Compositions and methods for treating CNS disorders

Abstract

To provide methods for treating diseases.SOLUTION: Provided herein is a compound of Formula (I-I) or a pharmaceutically acceptable salt thereof, where in the formula (I-I), R7, R3, R9, R6a, R6b, R11a, R11b, R15a, R15b, R16a, R16b, R17a, R17b, R18a, R18b, R19a, R19b, R5a, R5b, R8, and R13 are as defined in the disclosure. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I-I), and methods of using the compounds, e.g., in the treatment of CNS related disorders. Provided is a compound designed to act as a GABA regulator in the disclosure. In some embodiments, the compound is expected to be useful as a therapeutic agent for treating CNS related disorders.SELECTED DRAWING: None

Description

[Technical field]

[0001] CITED RELATED APPLICATIONS This application is a joint venture of U.S. Provisional Patent Applications Nos. 62 / 610,067 (filed December 22, 2017), 62 / 611,977 (filed December 29, 2017), 62 / 765,164 (filed August 17, 2018), 62 / 612,067 (filed December 29, 2017), and 62 / 728,499. No. 62 / 754,977, filed November 2, 2018, No. 62 / 612,070, filed December 29, 2017, No. 62 / 612,164, filed December 29, 2017, and No. 62 / 737,559, filed September 27, 2018, all of which are incorporated by reference in their entireties. [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 (respectively, progesterone, which is a hormonal steroid). These steroid metabolites are metabolites of gesterone and deoxycorticosterone. 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] Provided herein are compounds designed to act as GABA modulators. In some embodiments, it is envisioned that such compounds are useful as therapeutic agents for treating CNS-related disorders.

[0008] In one aspect, the present specification provides a compound of formula (II): [ka] or a pharma- ceutically acceptable salt thereof.

[0009] In some embodiments, the compound has the formula (I-Ia): [ka] or a pharma- ceutically acceptable salt thereof.

[0010] In some embodiments, the compound has the formula (I-Iab): [ka] or a pharma- ceutically acceptable salt thereof.

[0011] In some embodiments, the compound has formula (I-Ib) or formula (I-Ibb): [ka] or a pharma- ceutically acceptable salt thereof.

[0012] In some embodiments, the compound has formula (I-Ic) or formula (I-Icb) [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has formula (I-Id) or formula (I-Idb): [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has formula (I-Ie) or formula (I-Ieb) [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has formula (I-If) or formula (I-Ifb): [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has formula (I-Ig) or formula (I-Igb): [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has formula (I-Ih) or formula (I-Ihb): [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has formula (I-Ii) or formula (I-Iib) [ka] or a pharma- ceutically acceptable salt thereof. In some embodiments, the compound has the formula (I-Ik) or the formula (I-Ikb) [ka] or a pharma- ceutically acceptable salt thereof. In one aspect, the present specification provides a compound represented by formula (I-II): [ka] or a pharma- ceutically acceptable salt thereof is provided.

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

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

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

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

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

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

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

[0020] In some embodiments, the compound has formula (I-IIi) or formula (I-IIib) [ka] or a pharma- ceutically acceptable salt thereof.

[0021] In some embodiments, the compound has the formula (I-IIj): [ka] or a pharma- ceutically acceptable salt thereof.

[0022] In one aspect, the present specification provides a compound represented by formula (II-I): [ka] or a pharma- ceutically acceptable salt thereof.

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

[0024] In some embodiments, the compound has formula (II-Ia), (II-Iab) or (II-Iac): [ka] or a pharma- ceutically acceptable salt thereof.

[0025] In some embodiments, the compound has formula (II-Ib), (II-Ibb) or (II-Ibc): [ka] or a pharma- ceutically acceptable salt thereof.

[0026] In some embodiments, the compound has formula (II-Ic), (II-Icb) or (II-Icc): [ka] or a pharma- ceutically acceptable salt thereof.

[0027] In some embodiments, the compound has formula (II-Ie), (II-Ieb) or (II-Iec): [ka] or a pharma- ceutically acceptable salt thereof.

[0028] In some embodiments, the compound has formula (II-Ig), (II-Igb) or (II-Igc): [ka] or a pharma- ceutically acceptable salt thereof.

[0029] In some embodiments, the compound has the formula (II-Ieg), (II-Iegb) or (II-Iegc): [ka] or a pharma- ceutically acceptable salt thereof.

[0030] In some embodiments, the compound has the formula (II-Ih), (II-Ihb) or (II-Ihc): [ka] or a pharma- ceutically acceptable salt thereof.

[0031] In some embodiments, the compound has formula (II-Ii), (II-Iib) or (II-Iic): [ka] or a pharma- ceutically acceptable salt thereof.

[0032] In some embodiments, the compound has formula (II-IIa) or (II-IIab) [ka] or a pharma- ceutically acceptable salt thereof.

[0033] In some embodiments, the compound has formula (II-IIb) or (II-IIbb) [ka] or a pharma- ceutically acceptable salt thereof.

[0034] In some embodiments, the compound has formula (II-IIc) or (II-IIcb) [ka] or a pharma- ceutically acceptable salt thereof.

[0035] In some embodiments, the compound has formula (II-IIe) or (II-IIeb) [ka] or a pharma- ceutically acceptable salt thereof.

[0036] In some embodiments, the compound has formula (II-IIg) or (II-IIgb): [ka] or a pharma- ceutically acceptable salt thereof.

[0037] In some embodiments, the compound has the formula (II-IIh) or (II-IIhb): [ka] or a pharma- ceutically acceptable salt thereof.

[0038] In some embodiments, the compound has formula (II-IIi) or (II-IIib) [ka] is a compound of formula (III-I) or a pharmaceutically acceptable salt thereof.

[0039] In one aspect, provided herein is a compound of formula (III-I)

Chemical formula

[0040] In some embodiments, the compound is of formula (III-Ia)

Chemical formula

[0041] In some embodiments, the compound is of formula (III-Ib)

Chemical formula

[0042] In some embodiments, the compound is of formula (III-Ic)

Chemical formula

[0043] In some embodiments, the compound is of formula (III-Id)

Chemical formula

[0044] In some embodiments, the compound is of formula (III-Ie)

Chemical formula

[0045] In some embodiments, the compound has formula (III-If): [ka] or a pharma- ceutically acceptable salt thereof.

[0046] In some embodiments, the compound has formula (III-Ig): [ka] or a pharma- ceutically acceptable salt thereof.

[0047] In some embodiments, the compound has formula (III-Ih): [ka] or a pharma- ceutically acceptable salt thereof.

[0048] In some embodiments, the compound has formula (III-Ii): [ka] or a pharma- ceutically acceptable salt thereof.

[0049] In some embodiments, the compound has formula (III-Ij): [ka] or a pharma- ceutically acceptable salt thereof.

[0050] In some embodiments, the compound has formula (III-Ik): [ka] or a pharma- ceutically acceptable salt thereof.

[0051] In some embodiments, the compound has formula (III-IL): [ka] or a pharma- ceutically acceptable salt thereof.

[0052] In some embodiments, the compound has the formula (III-Im): [ka] or a pharma- ceutically acceptable salt thereof.

[0053] In some embodiments, the compound has formula (III-In) or formula (III-Io) [ka] or a pharma- ceutically acceptable salt thereof.

[0054] In one aspect, the present specification provides a compound represented by formula (III-II): [ka] or a pharma- ceutically acceptable salt thereof is provided.

[0055] In some embodiments, the compound has the formula (III-IIa): [ka] or a pharma- ceutically acceptable salt thereof.

[0056] In some embodiments, the compound has the formula (III-IIb): [ka] or a pharma- ceutically acceptable salt thereof.

[0057] In some embodiments, the compound has formula (III-IIc): [ka] or a pharma- ceutically acceptable salt thereof.

[0058] In some embodiments, the compound has the formula (III-IId): [ka] or a pharma- ceutically acceptable salt thereof.

[0059] In some embodiments, the compound has the formula (III-IIe): [ka] or a pharma- ceutically acceptable salt thereof.

[0060] In some embodiments, the compound has the formula (III-IIf): [ka] or a pharma- ceutically acceptable salt thereof.

[0061] In some embodiments, the compound has the formula (III-IIg): [ka] or a pharma- ceutically acceptable salt thereof.

[0062] In some embodiments, the compound has the formula (III-IIh): [ka] or a pharma- ceutically acceptable salt thereof.

[0063] In some embodiments, the compound has formula (III-IIi): [ka] or a pharma- ceutically acceptable salt thereof.

[0064] In some embodiments, the compound has the formula (III-IIj): [ka] or a pharma- ceutically acceptable salt thereof.

[0065] In some embodiments, the compound has the formula (III-IIk): [ka] or a pharma- ceutically acceptable salt thereof.

[0066] In some embodiments, the compound has the formula (III-IIL): [ka] or a pharma- ceutically acceptable salt thereof.

[0067] In some embodiments, the compound has the formula (III-IIm): [ka] or a pharma- ceutically acceptable salt thereof.

[0068] In some embodiments, the compound has formula (III-IIn) or formula (III-IIo) [ka] or a pharma- ceutically acceptable salt thereof.

