=O) 2 CF 3 , or -S(=O) 2 -aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x -SR GA , e.g., -SCH 3 , -SCF 3 ;-S(O)R GA For example, -S(=O)R GA For example, -S(=O)CH 3 , -S(=O)CF 3 ;-S(=O) 2 R GA For example, -S(=O) 2 CH 3 , -S(=O) 2 CF 3 , 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) 2 OR GA In certain embodiments, R m is -S(=O) 2 OR GA For example, -S(=O) 2 OCH 3 , -S(=O)2 OCF 3 , or -S(=O) 2 Oaryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n is -S(=O) 2 OR GA For example, -S(=O) 2 OCH 3 , -S(=O) 2 OCF 3 , or -S(=O) 2 Oaryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x is -S(=O) 2 OR GA For example, -S(=O) 2 OCH 3 , -S(=O) 2 OCF 3 , or -S(=O) 2 Oaryl, 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) 2 R GA In certain embodiments, R m -OS(=O) 2 R GA For example, -OS(=O) 2 CH 3 , -OS(=O) 2 CF 3 , or -OS(=O) 2 -aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n -OS(=O) 2 R GA For example, -OS(=O) 2 CH 3 , -OS(=O) 2 CF 3 , or -OS(=O) 2-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x -OS(=O) 2 R GA For example, -OS(=O) 2 CH 3 , -OS(=O) 2 CF 3 , or -OS(=O) 2 -aryl, where aryl is optionally substituted In certain embodiments, R is an unsubstituted aryl or heteroaryl. m , R n , and R x One of them is -S(=O) 2 N(R GA ) 2 In certain embodiments, R m is -S(=O) 2 N(R GA ) 2 For example, -S(=O) 2 NHCH 3 , -S(=O) 2 NHCF 3 , or -S(=O) 2 -NH-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R n is -S(=O) 2 N(R GA ) 2 For example, -S(=O) 2 NHCH 3 , -S(=O) 2 NHCF 3 , or -S(=O) 2 -NH-aryl, where aryl is substituted or unsubstituted aryl or heteroaryl. In certain embodiments, R x is -S(=O) 2 N(R GA ) 2 For example, -S(=O) 2 NHCH 3 , -S(=O) 2 NHCF 3, 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 them is -N(R GA )S(=O) 2 R GA In certain embodiments, R m is -N(R GA )S(=O) 2 R GA For example, -NHS(=O) 2 CH 3 , -NHS(=O) 2 CF 3 , 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) 2 R GA For example, -NHS(=O) 2 CH 3 , -NHS(=O) 2 CF 3 , 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) 2 R GA For example, -NHS(=O) 2 CH 3 , -NHS(=O) 2 CF 3 , or -NHS(=O) 2 -aryl, where aryl is substituted or unsubstituted aryl or heteroaryl.

[0146] In certain embodiments, R m , R n , and R x At least one of the following is substituted or unsubstituted C 1~6Alkyl, 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 The alkyl group may be substituted or unsubstituted methyl (C 1 ), ethyl (C 2 ), n-propyl (C 3 ), isopropyl (C 3 ), n-Butyl (C 4 ), tert-Butyl (C 4 ), sec-Butyl (C 4 ), iso-butyl (C 4 ), n-pentyl (C 5 ), 3-pentanyl (C 5 ), Amyl (C 5 ), neopentyl (C 5 ), 3-methyl-2-butanyl (C 5 ), tertiary amyl (C 5 ), n-hexyl (C 6 ), C substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more fluoro groups 1~6 Alkyl (e.g., -CF 3 , -CH 2 F, -CHF 2 , 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 Alkyl (e.g., -CH 2 Cl, -CHCl 2 ), and C substituted with an alkoxy group 1~6 Alkyl (e.g., -CH 2 OCH 3 and -CH 2 OCH 2 CH 3 In certain embodiments, R m , R n , and Rx At least one of the substitutions C 1~6 is alkyl (e.g., R m , R n , and R x At least one of R is haloalkyl, alkoxyalkyl, or aminoalkyl. In certain embodiments, R m , R n , and R x At 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 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 BiR x At least one of is ethenyl (C ) unsubstituted or substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, alkoxyalkyl, or hydroxyl. 2 ), propenyl (C 3 ), or butenyl (C 4 In certain embodiments, R 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 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 m , R n , and R x At least one of is unsubstituted or is alkyl, halo, haloalkyl (e.g., CF 3 ), ethynyl, propynyl, or butynyl substituted with alkoxyalkyl, cycloalkyl (eg, cyclopropyl or cyclobutyl), or hydroxyl.

