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] Citation of Related Applications This application is filed December 22, 2017, U.S. Provisional Patent Application No. 62 / 610,067, No. 62 / 611,977 (filed December 29, 2017), No. 62 / 765,16 No. 4 (filed on August 17, 2018), No. 62 / 612,067 (December 2, 2017) 9), No. 62 / 728,499 (filed September 7, 2018), No. 62 / 75 4,977 (filed November 2, 2018), 62 / 612,070 (2017) 62 / 612,164 (filed December 29, 2017), Claims priority of No. 62 / 737,559 (filed September 27, 2018). these The entirety is incorporated herein by reference. [Background technology]

[0002] Background of the invention Cerebral excitability is defined as the level of arousal of an animal on a continuum ranging from coma to convulsions and is variable. controlled by different neurotransmitters. In general, neurotransmitters cross neuronal membranes involved in the control of the ionic conductance. At rest, neuronal membranes are approximately -70 With a potential (or membrane voltage) of mV, the cell interior is negative with respect to the cell exterior. potential (voltage) is the ion (K + , Na + , Cl - , an organic anion ) is the result of balance. Neurotransmitters are stored in presynaptic vesicles and stimulate neuronal activity. Released under the influence of electrodynamics. -70 mV to -5 when released into the synaptic cleft A potential change to 0 mV occurs. This action is similar to that of Na + An agent that increases membrane permeability to ions It is mediated by postsynaptic nicotinic receptors stimulated by cetylcholine. low The lowered membrane potential stimulates neuronal excitability in the form of postsynaptic action potentials.

[0003] In the case of the GABA receptor complex (GRC), its effects on brain excitability depend on the neurotransmitter mediated by gamma-aminobutyric acid (GABA). Up to 40% neurons in the brain However, since GABA is used as a neurotransmitter, GABA has an effect on the excitability of the whole brain. Significant impact. GABA regulates the conductance of chloride ions across neuronal membranes control the excitability of individual neurons by controlling GABA on GRC Interaction with the recognition site directs the chloride ion down the electrochemical gradient of the GRC. promotes flow into cells. Intracellular elevation of the level of this anion is associated with transmembrane potential overload. cause polarization and reduce the sensitivity of neurons to excitatory inputs (i.e., neuron excitability is reduced). In other words, the higher the chloride ion concentration in the neuron, the , brain excitability and arousal levels decrease.

[0004] GRC is well documented to be involved in mediating anxiety, seizure activity and sedation. servant GABA and drugs that act like or potentiate the action of GABA substances (e.g. therapeutically useful barbiturates and benzodiazepines (BZ), e.g. Valium®) by interacting with specific regulatory sites on GRC provide its therapeutically useful effects. Accumulating evidence now suggests that GRC is In addition to the azepine and barbiturate binding sites, separate Suggested to contain parts. See, for example, Lan, N.C. et al., Neurochem. See S. (1991) 16:347-356.

[0005] Neuroactive steroids can occur endogenously. Most Potent Endogenous Neuroactive Steroid is 3α-hydroxy-5-reduced pregnan-20-one and 3α-21-dihydro xy-5-reduced pregnan-20-ones (each of which is a hormonal steroid metabolites of gesterone and deoxycorticosterone). These steroid bills The ability of metabolites to alter brain excitability was recognized in 1986 (Majewska, M.D. et al., Science 232:1004-1007 (1986); Harris on, N.L. et al., J Pharmacol. Exp. Ther. 241:346-35. 3 (1987)). Modulators of brain excitability and agents for the prevention and treatment of CNS-related diseases There is a need for new and improved compounds that act as described herein The compounds, compositions and methods 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, M.D. et al., Science 232:1004-1007 (1986) [Non-Patent Document 3] Harrison, N.L. et al., J Pharmacol. Exp. Ther. 241:346-353 (1987) [Outline of the invention] [Means for solving the problem]

[0007] Provided herein are compounds designed to act as GABA modulators. one In some embodiments, such compounds are useful as therapeutic agents for treating CNS-related disorders. is assumed to be

[0008] In one aspect, provided herein is Formula (I-I) [formation] or a pharmaceutically acceptable salt thereof.

[0009] In some embodiments, the compound has the formula (I-Ia) [formation] or a pharmaceutically acceptable salt thereof.

[0010] In some embodiments, the compound has the formula (I-Iab) [formation] or a pharmaceutically acceptable salt thereof.

[0011] In some embodiments, the compound is of Formula (I-Ib) or Formula (I-Ibb) [formation] or a pharmaceutically acceptable salt thereof.

[0012] In some embodiments, the compound is of Formula (I-Ic) or Formula (I-Icb) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-Id) or Formula (I-Idb) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-Ie) or Formula (I-Ieb) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-If) or Formula (I-Ifb) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-Ig) or Formula (I-Igb) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-Ih) or Formula (I-Ihb) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-Ii) or Formula (I-Iib) [formation] or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (I-Ik) or Formula (I-Ikb) [formation] or a pharmaceutically acceptable salt thereof. In one aspect, provided herein is Formula (I-II): [formation] or a pharmaceutically acceptable salt thereof.

[0013] In some embodiments, the compound is of Formula (I-IIa) or Formula (I-IIab) [formation] or a pharmaceutically acceptable salt thereof.

[0014] In some embodiments, the compound is of Formula (I-IIb) or Formula (I-IIbb) [formation] or a pharmaceutically acceptable salt thereof.

[0015] In some embodiments, the compound is of Formula (I-IId) or Formula (I-IIdb) [formation] or a pharmaceutically acceptable salt thereof.

[0016] In some embodiments, the compound is of Formula (I-IIe) or Formula (I-IIeb) [formation] or a pharmaceutically acceptable salt thereof.

[0017] In some embodiments, the compound is of Formula (I-IIf) or Formula (I-IIfb) [formation] or a pharmaceutically acceptable salt thereof.

[0018] In some embodiments, the compound is of Formula (I-IIg) or Formula (I-IIgb) [formation] or a pharmaceutically acceptable salt thereof.

[0019] In some embodiments, the compound is of Formula (I-IIh) or Formula (I-IIhb) [formation] or a pharmaceutically acceptable salt thereof.

[0020] In some embodiments, the compound is of Formula (I-IIi) or Formula (I-IIIb) [formation] or a pharmaceutically acceptable salt thereof.

[0021] In some embodiments, the compound is of formula (I-IIj) [formation] or a pharmaceutically acceptable salt thereof.

[0022] In one aspect, provided herein is Formula (II-I) [formation] or a pharmaceutically acceptable salt thereof.

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

[0024] In some embodiments, the compound is of formula (II-Ia), (II-Iab) or (II- Iac) [formation] or a pharmaceutically acceptable salt thereof.

[0025] In some embodiments, the compound is of formula (II-Ib), (II-Ibb) or (II- Ibc) [formation] or a pharmaceutically acceptable salt thereof.

[0026] In some embodiments, the compound is of formula (II-Ic), (II-Icb) or (II- Icc) [formation] or a pharmaceutically acceptable salt thereof.

[0027] In some embodiments, the compound is of formula (II-Ie), (II-Ieb) or (II- IEC) [formation] or a pharmaceutically acceptable salt thereof.

[0028] In some embodiments, the compound is of formula (II-Ig), (II-Igb) or (II- Igc) [formation] or a pharmaceutically acceptable salt thereof.

[0029] In some embodiments, the compound is of formula (II-Ieg), (II-Iegb) or (I I-Iegc) [formation] or a pharmaceutically acceptable salt thereof.

[0030] In some embodiments, the compound is of formula (II-Ih), (II-Ihb) or (II- Ihc) [formation] or a pharmaceutically acceptable salt thereof.

[0031] In some embodiments, the compound is of formula (II-Ii), (II-Iib) or (II- IC) [formation] or a pharmaceutically acceptable salt thereof.

[0032] In some embodiments, the compound is of formula (II-IIa) or (II-IIab) [formation] or a pharmaceutically acceptable salt thereof.

[0033] In some embodiments, the compound is of formula (II-IIb) or (II-IIbb) [formation] or a pharmaceutically acceptable salt thereof.

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

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

[0036] In some embodiments, the compound has the formula (II-IIg) or (II-IIgb) [formation] or a pharmaceutically acceptable salt thereof.

[0037] In some embodiments, the compound has the formula (II-IIh) or (II-IIhb) [formation] or a pharmaceutically acceptable salt thereof.

[0038] In some embodiments, the compound is of formula (II-IIi) or (II-IIIb) [formation] or a pharmaceutically acceptable salt thereof.

[0039] In one aspect, provided herein is formula (III-I) [formation] or a pharmaceutically acceptable salt thereof.

[0040] In some embodiments, the compound is of Formula (III-Ia) [formation] or a pharmaceutically acceptable salt thereof.

[0041] In some embodiments, the compound is of Formula (III-Ib) [formation] or a pharmaceutically acceptable salt thereof.

[0042] In some embodiments, the compound is of formula (III-Ic) [formation] or a pharmaceutically acceptable salt thereof.

[0043] In some embodiments, the compound has the formula (III-Id) [formation] or a pharmaceutically acceptable salt thereof.

[0044] In some embodiments, the compound is of formula (III-Ie) [formation] or a pharmaceutically acceptable salt thereof.

[0045] In some embodiments, the compound has the formula (III-If) [formation] or a pharmaceutically acceptable salt thereof.

[0046] In some embodiments, the compound is of formula (III-Ig) [formation] or a pharmaceutically acceptable salt thereof.

[0047] In some embodiments, the compound is of formula (III-Ih) [formation] or a pharmaceutically acceptable salt thereof.

[0048] In some embodiments, the compound is of formula (III-Ii) [formation] or a pharmaceutically acceptable salt thereof.

[0049] In some embodiments, the compound is of formula (III-Ij) [formation] or a pharmaceutically acceptable salt thereof.

[0050] In some embodiments, the compound is of formula (III-Ik) [formation] or a pharmaceutically acceptable salt thereof.

[0051] In some embodiments, the compound has the formula (III-IL) [formation] or a pharmaceutically acceptable salt thereof.

[0052] In some embodiments, the compound has the formula (III-Im) [formation] or a pharmaceutically acceptable salt thereof.

[0053] In some embodiments, the compound is of Formula (III-In) or Formula (III-Io) [formation] or a pharmaceutically acceptable salt thereof.

[0054] In one aspect, provided herein is formula (III-II): [formation] or a pharmaceutically acceptable salt thereof.

[0055] In some embodiments, the compound is of formula (III-IIa) [formation] or a pharmaceutically acceptable salt thereof.

[0056] In some embodiments, the compound is of Formula (III-IIb) [formation] or a pharmaceutically acceptable salt thereof.

[0057] In some embodiments, the compound is of formula (III-IIc) [formation] or a pharmaceutically acceptable salt thereof.

[0058] In some embodiments, the compound is of formula (III-IId) [formation] or a pharmaceutically acceptable salt thereof.

[0059] In some embodiments, the compound is of formula (III-IIe) [formation] or a pharmaceutically acceptable salt thereof.

[0060] In some embodiments, the compound is of formula (III-IIf) [formation] or a pharmaceutically acceptable salt thereof.

[0061] In some embodiments, the compound is of formula (III-IIg) [formation] or a pharmaceutically acceptable salt thereof.

[0062] In some embodiments, the compound is of formula (III-IIh) [formation] or a pharmaceutically acceptable salt thereof.

[0063] In some embodiments, the compound is of formula (III-IIi) [formation] or a pharmaceutically acceptable salt thereof.

[0064] In some embodiments, the compound is of formula (III-IIj) [formation] or a pharmaceutically acceptable salt thereof.

[0065] In some embodiments, the compound is of formula (III-IIk) [formation] or a pharmaceutically acceptable salt thereof.

[0066] In some embodiments, the compound has the formula (III-IIL) [formation] or a pharmaceutically acceptable salt thereof.

[0067] In some embodiments, the compound is of formula (III-IIm) [formation] or a pharmaceutically acceptable salt thereof.

[0068] In some embodiments, the compound is of Formula (III-IIn) or Formula (III-IIo) [formation] or a pharmaceutically acceptable salt thereof.

[0069] In one aspect, provided herein is Formula (IV-I): [formation] or a pharmaceutically acceptable salt thereof.

[0070] In some embodiments, the compound is of Formula (IV-Ia) [formation] or a pharmaceutically acceptable salt thereof.

[0071] In some embodiments, the compound is of Formula (IV-Ib) [formation] or a pharmaceutically acceptable salt thereof.

[0072] In some embodiments, the compound is of formula (IV-Ic) [formation] or a pharmaceutically acceptable salt thereof

[0073] In some embodiments, the formula (IV-Id) [formation] or a pharmaceutically acceptable salt thereof.

[0074] In some embodiments, the compound is of formula (IV-Ie) [formation] or a pharmaceutically acceptable salt thereof.

[0075] In some embodiments, the compound of formula (IV-I) is represented by formula (IV-If) [formation] or a pharmaceutically acceptable salt thereof.

[0076] In some embodiments, the compound of formula (IV-I) is represented by formula (IV-Ig) [formation] or a pharmaceutically acceptable salt thereof.