[0069] In one aspect, the present specification provides a compound represented by formula (IV-I): [ka] or a pharma- ceutically acceptable salt thereof.

[0070] In some embodiments, the compound has formula (IV-Ia): [ka] is a compound of formula (IV-Ib) or a pharmaceutically acceptable salt thereof.

[0071] In some embodiments, the compound is of formula (IV-Ib)

Chemical formula

[0072] In some embodiments, the compound is of formula (IV-Ic)

Chemical formula

[0073] In some embodiments, the compound is of formula (IV-Id)

Chemical formula

[0074] In some embodiments, the compound is of formula (IV-Ie)

Chemical formula

[0075] In some embodiments, the compound of formula (IV-I) is of formula (IV-If)

Chemical formula

[0076] In some embodiments, the compound of formula (IV-I) is of formula (IV-Ig)

Chemical formula

[0077] In some embodiments, the compound has formula (IV-Ih): [ka] or a pharma- ceutically acceptable salt thereof.

[0078] In some embodiments, the compound has formula (IV-Ii): [ka] or a pharma- ceutically acceptable salt thereof.

[0079] In some embodiments, the compound has formula (IV-Ij): [ka] or a pharma- ceutically acceptable salt thereof.

[0080] In some embodiments, the compound has the formula (IV-Ik): [ka] or a pharma- ceutically acceptable salt thereof.

[0081] In some embodiments, the compound has formula (IV-IL): [ka] or a pharma- ceutically acceptable salt thereof.

[0082] In some embodiments, the compound has the formula (IV-Im): [ka] or a pharma- ceutically acceptable salt thereof.

[0083] In some embodiments, the compound has formula (IV-In) or formula (IV-Io) [ka] or a pharma- ceutically acceptable salt thereof.

[0084] In one aspect, the compound of formula (IV-II): [ka] Provided herein are compounds of the formula:

[0085] In some embodiments, the compound has the formula (IV-IIa): [ka] or a pharma- ceutically acceptable salt thereof.

[0086] In some embodiments, the compound has formula (IV-IIb): [ka] or a pharma- ceutically acceptable salt thereof.

[0087] In some embodiments, the compound has the formula (IV-IIc): [ka] or a pharma- ceutically acceptable salt thereof.

[0088] In some embodiments, the compound has the formula (IV-IId): [ka] or a pharma- ceutically acceptable salt thereof.

[0089] In some embodiments, the compound has the formula (IV-IIe): [ka] or a pharma- ceutically acceptable salt thereof.

[0090] In some embodiments, the compound has formula (IV-IIf): [ka] or a pharma- ceutically acceptable salt thereof.

[0091] In some embodiments, the compound has the formula (IV-IIg): [ka] or a pharma- ceutically acceptable salt thereof.

[0092] In some embodiments, the compound has formula (IV-IIh): [ka] or a pharma- ceutically acceptable salt thereof.

[0093] In some embodiments, the compound has formula (IV-IIi): [ka] or a pharma- ceutically acceptable salt thereof.

[0094] In some embodiments, the compound has the formula (IV-IIj): [ka] or a pharma- ceutically acceptable salt thereof.

[0095] In some embodiments, the compound has the formula (IV-IIk): [ka] or a pharma- ceutically acceptable salt thereof.

[0096] In some embodiments, the compound has the formula (IV-IIL): [ka] or a pharma- ceutically acceptable salt thereof.

[0097] In some embodiments, the compound has the formula (IV-IIm): [ka] or a pharma- ceutically acceptable salt thereof.

[0098] In some embodiments, the compound has formula (IV-IIn) or formula (IV-IIo) [ka] or a pharma- ceutically acceptable salt thereof.

[0099] In one aspect, the compound of formula (IV-III) [ka] or a pharma- ceutically acceptable salt thereof.

[0100] In one aspect, the present specification provides a compound represented by formula (VI): [ka] or a pharma- ceutically acceptable salt thereof.

[0101] In some embodiments, the compound has formula (V-Ia): [ka] or a pharma- ceutically acceptable salt thereof.

[0102] In some embodiments, the compound has formula (V-Ib): [ka] or a pharma- ceutically acceptable salt thereof.

[0103] In some embodiments, the compound has formula (V-Ic): [ka] or a pharma- ceutically acceptable salt thereof.

[0104] In some embodiments, the compound has formula (V-Id): [ka] or a pharma- ceutically acceptable salt thereof.

[0105] In some embodiments, the compound has formula (V-Ie): [ka] or a pharma- ceutically acceptable salt thereof.

[0106] In some embodiments, the compound has the formula (V-If): [ka] or a pharma- ceutically acceptable salt thereof.

[0107] In some embodiments, the compound has the formula (V-Ig): [ka] or a pharma- ceutically acceptable salt thereof.

[0108] In some embodiments, the compound has formula (V-Ih): [ka] or a pharma- ceutically acceptable salt thereof.

[0109] In some embodiments, the compound has formula (V-Ii): [ka] or a pharma- ceutically acceptable salt thereof.

[0110] In some embodiments, the compound has formula (V-Ij): [ka] or a pharma- ceutically acceptable salt thereof.

[0111] In some embodiments, the compound has the formula (V-Ik): [ka] or a pharma- ceutically acceptable salt thereof.

[0112] In some embodiments, the compound has the formula (V-IL): [ka] or a pharma- ceutically acceptable salt thereof.

[0113] In some embodiments, the compound has the formula (V-Im): [ka] or a pharma- ceutically acceptable salt thereof.

[0114] In some embodiments, the compound has the formula (V-In) or the formula (V-Io): [ka] or a pharma- ceutically acceptable salt thereof.

[0115] In one aspect, the present specification provides a compound represented by formula (V-II): [ka] or a pharma- ceutically acceptable salt thereof.

[0116] In some embodiments, the compound has formula (V-IIa): [ka] or a pharma- ceutically acceptable salt thereof.

[0117] In some embodiments, the compound has formula (V-IIb): [ka] or a pharma- ceutically acceptable salt thereof.

[0118] In some embodiments, the compound has formula (V-IIc): [ka] or a pharma- ceutically acceptable salt thereof.

[0119] In some embodiments, the compound has formula (V-IId): [ka] or a pharma- ceutically acceptable salt thereof.

[0120] In some embodiments, the compound has formula (V-IIe): [ka] or a pharma- ceutically acceptable salt thereof.

[0121] In some embodiments, the compound has the formula (V-IIf): [ka] or a pharma- ceutically acceptable salt thereof.

[0122] In some embodiments, the compound has formula (V-IIg): [ka] or a pharma- ceutically acceptable salt thereof.

[0123] In some embodiments, the compound has formula (V-IIh): [ka] or a pharma- ceutically acceptable salt thereof.

[0124] In some embodiments, the compound has formula (V-IIi): [ka] or a pharma- ceutically acceptable salt thereof.

[0125] In some embodiments, the compound has formula (V-IIj): [ka] or a pharma- ceutically acceptable salt thereof.

[0126] In some embodiments, the compound has formula (V-IIk): [ka] or a pharma- ceutically acceptable salt thereof.

[0127] In some embodiments, the compound has the formula (V-IIL): [ka] or a pharma- ceutically acceptable salt thereof.

[0128] In some embodiments, the compound has the formula (V-IIm): [ka] or a pharma- ceutically acceptable salt thereof.

[0129] In some embodiments, the compound has formula (V-IIn) or formula (V-IIo) [ka] or a pharma- ceutically acceptable salt thereof.

[0130] In one aspect, the compound of formula (V-III) [ka] or a pharma- ceutically acceptable salt thereof.

[0131] In some embodiments, the pharmaceutical composition comprises a compound described herein, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable excipient.

[0132] In some embodiments, provided herein is 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 described herein or a pharma- ceutically 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.

[0133] In some embodiments, the compound is selected from the group consisting of the compounds identified in Table I-1, Table I-2, Table I-3, Table II-1, Table III-1, Table IV-1, Table V-1 herein.

[0134] In one aspect, provided herein are pharma- ceutically acceptable salts of the compounds described herein (e.g., compounds of Formula (II), Formula (I-II), Formula (II-I), Formula (II-II), Formula (III-I), Formula (III-II), Formula (IV-I), Formula (IV-II), Formula (IV-III), Formula (VI), Formula (V-II), or Formula (V-III).

[0135] In one aspect, provided herein is a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (II), Formula (I-II), Formula (II-I), Formula (II-II), Formula (III-I), Formula (III-II), Formula (IV-I), Formula (IV-II), Formula (IV-III), Formula (VI), Formula (V-II), or Formula (V-III)) or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable excipient. In certain embodiments, the compound of the present invention is provided in an effective amount in the pharmaceutical composition. In certain embodiments, the compound of the present invention is provided in a therapeutically effective amount. In certain embodiments, the compound of the present invention is provided in a prophylactically effective amount.

[0136] The compounds of the invention as described herein may, in certain embodiments, be used to treat, for example, GABA A These compounds act as GABA modulators, 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. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0137] Detailed Description of Specific Embodiments of the Invention As generally described herein, the present invention provides compounds designed to act as, for example, GABA 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

[0138] 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; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3rd ed., Cambridge University Press, 2001. University Press, Cambridge, 1987.