[0149] In certain embodiments, R m , R n , and R x At least one of the following is 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 xAt 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ).

[0152] Exemplary R as Non-hydrogen Substituents m , R n , and R x are contemplated herein.

[0153] For example, in certain embodiments, [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 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 of R is a trisubstituted pyrazolyl ring, m , R n , and R x Each of is a non-hydrogen substituent as defined herein.

[0156] For example, R 2a In certain embodiments, where R is a hydrogen or non-hydrogen alpha substituent, formula (II-A1) or (II-B1): [ka] or a pharma- ceutically acceptable salt thereof. In certain embodiments, R 3a is -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -CH 3 , -CH 2 CH 3, -CH 2 CH 2 CH 3 , 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 3 , or -CF 3 In certain embodiments where Ring B does not contain a C5-C6 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 Both are -CH 3 Or -CF 3 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, 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3In certain embodiments, the C21-pyrazolyl ring is an unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0157] R 2a In certain embodiments, where R is hydrogen or a non-hydrogen β-substituent, formula (II-A2) or (II-B2): [ka] or a pharma- ceutically acceptable salt thereof. In certain embodiments, R 3a is -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , 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 3 , or -CF 3 In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6aand R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b Both are -CH 3 Or -CF 3 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, 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 In certain embodiments, the C21-pyrazolyl ring is an 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 formula (II-A3) or (II-B3): [ka] or a pharma- ceutically acceptable salt thereof. In certain embodiments, R3a is -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , 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 3 , or -CF 3 In certain embodiments where Ring B does not contain a C5-C6 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 Both are -CH 3 Or -CF 3 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, 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 In certain embodiments, the C21-pyrazolyl ring is an unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0159] R 11a is hydrogen or a non-hydrogen β-substituent, and R 11b In certain embodiments, where R is hydrogen, the formula (II-A4) or (II-B4): [ka] or a pharma- ceutically acceptable salt thereof. In certain embodiments, R 3a is -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH2 CH 3 , -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , 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 3 , or -CF 3 In certain embodiments where Ring B does not contain a C5-C6 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 Both are -CH 3 Or -CF 3 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, 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH3 , -CF 3 In certain embodiments, the C21-pyrazolyl ring is an unsubstituted pyrazolyl, where R m , R n , and R x Each occurrence of is hydrogen.