[0077] In some embodiments, the compound is of formula (IV-Ih) [formation] or a pharmaceutically acceptable salt thereof.

[0078] In some embodiments, the compound is of formula (IV-Ii) [formation] or a pharmaceutically acceptable salt thereof.

[0079] In some embodiments, the compound is of formula (IV-Ij) [formation] or a pharmaceutically acceptable salt thereof.

[0080] In some embodiments, the compound is of formula (IV-Ik) [formation] or a pharmaceutically acceptable salt thereof.

[0081] In some embodiments, the compound is of formula (IV-IL) [formation] or a pharmaceutically acceptable salt thereof.

[0082] In some embodiments, the compound has the formula (IV-Im) [formation] or a pharmaceutically acceptable salt thereof.

[0083] In some embodiments, the compound is of Formula (IV-In) or Formula (IV-Io) [formation] or a pharmaceutically acceptable salt thereof.

[0084] In one aspect, Formula (IV-II): [formation] Provided herein are compounds of

[0085] In some embodiments, the compound is of Formula (IV-IIa) [formation] or a pharmaceutically acceptable salt thereof.

[0086] In some embodiments, the compound is of Formula (IV-IIb) [formation] or a pharmaceutically acceptable salt thereof.

[0087] In some embodiments, the compound is of Formula (IV-IIc) [formation] or a pharmaceutically acceptable salt thereof.

[0088] In some embodiments, the compound is of formula (IV-IId) [formation] or a pharmaceutically acceptable salt thereof.

[0089] In some embodiments, the compound is of Formula (IV-IIe) [formation] or a pharmaceutically acceptable salt thereof.

[0090] In some embodiments, the compound is of formula (IV-IIf) [formation] or a pharmaceutically acceptable salt thereof.

[0091] In some embodiments, the compound has the formula (IV-IIg) [formation] or a pharmaceutically acceptable salt thereof.

[0092] In some embodiments, the compound is of formula (IV-IIh) [formation] or a pharmaceutically acceptable salt thereof.

[0093] In some embodiments, the compound is of Formula (IV-IIi) [formation] or a pharmaceutically acceptable salt thereof.

[0094] In some embodiments, the compound is of formula (IV-IIj) [formation] or a pharmaceutically acceptable salt thereof.

[0095] In some embodiments, the compound is of formula (IV-IIk) [formation] or a pharmaceutically acceptable salt thereof.

[0096] In some embodiments, the compound is of formula (IV-IIL) [formation] or a pharmaceutically acceptable salt thereof.

[0097] In some embodiments, the compound is of formula (IV-IIm) [formation] or a pharmaceutically acceptable salt thereof.

[0098] In some embodiments, the compound is of Formula (IV-IIn) or Formula (IV-IIo) [formation] or a pharmaceutically acceptable salt thereof.

[0099] In one aspect, formulas (IV-III) [formation] or a pharmaceutically acceptable salt thereof is provided herein.

[0100] In one aspect, provided herein is Formula (V-I): [formation] or a pharmaceutically acceptable salt thereof.

[0101] In some embodiments, the compound is of Formula (V-Ia) [formation] or a pharmaceutically acceptable salt thereof.

[0102] In some embodiments, the compound is of Formula (V-Ib) [formation] or a pharmaceutically acceptable salt thereof.

[0103] In some embodiments, the compound is of formula (V-Ic) [formation] or a pharmaceutically acceptable salt thereof.

[0104] In some embodiments, the compound has the formula (V-Id) [formation] or a pharmaceutically acceptable salt thereof.

[0105] In some embodiments, the compound has the formula (V-Ie) [formation] or a pharmaceutically acceptable salt thereof.

[0106] In some embodiments, the compound has the formula (V-If) [formation] or a pharmaceutically acceptable salt thereof.

[0107] In some embodiments, the compound is of formula (V-Ig) [formation] or a pharmaceutically acceptable salt thereof.

[0108] In some embodiments, the compound is of formula (V-Ih) [formation] or a pharmaceutically acceptable salt thereof.

[0109] In some embodiments, the compound is of formula (V-Ii) [formation] or a pharmaceutically acceptable salt thereof.

[0110] In some embodiments, the compound is of formula (V-Ij) [formation] or a pharmaceutically acceptable salt thereof.

[0111] In some embodiments, the compound has the formula (V-Ik) [formation] or a pharmaceutically acceptable salt thereof.

[0112] In some embodiments, the compound has the formula (V-IL) [formation] or a pharmaceutically acceptable salt thereof.

[0113] In some embodiments, the compound has the formula (V-Im) [formation] or a pharmaceutically acceptable salt thereof.

[0114] In some embodiments, the compound is of Formula (V-In) or Formula (V-Io) [formation] or a pharmaceutically acceptable salt thereof.

[0115] In one aspect, provided herein is Formula (V-II): [formation] or a pharmaceutically acceptable salt thereof.

[0116] In some embodiments, the compound is of Formula (V-IIa) [formation] or a pharmaceutically acceptable salt thereof.

[0117] In some embodiments, the compound is of Formula (V-IIb) [formation] or a pharmaceutically acceptable salt thereof.

[0118] In some embodiments, the compound is of Formula (V-IIc) [formation] or a pharmaceutically acceptable salt thereof.

[0119] In some embodiments, the compound is of formula (V-IId) [formation] or a pharmaceutically acceptable salt thereof.

[0120] In some embodiments, the compound has the formula (V-IIe) [formation] or a pharmaceutically acceptable salt thereof.

[0121] In some embodiments, the compound has the formula (V-IIf) [formation] or a pharmaceutically acceptable salt thereof.

[0122] In some embodiments, the compound has the formula (V-IIg) [formation] or a pharmaceutically acceptable salt thereof.

[0123] In some embodiments, the compound is of formula (V-IIh) [formation] or a pharmaceutically acceptable salt thereof.

[0124] In some embodiments, the compound is of Formula (V-IIi) [formation] or a pharmaceutically acceptable salt thereof.

[0125] In some embodiments, the compound is of formula (V-IIj) [formation] or a pharmaceutically acceptable salt thereof.

[0126] In some embodiments, the compound is of formula (V-IIk) [formation] or a pharmaceutically acceptable salt thereof.

[0127] In some embodiments, the compound has the formula (V-IIL) [formation] or a pharmaceutically acceptable salt thereof.

[0128] In some embodiments, the compound has the formula (V-IIm) [formation] or a pharmaceutically acceptable salt thereof.

[0129] In some embodiments, the compound is of Formula (V-IIn) or Formula (V-IIo) [formation] or a pharmaceutically acceptable salt thereof.

[0130] In one aspect, formula (V-III) [formation] or a pharmaceutically acceptable salt thereof is provided herein.

[0131] In some embodiments, the pharmaceutical composition comprises a compound described herein or a pharmaceutically Including acceptable salts and pharmaceutically acceptable excipients.

[0132] In some embodiments, a CNS-related disorder is treated in a subject in need of treatment for a CNS-related disorder. A method of treating harm, comprising administering to a subject an effective amount of a compound described herein or a pharmacy thereof Methods are provided herein comprising the step of administering a pharmaceutically acceptable salt. some embodiments In , CNS-related disorders include sleep disorders, mood disorders, schizophrenia spectrum disorders, and convulsive disorders. , memory and / or cognitive impairment, movement disorders, personality disorders, autism spectrum disorders, pain pain, traumatic brain injury, vascular disease, substance abuse disorders and / or withdrawal syndrome, tinnitus, or He has status epilepticus. In some embodiments, the CNS-related disorder is depression. one In some embodiments, the CNS-related disorder is postpartum depression. In some embodiments, CNS Recurrent disorder is major depressive disorder. In some embodiments, major depressive disorder is Depressive disorder. In some embodiments, the major depressive disorder is severe major depressive disorder be.

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

[0134] In one aspect, compounds described herein (e.g., Formula (I-I), Formula (I-I I), formula (II-I), formula (II-II), formula (III-I), formula (III-II), formula (IV-I), formula (IV-II), formula (IV-III), formula (V-I), formula (V-II) or compounds of formula (V-III)) are provided herein.

[0135] In one aspect, compounds described herein (e.g., Formula (I-I), Formula (I-I I), formula (II-I), formula (II-II), formula (III-I), formula (III-II), formula (IV-I), formula (IV-II), formula (IV-III), formula (V-I), formula (V-II) or a compound of formula (V-III)) or a pharmaceutically acceptable salt thereof, and a pharmaceutically Pharmaceutical compositions containing acceptable excipients are provided herein. in certain embodiments In, the compounds of the invention are provided in an effective amount in a pharmaceutical composition. Certain embodiments In, the compounds of the invention are provided in therapeutically effective amounts. In certain embodiments, The compounds of the invention are provided in prophylactically effective amounts.

[0136] Compounds of the invention as described herein are, in certain embodiments, for example GABA A GABA regulation that effects receptors in a positive or negative manner act as a factor. Such compounds are GABA A by its ability to modulate receptors has CNS activity as a regulator of central nervous system (CNS) excitability mediated by expected to be Thus, in another aspect, in a subject in need of treatment for a CNS-related disorder, CN A method of treating an S-related disorder is provided, comprising administering to the subject an effective amount of a drug of the invention. administering the compound. In certain embodiments, the CNS-related disorder is sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, memory and / or cognitive disorders injury, movement disorder, personality disorder, autism spectrum disorder, pain, traumatic brain injury, vascular disease, material Quality abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus. a In certain embodiments, the CNS-related disorder is depression. In certain embodiments and the CNS-related disorder is postpartum depression. In certain embodiments, CNS-related disorders is major depressive disorder. In certain embodiments, major depressive disorder is moderate Major depressive disorder. In certain embodiments, major depressive disorder is severe major depression It is a pathological disorder. In certain embodiments, the compound is administered orally, subcutaneously, intravenously administration, or administered intramuscularly. In certain embodiments, the compound is administered orally. be. In certain embodiments, the compound is administered chronically. in certain embodiments , the compound is administered continuously, eg, by continuous intravenous infusion. [Mode for carrying out the invention]

[0137] Detailed Description of Specific Embodiments of the Invention As generally described herein, the present invention provides, for example, as GABA modulators Compounds designed to act are provided. In certain embodiments, such compounds The object is a CNS-related disorder (e.g., a disorder described herein, e.g., postpartum depression or It is envisioned that it will be useful as a therapeutic agent for treating depression, such as depressive disorders. definition chemical definition

[0138] Definitions of specific functional groups and chemical terms are described in detail below. A chemical element has an elemental cycle Table (CAS version, Handbook of Chemistry and Physics sics, 75th edition, inner cover) and specific functional groups are generally described therein. Defined as listed. In addition, general rules of organic chemistry, as well as specific functional moieties and reactivity according to Thomas Sorrell, Organic Chemistry ,University Science Books,Sausalito,1999 ;Smith and March, March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Meth. ods of Organic Synthesis, 3rd ed., Cambridge U. University Press, Cambridge, 1987.

[0139] Isomers (e.g., stereoisomers) can be separated by methods known to those skilled in the art (chiral high pressure liquid chromatography). can be isolated from mixtures by physics (HPLC) as well as chiral salt formation) or the preferred isomer may be prepared by asymmetric synthesis. For example, Jacques et al. , Enantiomers, Racemates and Resolutions (W iley Interscience, New York, 1981); Wilen et al. Tetrahedron 33:2725 (1977); Eliel, Stereoch emistry of carbon compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Ag. ents and Optical Resolutions p.268(E.L.E. Liel editor, Univ. of Notre Dame Press, Notre Da See Me, IN 1972). The present invention further provides compounds described herein as individual isomers substantially free of other isomers and / or as various isomers As a mixture, it contains

[0140] “Stereoisomer”: having the same molecular formula but differing in the nature or order of bonding of the atoms or in space; It should also be understood that compounds that differ in the arrangement of the atoms in . Isomers that differ in the arrangement of their atoms in space are termed "stereoisomers". mirror images of each other Stereoisomers that are not are termed "diastereomers" and are superimposable on each other. Those which are mirror images which cannot be separated are termed "enantiomers". For example, if the compound is asymmetric If it has a core, it is attached to four different groups, allowing a set of enantiomers is. Enantiomers can be characterized by the absolute configuration of their asymmetric centers, and or the molecule is represented by the R and S ordering rules of represented by the way it rotates the plane of polarized light, and can be dextrorotatory or levorotatory (i.e., respectively (+) or (-)-isomer). Chiral compounds are separated into individual enantiomers or as mixtures thereof. equal proportions of enantiomers A mixture containing mers is called a "racemic mixture".

[0141] As used herein, an enantiomerically pure compound refers to the other enantiomers of the compound. substantially free of omers or stereoisomers (ie, enantiomeric excess). In other words If the 'S' form of the compound is substantially free of the 'R' form of the compound, then the 'R' form of the ena There is an excess of thiomers. The term "enantiomerically pure" or "pure enantiomers" -” means that the compound contains more than 75% by weight, more than 80% by weight, more than 85% by weight, more than 90% by weight, 91% by weight, % 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, 9 more than 9.5% by weight, more than 99.6% by weight, more than 99.7% by weight, more than 99.8% by weight or 99. It means containing more than 9% by weight of the enantiomer. In certain embodiments, the weight is Based on the total weight of all enantiomers or stereoisomers of the compound.