[0139] 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 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.

[0140] "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."

[0141] 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.

[0142] As used herein, the term "diastereomeric purity" refers to the amount of a compound with the indicated absolute stereochemistry expressed as a percentage of the total amount of the indicated compound and its diastereomers. The term "diastereomerically pure" means that a compound contains more than 75% by weight, more than 80% by weight, more than 85% by weight, more than 90% by weight, more than 91% by weight, more than 92% by weight, more than 93% by weight, more than 94% by weight, more than 95% by weight, more than 96% by weight, more than 97% by weight, more than 98% by weight, more than 98.5% by weight, more than 99% by weight, more than 99.2% by weight, more than 99.5% by weight, more than 99.6% by weight, more than 99.7% by weight, more than 99.8% by weight, or more than 99.9% by weight of its diastereomer. Methods for determining diastereomeric and enantiomeric purity are well known in the art. Diastereomeric purity can be expressed as: The diastereomeric form can be determined by any analytical method capable of quantitatively distinguishing between a compound and its diastereomer, such as high performance liquid chromatography (HPLC).

[0143] In the compositions provided herein, the enantiomerically pure compound may be present together with other active or inactive ingredients. For example, a pharmaceutical composition comprising an enantiomerically pure R-compound may comprise, for example, about 90% of additives and about 10% of enantiomerically pure R-compound. In certain embodiments, the enantiomerically pure R-compound in such a composition 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 additives and about 10% of the enantiomerically pure S-compound. In certain embodiments, the enantiomerically pure S-compound in such a composition 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 additives or carriers or without additives or carriers.

[0144] 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.

[0145] 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, C 3~4 , C 4~6 , C 4~5 , and C 5~6 is intended to include alkyl of the formula:

[0146] The following terms are intended to have the meanings provided below relative thereto and are useful in understanding the specification and the intended scope of the invention.

[0147] "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"). C1~6 Examples 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 ), Amyl (C 5 ), neopentyl (C 5 ), 3-methyl-2-butanyl (C 5 ), 3rd class Ami Lu (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.

[0148] "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 CH2 CH 2 -, -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.

[0149] "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 2~4In some embodiments, the alkenyl group has 2 to 3 carbon atoms ("C 2~3 In 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 ) and the like. Further examples 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.

[0150] "Alkynyl" refers to the radical of a straight-chain or branched-chain hydrocarbon group having 2 to 20 carbon atoms, one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 carbon-carbon triple bonds), and optionally one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 carbon-carbon double bonds) ("C 2~20 In certain embodiments, 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 C2~4 Alkynyl groups, as well as pentynyl (C 5 ), Hexynyl (C 6 Further examples of alkynyl include heptynyl (C 7 ), Octynyl (C 8 Unless otherwise specified, each occurrence of an alkynyl group is independently optionally substituted, i.e., unsubstituted ("unsubstituted alkynyl") or substituted with one or more substituents; for example, 1-5 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.

[0151] 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, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1, 2, 3, or 4 heteroatoms ("heteroalkyl"). Terror C 1~7In some embodiments, a heteroalkyl group is a group having 1 to 6 carbon atoms and 1, 2, or 3 heteroatoms ("heteroC 1~6 In 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.

[0152] "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 6aryl"; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms ("C 10 Aryl"; 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.

[0153] In certain embodiments, the aryl group is halo, C 1 ~C 8 Alkyl, C 1 ~C 8 Haloalkyl, cyano, hydroxy, C 1 ~C 8Substituted with one or more groups selected from alkoxy and amino.

[0154] 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, C3 ~C 10 Cycloalkyl, 4-10 membered heterocyclyl, C 6 ~C 10 Aryl, Substituted C 6 ~C 10 It is aryl, 5- to 10-membered heteroaryl or substituted 5- to 10-membered heteroaryl.

[0155] "Fused aryl" refers to an aryl which shares two ring carbons with a second aryl or heteroaryl ring, or a carbocyclyl or heterocyclyl ring.

[0156] "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).

[0157] 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.

[0158] 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.

[0159] 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.

[0160] "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")), and 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.

[0161] 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.

[0162] "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.

[0163] 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.

[0164] 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.

[0165] 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.

[0166] "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).

[0167] "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.

[0168] "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.

[0169] 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.

[0170] "Amino" means -NH 2 It refers to radicals.

[0171] An "oxo group" refers to -C(=O)-.

[0172] "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.

[0173] 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.

[0174] "Carboxy" refers to the -C(O)OH radical.

[0175] "Cyano" refers to the -CN radical.

[0176] "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.

[0177] "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.

[0178] "Hydroxy" refers to the radical -OH.

[0179] "Nitro" means -NO 2 It refers to radicals.

[0180] "Thioketo" refers to the =S group.

[0181] 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.

[0182] 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;

[0183] 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;

[0184] 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;

[0185] 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;

[0186] 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;

[0187] 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;

[0188] 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;

[0189] 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.

[0190] 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.

[0191] 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.

[0192] Other definitions As used herein, the term "modulation" refers to the inhibition or potentiation of GABA receptor function. A "modulator" (e.g., a modulator compound) can be, for example, an agonist, partial agonist, antagonist, or partial antagonist of the GABA receptor.

[0193] "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.

[0194] "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.

[0195] 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.

[0196] In an alternative embodiment, the present invention provides a prodrug of a compound of formula (II), (I-II), (II-I), (II-II), (III-I), (III-II), (IV-I), (IV-II), (IV-III), (VI), (V-II), or (V-III), wherein the prodrug comprises a cleavable moiety on the C3 hydroxy shown in the compound of formula (II), (I-II), (II-I), (II-II), (III-I), (III-II), (IV-I), (IV-II), (IV-III), (VI), (V-II), or (V-III).

[0197] "Tautomer" refers to a compound of a particular compound structure in interchangeable form and with varying displacement of hydrogen atoms and electrons. Thus, two structures can be in equilibrium with the movement of pi 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 can be relevant to obtaining optimal chemical reactivity and biological activity of a compound of interest.

[0198] "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.

[0199] 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 , Rbb , 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.

[0200] 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).

[0201] 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) 2R 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 cc is 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.

[0202] 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 6~14 aryl, and 5- to 14-membered heteroaryl groups, where each of alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl independently has 0, 1, 2, 3, 4, or 5 R dd group, where R aa , R bb , R cc , and R dd is as defined herein. Amino protecting groups are well known in the art and are described in Protecting Groups in Organic Synthesis, T.W. Greene and P.G.M. Huts, 3 rd edition, John Wiley & Sons, 1999, which is incorporated herein by reference.

[0203] 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)).

[0204] Disease, disorder, and condition are used interchangeably herein.

[0205] 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, which lessen the severity of the disease, disorder, or condition, or delay or slow the progression of the disease, disorder, or condition. In an alternative embodiment, the present invention contemplates administration of a compound of the present invention as a prophylactic before a subject begins to suffer from a particular disease, disorder, or condition.

[0206] Generally, the "effective amount" of a compound refers to an amount sufficient to induce a desired biological response, for example, to treat a CNS-related disorder, and is sufficient to induce anesthesia or sedation.As will be understood by those skilled in the art, the effective amount of the compound of the present invention can vary depending on factors such as the desired biological goal, the pharmacokinetics of the compound, the disease to be treated, the mode of administration, and the age, weight, health status, and condition of the subject.The effective amount includes therapeutic treatment and prophylactic treatment.

[0207] 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.

[0208] As used herein, unless otherwise specified, a "prophylactically effective amount" of a compound is an amount sufficient to prevent a disease, disorder, or condition, or one or more symptoms associated with the disease, disorder, or condition, or to prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, that provides a prophylactic benefit in the prevention of the disease, disorder, or condition. The term "prophylactically effective amount" can include an amount that improves overall prophylaxis, or an amount that enhances the prophylactic efficacy of another prophylactic agent. compound

[0209] In one aspect, a compound represented by formula (II): [ka] or a pharma- ceutically acceptable salt thereof, In formula (II), t is 1 or 2; R 7 is hydrogen or methyl, or [ka] If is a double bond, R 7 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 9 is hydrogen or substituted or unsubstituted alkyl; 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; R11a , R 11b , R 15a , R 15b , R 16a , R 16b , R 17a , R 17b , R 18a , R 18b , R 19a , or R 19b 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 11a and R 11b , R 15a and R 15b , R 16a and R 16b , R 17a and R 17b , and R 18a and R 18b any one of these taken together form an oxo (=O) group; R 5a , R 5b , R 8 , and R 13each independently represents hydrogen, halogen, cyano, 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 , -C(=O)N(R A1 ) 2 , -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 A1each 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; or R 8 and R 13 together form an oxo (=O) group, where R 8 and R 13 When taken together, they form an oxo (=O) group, R 3 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; Here, R 5a , R 5b , R 8 , and R 13 at least one of is ethyl, substituted 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)RA1 , -C(=O)N(R A1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -SS(=O) 2 R A2 , -SS(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R A2 , or -S(=O) 2 OR A1 Must be; Here, R 8 and R 13 and cannot both be methyl; 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 and R 7 does not exist. Formula (II): group R 15a and R 15b

[0210] In some cases, R 15a and R 15beach 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.