[0160] R 11a and R 11b In certain embodiments, wherein taken together form an oxo group, formula (II-A5) or (II-B5): [ka] or a pharma- ceutically acceptable salt thereof. In certain embodiments, R 3a is -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , 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 3 , or -CF 3 In certain embodiments where Ring B does not contain a C5-C6 double bond, R6a and R 6b are hydrogen. In certain embodiments where Ring B does not contain a C5-C6 double bond, R 6a and R 6b Both are -CH 3 Or -CF 3 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, 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 In certain embodiments, the C21-pyrazolyl ring is an 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 pharma- ceutically acceptable salt thereof. In certain embodiments, R 3a is -CH3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 or substituted or unsubstituted cyclopropyl. In certain embodiments, R 2a -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -CH 3 , -CH 2 CH 3 , -CH 2 CH 2 CH 3 , 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 taken together form =O (oxo). In certain embodiments, R 6a Fluoro, -CH 3 , or -CF 3 and R 6b is hydrogen. In certain embodiments, R 6b Fluoro, -CH 3 , or -CF 3 and R 6a is hydrogen. In certain embodiments, R 6a and R 6b Both are -CH 3 Or -CF 3 In certain embodiments, R 6a and R 6bare 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 substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 In certain embodiments, the C21-pyrazolyl ring is an 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 pharma- ceutically acceptable salt thereof. In certain embodiments, R 3a is -CH 3 , -CH 2 CH 3 , -CH 2 F, -CHF 2 , -CF 3 , -CH 2 OCH 3 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 substituted or unsubstituted C1~2 Alkyl (e.g., -CH 3 , -CF 3 ), -CO 2 R GA , -C(=O)R GA , -CN, -NO 2 , or halogen, where R GA is a substituted or unsubstituted C 1~2 Alkyl (e.g., -CH 3 , -CF 3 In certain embodiments, the C21-pyrazolyl ring is an 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, the compound of formula (II-I): [ka] 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 a substituted or unsubstituted C 2 ~C 6 Alkyl, substituted or unsubstituted C 2 ~C 6 Alkenyl, or substituted or unsubstituted C 2 ~C6 is alkynyl; R 5 is hydrogen or methyl, or [ka] If 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; can be; 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 form an oxo (=O) group; 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, -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)SRA1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -SS(=O) 2 R A2 , -SS(=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, 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 , 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 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)ORA1 , -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 , -SS(=O) 2 R A2 , -SS(=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 aryl ... is an unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a 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, -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: [ka] represents a single bond or a double bond, and when a double bond is present in ring B, R6a or R 6b One of 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 basis

[0167] In some cases, 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 , -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.

[0168] In some cases, 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 , -NH 2 , 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 cases, R 2a and R 2b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 Each occurrence of is independently hydrogen, substituted or Preferably, the radical is unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0170] In some cases, 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 represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0173] In some embodiments, R 2a and R 2b But -CH3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 is. The R of formula (II-I) 4a and R 4b group

[0174] In some aspects, 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 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 , where each occurrence of R D1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclic, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0175] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where each occurrence of R D1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclic, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0176] In some aspects, R4a and R 4b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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.

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

[0178] In some cases, R 4a and R 4b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 In some other aspects, R 4a and R 4b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 Formula (II-I) Group R 11a and R 11b

[0179] 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 , -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.

[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 , -NH 2 , 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 cases, R 11a and R 11b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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.

[0182] In some cases, R 11a and R 11b is, each independently, hydrogen or substituted or unsubstituted alkyl. 11a and R 11b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0183] In some cases, R 11a and R 11b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is.

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

[0185] In some cases, R 15a and R 15b 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)RD1 , -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.

[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 , -NH 2 , or -N(R D1 ) 2 where R D1 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 substituted heteroaryl.

[0187] In some embodiments, R 15a and R 15b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 15a and R 15b is, each independently, hydrogen or substituted or unsubstituted alkyl. 15a and R 15b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 In some aspects, R 15a and R 15b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R in formula (II-I) 16a and R 16b base

[0190] In some cases, 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 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1Each 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.

[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 , -NH 2 , 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 each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 16a and R 16bis, each independently, hydrogen or substituted or unsubstituted alkyl. 16a and R 16b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0195] In some cases, R 16a and R 16b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R in formula (II-I) 7a and R 7b basis

[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 , -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, or R 7a and R 7b taken together to form 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 , -NH 2 , 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.

[0198] In some cases, R 7a and R 7b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 7a and R 7b All of the is hydrogen.

[0200] In some cases, R 7a and R 7b is, each independently, hydrogen or substituted or unsubstituted alkyl. 7a and R 7b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0201] In some cases, R 7a and R 7b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is.

[0202] In some embodiments, R 7a and R 7b taken together to form an oxo (=O). R in formula (II-I) 5 base

[0203] In some cases, R 5 is a hydrogen cis to C19. In some other aspects, R 5 is a hydrogen trans to C19. 5 is 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 substituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0206] In some embodiments, R3 is substituted or unsubstituted alkyl.

[0207] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a substituted alkyl (e.g., -CH 2 OMe or -CH 2 In some embodiments, R 3 is unsubstituted alkyl. In some embodiments, R 3 is methyl. R in formula (II-I) 19 basis

[0208] In some cases, R 19 is C 2 ~C 6 In some aspects, R 19 is a deuterium-substituted C 2 ~C 6 It is an alkyl.