[0142] As used herein, the term "diastereomeric purity" refers to the indicated compound and its Compounds with the indicated absolute stereochemistry expressed as a percentage of the total amount of diastereomers refers to the amount of The term "diastereomerically pure" means greater than 75% by weight of a compound more than 80% by weight more than 85% by weight more than 90% by weight more than 91% by weight greater than 92% by weight greater than 93% by weight greater than 94% by weight greater than 95% by weight 96% by weight, 97% by weight, 98% by weight, 98.5% by weight more than 99% by weight more than 99.2% by weight more than 99.5% by weight 99 greater than 6% by weight, greater than 99.7% by weight, greater than 99.8% by weight, or 99%. It is meant to contain more than 9% by weight of its diastereomer. diastereomeric purity and and methods for determining enantiomeric purity are well known in the art. The diastereomeric purity is , any analytical method capable of quantitatively distinguishing between a compound and its diastereomers (high high performance liquid chromatography (HPLC), etc.).

[0143] In the compositions provided herein, enantiomerically pure compounds are free from other active ingredients. may be present with ingredients or inert ingredients. For example, enantiomerically pure R-compounds A pharmaceutical composition comprising, for example, about 90% excipients and about 10% enantiomerically pure It can contain neat R-compounds. In certain embodiments, enantiomers in such compositions A merically pure R-compound is, for example, at least about 95% by weight relative to the total weight of the compound. of R-compounds and up to about 5% by weight of S-compounds. For example, the enantiomer A pharmaceutical composition comprising a substantially pure S-compound, for example, contains about 90% excipient and about 10% % enantiomerically pure S-compounds. In certain embodiments, such An enantiomerically pure S-compound in such a composition is, for example, may contain at least about 95% by weight of the S-compound and at most about 5% by weight of the R-compound. be. In certain embodiments, the active ingredient is formulated with minor excipients or carriers. or formulated without excipients or carriers.

[0144] The articles ``a'' and ``an'' have one or more grammatical objects of the article ( ie, at least one). as an example ``an analogue'' means one analogue or more than one analogue means analog.

[0145] When a range of values ​​is recited, each value and subrange within that range is meant to be included. is illustrated. 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 Archi of is intended to encompass all

[0146] The following terms are intended to have the meanings set forth below for them, and in this It is helpful in understanding the specification and the intended scope of the invention.

[0147] “Alkyl” means a linear or branched saturated hydrocarbon group having 1 to 20 carbon atoms Radical (“C 1~20 Alkyl”). In some embodiments, alkyl The group has 1 to 12 carbon atoms ("C 1~12 alkyl”). in some embodiments , the alkyl group has 1 to 10 carbon atoms ("C 1~10 alkyl”). In some embodiments, the alkyl group has 1-9 carbon atoms (“C 1~9 a Rukir"). In some embodiments, the alkyl group has 1-8 carbon atoms ( "C 1~8 alkyl”). In some embodiments, the alkyl group has 1-7 carbon atoms. have children ("C 1~7 alkyl”). In some embodiments, alkyl groups range from 1 to having 6 carbon atoms ("C 1~6 Archi le”). In some embodiments, the alkyl group has 1-5 carbon atoms (“C 1~5 alkyl”). In some embodiments, alkyl groups have 1-4 carbon atoms. have (“C 1~4 alkyl”). In some embodiments, the alkyl group has 1-3 carbon atoms (“C 1~3 alkyl”). In some embodiments, the alkyl group is , with 1 to 2 carbon atoms (“C 1~2 alkyl”). In some embodiments, Alkyl groups have one carbon atom (“C 1 alkyl”). in some embodiments , the alkyl group has 2 to 6 carbon atoms (“C 2~6 alkyl”). C. 1~6 a Examples of alkyl groups include methyl (C 1 ), ethyl (C 2 ), n-propyl (C 3 ), iso Propyl (C 3 ), n-butyl (C 4 ), tert-butyl (C 4 ), sec-butyl( C. 4 ), iso-butyl (C 4 ), n-pentyl (C 5 ), 3-pentanyl (C 5 ),a Mil (C 5 ), neopentyl (C 5 ), 3-methyl-2-butanyl (C 5 ), tertiary mesh Le (C 5 ) and n-hexyl (C 6 ). Further examples of alkyl groups are , n-heptyl (C 7 ), n-octyl (C 8 ) and the like. Unless otherwise specified and each occurrence of an alkyl group is independently optionally substituted, i.e. unsubstituted (“unsubstituted alkyl”) or one or more substituents; for example, 1-5 substituted with 1 substituent, 1 to 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 substituted C 1~10 Alkyl is. Common alkyl abbreviations include 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 ).

[0148] “Alkylene” refers to an alkyl group with two hydrogens removed to yield a divalent radical. and can be substituted or unsubstituted. Methylene (-C H. 2 -), ethylene (-CH 2 CH 2 -), propylene (-CH 2 CH 2 CH 2 -), ethylene (-CH 2 CH 2 CH 2 CH 2 -), pentylene (-CH 2 CH 2 CH 2 CH 2 C. H. 2 -), and hexylene (-CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 -) etc. include but are not limited to: Exemplary, e.g., one or more Substituted methylene (-CH(CH 3 )-, (-C(CH 3 ) 2 -), substituted ethylene (-CH(CH 3 )CH 2 -, -CH2 CH(CH 3 )-, -C(CH 3 ) 2 CH 2 -, -CH 2 C(CH 3 ) 2 -), replacement pro Pyrene(-CH(CH 3 )CH 2 CH 2 -, -CH 2 CH(CH 3 )CH 2 -, -CH 2 CH 2 CH(CH 3 )-, -C(CH 3 ) 2 CH 2 CH 2 -, -CH 2 C(CH 3 ) 2 C. H. 2 -, and -CH 2 CH 2 C(CH 3 ) 2 -), etc., but not limited to can't Where ranges or numbers of carbons are given for a particular alkylene group, A number or number is understood to refer to the range or number of carbons in a straight chain of divalent carbons. The alkylene group is , optionally substituted with one or more substituents described herein, or non- It can be replaced.

[0149] "Alkenyl" means 2 to 20 carbon atoms and 1 or more carbon -has 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 straight-chain or branched-chain hydrocarbon radicals (“C 2~2 0 alkenyl”). In certain embodiments, alkenyl is any It does not contain triple bonds. In some embodiments, alkenyl groups have 2-10 carbon atoms. have children ("C 2~10 alkenyl”). In some embodiments, the alkenyl group is having 2 to 9 carbon atoms (“C 2~9 alkenyl”). In some embodiments, Alkenyl groups have from 2 to 8 carbon atoms ("C 2~8 alkenyl”). some fruit In embodiments, alkenyl groups have from 2 to 7 carbon atoms ("C 2~7 alkeny le”). In some embodiments, the alkenyl group has 2-6 carbon atoms (" C. 2~6 alkenyl”). In some embodiments, alkenyl groups have 2-5 carbons has an atom (“C 2~5 alkenyl”). In some embodiments, the alkenyl group is having 2 to 4 carbon atoms (“C 2~4 alkenyl”). In some embodiments, Alkenyl groups have 2 to 3 carbon atoms ("C 2~3 alkenyl”). some fruit In embodiments, an alkenyl group has 2 carbon atoms ("C 2 alkenyl”). 1 One or more carbon-carbon double bonds may be present internally (e.g., 2-bute nil) or can be terminal (eg 1-butenyl). C. 2~4 Examples of alkenyl groups as ethenyl (C 2 ), 1-propenyl (C 3 ), 2-propenyl (C 3 ), 1- butenyl (C 4 ), 2-butenyl (C 4 ), butadienyl (C 4 ) and the like. C. 2~6 Examples of alkenyl groups include the C 2~4 alkenyl groups, as well as pentenyl ( C. 5 ), pentadienyl (C 5 ), hexenyl (C 6 ) and the like. alkenyl A further example is heptenyl (C 7 ), octenyl (C 8 ), octatrienyl (C 8 ) and the like. Unless otherwise specified, each occurrence of an alkenyl group is independently optionally substituted, i.e., unsubstituted (“unsubstituted alkenyl”), or one or more substituents, such as 1 to 5 substituents, 1 to 3 substituents or substituted with one substituent (“substituted alkenyl”). In certain embodiments, al A kenyl group is an unsubstituted C 2~10 It is alkenyl. In certain embodiments, the alkane Nyl groups are substituted C 2~10 It is alkenyl.

[0150] "Alkynyl" means 2 to 20 carbon atoms, 1 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 bond), the radical of a straight or branched hydrocarbon group (“C 2~20 a Lukynyl”). In certain embodiments, alkenyl is any double Does not include joins. In some embodiments, alkynyl groups contain 2-10 carbon atoms. have (“C 2~10 alkynyl”). In some embodiments, two alkynyl groups are have ~9 carbon atoms (“C 2~9 alkynyl”). In some embodiments, al A quinyl group has 2 to 8 carbon atoms (“C 2~8 alkynyl”). some implementations In embodiments, alkynyl groups have from 2 to 7 carbon atoms ("C 2~7 alkynyl" ). In some embodiments, alkynyl groups have 2-6 carbon atoms ("C 2 ~6 alkynyl”). In some embodiments, alkynyl groups have 2-5 carbon atoms ("C 2~5 alkynyl”). In some embodiments, two alkynyl groups are have ~4 carbon atoms (“C 2~4 alkynyl”). In some embodiments, al A quinyl group has 2 to 3 carbon atoms (“C 2~3 alkynyl”). some implementations In embodiments, an alkynyl group has 2 carbon atoms ("C 2 alkynyl”). even one or more carbon-carbon triple bonds may be present internally (e.g., 2-butynyl ) or terminally (eg 1-butynyl). C. 2~4 Examples of alkynyl groups are ethynyl (C 2 ), 1-propynyl (C 3 ), 2-propynyl (C 3 ), 1-buty Nil (C 4 ), 2-butynyl (C 4 ) and the like, but are not limited to these. C. 2~ 6 Examples of alkenyl groups include the C 2~4 alkynyl groups, as well as pentynyl (C 5 ), hexynyl (C 6 ) and the like. Further examples of alkynyls include heptini Le (C 7 ), octynyl (C 8 ) and the like. alkynyl unless otherwise specified Each occurrence of a group is independently optionally substituted, i.e., unsubstituted ("unsubstituted alkynyl”) or one or more substituents; for example, 1-5 substituents , substituted with 1 to 3 substituents or 1 substituent (“substituted alkynyl”). a particular In certain embodiments, an alkynyl group is an unsubstituted C 2~10 is alkynyl. certain In embodiments of the alkynyl group is substituted C 2~10 is alkynyl.

[0151] The term "heteroalkyl," as used herein, refers to one or more more (e.g., 1, 2, 3, or 4) heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus), wherein the one or more Heteroatoms are interposed between adjacent carbon atoms in the parent carbon chain and / or if one or more heteroatoms are inserted between the carbon atom and the parent molecule (i.e., between the points of attachment). Refers to an alkyl group, as defined herein, as defined herein. In certain embodiments, Heteroalkyl groups are groups of 1 to 10 carbon atoms and 1, 2, 3, or 4 heteroatoms. Saturated groups with 1~10 Alkyl”). In some embodiments , a heteroalkyl group has 1 to 9 carbon atoms and 1, 2, 3, or 4 heteroatoms saturated groups (“hetero C 1~9 alkyl”). In some embodiments, a heteroa Alkyl groups are saturated alkyl groups having from 1 to 8 carbon atoms and 1, 2, 3, or 4 heteroatoms. KM ("hetero C 1~8 alkyl”). In some embodiments, the heteroalkyl group is , saturated groups having 1 to 7 carbon atoms and 1, 2, 3, or 4 heteroatoms (“he Terror C 1~7 alkyl”). In some embodiments, the heteroalkyl group has 1-6 carbon atoms and 1, 2, or 3 heteroatoms ("heteroC 1~6 Archi le”). In some embodiments, the heteroalkyl group has 1-5 carbon atoms and 1 or a saturated group with two heteroatoms ("heteroC 1~5 alkyl”). Part of In embodiments, the heteroalkyl group has 1-4 carbon atoms and 1 or 2 heteroatoms. Saturated groups with 1~4 alkyl”). In some embodiments, hetero Alkyl groups are saturated groups having 1 to 3 carbon atoms and 1 heteroatom ("heteroC 1~3 alkyl”). In some embodiments, the heteroalkyl group has 1-2 carbons saturated groups with atoms and one heteroatom ("heteroC 1~2 alkyl”). one In some embodiments, the heteroalkyl group has 1 carbon atom and 1 heteroatom. saturated groups (“hetero C 1 alkyl”). In some embodiments, the heteroalkyl group is , a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms (“hetero C 2~ 6 alkyl”). Unless otherwise specified, each occurrence of a heteroalkyl group is independently is unsubstituted (“unsubstituted heteroalkyl”) or has one or more substituents (“substituted heteroalkyl”). In certain embodiments, heteroalkyl group is an unsubstituted hetero C 1~10 is alkyl. In certain embodiments, heteroal A alkyl group is a substituted heteroC 1~10 is alkyl.