[0211] In some cases, 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.

[0212] In some cases, 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 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.

[0213] In some cases, R 15a and R 15b are both hydrogen.

[0214] In some embodiments, R 15a and R 15b is each independently hydrogen or substituted or unsubstituted alkyl.

[0215] In some embodiments, R 15a and R 15b 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.

[0216] In some embodiments, R 15a or R 15b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II): group R 16a and R 16b

[0217] In some cases, R 16a or R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 Each occurrence is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbo cyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0218] In some cases, R 16a or 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.

[0219] In some cases, R 16a or 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.

[0220] In some cases, R16a and R 16b and R are both hydrogen. 16a and R 16b is each independently hydrogen or substituted or unsubstituted alkyl.

[0221] In some cases, 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 In some other aspects, R 16a or R 16b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II): group R 17a and R 17b

[0222] In some embodiments, R 17a 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 -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.

[0223] In some further embodiments, R 17a or R 17b 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.

[0224] In some cases, R 17a or R 17b 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. 17a and R 17b are both hydrogen.

[0225] In some cases, R 17a and R 17b is, each independently, hydrogen or substituted or unsubstituted alkyl.17a and R 17b 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.

[0226] In some cases, R 17a or R 17b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II): group R 18a and R 18b

[0227] In some cases, R 18a or R 18b 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.

[0228] In some embodiments, R 18a or R 18beach 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.

[0229] In some embodiments, R 18a or R 18b 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.

[0230] In some further embodiments, R 18a and R 18b are both hydrogen.

[0231] In some cases, R 18a and R 18b is, each independently, hydrogen or substituted or unsubstituted alkyl. 18a and R 18b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C6 Alkoxyhalo, or -OH.

[0232] In some cases, R 18a or R 18b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II): group R 19a and R 19b

[0233] In some embodiments, R 19a or R 19b 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 is a substituted or unsubstituted heteroaryl.

[0234] In some further embodiments, R 19a or R 19b 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.

[0235] In some cases, R 19a or R 19b 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.

[0236] In some cases, R 19a and R 19b are both hydrogen.

[0237] In some cases, R 19a and R 19b is each independently hydrogen or substituted or unsubstituted alkyl.

[0238] In some cases, R 19a and R 19b 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.

[0239] In some cases, R 19a or R 19b But -CH 3 , -CH 2CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II): Group R 7

[0240] In some cases, R 7 is a hydrogen atom at the cis position. In some other aspects, R 7 is a hydrogen in the trans position. 7 is methyl in the cis position. In some further embodiments, R 7 is a methyl in the trans position. Formula (II): Group t

[0241] In some embodiments, t is 1.

[0242] In some embodiments, t is 2. Formula (II): Group R 3

[0243] In some embodiments, R 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

[0244] In some embodiments, R 3 is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0245] In some embodiments, R 3 is substituted or unsubstituted alkyl.

[0246] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is substituted alkyl. In some embodiments, R 3 is unsubstituted alkyl. In some embodiments, R 3 is methyl. Formula (II): Group R 9

[0247] In some cases, R 9 is hydrogen.

[0248] In some embodiments, R 9 is substituted alkyl. In some embodiments, R 9 is an unsubstituted alkyl.

[0249] In some embodiments, R 9 is methyl. In some embodiments, R 9 But, -OCH 3 In some cases, R 9 is ethyl. Formula (II): Group R 6a and R 6b

[0250] 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.

[0251] In some cases, R 6a and R 6b is independently hydrogen or substituted or unsubstituted alkyl.

[0252] 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.

[0253] 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 6aand R 6b Both are halos.

[0254] In some cases, R 6a and R 6b are both alkyl.

[0255] In some embodiments, R 6a and R 6b together form an oxo group. Formula (II): group R 11a and R 11b

[0256] In some embodiments, 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 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.

[0257] In some cases, 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 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.

[0258] In some embodiments, 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 each occurrence independently represents hydrogen, It is substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0259] In some embodiments, R 11a and R 11b are both hydrogen.

[0260] In some further embodiments, R 11a and R 11b is each independently hydrogen or substituted or unsubstituted alkyl. Formula (II): group R 8 and R 13

[0261] In some cases, R 8 or R 13 is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -C(=O)N(RA1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , or -OC(=O)N(R A1 ) 2 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, or substituted or unsubstituted heteroaryl.

[0262] In some embodiments, R 8 or R 13 is a substituted or unsubstituted alkyl, -C(O)R A1 , -OC(=O)R A1 , -C(=O)N(R A1 ) 2 , or -OC(=O)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, or substituted or unsubstituted heteroaryl.

[0263] In some cases, R 8 or R 13 But -C(O)R A1 where R A1 is a substituted alkyl.

[0264] In some embodiments, the alkyl is substituted with a heteroaryl.

[0265] In some further embodiments, the alkyl is substituted with a 5-membered heteroaryl. Formula (II): group R 5a and R 5b

[0266] In some cases, R 5a and R 5b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , or -OC(=O)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, or substituted or unsubstituted heteroaryl.

[0267] In some embodiments, R 5a and R 5b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , or -OC(=O)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 heterocyclyl, substituted or unsubstituted aryl, or substituted or is unsubstituted heteroaryl.

[0268] In some cases, R5a and R 5b are each hydrogen.

[0269] In some embodiments, the compound has the formula (I-Ia): [ka] or a pharma- ceutically acceptable salt thereof, Here, 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 A1each 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; and n is 0, 1, 2, or 3.

[0270] In some embodiments, the compound has the formula (I-Iab): [ka] or a pharma- ceutically acceptable salt thereof, 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; and n is 0, 1, 2, or 3.

[0271] In some embodiments, the compound has formula (I-Ib) or formula (I-Ibb): [ka] or a pharma- ceutically acceptable salt thereof.

[0272] In some embodiments, the compound has formula (I-Ic) or formula (I-Icb): [ka] or a pharma- ceutically acceptable salt thereof, 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 A1each 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; and n is 0, 1, 2, or 3.

[0273] 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.

[0274] In some embodiments, 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(RGA ) 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; n or e are 0, 1, 2, 3, 4, or 5.

[0275] In some embodiments, R 1 but, [ka] and Here, R 20Each 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 3~6carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R GA the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; n or e are 0, 1, 2, 3, 4, or 5.

[0276] In some embodiments, the compound has formula (I-Id) or formula (I-Idb): [ka] is a compound of Here, R 10 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

[0277] In some embodiments, the compound has formula (I-Ie) or formula (I-Ieb): [ka] or a pharma- ceutically acceptable salt thereof, where e is 0, 1, 2, or 3; p is 0, 1, 2 or 3; R 5 Each of is independently halogen, alkyl, hydroxyl, or cyano.

[0278] In some embodiments, the compound has formula (I-If) or formula (I-Ifb): [ka] or a pharma- ceutically acceptable salt thereof, Here, R 10 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

[0279] In some embodiments, the compound has formula (I-Ig) or formula (I-Igb): [ka] or a pharma- ceutically acceptable salt thereof, where 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.

[0280] In some embodiments, the compound has formula (I-Ih) or formula (I-Ihb): [ka] or a pharma- ceutically acceptable salt thereof, Here, R 10each is independently halogen, alkyl, hydroxyl, or cyano; and m is 0, 1, 2, or 3.

[0281] In some embodiments, the compound has formula (I-Ii) or formula (I-Iib): [ka] or a pharma- ceutically acceptable salt thereof, where n is 0, 1, or 2, and 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.

[0282] In some embodiments, the compound has the formula (I-Ik) or the formula (I-Ikb): [ka] or a pharma- ceutically acceptable salt thereof, where s is 0, 1, or 2; R 12 is -N(R ab ) 2 where R ab each independently represents H, substituted or unsubstituted alkyl, -OR ab , -SO 2 (R 15 ), -C(O)R 15 where R 15 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted cycloalkane.

[0283] In one aspect, the compound has formula (I-II): [ka] or a pharma- ceutically acceptable salt thereof, wherein the compound is represented by formula (I-II): R 77 is hydrogen or methyl; R 23 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 29 is hydrogen or substituted or unsubstituted alkyl; R 26a and R 26b each is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or R 26a and R 26b together form an oxo (=O) group; R 21a , R 21b , R 25a , R 25b , R36a , R 36b , R 27a , R 27b , R 29a , or R 29b 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 21a and R 21b , R 25a and R 25b , R 36a and R 36b , R 27a and R 27b , and R 29a and R 29b taken together to form an oxo (=O) group; R 55a , R 55b , R 33a , and R 33b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 )2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -C(=O)N(R A1 ) 2 , -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 selected from 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, oxygen when attached to an oxygen atom Protecting groups, sulfur protecting groups when attached to a sulfur atom, nitrogen protecting groups when attached to a nitrogen atom, -SO 2 R A2 , -C(O)R A2 or two R A1groups 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 26a or R 26b and R 77 is not present and a single bond is present in ring B, the hydrogen at C5 is in the α or β position. Formula (I-II): Group R 25a and R 25b

[0284] In some embodiments, R 25a and R 25b 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.

[0285] In some embodiments, R 25a and R 25beach 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.

[0286] In some embodiments, R 25a and R 25b 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.