[0209] In some embodiments, R 19 is a substitution C 2 ~C 6 In some embodiments, R 19 is unsubstituted C 2 ~C 6 It is an alkyl.

[0210] In some embodiments, R 19 is a substitution C 2 ~C 6 In some embodiments, R is alkenyl. 19 is unsubstituted C 2 ~C 6 It is alkenyl.

[0211] In some embodiments, R 19 is a substitution C 2 ~C 6 In some embodiments, R is alkynyl. 19 is unsubstituted C 2 ~C 6 It is alkynyl.

[0212] In some cases, 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 cases, R 6a and R 6b is independently hydrogen or substituted or unsubstituted alkyl.

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

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

[0217] In some cases, R 6a and R 6b Both of are 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 , -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 a The group is preferably 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 cases, 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 , -NH 2 , 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.

[0221] In some embodiments, R 12a and R 12b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NRD1 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 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 1is 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 Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -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) 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 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- to 4-membered carbocyclic or heterocyclic ring; Here, 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 Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -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) 2 RGA , -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 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- to 4-membered carbocyclic or heterocyclic ring; Here, 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 of the substituted carbocyclyl, substituted heterocyclyl, substituted aryl, or substituted heteroaryl is independently substituted with 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 pharma- ceutically acceptable salt thereof.

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

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

[0235] In some embodiments, the compound of formula (II-I) has the formula (II-Ie): [ka] 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 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 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 -, -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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 heterocyclyl or heteroaryl ring.

[0237] In some embodiments, the compound of formula (II-I) has the formula (II-Iga): [ka] or a pharma- ceutically 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 heterocyclyl or heteroaryl ring.

[0238] In some embodiments, the compound of formula (II-I) has the formula (II-Ih): [ka] or a pharma- ceutically acceptable salt thereof, In formula (II-Ih), R 35 each 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 pharma- ceutically 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 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, the compound of formula (III-I): [ka] or a pharma- ceutically acceptable salt thereof, In formula (III-I), n is 0, 1, or 2; R 3ais 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 C 2 ~C 6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted C 2 ~C 6 alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; R 5 is hydrogen or methyl, or [ka] If 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 form an oxo (=O) group; 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, -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 , -SS(=O) 2 R A2 , -SS(=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, 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 , R11b , 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 , -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, 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 1 2a 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, the compound of formula (III-II): [ka] or a pharma- ceutically 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, C 1 ~C 6 Substituted alkyl, C 2 ~C 6 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 If is hydrogen, R 18 is a substitution C 1 ~C 6 Alkyl, unsubstituted C 3 ~C 6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, where R 18 When is a substituted methyl, the methyl is not a halogen, -CN, -NO 2 ,-SO 2 H, -SO 3 H, -OR aa , -ON(R bb ) 2 , -N(R bb ) 2 , -C(=O)R aa , -C(O)H, -CO 2 H, carbocyclyl, heterocyclyl, aryl, or heteroaryl, where R aa Each occurrence of is independently 1~10 Alkyl, C 1~10 Haloalkyl, C 2~10 Alkenyl, C 2~10 Alkynyl, C 3~10 Carbocyclyl, 3-14 membered heterocyclyl, C 6~14 aryl, and 5- to 14-membered heteroaryl, or two R aa the groups taken together 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 , -CO 2 R aa , -SO 2 R aa , or -C(=NR cc ) OR aa is selected from. R of formula (III-I) and formula (III-II) 18 basis

[0243] In some cases, R 18 is halogen, cyano, -CO 2 H, or phenyl substituted It is an alkyl group.

[0244] In some embodiments, R 18 is a substituted or unsubstituted C 2 ~C 6 It is an alkyl.

[0245] In some embodiments, R 18 is -CH(CH 3 ) 2 It is.

[0246] In some embodiments, R 18 is a substituted alkyl. In some embodiments, alkyl is -OCH 3 , -CH 2 CN, or -OCH(CH 3 ) 2 has been replaced with.