[0152] "Aryl" means 6 to 14 ring carbon atoms and 0 heteroatoms provided in an aromatic ring system monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring systems ( for example, with 6, 10 or 14 π-electrons shared in a cyclic arrangement. Cull ("C 6~14 aryl”). In some embodiments, the aryl group is , with 6 ring carbon atoms (“C 6 aryl"; e.g., phenyl). some embodiments , the aryl group has 10 ring carbon atoms ("C 10 aryl"; e.g. naphthyl, such as 1-naphthyl and 2-naphthyl). In some embodiments, aryl The group has 14 ring carbon atoms ("C 14 aryl"; e.g., anthracyl). " Aryl" means a carbosyl group containing one or more aryl rings as defined above. Also included are ring systems fused with lyl or heterocyclyl groups, where the linking radical or The point of attachment is on the aryl ring and in such cases the number of carbon atoms continues to be the aryl Indicate the number of carbon atoms in the ring system. Typical aryl groups include aceanthrylene, senaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as -indacene, s-indacene, indane, indene, naphthalene, octacene, octane phen, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, ntafen, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, Includes groups derived from pyrantrene, rubicene, triphenylene, and trinaphthalene but not limited to these. In particular, as aryl groups, phenyl, naphthyl, indenyl , and tetrahydronaphthyl. Each occurrence of an aryl group unless otherwise specified are independently optionally substituted, i.e., unsubstituted (“unsubstituted aryl” ) or substituted with one or more substituents (“substituted aryl”). a In certain embodiments, the aryl group is an unsubstituted C 6~14 is aryl. certain In embodiments of, the aryl group is substituted C 6~14 is aryl.

[0153] In certain embodiments, aryl groups are halo, C 1 ~C 8 Alkyl, C 1 ~C 8 haloalkyl, cyano, hydroxy, C 1 ~C 8 selected from alkoxy and amino , substituted with one or more groups.

[0154] Examples of representative substituted aryls include: [formation] where R 56 and R 57 can be hydrogen and one of R 56 and R 57 at least of 1, each independently, C 1 ~C 8 Alkyl, C 1 ~C 8 haloalkyl, 4-10 membered hete Rocyclyl, Alkanoyl, C 1 ~C 8 alkoxy, heteroaryloxy, alkyl mino, arylamino, heteroarylamino, NR 58 COR 59 , NR 58 SOR 5 9 , NR 58 SO 2 R. 59 , COO Alkyl, COO Aryl, CONR 58 R. 59 , C ONR 58 OR 59 , NR 58 R. 59 , SO 2 NR 58 R. 59 , S-alkyl, SO-alkyl Kill, SO 2 Alkyl, S aryl, SO aryl, SO 2 selected from aryl; or R 56 and R 57 are linked to form 5-8 atoms (N, O or contains one or more heteroatoms selected from the group S) cyclic ring (saturated or or unsaturated). R. 60 and R 61 are independently hydrogen, C 1 ~C 8 Archi L, C 1 ~C 4 haloalkyl, C 3 ~C 10 cycloalkyl, 4-10 membered heterocyclyl , C 6 ~C 10 aryl, substituted C 6 ~C 10 aryl, 5-10 membered heteroaryl or It is a substituted 5- to 10-membered heteroaryl.

[0155] "Fused aryl" means a second aryl or heteroaryl ring or Refers to an aryl that shares two ring carbons with a lyl or heterocyclyl ring.

[0156] "Heteroaryl" means ring carbon atoms and from 1 to 4 ring heteroatoms provided in an aromatic ring system 5- to 10-membered monocyclic or bicyclic 4n+2 aromatic ring systems (e.g., in a cyclic arrangement (having 6 or 10 π electrons shared in the The teroatoms are independently selected from nitrogen, oxygen and sulfur ("5- to 10-membered heteroali rule”). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment is It can be a carbon or nitrogen atom when valency permits. A heteroaryl bicyclic ring system is One or both rings may contain one or more heteroatoms. "heteroary is a carbosyl containing one or more heteroaryl rings as defined above; Including ring systems fused to aryl or heterocyclyl groups, where the point of attachment is a heteroaryl on a aryl ring and in such cases the number of ring members continues to be a heteroaryl ring system indicates the number of ring members in . "Heteroaryl" means heteroaryl as defined above. Also includes ring systems in which the aryl ring is fused to one or more aryl groups, where the point of attachment is present on an aryl or heteroaryl ring and in such cases the number of ring members indicates the number of ring members in a fused (aryl / heteroaryl) ring system. one ring Bicyclic heteroaryl groups that do not contain heteroatoms (e.g., indolyl, quinolinyl, bazolyl, etc.), the point of attachment may be on any ring, i.e., a ring containing a heteroatom (e.g. , 2-indolyl) or on a heteroatom-free ring (e.g., 5-indolyl) can.

[0157] In some embodiments, heteroaryl groups have ring carbon atoms and 1-4 ring hetero A 5- to 10-membered aromatic ring system in which atoms are provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur (“5-10 membered heteroaryl”); one In some embodiments, the heteroaryl group has ring carbon atoms and from 1 to 4 ring heteroatoms. is a 5- to 8-membered aromatic ring system provided for the aromatic ring system, wherein each heteroatom is independently are selected from nitrogen, oxygen and sulfur (“5- to 8-membered heteroaryl”). Partial implementation In form, heteroaryl groups are aromatic ring carbon atoms and from 1 to 4 ring heteroatoms. A 5- to 6-membered aromatic ring system, wherein each heteroatom is independently nitrogen , oxygen and sulfur (“5-6 membered heteroaryl”). In some embodiments 5- to 6-membered heteroaryl is a 1- to 3-ring group selected from nitrogen, oxygen and sulfur. It has a terrorism atom. In some embodiments, the 5-6 membered heteroaryl is nitrogen, oxygen and and 1 to 2 ring heteroatoms selected from sulfur. In some embodiments, 5 A ~6-membered heteroaryl has one ring heteroatom selected from nitrogen, oxygen and sulfur. do. Unless otherwise specified, each occurrence of a heteroaryl group is independently an optionally substituted substituted, i.e. unsubstituted (“unsubstituted heteroaryl”), or one or It is substituted with more substituents (“substituted heteroaryl”). in certain embodiments , the heteroaryl group is an unsubstituted 5- to 14-membered heteroaryl. a particular implementation In one aspect, the heteroaryl group is a substituted 5-14 membered heteroaryl.

[0158] Exemplary 5-membered heteroaryl groups containing one heteroatom include pyrrolyl, furanyl and thiophenyl. Examples with two heteroatoms Typical 5-membered heteroaryl groups include imidazolyl, pyrazolyl, oxazolyl, iso- Examples include, but are not limited to, xazolyl, thiazolyl and isothiazolyl. 3 Exemplary 5-membered heteroaryl groups containing five heteroatoms include triazolyl, oxadi Examples include, but are not limited to, azolyl and thiadiazolyl. 4 heteroatoms Exemplary 5-membered heteroaryl groups containing include, but are not limited to, tetrazolyl not. Exemplary 6-membered heteroaryl groups containing one heteroatom include pyridinyl but not limited to. Exemplary 6-membered heteroary containing two heteroatoms Groups include but are not limited to pyridazinyl, pyrimidinyl and pyrazinyl. not specified. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include: Examples include, but are not limited to, triazinyl and tetrazinyl, respectively. 1 Exemplary 7-membered heteroaryl groups containing heteroatoms include azepinyl, oxepinyl and and thiepinyl. Exemplary 5,6-Bicyclic Heteroa Examples of aryl groups include indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, Benzimidazolyl, Benzooxazolyl, Benzoisoxazolyl, Benzodia zolyl, benzothiazolyl, benzisothiazolyl, benzothiadiazolyl, indolidi Examples include, but are not limited to, nyl and purinyl. Exemplary 6,6-bicyclic hete Loaryl groups include naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl and quinazolinyl; is not limited to

[0159] Examples of representative heteroaryls include the following formulas: [formation] where each Z is carbonyl, N, NR 65 , 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- to 10-membered heteroaryl.

[0160] "Carbocyclyl" or "carbocyclic" means a non-aromatic ring system containing 3 to 10 ring carbon atoms ( "C 3~10 carbocyclyl”) and non-aromatic cyclic hydrocarbons with 0 heteroatoms It refers to the radical of the group. In some embodiments, 3 to 8 carbocyclyl groups ring carbon atoms (“C 3~8 carbocyclyl”). In some embodiments, the cal Bocyclyl groups have 3 to 6 ring carbon atoms ("C 3~6 carbocyclyl”). one In some embodiments, the carbocyclyl group has 3 to 6 ring carbon atoms ("C 3 ~6 carbocyclyl”). In some embodiments, the carbocyclyl group has 5-10 have a ring carbon atom (“C 5~10 carbocyclyl”). Exemplary C 3~6 Carbocycli 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, but are not limited to these. Exemplary C 3~8 As a carbocyclyl group, C above 3~6carbocyclyl group, and cycloheptyl (C 7 ), cycloheptenyl (C 7 ), cycloheptadienyl (C 7 ), cycloheptatrienyl (C 7 ), cycloo Cutyl (C 8 ), cyclooctenyl (C 8 ), bicyclo[2.2.1]heptanyl (C 7 ), bicyclo[2.2.2]octanyl (C 8 ), including but not limited to stomach. Exemplary C 3~10 As a carbocyclyl group, the above C 3~8 a carbocyclyl group, and cyclononyl (C 9 ), cyclononenyl (C 9 ), cyclodecyl (C 10 ), Clodecenyl (C 10 ), octahydro-1H-indenyl (C 9 ), decahydronaphtha Renyl (C 10 ), spiro[4.5]decanyl (C 10 ), but limited to these not specified. When the preceding examples are exemplified, in certain embodiments carbocyclyl The group may be monocyclic (“monocyclic carbocyclyl”) or may be a fused ring system, bridged ring system or contains spiro ring systems (e.g., bicyclic systems (“bicyclic carbocyclyl”)) and can be saturated or partially unsaturated. "Carbocyclyl" means carbocyclyl as defined above. a bocyclyl ring fused with one or more aryl or heteroaryl groups Also includes ring systems wherein the point of attachment is on the carbocyclyl ring and in such cases the carbon Numbers continue to indicate the number of carbons in the carbocyclic ring system. Carbocycli unless otherwise specified Each occurrence of a 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 Carbocyclyl. In certain embodiments, the carbocyclyl group is substituted C 3~10 Carbocyclyl.

[0161] In some embodiments, "carbocyclyl" is a single ring having 3-10 ring carbon atoms. A cyclic saturated carbocyclyl group (“C 3~10 cycloalkyl”). some embodiments In the cycloalkyl group has 3 to 8 ring carbon atoms ("C 3~8 Cycloa Rukir"). In some embodiments, cycloalkyl groups have 3-6 ring carbon atoms. have (“C 3~6 cycloalkyl"). In some embodiments, the cycloalkyl group is , with 5 to 6 ring carbon atoms (“C 5~6 cycloalkyl"). In some embodiments and cycloalkyl groups have 5 to 10 ring carbon atoms (“C 5~10 cycloal kill"). C. 5~6 Examples of cycloalkyl groups include cyclopentyl (C 5 ) and sik Rohexyl (C 5 ). C. 3~6 Examples of cycloalkyl groups include the C 5 ~6 Cycloalkyl groups, and cyclopropyl (C 3 ) and cyclobutyl (C 4 )but mentioned. C. 3~8 Examples of cycloalkyl groups include the C 3~6 cycloalkyl group , as well as cycloheptyl (C 7 ) and cyclooctyl (C 8 ). special special Unless specified, each occurrence of a cycloalkyl group is independently unsubstituted (“unsubstituted cycloalkyl”). (“substituted alkyl”) or substituted with one or more substituents (“substituted alkyl”) roalkyl”). In certain embodiments, a cycloalkyl group is an unsubstituted C 3~10 is cycloalkyl. In certain embodiments, a cycloalkyl group is substituted C 3~ 10 is cycloalkyl.

[0162] “Heterocyclyl” or “heterocyclic” means ring carbon atoms and 1 to 4 ring heteroatoms A 3- to 10-membered non-aromatic ring system radical having a group, where each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus and silicon (3-10 membered heterocyclyl"). heterocyclyl groups containing one or more nitrogen atoms Thus, the point of attachment can be a carbon or nitrogen atom when valences permit. heterocyclyl The group may be a monocyclic ring system (“monocyclic heterocyclyl”) or a fused, bridged or sp can be a ring system (e.g., a bicyclic system (“bicyclic heterocyclyl”)) and can be saturated , or partially unsaturated. Heterocyclyl bicyclic ring systems have in one or both rings It may contain one or more heteroatoms. "Heterocyclyl" is defined above ring systems in which the heterocyclyl ring is fused with one or more carbocyclyl groups, such as where the point of attachment is defined on or on the carbocyclyl or heterocyclyl ring one or more aryl or heteroaryl groups in which the heterocyclyl ring as defined on a ring system fused with a aryl group, wherein the point of attachment is on the heterocyclyl ring, In such cases, the number of ring members continues to refer to the number of ring members in the heterocyclyl ring system. Point out. Unless otherwise specified, each occurrence of heterocyclyl is independently optionally substituted, i.e., unsubstituted (“unsubstituted heterocyclyl”), or one or is substituted with more substituents (“substituted heterocyclyl”). Certain embodiments , the heterocyclyl group is an unsubstituted 3- to 10-membered heterocyclyl. a certain fruit In embodiments, the heterocyclyl group is a substituted 3-10 membered heterocyclyl.