[0287] In some embodiments, R 25a and R 25b are both hydrogen.

[0288] In some embodiments, R 25a and R 25b is each independently hydrogen or substituted or unsubstituted alkyl.

[0289] In some embodiments, R 25a and R 25b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 1 ~C6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH.

[0290] In some embodiments, R 25a or R 25b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (I-II): Group R 36a and R 36b

[0291] In some embodiments, R 36a or R 36b 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.

[0292] In some embodiments, R 36a or R 36b 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 RD1 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.

[0293] In some embodiments, R 36a or R 36b 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.

[0294] In some embodiments, R 36a and R 36b are both hydrogen.

[0295] In some embodiments, R 36a and R 36b is each independently hydrogen or substituted or unsubstituted alkyl.

[0296] In some embodiments, R 36a and R 36b 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.

[0297] In some embodiments, R 36a or R 36b But -CH3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (I-II): Group R 27a and R 27b

[0298] In some embodiments, R 27a or R 27b 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.

[0299] In some embodiments, R 27a or R 27b 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 It is carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0300] In some embodiments, R 27a or R 27b 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.

[0301] In some embodiments, R 27a and R 27b are both hydrogen.

[0302] In some embodiments, R 27a and R 27b is each independently hydrogen or substituted or unsubstituted alkyl.

[0303] In some embodiments, R 27a and R 27b 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.

[0304] In some embodiments, R 27a or R 27b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (I-II): Group R 29a and R29b

[0305] In some embodiments, R 29a or R 29b 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.

[0306] In some embodiments, R 29a or R 29b 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.

[0307] In some embodiments, R 29a or R 29b 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.

[0308] In some embodiments, R 29a and R 29b are both hydrogen.

[0309] In some embodiments, R 29a and R 29b is each independently hydrogen or substituted or unsubstituted alkyl.

[0310] In some embodiments, R 29a and R 29b 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.

[0311] In some embodiments, R 29a or R 29b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (I-II): Group R 21a and R 21b

[0312] In some embodiments, R 21a or R 21beach 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.

[0313] In some embodiments, R 21a or R 21b 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.

[0314] In some embodiments, R 21a or R 21b 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.

[0315] In some embodiments, R 21a and R 21b are both hydrogen.

[0316] In some embodiments, R 21a and R 21b is each independently hydrogen or substituted or unsubstituted alkyl.

[0317] In some embodiments, R 21a and R 21b 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.

[0318] In some embodiments, R 21a or R 21b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is.

[0319] In some embodiments, R 77 is a hydrogen at the cis position. 77 is a hydrogen atom in the trans position.

[0320] In some embodiments, R 77 is methyl in the cis position. 77 is a methyl in the trans position. Formula (I-II): Group R 23

[0321] In some embodiments, R 23 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. 23 is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 23 is substituted or unsubstituted alkyl.

[0322] In some embodiments, R 23 is hydrogen.

[0323] In some embodiments, R 23 is substituted alkyl. In some embodiments, R 23 is an unsubstituted alkyl.

[0324] In some embodiments, R 23 is methyl. Formula (I-II): Group R 29

[0325] In some embodiments, R 29 is hydrogen.

[0326] In some embodiments, R 29 is substituted alkyl. In some embodiments, R 29 is an unsubstituted alkyl. In some embodiments, R 29 is methyl. In some embodiments, R 29 But, -OCH 3 In some embodiments, R 29 is ethyl. Formula (I-II): Group R 26a and R 26b

[0327] In some embodiments, R 26a and R 26bis independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl.

[0328] In some embodiments, R 26a and R 26b is independently hydrogen or substituted or unsubstituted alkyl.

[0329] In some embodiments, R 26a and R 26b is independently hydrogen or substituted alkyl.

[0330] In some embodiments, R 26a and R 26b is independently hydrogen or unsubstituted alkyl. In some embodiments, R 26a and R 26b is hydrogen. In some embodiments, R 26a is halo or alkyl, R 26b is hydrogen. In some embodiments, R 26a and R 26b In some embodiments, both of R 26a and R 26b In some embodiments, both of R 26a and R 26b together form an oxo group. Formula (I-II): Group R 55a and R 55b

[0331] In some embodiments, R 55a or R 55b is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, -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)ORA1 , -C(=O)N(R A1 ) 2 , -OC(=O)SR A1 , or -OC(=O)N(R A1 ) 2 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, or substituted or unsubstituted heteroaryl.

[0332] In some embodiments, R 55a or R 55b is a substituted or unsubstituted alkyl, -C(O)R A1 , -OC(=O)R A1 , -C(=O)N(R A1 ) 2 , or -OC(=O)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, or substituted or unsubstituted heteroaryl.

[0333] In some embodiments, R 55a or R 55b But -C(O)R A1 where R A1 is a substituted alkyl. In some embodiments, the alkyl is substituted with a heteroaryl. In some embodiments, the alkyl is substituted with a 5-membered heteroaryl. Formula (I-II): The group R 33a and R 33b

[0334] In some embodiments, R 33a and R 33bare each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclic, substituted or unsubstituted heterocyclic, 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 , or -OC(=O)OR A1 wherein each occurrence of R A1 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.

[0335] In some embodiments, R 33a and R 33b are each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , or -OC(=O)OR A1 wherein each occurrence of R A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heterocyclic, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0336] In some embodiments, R 33a and R 33b are each hydrogen.

[0337] In some embodiments, the compound has formula (I-IIa) or formula (I-IIab) [ka] or a pharma- ceutically acceptable salt thereof, Here, R 31 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 A1each 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; v is 0, 1, or 2 and d is 0, 1, 2, or 3.

[0338] In some embodiments, the compound has formula (I-IIb) or formula (I-IIbb): [ka] or a pharma- ceutically acceptable salt thereof, wherein the variables are defined as above in Formula (I-IIa) or Formula (I-IIab).

[0339] In some embodiments, R 31 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.

[0340] In some embodiments, R 31 but, [ka] and Here, R 20 Each occurrence of is independently a halogen, -NO 2 , -CN, -ORGA , -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 GAthe groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; e or n is 0, 1, 2, 3, 4, or 5.

[0341] In some embodiments, R 31 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, RGA 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.

[0342] In some embodiments, the compound has formula (I-IId) or formula (I-IIdb): [ka] or a pharma- ceutically acceptable salt thereof, where v is 0, 1, 2, or 3; R 10 is independently halogen, alkyl, hydroxyl, or cyano.

[0343] In some embodiments, the compound has formula (I-IIe) or formula (I-IIeb): [ka] or a pharma- ceutically acceptable salt thereof, where n is 0, 1, 2, or 3; p is 0, 1, or 3; v is 0, 1, 2, or 3; R 5 Each of is independently halogen, alkyl, hydroxyl, or cyano.

[0344] In some embodiments, the compound has formula (I-IIf) or formula (I-IIfb): [ka] or a pharma- ceutically acceptable salt thereof, wherein v is 0, 1, 2, or 3; 10 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

[0345] In some embodiments, the compound has formula (I-IIg) or formula (I-IIgb): [ka] or a pharma- ceutically acceptable salt thereof, where v is 0, 1, 2, or 3; and 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.

[0346] In some embodiments, the compound has formula (I-IIh) or formula (I-IIhb) [ka] or a pharma- ceutically acceptable salt thereof, where v is 0, 1, 2, or 3, and R 10 each is independently halogen, alkyl, hydroxyl, or cyano; and m is 0, 1, 2, or 3.

[0347] In some embodiments, the compound has formula (I-IIi) or formula (I-IIib) [ka] or a pharma- ceutically acceptable salt thereof, where v is 0, 1, 2, or 3; n is 0, 1, or 2; and 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 3~6carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R GA The groups, together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring.

[0348] In some embodiments, R 3 is methoxymethyl or ethoxymethyl.

[0349] In some embodiments, R 8 or R 13 -C(O)CH 3 If R 3 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.

[0350] In some embodiments, the compound has the formula (I-IIj): [ka] or a pharma- ceutically acceptable salt thereof, where s is 0, 1, or 2; R 12 is -N(R ab ) 2 , -OR ab where R ab each independently represents H, substituted or unsubstituted alkyl, -SO 2 (R 15 ), -C(O)R 15 where R 15 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted cycloalkane.

[0351] In some embodiments, R8 or R 13 But -C(O)R A1 , -C(=O)N(R A1 ) 2 where R A1 is a substituted alkyl.

[0352] In some embodiments, R 8 and R 13 together form an oxo (=O) group.

[0353] In some embodiments, the compound is selected from the group consisting of the compounds identified in Table I-1 below: [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10] [Table 1-11] [Table 1-12] [Table 1-13] [Table 1-14] [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5]

[0001] 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. It should be recognized that the stereochemistry of C17 can be depicted in any of the following equivalent ways: [ka] .