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

[0248] In some cases, R 1a and R 1b 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)RD1 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.

[0249] In some cases, 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 , -NH 2 , 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 cases, R 1a and R 1b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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.

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

[0252] In some embodiments, R1a and R 1b is each independently hydrogen or substituted or unsubstituted alkyl.

[0253] In some embodiments, R 1a and R 1b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 In some embodiments, R 1a and R 1b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R of formula (III-I) and formula (III-II) 2a and R 2b base

[0254] In some cases, 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 , -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.

[0255] In some cases, 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 , -NH 2 , 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 cases, R 2a and R 2b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, 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 represents hydrogen, C 1 ~C 6Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0260] In some embodiments, R 2a and R 2b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R of formula (III-I) and formula (III-II) 4a and R 4b base

[0261] In some cases, 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 , -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.

[0262] In some cases, 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, -NH 2 , 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.

[0263] In some cases, R 4a and R 4b are each independently hydrogen, a substituted or unsubstituted alkyl group, Rukill, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 4a and R 4b and R are both hydrogen. 16a and R 16b is each independently hydrogen or substituted or unsubstituted alkyl.

[0265] In some cases, R 4a and R 4b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 In some other aspects, R 4a and R 4b But -CH 3 , -CH2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R of formula (III-I) and formula (III-II) 11a and R 11b base

[0266] 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 , -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.

[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 , -NH 2 , 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 cases, R 11a and R 11b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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.

[0269] In some cases, R 11a and R 11b is, each independently, hydrogen or substituted or unsubstituted alkyl. 11a and R 11b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0270] In some cases, R 11a and R 11b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is.

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

[0272] In some cases, R 15a and R 15b 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.

[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 , -NH 2 , 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 each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 15a and R 15b is, each independently, hydrogen or substituted or unsubstituted alkyl. 15a and R 15b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 In some aspects, R 15a and R 15b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R of formula (III-I) and formula (III-II) 16a and R 16b base

[0277] In some cases, 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, -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.

[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 , -NH 2 , 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, a substituent or Unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 16a and R 16b is, each independently, hydrogen or substituted or unsubstituted alkyl. 16a and R 16b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0282] In some cases, R 16a and R 16b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. R of 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 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1each 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 taken together to form 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 , -NH 2 , 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 cases, R 7a and R 7b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 cases, R 7a and R 7b All of the is hydrogen.

[0287] In some cases, R 7a and R 7b is, each independently, hydrogen or substituted or unsubstituted alkyl. 7a and R 7b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0288] In some cases, R 7a and R 7b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is.

[0289] In some embodiments, R 7a and R 7b taken together to form an oxo (=O). R of formula (III-I) and formula (III-II) 5 basis

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

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

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

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

[0294] In some embodiments, R 3a is hydrogen. In some embodiments, R 3a is a substituted alkyl (e.g., -CH 2 OMe or -CH 2 In some embodiments, R 3a is unsubstituted alkyl. In some embodiments, R 3a is methyl.

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

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

[0297] In some cases, R 19 is C 2 ~C 6 In some embodiments, R 19 is hydrogen. In some aspects, R 19 is a deuterium-substituted C 2 ~C 6 It is an alkyl.

[0298] In some embodiments, R 19is a substitution C 2 ~C 6 In some embodiments, R 19 is unsubstituted C 2 ~C 6 It is an alkyl.

[0299] In some embodiments, R 19 is a substitution C 2 ~C 6 In some embodiments, R is alkenyl. 19 is unsubstituted C 2 ~C 6 It is alkenyl.

[0300] In some embodiments, R 19 is a substitution C 2 ~C 6 In some embodiments, R is alkynyl. 19 is unsubstituted C 2 ~C 6 It is alkynyl.

[0301] In some cases, R 19 is ethyl. R of formula (III-I) and formula (III-II) 6a and R 6b basis

[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 cases, R 6a and R 6b is independently hydrogen or substituted or unsubstituted alkyl.

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

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

[0306] In some cases, R 6a and R 6b Both of are alkyl.