[0163] In some embodiments, a heterocyclyl group has ring carbon atoms and 1-4 ring heterocycles. A 5- to 10-membered non-aromatic ring system having atoms wherein each heteroatom is independently nitrogen , oxygen, sulfur, boron, phosphorus and silicon ("5- to 10-membered heterocyclyl ”). In some embodiments, the heterocyclyl group has ring carbon atoms and 1-4 ring atoms. A 5- to 8-membered non-aromatic ring system having teroatoms, wherein each heteroatom is independently a nitrogen is selected from nitrogen, oxygen and sulfur (“5- to 8-membered heterocyclyl”); in some embodiments , the heterocyclyl group has 5 to 6 ring carbon atoms and 1 to 4 ring heteroatoms. a non-aromatic ring system wherein each heteroatom is independently from nitrogen, oxygen and sulfur Selected (“5-6 membered heterocyclyl”). In some embodiments, a 5- to 6-membered hetero A cyclyl has 1 to 3 ring heteroatoms selected from nitrogen, oxygen and sulfur. one In some embodiments, the 5-6 membered heterocyclyl is selected from nitrogen, oxygen and sulfur. has 1 to 2 ring heteroatoms. In some embodiments, 5-6 membered heterocyclyl has one ring heteroatom selected from nitrogen, oxygen and sulfur.

[0164] Exemplary 3-membered heterocyclyl groups containing one heteroatom include azirdinyl (az irdinyl), oxiranyl, thiorenyl). 1 Exemplary 4-membered heterocyclyl groups containing five heteroatoms include azetidinyl, oxeta Non-limiting examples include nyl and thietanyl. Examples containing one heteroatom Exemplary 5-membered heterocyclyl groups include tetrahydrofuranyl, dihydrofuranyl, tet lahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl and Examples include, but are not limited to, pyrrolyl-2,5-dione. contains two heteroatoms Exemplary 5-membered heterocyclyl groups including dioxolanyl, oxasulfuranyl, dis- Examples include, but are not limited to, lufuranil and oxazolidin-2-ones. Three Exemplary 5-membered heterocyclyl groups containing a heteroatom include triazolinyl, oxadi Examples include, but are not limited to, azolinyl and thiadiazolinyl. 1 hetero Exemplary 6-membered heterocyclyl groups containing atoms include piperidinyl, tetrahydropyrani include, but are not limited to, aryl, dihydropyridinyl and thianyl. 2 heads Exemplary 6-membered heterocyclyl groups containing teroatoms include piperazinyl, morpholinyl, Dithianil, dioxanyl, but are not limited to these. contains two heteroatoms Exemplary 6-membered heterocyclyl groups including, but are not limited to, triazinanyl. can't Exemplary 7-membered heterocyclyl groups containing 1 heteroatom include azepanyl, Examples include, but are not limited to, oxepanyl and thiepanyl. 1 heteroatom Exemplary 8-membered heterocyclyl groups containing include azocanyl, oxecanyl and thioca Examples include, but are not limited to, nil. C. 6 Exemplary 5-membered hexanes fused to aryl rings As a terocyclyl group (also referred to herein as a 5,6-bicyclic heterocyclic ring), Dolinyl, Isoindolinyl, Dihydrobenzofuranyl, Dihydrobenzothienyl, Ben Examples include, but are not limited to, zoxazolinonyl and the like. fused to an aryl ring Exemplary 6-membered heterocyclyl groups (also referred to herein as 6,6-bicyclic heterocyclic rings) Examples include tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like. are not limited to these.

[0165] A "nitrogen-containing heterocyclyl" group is a 4- to 7-membered non-aromatic compound containing at least one nitrogen atom. means a tricyclic group 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 , imidazolidinones, 2-pyrazolines, pyrazolidines, piperazines, and N-alkyl Piperazine (such as N-methylpiperazine). Specific examples include azetidine, pipet Lydone, and piperazone.

[0166] "Hetero" when used to describe a compound or group present on a compound one or more carbon atoms in the compound or group are nitrogen, oxygen, or sulfur It means that it is replaced by a B atom. hetero to any of the above hydrocarbyl groups (for example, alkyl having 1 to 5, especially 1 to 3 heteroatoms, For example, heteroalkyl, cycloalkyl, such as heterocyclyl, aryl, such as , heteroaryl, and cycloalkenyl, eg, cycloheteroalkenyl).

[0167] "Acyl" means -C(O)R 20 refers to radicals, where R 20 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted al kenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted It is roaryl. "Alkanoyl" is R 20 is an acyl group other than hydrogen. Representative acyl groups include 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 Cycloa alkyl) and -C(O)-(CH 2 ) t (4-10 membered heterocyclyl) (t is 0-4 is an integer of ), but is not limited to these. In certain embodiments, R. 21 is C substituted with halo or hydroxy 1 ~C 8 alkyl; or C 3 ~C 1 0 cycloalkyl, 4-10 membered heterocyclyl, C 6 ~C 10 aryl, arylalkyl 5- to 10-membered heteroaryl or heteroarylalkyl (each of which is an unsubstituted Conversion C 1 ~C 4 alkyl, halo, unsubstituted C 1 ~C 4 alkoxy, unsubstituted C 1 ~C 4 Haloal kill, unsubstituted C 1 ~C 4 hydroxyalkyl or unsubstituted C 1 ~C 4 haloalkoxy or hydroxy substituted).

[0168] "Alkoxy" means -OR 29 refers to the group, where R 29 is a replacement or a non substituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, also substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted Aryl or substituted or unsubstituted heteroaryl. Certain alkoxy groups are oxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy , sec-butoxy, n-pentoxy, n-hexoxy and 1,2-dimethylbutoxy is. Particular alkoxy groups are lower alkoxy, i.e. from 1 to 6 carbon atoms have 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 terocyclyl, halogen, 5-10 membered heteroaryl, hydroxyl, nitro, thioaryl Coxy, Thioaryloxy, Thiol, Alkyl-S(O)-, Aryl-S(O)- , alkyl-S(O) 2 - and aryl-S(O) 2 one selected from the group consisting of - or more substituents, such as 1 to 5 substituents, especially 1 to 3 substituents, especially is a group having one substituent. 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 (Four ~10-membered heterocyclyl), wherein t is 0-4 and any aryl, heteroaryl, cycloalkyl or hetero A cyclyl group is itself an unsubstituted C 1 ~C 4 alkyl, halo, unsubstituted C 1 ~C 4 Arco oxy, unsubstituted C 1 ~C 4 haloalkyl, unsubstituted C 1 ~C 4 hydroxyalkyl or unsubstituted Conversion C 1 ~C 4 It can be substituted by haloalkoxy or hydroxy. In particular the exemplary " A 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 is.

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

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

[0172] "Substituted amino" means a compound of the formula -N(R 38 ) 2 refers to the amino group of, where R 38 teeth , hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl aryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or amino protected group, where R 38 is not hydrogen. in certain embodiments and each R 38 are independently hydrogen, C 1 ~C 8 Alkyl, C 3 ~C 8 alkenyl, C 3 ~C 8 alkynyl, C 6 ~C 10 aryl, 5-10 membered heteroaryl, 4-10 membered heteroaryl Rocyclyl or C 3 ~C 10 cycloalkyl; or substituted with halo or hydroxy Done C 1 ~C 8 Alkyl; C substituted with halo or hydroxy 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 ), wherein 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, nonpositional Conversion C 1 ~C 4 hydroxyalkyl or unsubstituted C 1 ~C 4 haloalkoxy or hydro is substituted by oxy; or both R 38 The groups together form an alkylene group to form

[0173] Exemplary "substituted amino" groups include -NR 39 -C 1 ~C 8 Alkyl, -NR 39 - (CH 2 ) t (C 6 ~C 10 aryl), -NR 39 -(CH 2 ) t (5-10 membered hetero aryl), -NR 39 -(CH 2 ) t (C 3 ~C 10 cycloalkyl) and -NR 3 9 -(CH 2 ) t (4- to 10-membered heterocyclyl), but are not limited to where t is an integer from 0 to 4, such as 1 or 2, and each R 39 independently, H or or C 1 ~C 8 represents alkyl; any alkyl group present may itself be halo, substituted or may be substituted by unsubstituted amino or hydroxy; any aryl present, A heteroaryl, cycloalkyl or heterocyclyl group may itself be an unsubstituted C 1 ~ C. 4 alkyl, halo, unsubstituted C 1 ~C 4 alkoxy, unsubstituted C 1 ~C 4 haloalkyl, non permutation C 1 ~C 4 hydroxyalkyl or unsubstituted C 1 ~C 4 haloalkoxy or hydr can be replaced by roxy. For the avoidance of doubt, the term "substituted amino" is defined below Alkylamino, substituted alkylamino, alkylarylamino, substituted amino, such as alkylarylamino, arylamino, substituted arylamino, dialkylamino and Contains substituted dialkylamino groups. Substituted amino includes both monosubstituted and disubstituted amino groups encompasses

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

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

[0176] "Halo" or "halogen" means fluoro (F), chloro (Cl), bromo (Br) , and iodine (I). In certain embodiments, halo groups are fluoro or is either chloro.

[0177] "Haloalkyl" means an alkyl group substituted with one or more halogens It refers to an alkyl radical that contains Typical haloalkyl groups include trifluoro methyl, difluoromethyl, fluoromethyl, chloromethyl, dichloromethyl, dibromo Ethyl, tribromomethyl, tetrafluoroethyl, and the like, which include Not limited.

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

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

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

[0181] Alkyl, alkenyl, alkynyl, carbocyclyl as defined herein , heterocyclyl, aryl and heteroaryl groups are optionally substituted (e.g. For example, “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “ substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" carbocyclyl, " substituted” or “unsubstituted” heterocyclyl, “substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl groups). In general, the term "replaced" means that A group (e.g., carbon or is a nitrogen atom) is substituted with an acceptable substituent, e.g. stable compounds, e.g., spontaneous transformations (e.g., rearrangement, cyclization, elimination or replaced by a substituent that yields a compound that does not undergo other reactions) be. Unless otherwise indicated, a "substituted" group includes one or more substitutions of the group. Substituted at any possible position, with two or more positions substituted in any given structure , the substituents are the same or different at each position. The term "substitution The term "with" includes all permissible substituents of organic compounds, the present invention, which form stable compounds. It is intended to include substitution by any substituent described herein. The present invention provides stable compounds Any and all such combinations are contemplated to arrive at the object. The eye of the invention For the purposes of this study, a heteroatom such as nitrogen satisfies its heteroatom valences, resulting in a safety Hydrogen substituents and / or any hydrogen substituents as described herein and / or any It may have suitable substituents.

[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 R. aa , -S(=O)R aa , -O S(=O)R aa , -Si(R aa ) 3 , -OSi(R aa ) 3 -C(=S)N(R b b ) 2 , -C(=O)SR aa , -C(=S)SR aa , -SC(=S)SR aa , -S C(=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)(N R. bb ) 2 , -P(R cc ) 2 , -P(R cc ) 3 , -OP(R cc ) 2 , -OP(R c c ) 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 5~1 Examples include, but are not limited to, 4-membered heteroaryl, where each alkyl, alkene Nyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl are , independently 0, 1, 2, 3, 4 or 5 R dd substituted with a group; or a carbon atom The two geminal hydrogens on the child are the 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 C 1~10 Alkyl, C 1~10 haloalkyl, C 2~ 10 alkenyl, C 2~10 alkynyl, C 3~10 Carbocyclyl, 3-14 membered hetero Cyclyl, C 6~14 is selected from aryl and 5- to 14-membered heteroaryl; is two R aa groups are linked to form a 3- to 14-membered heterocyclyl or a 5- to 14-membered heteroaryl each alkyl, alkenyl, alkynyl, carbocyclyl, hete Rocyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or 5 of R dd substituted with a group;

[0184] R. bb each occurrence of is independently hydrogen, -OH, -OR aa , -N(R cc ) 2 , -CN , -C(=O)R aa , -C(=O)N(R cc ) 2 , -CO 2 R. aa , -SO 2 R. aa , -C(=NR cc ) OR aa , -C(=NR cc )N(R cc ) 2 , -SO 2 N(R c c ) 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 ~14-membered heteroaryl or two R bb 3~14 forming a membered heterocyclyl or 5- to 14-membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and heteroaryl 0, 1, 2, 3, 4 or 5 R dd substituted with a group;

[0185] R. cc Each occurrence of is independently hydrogen, C 1~10 Alkyl, C 1~10 haloalkyl, C. 2~10 alkenyl, C 2~10 alkynyl, C 3~10 Carbocyclyl, 3-14 membered heterocyclyl, C 6~14 selected from aryl and 5- to 14-membered heteroaryl , or two R cc groups are linked to form a 3- to 14-membered heterocyclyl or a 5- to 14-membered hete forming a loaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl , heterocyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or or 5 R dd substituted with a group;