[0002] In one aspect, formula (II-I) [ka] or a pharma- ceutically acceptable salt thereof, In formula (II-I), t is 1; n is 0, 1, or 2; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted C 2 ~C 6 alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R 5 is hydrogen or methyl; 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, aryl, 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)ORA1 , -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 2aa, R 2ab , R 3a , R 3b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , or R 12b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, 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 taken together to form an oxo (=O) group; Here, R 1a , R 1b , R 2a , R 2b , R 2aa , R 2ab , R 3a , R 3b , R 4a , or R 4bat least one of is hydroxyl; R 15a , R 15b , R 16a , and R 16b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 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 A1each 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 n is 0, t is 1, and R 19 is methyl and R 5 is hydrogen and R 3a is hydroxyl, ring B has a double bond, and R 6a , R 6b , R 1a , R 1b , R 2a , R 2b , R 2aa , R 2ab , R 3b , R 4a , R 4b , R 7a , R 7b , R 11a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , and R 16b When each is hydrogen, R 1 is not methyl; 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 and R 5 does not exist.

[0003] In some embodiments, the formula (II-II) [ka] or a pharma- ceutically acceptable salt thereof, The variables are defined as described in formula (II-I); 1a , R 1b , R 2a , R 2b , R 3a , or R 3b At least one of is hydroxyl.

[0004] In some embodiments, n is 1. In other embodiments, n is 2. Formula (II-I) and Formula (II-II): Group R 3a and R 3b

[0005] In some cases, R 3a and R 3b each independently represents hydrogen, halogen, cyano, nitro, azido, 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 3a and R 3btogether form oxo (=O).

[0006] In some cases, R 3a and R 3b 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 it is an unsubstituted heteroaryl.

[0007] In some cases, R 3a and R 3b 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.

[0008] In some cases, R 3a and R 3b are both hydrogen.

[0009] In some embodiments, R 3a and R 3b is each independently hydrogen or substituted or unsubstituted alkyl.

[0010] In some embodiments, R 3a and R 3b 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.

[0011] In some embodiments, R 3a and R 3b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II-I) and Formula (II-II): Group R 2a and R 2b

[0012] In some cases, 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 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.

[0013] 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 , -NH2 , or -N(R D1 ) 2 where R D1 Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0014] 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.

[0015] In some cases, R 2a and R 2b are both hydrogen.

[0016] In some embodiments, R 2a and R 2b is each independently hydrogen or substituted or unsubstituted alkyl.

[0017] 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.

[0018] In some embodiments, R 2a and R2b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II-I): Group R 2aa and R 2ab

[0019] In some cases, R 2aa and R 2ab 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.

[0020] In some cases, R 2aa and R 2ab 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.

[0021] In some cases, R2aa and R 2ab 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.

[0022] In some cases, R 2aa and R 2ab are both hydrogen.

[0023] In some embodiments, R 2aa and R 2ab is each independently hydrogen or substituted or unsubstituted alkyl.

[0024] In some embodiments, R 2aa and R 2ab 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. In some embodiments, R 2aa and R 2ab But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II-I) and Formula (II-II): Group R 1a and R 1b

[0025] In some cases, R1a and R 1b each independently represents hydrogen, halogen, cyano, nitro, azido, 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, substituted or unsubstituted aryloxy ... or substituted or unsubstituted heteroaryl.

[0026] 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.

[0027] 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 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.

[0028] In some cases, R 1a and R 1b are both hydrogen.

[0029] In some embodiments, R 1a and R 1b is each independently hydrogen or substituted or unsubstituted alkyl.

[0030] In some embodiments, R 1a and R 1b 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. 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. Formula (II-I): group R 4a and R 4b

[0031] In some cases, R 4a and R 4b each independently represents hydrogen, halogen, cyano, nitro, azido, 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.

[0032] 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.

[0033] In some cases, 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.

[0034] In some cases, R 4a and R 4b and R are both hydrogen. 16a and R 16bis each independently hydrogen or substituted or unsubstituted alkyl.

[0035] In some cases, 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 In some other aspects, R 4a and R 4b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II-I) and Formula (II-II): Group R 11a and R 11b

[0036] In some embodiments, R 11a and R 11b each independently represents hydrogen, halogen, cyano, nitro, azido, 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.

[0037] In some further embodiments, R 11a and R11b 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.

[0038] 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.

[0039] 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.

[0040] 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.

[0041] In some embodiments, R 11a and R 11b together form oxo (=O). Formula (II-I) and Formula (II-II): Group R 15a and R 15b

[0042] 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 in 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.

[0043] 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 RD1 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.

[0044] 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.

[0045] In some further embodiments, R 15a and R 15b are both hydrogen.

[0046] In some cases, R 15a and R 15b is, each independently, hydrogen or substituted or unsubstituted alkyl. 15a and R 15b 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 aspects, R 15a and R 15b But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. Formula (II-I) and Formula (II-II): Group R 16a and R 16b

[0047] In some cases, R 16a and 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.

[0048] 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.

[0049] 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.

[0050] In some further embodiments, R 16a and R 16b are both hydrogen.

[0051] 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.

[0052] 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. Formula (II-I) and Formula (II-II): Group R 7a and R 7b

[0053] In some embodiments, R 7a and R 7beach independently represents hydrogen, halogen, cyano, nitro, azido, 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).

[0054] 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.

[0055] 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)RD1 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.

[0056] In some cases, R 7a and R 7b All of the is hydrogen.

[0057] 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.

[0058] 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.

[0059] In some embodiments, R 7a and R 7b taken together to form an oxo (=O). Formula (II-I) and Formula (II-II): Group R 5

[0060] In some cases, R 5 is a hydrogen cis to C19. 5 is a hydrogen trans to C19. 5and methyl cis to C19. In some further embodiments, R 5 is methyl in the trans position relative to C19. Formula (II-I) and Formula (II-II): Group R 19

[0061] In some cases, R 19 is hydrogen.

[0062] In other embodiments, R 19 is a substituted alkyl.

[0063] In other embodiments, R 19 But substitution C 2 ~C 6 In another embodiment, R 19 But non-substituted C 2 ~C 6 It is an alkyl.

[0064] In other embodiments, R 19 is substituted alkenyl. In other embodiments, R 19 is an unsubstituted alkenyl.

[0065] In other embodiments, R 19 is substituted alkynyl. In other embodiments, R 19 is unsubstituted alkynyl.

[0066] In some embodiments, R 19 Deuterium substituted C 2 -C 6 It is an alkyl.

[0067] In some embodiments, R 19 is ethyl. Formula (II-I) and Formula (II-II): Group R 6a and R 6b

[0068] 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.

[0069] In some cases, R 6a and R 6b is independently hydrogen or substituted or unsubstituted alkyl.

[0070] 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.

[0071] 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.

[0072] In some cases, R 6a and R 6b are both alkyl.

[0073] In some embodiments, R 6a and R 6b together form an oxo group. Formula (II-I) and Formula (II-II): Group R 12a and R 12b

[0074] In some embodiments, R 12a and R 12b each independently represents hydrogen, halogen, cyano, nitro, azido, 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 of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted Or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0075] 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.

[0076] 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.

[0077] In some embodiments, R 12a and R 12b are both hydrogen.

[0078] In some further embodiments, R 12a and R 12bis each independently hydrogen or substituted or unsubstituted alkyl.

[0079] In some embodiments, R 12a and R 12b together form an oxo group (=O).

[0080] In some embodiments, ring A is [ka] is selected from the group consisting of Where: [ka] indicates that ring A is bonded to ring B.

[0081] 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, or substituted or unsubstituted heteroaryl.

[0082] In some embodiments, 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; e is 0, 1, 2, 3, 4, or 5; and n is 0, 1, 2, 3, 4, or 5.

[0083] In some embodiments, R 1 but, [ka] and Here, R 20 Each occurrence of is independently hydrogen, halogen, -NO 2 , -CN, -ORGA , -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 GAthe 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.

[0084] In some embodiments, the compound has formula (II-Ia), (II-Iab) or (II-Iac): [ka] or a pharma- ceutically acceptable salt thereof.

[0085] In some embodiments, the compound has formula (II-Ib), (II-Ibb) or (II-Ibc): [ka] or a pharma- ceutically acceptable salt thereof.

[0086] In some embodiments, the compound has formula (II-Ic), (II-Icb) or (II-Icc): [ka] or a pharma- ceutically acceptable salt thereof.

[0087] In some embodiments, the compound has formula (II-Ie), (II-Ieb) or (II-Iec): [ka] or a pharma- ceutically acceptable salt thereof, where m is 0, 1, 2, or 3; p is 0, 1, or 3; R 32 Each of is independently halogen, alkyl, hydroxyl, or cyano.

[0088] In some embodiments, the compound has formula (II-Ig), (II-Igb) or (II-Igc): [ka] is a compound of where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -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 radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring; or a pharma- ceutically acceptable salt thereof.

[0089] In some embodiments, the compound has the formula (II-Ieg), (II-Iegb) or (II-Iegc): [ka] is a compound of where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -S-, -N-, or N(R N )-where R Nare 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 radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring; or a pharma- ceutically acceptable salt thereof.

[0090] In some embodiments, the compound has formula (II-Ih), (II-Ihb) or (II-Ihc): [ka] or a pharma- ceutically acceptable salt thereof, wherein R 35 each is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2, or 3.