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

[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 , -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.

[0309] In some cases, R 12a and R 12beach independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , 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 each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -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 other embodiments, n is 2. R of formula (III-I) and formula (III-II) 1 basis

[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, R 1 teeth, [ka] and Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -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) 2 R GA , -S(=O) 2 OR GA , -OS(=O) 2 R GA , -S(=O) 2 N(RGA ) 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, 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 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.

[0318] In some embodiments, R 1 teeth, [ka] and Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -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) 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, 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 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 pharma- ceutically acceptable salt thereof.

[0320] In some embodiments, the compound of formula (III-I) or (III-II) has the formula (III-Ib): [ka] or a pharma- ceutically 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 pharma- ceutically acceptable salt thereof, In formula (III-Ie), m is 0, 1, 2, or 3; p is 0, 1, 2, or 3; R 32 is 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 pharma- ceutically 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) 2 R GA , or -S(=O) 2 N(R GA) 2 and; 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 heterocyclyl or heteroaryl ring. In some embodiments, the compound of formula (III-I) or (III-II) has the formula (III-Ih): [ka] or a pharma- ceutically 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 formula (III-Ii): [ka] or a pharma- ceutically 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) 2 R GA , or -S(=O) 2 N(R GA ) 2 and; 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 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 pharma- ceutically 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 pharma- ceutically acceptable salt thereof, and a pharma- ceutically 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 GABA modulators. 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 said subject an effective amount of a compound of the present invention or a pharma- ceutically acceptable salt thereof. In certain embodiments, the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a convulsive 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 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 pharma- ceutically 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 can 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, 18O; the nitrogen can be, for example, 15 N, etc. In other embodiments, a particular 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 pharma- ceutically acceptable salt thereof, and a pharma- ceutically 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.

[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 may 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 effective amounts.The amount of compound actually administered is typically determined by the physician in light of the relevant circumstances, including the condition being treated, the route of administration selected, 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 development of CNS disorder, the compounds provided herein can typically be administered to subjects at risk of developing the condition at the dosage levels described above, with the advice and under the 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 may also be administered chronically ("chronic administration"). Chronic administration refers to administration of a compound or pharmaceutical composition thereof for an extended period of time, e.g., 3 months, 6 months, 1 year, 2 years, 3 years, 5 years, etc., or may continue 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 composition 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 (for example, by IV drip) allows for a faster delivery, which may increase the amount of active ingredient in the blood. The composition rapidly increases the concentration of the ingredient to an effective level. In other embodiments, the pharmaceutical composition can be administered as a continuous infusion, for example, by IV drip, to provide for the maintenance of a steady-state concentration of the active ingredient in the subject's body. In addition, in still other embodiments, the pharmaceutical composition can be administered as an initial bolus dose, followed by continuous infusion. Compositions for oral administration can take the form of bulk liquid solutions or suspensions or bulk powders. More commonly, however, 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 material calculated to produce the desired therapeutic effect together with suitable pharmaceutical excipients. Typical unit dosage forms include premeasured, prefilled ampoules or syringes of liquid compositions, or pills, tablets, capsules, and the like for solid compositions. In such compositions, the compound will usually be 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 that help form the desired dosage form.

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

[0337] Transdermal doses are generally selected to provide blood levels similar to or lower than those achieved using injected 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 flavoring).

[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 and the like.

[0341] Transdermal compositions are typically formulated as topical ointments or creams containing the active ingredient(s). When formulated as an ointment, the active ingredient is typically mixed with a paraffinic ointment base or a water-miscible ointment base. Alternatively, the active ingredient can be formulated as a cream, for example, with an oil-in-water cream base. Such transdermal formulations are well known in the art and generally include additional ingredients that enhance the skin penetration or stability of the 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.Thus, 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, as well as processing techniques, etc., are set forth in Part 8 of Remington's Pharmaceutical Sciences, 17th Edition, 1985, Mack Publishing Company, Easton, Pennsylvania (herein incorporated by reference).