[0186] R. dd Each occurrence of is independently 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 e e , -NR ff CO 2 R. ee , -NR ff C(=O)N(R ff ) 2 , -C(=NR ff ) OR ee , -OC(=NR ff )R ee , -OC(=NR ff ) OR ee , -C(=N R. 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 e e ) 2 , -OP(=O)(R ee ) 2 , -OP(=O)(OR ee ) 2 , C 1~6 Archi L, C 1~6 haloalkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 3~10 Cal Bocyclyl, 3-10 membered heterocyclyl, C 6~10 Aryl, 5-10 membered heteroary wherein each alkyl, alkenyl, alkynyl, carbocyclyl, hete Rocyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or 5 R's gg or two geminal R dd Substituents taken together = can form O or =S;

[0187] R. ee Each occurrence of C 1~6 Alkyl, C 1~6 haloalkyl, C 2~6 a lukenyl, C 2~6 alkynyl, C 3~10 Carbocyclyl, C 6~10 Aryl, 3~ is selected from 10-membered heterocyclyl and 3- to 10-membered heteroaryl, wherein each alkyl alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl and hetero Aryl is independently 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 heterozygous Krill, C. 6~10 is selected from aryl and 5- to 10-membered heteroaryl; or two R's ff groups are linked to form a 3- to 14-membered heterocyclyl or a 5- to 14-membered heteroary ring, where each alkyl, alkenyl, alkynyl, carbocyclyl, hetero Cyclyl, aryl and heteroaryl are independently 0, 1, 2, 3, 4 or 5 the R gg substituted with a group;

[0189] R. gg Each occurrence of is independently halogen, -CN, -NO 2 , -N 3 , -SO 2 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 Al Kill)(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 a Rukir), -CO 2 H, -CO 2 (C 1~6 alkyl), -OC(=O)(C 1~6 Al kill), -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), -NHC O 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 1~6 alkyl), -OC(=NH)OC 1~6 Al Kill, -C(=NH)N(C 1~6 alkyl) 2 , -C(=NH)NH(C 1~6 Archi ), -C(=NH)NH 2 , -OC(=NH)N(C 1~6 alkyl) 2 , -OC(N H)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 OC 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 Al kill, -SC(=S)SC 1~6 Alkyl, -P(=O) 2 (C 1~6 alkyl), -P (=O)(C 1~6 alkyl) 2 , -OP(=O)(C 1~6 alkyl) 2 , -OP(= O)(OC 1~6 alkyl) 2 , C 1~6 Alkyl, C 1~6 haloalkyl, C 2~6 a lukenyl, C 2~6 alkynyl, C 3~10 Carbocyclyl, C 6~10 Aryl, 3~ 10-membered heterocyclyl, 5- to 10-membered heteroaryl, or two geminal R gg The substituents can be taken together to form =O or =S; where X - is against is on.

[0190] A "counterion" or "anionic counterion" is a cation to maintain electroneutrality. It is a negatively charged group that associates with a quaternary amino group. Exemplary counterions include halo Genide ions (e.g., F - , Cl - , Br - , I - ), NO 3 - , ClO 4 - , OH - , H 2 P.O. 4 - , HSO 4 - , sulfonate ions (e.g., methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, benzenesulfonate, 1 0-Camphorsulfonate, naphthalene-2-sulfonate, naphthalene-1-sulfo acid-5-sulfonate, ethane-1-sulfonic acid-2-sulfonate, etc.) and Boxylate ions (e.g. acetate, ethanoate, propanoate, benzoate , glycerate, lactate, tartrate, glycolate, etc.).

[0191] These and other exemplary substituents are described in detail in the detailed description and claims. Are listed. The present invention is directed in any manner by the exemplary listing of substituents set forth above. is intended to be non-limiting.

[0192] other definitions As used herein, the term “modulation” refers to inhibition of GABA receptor function or refers to synergy. A "modulator" (eg, a modulator compound) is, for example, GAB A receptor agonist, partial agonist, antagonist, or partial antagonist can be

[0193] “Pharmaceutically acceptable” means a federal or state governmental regulatory agency or a non-U.S. Recognized or recognisable by the corresponding authority or the United States Pharmacopoeia or other generally accepted pharmacopoeia for use in animals (more particularly in humans) means that it is described in

[0194] "Pharmaceutically acceptable salt" means a compound that is pharmaceutically acceptable and contains the desired drug of the parent compound. Refers to salts of the compounds of the present invention that have physical activity. In particular, such salts are non-toxic. , inorganic or organic acid addition salts and inorganic or organic base addition salts. be. Specifically, such salts include: (1) inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid; , nitric acid, phosphoric acid, etc.; or organic acids such as acetic acid, propionic acid, hexa acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid Citric acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxy (roxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzene fonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid fonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene -1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butyl acetate, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, Acid addition salts formed with lycylic acid, stearic acid, muconic acid, etc.; or (2) the parent compound. The acidic protons present in the metal ion, e.g. alkali metal ion, alkaline earth or aluminum ions; or organic bases such as ethanol. lyamine, diethanolamine, triethanolamine, N-methylglucamine, etc. Examples include salts formed when the As a salt also, as just an example, Natri Ammonium, Potassium, Calcium, Magnesium, Ammonium, Tetraalkylammonium and salts of non-toxic organic or inorganic acids, if the compound contains a basic functional group, For example hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalic acid Examples include salt. The term "pharmaceutically acceptable cation" means an acceptable A cationic counterion. Such cations are sodium cation, potassium ammonium cation, calcium cation, magnesium cation, ammonium cation, exemplified by tetraalkylammonium cations and the like. For example, Berge et al., J. See Pharm.Sci.(1977)66(1):1-79.

[0195] The term "prodrug" refers to therapeutically non-therapeutic agents that are converted under physiological conditions to the therapeutically active agents of the present invention. It is intended to include active compounds. One method of making prodrugs is to subject them to physiological conditions. hydrolyzed or cleaved at the targeted in vivo site of action to release the desired molecule; The next step is to design selected moieties that provide that therapeutic effect. in certain embodiments , the prodrug is converted by the subject's enzymatic activity.

[0196] In alternative embodiments, the present invention provides formula (I-I), formula (I-II), formula (II-I), formula ( II-II), formula (III-I), formula (III-II), formula (IV-I), formula (IV-I I), formula (IV-III), formula (V-I), formula (V-II), or formula (V-III) A prodrug of a compound is provided, wherein the prodrug is of formula (I-I), 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 (V-I), Formula (V-II ), or containing a cleavable moiety on the C3 hydroxy shown in compounds of formula (V-III). nothing.

[0197] "Tautomer" means a compound of a particular compound structure in which there are interchangeable forms and a water Refers to a compound in which the displacement of elementary atoms and electrons varies. Therefore, the two structures are π electrons and can be in equilibrium due to the movement of atoms (usually H). For example, enol and que tautomers because they are rapidly interconverted by treatment with either acid or base is the body. Another example of tautomerism is the similarly formed phenyl nitrite in the presence of acid or base. The acid and nitro forms of romethane. Tautomers are the optimal chemical It can be associated with acquisition of reactivity and biological activity.

[0198] "Subjects" contemplated for administration include humans (i.e., any age group, e.g., children subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle-aged or elderly adults) male or female) and / or non-human animals, e.g. mammals (e.g. primates (e.g. cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats and / or dogs), but are not limited to these. certain In embodiments of, the subject is human. In certain embodiments, the subject is It is a non-human animal.

[0199] In certain embodiments, the substituent present on the oxygen atom is an oxygen protecting group (hydroxyl (also referred to as a protecting group). As an oxygen protecting group, -R aa , -N(R bb ) 2 , -C (=O)SR aa , -C(=O)R aa , -CO 2 R. aa , -C(=O)N(R bb ) 2 , -C(=NR bb )R aa , -C(=NR bb ) OR aa , -C(=NR bb )N(R bb ) 2 , -S(=O)R aa , -SO 2 R. aa , -Si(R aa ) 3 , -P(R cc ) 2 , -P(R cc ) 3 , -P(=O) 2 R. aa , -P(=O)(R aa ) 2 , -P(=O )(OR cc ) 2 , -P(=O) 2 N(R bb ) 2 , and -P(=O)(NR bb ) 2 (where R aa , R bb , and R cc is as defined herein) include, but are not limited to: Oxygen protecting groups are well known in the art and can be Control Groups in Organic Synthesis,T.W.Gr eene and P.G.M. Wuts,3 rd edition, John Wil ey & Sons, 1999 (incorporated herein by reference). Things are mentioned.

[0200] Exemplary oxygen protecting groups include methyl, methoxymethyl (MOM), 2-methoxyethyl Toxymethyl (MEM), benzyl (Bn), triisopropylsilyl (TIPS), t -Butyldimethylsilyl (TBDMS), t-Butylmethoxyphenylsilyl (TBMP S), methanesulfonate (mesylate), and tosylate (Ts), but It is not limited to these.

[0201] In certain embodiments, the substituents present on the sulfur atom are sulfur protecting groups (thiol protecting (also referred to as a group). As a sulfur protecting group, -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 is raised include, but are not limited to, where R aa , R bb , and R cc in this specification as defined in Sulfur protecting groups are well known in the art and Protecting Groups in Organic Synthesis, T.W.Greene and P.G.M. Wuts,3 rd edition, John Wiley & So ns, 1999 (incorporated herein by reference). can be lifted.

[0202] In certain embodiments, the substituent present on the nitrogen atom is an amino protecting group (herein (also referred to 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 include, but are not limited to, alkyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl each independently 0, 1, 2, 3, 4, or 5 R dd is substituted with where R aa , R bb , R cc , and R dd is as defined herein . Amino protecting groups are well known in the art and can be found in Protecting Groups in Organic Synthesis,T.W.Greene and P.G.M.W. uts,3 rd edition, John Wiley & Sons, 1999 (see which is further incorporated herein by reference).

[0203] Exemplary amino-protecting groups include amide groups (e.g., -C(=O)R aa )(Holmua amides and acetamides); carbamate groups (e.g. For example, -C(=O)OR aa )(9-fluorenylmethyl carbamate (Fmoc), t -butyl carbamate (BOC), and benzyl carbamate (Cbz) but not limited to); sulfonamide groups (e.g., -S(=O) 2 R. aa )(p -toluenesulfonamide (Ts), methanesulfonamide (Ms), and N-[2- (trimethylsilyl)ethoxy]methylamine (SEM) not limited).

[0204] Diseases, disorders, and conditions are used interchangeably herein.

[0205] As used herein, unless otherwise specified, the term "treat" ', 'treating' and 'treatment' refer to taking place while the body is afflicted with a particular disease, disorder or condition reduce the severity of disease or delay or slow the progression of a disease, disorder or condition Assume the act of stealing. In an alternative embodiment, the invention provides a method for treating a subject with a particular disease, disorder, or disease. Or, administration of the compounds of the present invention as a prophylactic agent before the condition begins is contemplated.

[0206] Generally, an "effective amount" of a compound is one to elicit the desired biological response, e.g., CN Sufficient volume to induce anesthesia or sedation to treat an S-related disorder. minutes. As will be appreciated by those skilled in the art, an effective amount of the compounds of the invention will target, pharmacokinetics of the compound, disease to be treated, mode of administration, and age, weight of the subject may vary depending on factors such as, health, and condition. The effective amount is therapeutic treatment and Including preventative measures.

[0207] As used herein, unless otherwise specified, a "therapeutically effective amount" of a compound is provide a therapeutic benefit in the treatment of a disease, disorder or condition; delay or minimize one or more symptoms associated with the harm or condition is sufficient for A therapeutically effective amount of a compound is an amount effective in treating the disease, disorder or condition. the amount of therapeutic agent, alone or in combination with other treatments, that provides a therapeutic benefit in means. The term "therapeutically effective amount" refers to an amount that ameliorates overall treatment, disease or condition symptoms or is an amount that reduces or avoids the cause or that enhances the therapeutic efficacy of another therapeutic agent can be included.