[0091] In some embodiments, the compound has formula (II-Ii), (II-Iib) or (II-Iic): [ka] is a compound of where s is 0, 1, or 2; each X is independently -C(R N )-, -C(RN ) 2 -, -O-, -S-, -N-, or N(R N )-where R N are independently hydrogen, substituted or unsubstituted C1-6 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 radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring; or a pharma- ceutically acceptable salt thereof.

[0092] In some embodiments, the compound has formula (II-IIa) or (II-IIab) [ka] or a pharma- ceutically acceptable salt thereof.

[0093] In some embodiments, the compound has formula (II-IIb) or (II-IIbb) [ka] or a pharma- ceutically acceptable salt thereof.

[0094] In some embodiments, the compound has formula (II-IIc) or (II-IIcb) [ka] or a pharma- ceutically acceptable salt thereof.

[0095] In some embodiments, the compound has formula (II-IIe) or (II-IIeb) [ka] is a compound of where m is 0, 1, 2, or 3; p is 0, 1, or 3; R 32 each is independently halogen, alkyl, hydroxyl, or cyano; or a pharma- ceutically acceptable salt thereof.

[0096] In some embodiments, the compound has formula (II-IIg) or (II-IIgb): [ka] is a compound of where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -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 2~6Alkynyl, 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 radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring; or a pharma- ceutically acceptable salt thereof.

[0097] In some embodiments, the compound has the formula (II-IIh) or (II-IIhb): [ka] or a pharma- ceutically acceptable salt thereof, Here, R 35 each is independently halogen, alkyl, hydroxyl, or cyano; and r is 0, 1, 2, or 3.

[0098] In some embodiments, the compound has formula (II-IIi) or (II-IIib): [ka] is a compound of where v is 0, 1, 2, or 3; n is 0, 1, or 2; and 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;