[0344] The compounds of the 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 pharma- ceutically acceptable acid addition salts of the compounds of the present invention. Acids that can be used to prepare pharma- ceutically 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 a pharmaceutical composition (eg, a composition suitable for injection, such as intravenous (IV) administration) comprising a compound of the present invention and a pharma- ceutically 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, isotonicity 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 6, 7, and 8 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 substitutions. In certain embodiments, the cyclodextrin is a sulfoalkyl ether β-cyclodextrin, such as sulfobutyl ether β-cyclodextrin, also known as CAPTISOL®. For example, See, for example, U.S. Patent No. 5,376,645. In certain embodiments, the composition includes hexapropyl-β-cyclodextrin. In more specific embodiments, the composition includes 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 effective amounts.The amount of compound actually administered is typically determined by the physician in light of the relevant circumstances, including the condition being treated, the route of administration selected, the actual compound being administered, the age, weight, response of the individual patient, the severity of the patient's symptoms, etc.

[0352] The composition is provided in a unit dosage form 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 material 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 that help form the desired dosage form.

[0353] The compound 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 compound of the present invention and another pharmacologically active agent.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.

[0354] Although the description of pharmaceutical compositions provided herein is primarily directed to pharmaceutical compositions suitable for administration to humans, one of skill in the art will appreciate that such compositions are generally suitable for administration to animals of all kinds. Modifications to pharmaceutical compositions suitable for administration to humans to make them suitable for administration to a variety of animals are well understood, and a veterinary pharmacologist of ordinary skill may 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, 1999, 14th ed. ... 21st ed., 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., sleep disorder, mood disorder (e.g., depression), schizophrenia spectrum disorder, seizure disorder, epileptogenesis, memory and / or cognition disorders, movement disorder, personality disorder, autism spectrum disorder, pain, traumatic brain injury, vascular disease, substance abuse disorder and / or withdrawal syndrome, or tinnitus) in a subject in need thereof (e.g., a subject having Rett syndrome, fragile X syndrome, or Angelman syndrome). Exemplary CNS conditions associated with GABA modulation include sleep disorders [e.g., insomnia], mood disorders, and the like. harm [e.g., depression (e.g., major depressive disorder (MDD)), dysthymic disorder (e.g., minor depression), bipolar disorder (e.g., types I and / or II), anxiety disorder (e.g., generalized anxiety disorder (GAD), social anxiety disorder), stress, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (e.g., obsessive-compulsive disorder (OCD))], schizophrenia spectrum disorder (e.g., schizophrenia, schizoaffective disorder), seizure disorder [e.g., epilepsy (e.g., status epilepticus (SE)), seizures], memory and / or cognition impairment [e.g., attention disorder (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 cause 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 present 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 and 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, a method of treating or preventing stress or anxiety in a subject is provided 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, a method of reducing or preventing insomnia in a subject is provided 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, a method for inducing sleep and reducing the levels of REM sleep seen in normal sleep is provided. In one embodiment, a method is provided for substantially maintaining sleepiness without inducing substantial rebound insomnia, the method comprising administering an effective amount of a compound of the present 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, a method of treating or preventing a mood disorder 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 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 to a subject a therapeutically effective amount of the compound of the present invention.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, hi 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 imbalances in the body's hormone production that are directly related to the brain. Neuroendocrine disorders involve interactions between the nervous system and the endocrine system. The hypothalamus and pituitary gland are two areas of the brain that control the production of hormones, so damage to the hypothalamus or pituitary gland, for example, by traumatic brain injury, can affect the production of hormones and other neuroendocrine functions of the brain. In some embodiments, neuroendocrine disorders or dysfunctions are associated with women's health disorders or conditions (e.g., women's health disorders or conditions described herein). In some embodiments, the neuroendocrine disorder or dysfunction associated with women's health disorders or conditions is polycystic ovarian 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 lipido, 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 are provided herein that can be used to treat neurodegenerative diseases and disorders. The term "neurodegenerative disease" includes diseases and disorders associated with progressive loss of neuronal structure or function, or 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 convulsions (including for treatment and prevention, and for prevention of seizures caused by schizoaffective disorder or drugs used to treat schizophrenia); benign amnesia; cerebral edema; cerebellar ataxia (McLeod neuroacanthocytosis) syndrome (MLS);close head injury;coma;contusion injury (e.g., spinal cord injury and head injury);dementia (including multi-infarct dementia and senile dementia);impaired consciousness;Down's syndrome;drug-induced or drug-induced tremor palsy (e.g., psycholeptic-induced acute akathisia, acute ataxia, tremor palsy 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;spira mental retardation; movement disorders including akinesia and akinetic (rigid) syndromes (including brainstem neurocalcification, corticobasal degeneration, multiple system atrophy, tremor palsy-ALS dementia complex, Parkinson's disease, postencephalitic tremor palsy 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 chorea and symptomatic chorea), dyskinesias (tics including complex tics, simple tics and symptomatic tics), myoclonus (generalized myoclonus and focal schizophrenia) cyloclonus), tremor (e.g., rest tremor, postural tremor, and intention tremor), and ataxia (axial ataxia, dystonic writer's cramp, hemiplegic ataxia, paroxysmal ataxia, and focal ataxia (e.g., blepharospasm, oromandibular dystonia, neuronal damage (including eye damage, ocular retinopathy or macular degeneration); neurotoxicity disorders following stroke, thromboembolic stroke, hemorrhagic stroke, cerebral ischemia, cerebral vasospasm, hypoglycemia, amnesia, hypoxia, anoxia, perinatal asphyxia and cardiac arrest; Parkinson's disease; seizures; status epilepticus; stroke; tinnitus; tubular sclerosis, and neurodegeneration induced by viral infections (such as those caused by acquired immune deficiency 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 disorder after cardiac arrest.The method of treating or preventing neurodegenerative diseases also includes treating or preventing the loss of neuronal function that is characteristic of neurodegenerative disorders.