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

[0209] In one aspect, Formula (I-I): [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, wherein In formula (I-I), t is 1 or 2; R. 7 is hydrogen or methyl, or [formation] is a double bond, then 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 rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl can be; R. 9 is hydrogen or substituted or unsubstituted alkyl; R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, or R 6a and R 6b together form an oxo (=O) group ; R. 11a , R 11b , R 15a , R 15b , R 16a , R 16b , R 17a , R 17b , R 18a , R 18b , R 19a , or R 19b each of independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 , where R D1 each occurrence 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 or substituted or unsubstituted heteroaryl, oxygen protecting group when attached to oxygen atom, nitrogen atom is a nitrogen protecting group when attached to a child, or two R D1 If the groups together substitute or an unsubstituted heterocyclic ring; or R 11a and R 11b , R 15a and R 15 b , R 16a and R 16b , R 17a and R 17b , as well as R 18a and R 18 b together form an oxo (=O) group; R. 5a , R 5b , R 8 , and R 13 are each independently hydrogen, halogen, cyan no, 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 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 ,or -S(=O) 2 OR A1 , where R A1 each occurrence of is independently hydrogen, substituted if 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-supporting protecting group, sulfur protecting group when attached to a sulfur atom, nitrogen protecting group when attached to a nitrogen atom, - SO 2 R. A2 , -C(O)R A2 or two R A1 The groups together are also substituted or form an unsubstituted heterocyclic or heteroaryl ring; R A2 is a replacement or a non substituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, also substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted is aryl, or substituted or unsubstituted heteroaryl; or R 8 and R 13 together form an oxo (=O) group, where R 8 and R 13 together form an oxo (=O) group, then R 3 is a substituted or unsubstituted al alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted substituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl , or substituted or unsubstituted heteroaryl; where R 5a , R 5b , R 8 , and R 13 at least one of is ethyl, substituted al alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted substituted 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 , -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 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 in must; where R 8 and R 13 and cannot both be methyl; here, [formation] represents a single or double bond, and if the double bond is in ring B, then R 6a or R 6 b one of and R 7 does not exist. Formula (I-I): Group R 15a and R 15b

[0210] In some aspects, R 15a and R 15b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl.

[0211] In some aspects, R15a and R 15b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl.

[0212] In some aspects, R 15a and R 15b are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be.

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

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

[0215] In some embodiments, R 15a and R 15b are each independently hydrogen, C 1 ~C 6 a Rukir, 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 is. Formula (I-I): Group R 16a and R 16b

[0217] In some aspects, R 16a or R 16b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl.

[0218] In some aspects, R 16a or R 16b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl.

[0219] In some aspects, R 16a or R 16b are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be.

[0220] In some aspects, R 16a and R 16b are both hydrogen. In a further embodiment , R 16a and R 16b are each independently hydrogen or substituted or unsubstituted alkyl be.

[0221] In some aspects, R 16a and R 16b are each independently hydrogen, C 1 ~C 6 Archi L, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, also is -OH. In some other aspects, R 16a or R 16b but -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 is. Formula (I-I): Group R 17a and R 17b

[0222] In some embodiments, R 17a or R 17b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0223] In some further embodiments, R 17a or R 17b are each independently hydrogen, halo gen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk nil, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl.

[0224] In some aspects, R 17a or R 17b are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be. In some aspects, R 17a and R 17b are both hydrogen.

[0225] In some aspects, R 17a and R 17b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 17a and R 17b each of the water independently elementary, 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 aspects, R 17a or R 17b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (I-I): Group R 18a and R 18b

[0227] In some aspects, R 18a or R 18b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl.

[0228] In some embodiments, R 18a or R 18b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0229] In some embodiments, R 18a or R 18b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

[0231] In some aspects, R 18a and R 18b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 18a and R 18b each of the water independently elementary, C 1 ~C 6 Alkyl, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, or -OH.

[0232] In some aspects, R 18a or R 18b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (I-I): Group R 19a and R 19b

[0233] In some embodiments, R 19a or R 19b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0234] In some further embodiments, R 19a or R 19b are each independently hydrogen, halo gen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk nil, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl.

[0235] In some aspects, R 19a or R 19b are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be.

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

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

[0238] In some aspects, R 19a and R 19b are each independently hydrogen, C 1 ~C 6 Archi L, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, also is -OH.

[0239] In some aspects, R 19a or R 19b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (I-I): Group R 7

[0240] In some aspects, R 7 is a cis hydrogen. In some other aspects, R 7 but hydrogen at the position. In some embodiments, R 7 is cis-methyl. some more In an embodiment where R 7 is methyl in trans position. Formula (I-I): group t

[0241] In some embodiments, t is 1.

[0242] In some embodiments, t is two. Formula (I-I): Group R 3

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

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

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

[0246] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a substituted alkyl is le. In some embodiments, R 3 is an unsubstituted alkyl. In some embodiments R. 3 is methyl. Formula (I-I): Group R 9

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

[0248] In some embodiments, R 9 is a substituted alkyl. In some embodiments, R 9 but non is substituted alkyl.

[0249] In some embodiments, R 9 is methyl. In some embodiments, R 9 but -OCH 3 is. In some aspects, R 9 is ethyl. Formula (I-I): 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 is.

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

[0252] In some aspects, R 6a and R 6b is independently hydrogen or substituted alkyl. one In some embodiments, R 6a and R 6b is independently hydrogen or unsubstituted alkyl.

[0253] In some aspects, R 6a and R 6b are both hydrogen. In some aspects, R 6a but , halo or alkyl, and R 6b is hydrogen. In some embodiments, R 6a and and R 6b are both halos.

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

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

[0256] In some embodiments, R 11a or R 11b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0257] In some aspects, R 11a or R 11b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl.

[0258] In some embodiments, R 11a or R 11b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

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

[0261] In some aspects, R 8 or R 13 is substituted or unsubstituted alkyl, substituted or unsubstituted substituted alkenyl, substituted or unsubstituted alkynyl, -OR A1 , -SR A1 , -N(R A 1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -C(=O)N(R A1 ) 2 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , or -OC(=O)N(R A1 ) 2 , where R A1 independently of each other, water elemental, 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)O R. A1 , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted substituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

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

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

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

[0266] In some aspects, R 5a and R 5b are each independently 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 substituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -SR A1 , -N(R A 1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A 1 , or -OC(=O)OR A1 , where R A1 each occurrence of is independently a hydrogen , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0267] In some embodiments, R 5a and R 5b are each independently hydrogen, halogen, or 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 ,Also is -OC(=O)OR A1 , where R A1 each occurrence of is independently hydrogen, substitution 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 aspects, R 5a and R 5b are each hydrogen.

[0269] In some embodiments, the compound has the formula (I-Ia) [formation] or a pharmaceutically acceptable salt thereof, where R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted terocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -O R. A1 , -SR A1 , -N(R A1 ) 2 , -N(R A1 ), -OC(=O)R A1 , -O C(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC (=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N (R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O) SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid Oxygen protecting group when bonding to a nitrogen atom, sulfur protecting group when bonding to a sulfur atom, nitrogen atom is a nitrogen protecting group when attached, or two R A1 the groups together are substituted or forming an unsubstituted heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3 be.

[0270] In some embodiments, the compound has the formula (I-Iab) [formation] or a pharmaceutically acceptable salt thereof, R. 1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl lyl, 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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3.

[0271] In some embodiments, the compound is of Formula (I-Ib) or Formula (I-Ibb) [formation] or a pharmaceutically acceptable salt thereof.

[0272] In some embodiments, the compound has Formula (I-Ic) or Formula (I-Icb) [formation] or a pharmaceutically acceptable salt thereof, R. 1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl lyl, 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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3.

[0273] In some embodiments, R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted kenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl is the reel.

[0274] In some embodiments, R 1 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; n or is 0, 1, 2, 3, 4, or 5.

[0275] In some embodiments, R 1 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; n or is 0, 1, 2, 3, 4, or 5.

[0276] In some embodiments, the compound is of Formula (I-Id) or Formula (I-Idb) [formation] is a compound of where R 10 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxy Sil, or cyano.

[0277] In some embodiments, the compound has Formula (I-Ie) or Formula (I-Ieb) [formation] or a pharmaceutically acceptable salt thereof, where e is 0, 1, 2, or 3; p is 0, 1, 2 or 3; R. 5 is independently halogen, alkyl, hydroxyl, or cyano.

[0278] In some embodiments, the compound is of Formula (I-If) or Formula (I-Ifb) [formation] or a pharmaceutically acceptable salt thereof, where R 10 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxy Sil, or cyano.

[0279] In some embodiments, the compound is of Formula (I-Ig) or Formula (I-Igb) [formation] or a pharmaceutically 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 independently , hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O) OR G A , -C(=O)N(R GA ) 2 , -S(=O) 2 R. GA , or -S(=O) 2 N(R GA ) 2 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3~ 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's GA groups together with intervening atoms form a substituted or unsubstituted heterocyclyl ring or forms a heteroaryl ring.

[0280] In some embodiments, the compound is of Formula (I-Ih) or Formula (I-Ihb) [formation] or a pharmaceutically acceptable salt thereof, where R 10 is independently halogen, alkyl, hydroxyl, or cyano and m is 0, 1, 2, or 3.

[0281] In some embodiments, the compound is of Formula (I-Ii) or Formula (I-Iib) [formation] or a pharmaceutically 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 is 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 G A ) 2 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do.

[0282] In some embodiments, the compound is of Formula (I-Ik) or Formula (I-Ikb) [formation] or a pharmaceutically acceptable salt thereof, where s is 0, 1, or 2; R 12 is -N(R ab ) 2 and where R. ab is independently 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 Rocyclyl, or substituted or unsubstituted cycloalkane.

[0283] In one aspect, the compound has the formula (I-II): [formation] or a pharmaceutically acceptable salt thereof, wherein in formula (I-II), R. 77 is hydrogen or methyl; R. 23 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl ; R. 29 is hydrogen or substituted or unsubstituted alkyl; R. 26a and R 26b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is substituted alkynyl, or R 26a and R 26b are combined together into an oxo (=O) group to form; R. 21a , R 21b , R 25a , R 25b , R 36a , R 36b , R 27a , R 27b , R 29a , or R 29b each independently hydrogen, halogen, cyano, hydroxyl , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted terocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC(=O)R D 1 , -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 alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted substituted heteroaryl, oxygen protecting group when attached to an oxygen atom, nitrogen when attached to a nitrogen atom or two R D1 groups taken together in a substituted or unsubstituted heterocyclic ring or R 21a and R 21b , R 25a and R 25b , R 36a and and R 36b , R 27a and R 27b , as well as R 29a and R 29b one of together form an oxo (=O) group; R. 55a , R 55b , R 33a , and R 33b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -S R. 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 , -S-S(=O ) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 ,Also is -S(=O) 2 OR A1 , where R A1 each occurrence of is independently hydrogen, substitution or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl , substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or is 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 A1 groups together substituted or form an unsubstituted heterocyclic or heteroaryl ring; R A2 is replaced or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted substituted aryl, or substituted or unsubstituted heteroaryl; here, [formation] represents a single or double bond, and if the double bond is in ring B, then R 26a or R 26b one of and R 77 is absent and the single bond is in ring B, the hydrogen at C5 is α position or β position. Formula (I-II): Group R 25a and R 25b

[0284] In some embodiments, R 25a and R 25b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0285] In some embodiments, R 25a and R 25b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0286] In some embodiments, R 25a and R 25b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

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

[0289] In some embodiments, R 25a and R 25b are each independently hydrogen, C 1 ~C 6 a Rukir, C 1 ~C 6 haloalkyl, C 1 ~C 6 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 is. Formula (I-II): Group R 36a and R 36b

[0291] In some embodiments, R 36a or R 36b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0292] In some embodiments, R 36a or R 36b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0293] In some embodiments, R 36a or R 36b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

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

[0296] In some embodiments, R 36a and R 36b are each independently hydrogen, C 1 ~C 6 a Rukir, 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 -CH 3 , -CH 2 CH 3 , -OH , -OCH 3, or -CH(CH 3 ) 2 is. Formula (I-II): Group R 27a and R 27b

[0298] In some embodiments, R 27a or R 27b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0299] In some embodiments, R 27a or R 27b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0300] In some embodiments, R 27a or R 27b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

[0302] In some embodiments, R 27a and R 27b are 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 is. Formula (I-II): Group R 29a and R 29b

[0305] In some embodiments, R 29a or R 29b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0306] In some embodiments, R 29a or R 29b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0307] In some embodiments, R 29a or R 29b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

[0309] In some embodiments, R 29a and R 29b are 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 is. Formula (I-II): Group R 21a and R 21b

[0312] In some embodiments, R 21a or R 21b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl.

[0313] In some embodiments, R 21a or R 21b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0314] In some embodiments, R 21a or R 21b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

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

[0317] In some embodiments, R 21a and R 21b are each independently hydrogen, C 1 ~C 6 a Rukir, 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 is.

[0319] In some embodiments, R 77 is a cis hydrogen. In some embodiments, R 77 but , is a trans-hydrogen.

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

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

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

[0323] In some embodiments, R 23 is a substituted alkyl. In some embodiments, R 23 but , 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 a substituted alkyl. In some embodiments, R 29 but , is an unsubstituted alkyl. In some embodiments, R 29 is methyl. In some embodiments, R 29 but -OC H. 3 is. In some embodiments, R 29 is ethyl. Formula (I-II): Group R 26a and R 26b

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

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

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

[0330] In some embodiments, R 26a and R 26b is independently hydrogen or unsubstituted alkyl is. In some embodiments, R 26a and R 26b is hydrogen. in some embodiments is R 26a is halo or alkyl, and R 26b is hydrogen. some embodiments Then R. 26a and R 26b are both halos. In some embodiments, R 26a and and R 26b are both alkyl. In some embodiments, R 26a and R 26b is one Together they form an oxo group. Formula (I-II): Group R 55a and R 55b

[0331] In some embodiments, R 55a or R 55b is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, 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)OR A1 , -C(=O)N(R A1 ) 2 , -OC(=O) SR A1 , or -OC(=O)N(R A1 ) 2 , where R A1 each existence is unique hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted hetero cyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be.