[0099] RGA 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 radicals taken together with the intervening atoms form a substituted or unsubstituted heterocyclyl or heteroaryl ring; or a pharma- ceutically acceptable salt thereof. [000100] In some embodiments, the compound is selected from the group consisting of the compounds identified in Table II-1 below: [Table 4-1] [Table 4-2] [Table 4-3] [Table 4-4] [Table 4-5] [Table 4-6] [Table 4-7] [Table 4-8] [Table 4-9] [000101] In one aspect, the compound of formula (III-I) [ka] or a pharma- ceutically acceptable salt thereof, In formula (III-I), R 5 is hydrogen or a substituted or unsubstituted methyl (e.g., -CH 3 ) 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 19 is hydrogen, substituted or unsubstituted alkyl (e.g., substituted or unsubstituted C 1 -C 6 alkyl), substituted or unsubstituted alkenyl (e.g., substituted or unsubstituted C 2 -C 6 alkenyl), or substituted or unsubstituted alkynyl (e.g., substituted or unsubstituted C 2 -C 6 alkynyl); 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 1a , R 1b , R 12a , R 12b , R 2a , R 2b , R 4a , R 4b , R 11a , R 11b , R18a , and R 18b 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 1a and R 1b , R 12a and R 12b , R 2a and R 2b , R 4a and R 4b , R 11a and R 11b , and R 18a and R 18b taken together to form an oxo (=O) group; R 7a , R 7b , R 7aa , and R 7bb 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 D1where 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 7a and R 7b And R 7aa and R 7bb taken together to form an oxo (=O) group; R 16a , R 16b , R 17a , and R 17b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2, -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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, or R 17a and R 17b Together, Oxo Forming a base; Where: [ka] represents a single or double bond, and when a double bond is present, R 5 and R 6a or R 6b One of them does not exist. [000102] In one aspect, the compound of formula (III-I) [ka] or a pharma- ceutically acceptable salt thereof, In formula (III-I), R 5 is hydrogen or a substituted or unsubstituted methyl (e.g., -CH 3 ) or [ka] If is a double bond, R 5 does not exist; R 3 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 19 is a substituted or unsubstituted alkyl (e.g., substituted or unsubstituted C 1 -C 6 alkyl), substituted or unsubstituted alkenyl (e.g., substituted or unsubstituted C 2 -C 6 alkenyl), or substituted or unsubstituted alkynyl (e.g., substituted or unsubstituted C 2 -C 6 alkynyl); 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 1a , R 1b , R 12a , R 12b , R 2a , R 2b , R 4a , R 4b , R 11a , R 11b , R 18a , and R18b 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 1a and R 1b , R 12a and R 12b , R 2a oh YobiR 2b , R 4a and R 4b , R 11a and R 11b , and R 18a and R 18b taken together to form an oxo (=O) group; R 7a , R 7b , R 7aa , and R 7bb 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 D1where 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 7a and R 7b And R 7aa and R 7bb taken together to form an oxo (=O) group; R 16a , R 16b , R 17a , and R 17b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2, -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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, or R 17a and R 17b together to form an oxo group; Where: [ka] represents a single or double bond, and when a double bond is present, R 5 and R 6a or R 6b One of them does not exist. [000103] In one aspect, the compound of formula (III-II) [ka] or a pharma- ceutically acceptable salt thereof, In formula (III-II), R 5 is hydrogen or a substituted or unsubstituted methyl (e.g., -CH 3 ) 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 1a , R 1b , R 12a , R 12b , R 2a , R 2b , R 4a , R 4b , R 11a , R 11b , R 18a , and R 18b 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 RD1 each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom, or two R D1 groups taken together form a substituted or unsubstituted heterocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a and R 2b , R 4a and R 4b , R 11a and R 11b , and R 18a and R 18b taken together to form an oxo (=O) group; R 7a , R 7b , R 7aa , and R 7bb 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 7a and R7b And R 7aa and R 7bb taken together to form an oxo (=O) group; R 16a , R 16b , R 17a , and R 17b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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 RA1 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 or double bond, and when a double bond is present, R 5 and R 6a or R 6b One of them does not exist. Formula (III-I) and Formula (III-II): Group R 1a and R 1b [000104] 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)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. [000105] 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. [000106] 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 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclic It is preferably aryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000107] In some cases, R 1a and R 1b are both hydrogen. [000108] In some embodiments, R 1a and R 1bis each independently hydrogen or substituted or unsubstituted alkyl. [000109] In some embodiments, R 1a and R 1b 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. [000110] 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. Formula (III-I) and Formula (III-II): Group R 2a and R 2b [000111] In some cases, 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 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. [000112] 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. [000113] 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. [000114] In some cases, R 2a and R 2b are both hydrogen. [000115] In some embodiments, R 2a and R 2b is each independently hydrogen or substituted or unsubstituted alkyl. [000116] In some embodiments, R 2a and R 2b each independently represents hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxyhalo, or -OH. [000117] 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. Formula (III-I) and Formula (III-II): Group R 4a and R 4b [000118] In some cases, R 4a and 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 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. [000119] 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 ) 2where 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. [000120] In some cases, 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. [000121] In some cases, R 4a and R 4b and R are both hydrogen. 4a and R 4b is each independently hydrogen or substituted or unsubstituted alkyl. [000122] 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 It is. Formula (III-I) and Formula (III-II): Group R 11a and R 11b [000123] In some embodiments, R 11a and 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 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. [000124] 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. [000125] In some cases, R 11a and R 11b each independently represents hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)RD1 , -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. [000126] 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. [000127] 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. [000128] In some embodiments, R 11a and R 11b together form oxo (=O). Formula (III-I) and Formula (III-II): Group R 16a and R 16b [000129] In some cases, R 16a and R 16beach 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. [000130] 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. [000131] 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 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. [000132] In some further embodiments, R 16a and R 16b are both hydrogen. [000133] In some cases, R 16a and R 16b is, each independently, hydrogen or substituted or unsubstituted alkyl. 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 Alkoxyhalo, or -OH. [000134] 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. Formula (III-I) and Formula (III-II): Group R 7a , R 7b , R 7aa , and R 7bb [000135] In some embodiments, R 7a , R 7b , R 7aa , and R 7bb each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -ORD1 , -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 , or R 7aa and R 7bb together form oxo (=O). [000136] In some further embodiments, R 7a , R 7b , R 7aa , and R 7bb 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. [000137] In some cases, R 7a , R 7b , R 7aa , and R 7bb 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 D1where 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. [000138] In some cases, R 7a , R 7b , R 7aa , and R 7bb All of the is hydrogen. [000139] In some cases, R 7a , R 7b , R 7aa , and R 7bb is, each independently, hydrogen or substituted or unsubstituted alkyl. 7a , R 7b , R 7aa , and R 7bb 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. [000140] In some cases, R 7a , R 7b , R 7aa , and R 7bb But -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 It is. [000141] In some embodiments, R 7a and R 7b or R 7aa and R 7bb taken together to form an oxo (=O). Formula (III-I) and Formula (III-II): Group R5 [000142] In some cases, R 5 is a hydrogen atom at the cis position. In some other aspects, R 5 is a hydrogen in the trans position. 5 is methyl in the cis position. In some further embodiments, R 5 is a methyl in the trans position. Formula (III-I) and Formula (III-II): Group R 3 [000143] In some embodiments, R 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl. [000144] In some embodiments, R 3 is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000145] In some embodiments, R 3 is substituted or unsubstituted alkyl. [000146] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is substituted alkyl. In some embodiments, R 3 is unsubstituted alkyl. In some embodiments, R 3 is methyl. Formula (III-I): Group R 19 [000147] In some cases, R 19 is hydrogen. [000148] In some embodiments, R 19 is substituted alkyl. In some embodiments, R 19 is an unsubstituted alkyl. [000149] In some embodiments, R19 is methyl. In some embodiments, R 19 But, -OCH 3 In some cases, R 19 is ethyl. Formula (III-I) and Formula (III-II): Group R 6a and R 6b [000150] 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. [000151] In some cases, R 6a and R 6b is independently hydrogen or substituted or unsubstituted alkyl. [000152] 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. [000153] 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. [000154] In some cases, R 6a and R 6b are both alkyl. [000155] In some embodiments, R 6a and R 6b together form an oxo group. Formula (III-I) and Formula (III-II): Group R 12a and R 12b [000156] In some embodiments, R 12a and R 12b each independently represents hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 where R D1 Each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000157] 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. [000158] 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. [000159] In some embodiments, R 12a and R 12b are both hydrogen. [000160] In some further embodiments, R 12a and R 12b is each independently hydrogen or substituted or unsubstituted alkyl. [000161] In some embodiments, R 12a and R 12b together form an oxo group (=O). Formula (III-I) and Formula (III-II): Group R 17a and R 17b [000162] In some cases, R 17a and R 17b is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -C(=O)N(R A1 ) 2 , -OC(=O)SR A1 , or -OC(=O)N(R A1 ) 2 where R A1Each 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. [000163] In some embodiments, R 17a and R 17b is a substituted or unsubstituted alkyl, -C(O)R A1 , -OC(=O)R A1 , or -OC(=O)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, or substituted or unsubstituted heteroaryl. [000164] In some cases, R 17a and R 17b But -C(O)R A1 where R A1 is a substituted alkyl. [000165] In some embodiments, the alkyl is substituted with a heteroaryl. [000166] In some further embodiments, the alkyl is substituted with a 5-membered heteroaryl. Formula (III-I) and Formula (III-II): Group R 18a and R 18b [000167] In some embodiments, R 18a and R 18b 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(RD1 ) 2 , or -NR D1 C(=O)R D1 where R D1 each occurrence is independently hydrogen, substituted or unsubstituted alkyl, It is 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. [000168] In some cases, R 18a and R 18b 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. [000169] In some embodiments, R 18a and R 18b 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. [000170] In some embodiments, R 18a and R 18bare both hydrogen. [000171] In some further embodiments, R 18a and R 18b is each independently hydrogen or substituted or unsubstituted alkyl. [000172] In some embodiments, R 18a and R 18b together form an oxo group (=O). Formula (III-I) [000173] In some embodiments, the compound has formula (III-Ia): [ka] or a pharma- ceutically acceptable salt thereof. [000174] In some embodiments, the compound has formula (III-Ib): [ka] or a pharma- ceutically acceptable salt thereof. [000175] In some embodiments, the compound has formula (III-Ic): [ka] or a pharma- ceutically acceptable salt thereof. [000176] In some embodiments, the compound has formula (III-Id): [ka] or a pharma- ceutically acceptable salt thereof. [000177] In some embodiments, the compound has formula (III-Ie): [ka] or a pharma- ceutically acceptable salt thereof. [000178] In some embodiments, the compound has formula (III-If): [ka] or a pharma- ceutically acceptable salt thereof, R 1 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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 A1each 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; and n is 0, 1, or 2. [000179] In some embodiments, the compound has formula (III-Ig): [ka] or a pharma- ceutically acceptable salt thereof, R 1 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)ORA1 , -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; and n is 0, 1, 2, or 3. [000180] In some embodiments, the compound has the formula (III-Ih): [ka] or a pharma- ceutically acceptable salt thereof, where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -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. [000181] In some embodiments, the compound has formula (III-Ii): [ka] or a pharma- ceutically acceptable salt thereof, where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -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. [000182] In some embodiments, the compound has formula (III-Ij): [ka] or a pharma- ceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; R 21 is independently halogen, alkyl, hydroxyl, or cyano. [000183] In some embodiments, the compound has formula (III-Ik): [ka] or a pharma- ceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, or 2; R 21 Each of is independently halogen, alkyl, hydroxyl, or cyano. [000184] In some embodiments, R 21 In some embodiments, m is 1 and n is 1. [000185] In some embodiments, the compound has formula (III-IL): [ka] or a pharma- ceutically acceptable salt thereof. [000186] In some embodiments, the compound has the formula (III-Im): [ka] or a pharma- ceutically acceptable salt thereof. [000187] In some embodiments, the compound of formula (III-I) is of formula (III-In) or formula (III-Io): [ka] or a pharma- ceutically acceptable salt thereof, where s is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -O-, -S-, -N-, or N(R N )-where R N is independent , 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 3~6carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R GA The groups, together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring. Formula (III-II) [000188] In some embodiments, the compound has the formula (III-IIa): [ka] or a pharma- ceutically acceptable salt thereof. [000189] In some embodiments, the compound has the formula (III-IIb): [ka] or a pharma- ceutically acceptable salt thereof. [000190] In some embodiments, the compound has the formula (III-IIc): [ka] or a pharma- ceutically acceptable salt thereof. [000191] In some embodiments, the compound has the formula (III-IId): [ka] or a pharma- ceutically acceptable salt thereof. [000192] In some embodiments, the compound has the formula (III-IIe): [ka] or a pharma- ceutically acceptable salt thereof. [000193] In some embodiments, the compound has the formula (III-IIf): [ka] or a pharma- ceutically acceptable salt thereof, Here, R 1 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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 A1each 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; and n is 0, 1, 2, or 3. [000194] In some embodiments, the compound has the formula (III-IIg): [ka] or a pharma- ceutically acceptable salt thereof, R 1 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1, -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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; and n is 0, 1, 2, or 3. [000195] In some embodiments, the compound has the formula (III-IIh): [ka] or a pharma- ceutically acceptable salt thereof, where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -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. [000196] In some embodiments, the compound has the formula (III-IIi): [ka] or a pharma- ceutically acceptable salt thereof, where u is 0, 1, or 2, and each X is independently -C(R N )-, -C(R N ) 2 -, -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. [000197] In some embodiments, the compound has the formula (III-IIj): [ka] or a pharma- ceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, or 2; R 21 is independently halogen, alkyl, hydroxyl, or cyano. [000198] In some embodiments, the compound has the formula (III-IIk): [ka] or a pharma- ceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; R 21 Each of is independently halogen, alkyl, hydroxyl, or cyano. [000199] In some embodiments, R 21 In some embodiments, m is 1 and n is 1. [000200] In some embodiments, the compound has the formula (III-IIL): [ka] or a pharma- ceutically acceptable salt thereof. [000201] In some embodiments, the compound has the formula (III-IIm): [ka] or a pharma- ceutically acceptable salt thereof. [000202] In some embodiments, the compound has formula (III-IIn) or formula (III-IIo): [ka] or a pharma- ceutically acceptable salt thereof, where 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 C1-6 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 3~6carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to oxygen, a nitrogen protecting group when attached to nitrogen, or two R GA The groups, together with the intervening atoms, form a substituted or unsubstituted heterocyclyl or heteroaryl ring. [000203] 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. [000204] In some embodiments, 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(RGA )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. [000205] In some embodiments, 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)RGA , -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 or n is 0, 1, 2, 3, 4, or 5. [000206] In one aspect, the compound of formula (IV-I): [ka] or a pharma- ceutically acceptable salt thereof, In formula (IV-I), R 5 is hydrogen or substituted or unsubstituted 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 heptane, aryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl; 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 1a , R 1b , R 12a , R 12b , R 2a , R 2b , R 4a , R 4b , R 11a , R 11b , R 18a , and R 18b 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 1a and R 1b , R 12a and R 12b , R 2a and R 2b , R 4a and R 4b , R 11a and R 11b , and R 18a and R 18b taken together to form an oxo (=O) group; R 16a , R 16b , R 17a , and R 17b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -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 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 or double bond, and when a double bond is present, R 5and R 6a or R 6b One of them does not exist. [000207] In one aspect, the compound of formula (IV-I): [ka] or a pharma- ceutically acceptable salt thereof, In formula (IV-I), R 5 is hydrogen or substituted or unsubstituted methyl, or [ka] If is a double bond, R 5 does not exist; R 3 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 19 is a substituted or unsubstituted alkyl (e.g., substituted or unsubstituted C 1 -C 6 alkyl), substituted or unsubstituted alkenyl (e.g., substituted or unsubstituted C 2 -C 6 alkenyl), or substituted or unsubstituted alkynyl; 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 1a , R 1b , R 12a , R 12b , R 2a , R 2b , R4a , R 4b , R 11a , R 11b , R 18a , and R 18b 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 1a and R 1b , R 12a and R 12b , R 2a and R 2b , R 4a and R 4b , R 11a and R 11b , and R 18a and R 18b taken together to form an oxo (=O) group; R 16a , R 16b , R 17a , and R 17b each independently represents hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SRA1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R A2 , -OS(=O) 2 OR A1 , -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; RA2 is a 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; wherein

Chem.

Chem.

Chem.

Claims

[Claim 1] The invention described in the specification.

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