[0372] Mood disorders Also provided herein is a method for treating mood disorders, such as clinical depression, postpartum or postpartum depression, perinatal depression, atypical depression, melancholic depression, psychogenic major depression, catatonic depression, seasonal affective disorder, dysthymia, bipolar depression, depressive personality disorder, recurrent brief depression, minor depressive disorder, bipolar disorder or manic-depressive disorder, depression caused by chronic medical conditions, 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 disease and disorder, neurodegenerative disease and disorder (e.g., epilepsy), movement disorder, tremor (e.g., Parkinson's disease), women's health disorder or health condition).

[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 loss of interest or pleasure in activities that are usually enjoyed. Some people with clinical depression have difficulty sleeping, become thin, generally feel agitated and irritable. Clinical depression affects how an individual feels, thinks and behaves, 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 called 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 (e.g., treatment-resistant depression as described herein). In some embodiments, PND is treatment-refractory depression (e.g., 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 referred to herein as perinatal depression.In some embodiments, the subject experiencing perinatal depression is at 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 suffering from AD may also have significant social impairment as a result of excessive sleep or somnolence (hypersomnia), heaviness in the limbs, and hypersensitivity to perceived interpersonal rejection.

[0378] Melancholic depression is characterized by loss of pleasure from most or all activities (anhedonia), unresponsiveness to pleasurable stimuli, a depressed mood that is more pronounced than feelings 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 purposeless 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. They tend to be less severe and last longer (e.g., at least 2 years).

[0383] Dual depression refers to a period of very depressed mood (dysthymia) lasting at least 2 years and interrupted by periods of major depression.

[0384] Depressive personality disorder (DPD) refers to a personality disorder that has 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 for 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 or manic-depressive disorder causes extreme mood swings that include high emotions (mania or hypomania) and low emotions (depression). During manic periods, individuals may feel or act unusually happy, energetic, or irritable. They often make ill-considered decisions with little regard for the consequences. There is usually a decreased need for sleep. During periods of depression, individuals may cry a lot, make less eye contact with others, and have a negative outlook on life. The risk of suicide for those with the disorder is high at over 6% over a 20-year period, and 30-40% will commit self harm. Other mental health problems, such as anxiety disorders and substanc...

Claims

[Claim 1] The invention described in the specification.

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