[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 of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl.

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

[0334] In some embodiments, R 33a and R 33b are each independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted if 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 existence of is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl lyl, 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 , where R A1 each occurrence of is independently a hydrogen, a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyl nyl, substituted or unsubstituted heterocyclyl, 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) [formation] or a pharmaceutically acceptable salt thereof, where R 31 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 , -S C(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O) N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O )SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R. A2 , -OS(=O ) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O) R. A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 each of the occurrences are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted substituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, Oxygen protecting group when attached to oxygen atom, sulfur protecting group when attached to sulfur atom, nitrogen atom is a nitrogen protecting group when attached to or two R A1 the groups together are substituted or forms an unsubstituted heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl; v is 0, 1, or 2 , d is 0, 1, 2, or 3.

[0338] In some embodiments, the compound is of Formula (I-IIb) or Formula (I-IIbb) [formation] or a pharmaceutically acceptable salt thereof, wherein the variable group is the above formula (I-I Ia) or defined as in 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, also substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted hetero is aryl.

[0340] In some embodiments, R 31 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; e or is 0, 1, 2, 3, 4, or 5.

[0341] In some embodiments, R 31 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; 0, 1, 2, 3, 4, or 5.

[0342] In some embodiments, the compound is of Formula (I-IId) or Formula (I-IIdb) [formation] or a pharmaceutically 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 is of Formula (I-IIe) or Formula (I-IIeb) [formation] or a pharmaceutically acceptable salt thereof, where n is 0, 1, 2, or 3; p is 0, 1, or 3; v is is 0, 1, 2, or 3;R 5 is independently halogen, alkyl, hydroxy le, or cyano.

[0344] In some embodiments, the compound is of Formula (I-IIf) or Formula (I-IIfb) [formation] or a pharmaceutically acceptable salt thereof, wherein v is 0, 1, 2, or 3 is; R 10 is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxy le, or cyano.

[0345] In some embodiments, the compound is of Formula (I-IIg) or Formula (I-IIgb) [formation] or a pharmaceutically 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 is independent is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do.

[0346] In some embodiments, the compound is of Formula (I-IIh) or Formula (I-IIhb) [formation] or a pharmaceutically acceptable salt thereof, where v is 0, 1, 2, or 3 and R 10 are independently halogen, aluminum alkyl, hydroxyl, or cyano; m is 0, 1, 2, or 3.

[0347] In some embodiments, the compound is of Formula (I-IIi) or Formula (I-IIIb) [formation] or a pharmaceutically acceptable salt thereof, where v is 0, 1, 2, or 3, n is 0, 1, or 2, and each X is unique. -C(R N )-, -C(R N ) 2 -, -O-, -S-, -N-, or N(R N )-, where R N is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do.

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

[0349] In some embodiments, R 8 or R 13 is -C(O)CH 3 , then R 3 replace or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted if or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0350] In some embodiments, the compound is of formula (I-IIj) [formation] or a pharmaceutically acceptable salt thereof, where s is 0, 1, or 2; R 12 is -N(R ab ) 2 , -OR ab in Yes, where R ab is independently 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 Rocyclyl, or substituted or unsubstituted cycloalkane.

[0351] In some embodiments, R 8 or R 13 is -C(O)R A1 , -C(=O)N(R A 1 ) 2 , where R A1 is 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 compounds identified in Table I-1 below. Selected: [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] The formulas described herein refer to specific carbon atoms (C17, C3, C19, etc.). It should be recognized that These references are known and used in the industry as listed below. Based on carbon atom positions according to steroid nomenclature: [formation] . 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 is: [formation] .

[0002] In one aspect, formula (II-I) [formation] Provided herein is a compound of or a pharmaceutically 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 Archi substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl; R. 5 is hydrogen or methyl; R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, or R 6a and R 6b together form an oxo (=O) group ; R. 1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl lyl, 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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is 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 of the independent hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted Lukynyl, -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, substitution or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl , substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or is unsubstituted aryl, or substituted or unsubstituted heteroaryl, when attached to an oxygen atom an oxygen protecting group, a nitrogen protecting group when attached to a nitrogen atom, or two R D1 base 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 , as well as R 12a and R 12b together form an oxo (=O) group; where R 1a , R 1b , R 2a , R 2b , R 2aa , R 2ab , R 3a , R 3b , R 4 a , or R 4b at least one of is hydroxyl; R. 15a , R 15b , R 16a , and R 16b are each independently hydrogen, halo gen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk nyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or is 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)O R. A1 , -SC(=O)SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S (=O) 2 OR A1 , where R A1 each occurrence 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 substituted aryl, substituted or unsubstituted heteroaryl, 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 the groups together are substituted or forms an unsubstituted heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl 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 1 1a , R 11b , R 12a , R 12b , R 15a , R 15b , R 16a , and R 16b are each hydrogen, then R 1 is not methyl; here, [formation] represents a single or double bond, and if the double bond is in ring B, then R 6a or R 6 b one of and R 5 does not exist.

[0003] In some embodiments, formula (II-II) [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, Variables are defined as described in Formula (II-I); 1a , R 1b , R 2a , R 2b , R 3a , or R 3b is hydroxyl.

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

[0005] In some aspects, R 3a and R 3b are each independently hydrogen, halogen, cyano, di toro, azido, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk Nyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, —O R. 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 alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl is substituted or unsubstituted heteroaryl; or R 3a and R 3b are together to form oxo (=O).

[0006] In some aspects, R 3a and R 3b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0007] In some aspects, R 3a and R 3b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl .

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

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

[0010] In some embodiments, R 3a and R 3b are each independently hydrogen, C 1 ~C 6 Archi L, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, also is -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 is. Formula (II-I) and Formula (II-II): Group R 2a and R 2b

[0012] In some aspects, R 2a and R 2b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -OC( =O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NRD1 C(=O)R D1 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0013] In some aspects, R 2a and R 2b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0014] In some aspects, R 2a and R 2b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl .

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

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

[0017] In some embodiments, R 2a and R 2b are each independently hydrogen, C 1 ~C 6 Archi L, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, also is -OH.

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

[0019] In some aspects, R 2aa and R 2ab are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl.

[0020] In some aspects, R 2aa and R 2ab are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl.

[0021] In some aspects, R 2aa and R 2ab are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be.

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

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

[0024] In some embodiments, R 2aa and R 2ab are each independently hydrogen, C 1 ~C 6 a Rukir, 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 is. Formula (II-I) and Formula (II-II): Group R 1a and R 1b

[0025] In some aspects, R 1a and R 1b are each independently hydrogen, halogen, cyano, di toro, azido, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk Nyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, —O R. 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 alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl.

[0026] In some aspects, R 1a and R 1b are each independently hydrogen, halogen, cyano, droxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -ORD1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0027] In some aspects, R 1a and R 1b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl .

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

[0029] In some embodiments, R 1a and R 1b are each independently hydrogen or substituted or It is 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 -O is H. In some embodiments, R 1a and R 1b but -CH 3 , -CH 2 CH 3 , -OH, -O CH 3 , or -CH(CH 3 ) 2 is. Formula (II-I): Group R 4a and R 4b

[0031] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, di toro, azido, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk Nyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, —O R. 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 alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl.

[0032] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0033] In some aspects, R 4a and R 4b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl .

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

[0035] In some aspects, R 4a and R 4b are each independently hydrogen, C 1 ~C 6 alkyl, C. 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, or - is OH. In some other aspects, R 4a and R 4b but -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 is. Formula (II-I) and Formula (II-II): Group R 11a and R 11b

[0036] In some embodiments, R 11a and R 11b are each independently hydrogen, halogen, ano, nitro, azido, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted substituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl le, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D 1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted substituted aryl, or substituted or unsubstituted heteroaryl.

[0037] In some further embodiments, R 11a and R 11b are each independently hydrogen, halo gen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk nil, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl.

[0038] In some aspects, R 11a and R 11b are each independently hydrogen, substituted or unsubstituted substituted alkyl, -OR D1 , -OC(=O)R D1 , -NH2 , -N(R D1 ) 2 ,or -NR D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be. In some aspects, R 11a and R 11b are both hydrogen.

[0039] In some aspects, R 11a and R 11b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 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 Arco xyhalo, or -OH.

[0040] In some aspects, R 11a and R 11b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is.

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

[0042] In some aspects, R 15a and R 15b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl.

[0043] In some embodiments, R 15a and R 15b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0044] In some embodiments, R 15a and R 15b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

[0046] In some aspects, R 15a and R 15b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 15a and R 15b each of the water independently elementary, C 1 ~C 6 Alkyl, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, or -OH. In some aspects, R 15a and R 15b but,- CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 is. Formula (II-I) and Formula (II-II): Group R 16a and R 16b

[0047] In some aspects, R 16a and R 16b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl.

[0048] In some embodiments, R 16a and R 16b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl.

[0049] In some embodiments, R 16a and R 16b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

[0051] In some aspects, R16a and R 16b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 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 Arco xyhalo, or -OH.

[0052] In some aspects, R 16a and R 16b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (II-I) and Formula (II-II): Group R 7a and R 7b

[0053] In some embodiments, R 7a and R 7b are each independently hydrogen, halogen, cyano , nitro, azide, 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 of is independently hydrogen, substituted or unsubstituted substituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted if or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted is aryl, or substituted or unsubstituted heteroaryl, or R 7a and R 7b together form oxo (=O).

[0054] In some further embodiments, R 7a and R 7b are each independently hydrogen, halogen , cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl , -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 and here at R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted substituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl , or substituted or unsubstituted heteroaryl.

[0055] In some aspects, R 7a and R 7b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl .

[0056] In some aspects, R 7a and R 7b are all hydrogen.

[0057] In some aspects, R 7a and R 7b are each independently hydrogen or substituted or unsubstituted It is a substituted alkyl. In some aspects, R 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 aspects, R 7a and R 7b but -CH 3 , -CH 2 CH 3 , -OH, -OC H. 3 , or -CH(CH 3 ) 2 is.

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

[0060] In some aspects, R 5 is a hydrogen cis to the C19 position. in some other aspect , R 5 is a hydrogen trans to the C19 position. In some embodiments, R 5 , C1 It is methyl cis to the 9-position. In some further embodiments, R 5 but ranked C19 It is methyl in trans position. Formula (II-I) and Formula (II-II): Group R 19

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

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

[0063] In other embodiments, R 19 is replaced by C 2 ~C 6 is alkyl. In other embodiments, R 19 is the unsubstituted C 2 ~C 6 is alkyl.

[0064] In other embodiments, R 19 is a substituted alkenyl. In other embodiments, R 19 but, It is unsubstituted alkenyl.

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

[0066] In some embodiments, R 19 is the deuterium-substituted C 2 -C 6 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 is.

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

[0070] In some aspects, R 6a and R 6b is independently hydrogen or substituted alkyl. one In some embodiments, R 6a and R 6b is independently hydrogen or unsubstituted alkyl.

[0071] In some aspects, R 6a and R 6b are both hydrogen. In some aspects, R 6a but , halo or alkyl, and R 6b is hydrogen. In some embodiments, R 6a and and R6b are both halos.

[0072] In some aspects, 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 are each independently hydrogen, halogen, ano, nitro, azido, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted substituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl le, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D 1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted substituted aryl, or substituted or unsubstituted heteroaryl.

[0075] In some aspects, R 12a and R 12b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl.

[0076] In some embodiments, R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le.

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

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

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

[0080] In some embodiments, Ring A is [formation] is selected from the group consisting of here, [formation] indicates that ring A is attached to ring B.

[0081] In some embodiments, R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted kenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted It is a teroaryl.

[0082] In some embodiments, R 1 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; 0, 1, 2, 3, 4, or 5 and n is 0, 1, 2, 3, 4, or 5.

[0083] In some embodiments, R 1 but, [formation] and where R 20 each occurrence of is independently hydrogen, halogen, -NO 2 , -CN, -OR G A , -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 Archi nyl, substituted or unsubstituted C 3~4 Carbocyclyl, substituted or unsubstituted 3- to 4-membered hete is rocyclyl or optionally two R GA together with the intervening atoms, the substitution or forming an unsubstituted 3- to 4-membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 Carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; 0, 1, 2, 3, 4, or 5 and n is 0, 1, 2, 3, 4, or 5.

[0084] In some embodiments, the compound is of formula (II-Ia), (II-Iab) or (II- Iac) [formation] or a pharmaceutically acceptable salt thereof.

[0085] In some embodiments, the compound is of formula (II-Ib), (II-Ibb) or (II- Ibc) [formation] or a pharmaceutically acceptable salt thereof.

[0086] In some embodiments, the compound is of formula (II-Ic), (II-Icb) or (II- Icc) [formation] or a pharmaceutically acceptable salt thereof.

[0087] In some embodiments, the compound has the formula (II-Ie), (II-Ieb) or (II- IEC) [formation] or a pharmaceutically acceptable salt thereof, where m is 0, 1, 2, or 3; p is 0, 1, or 3; R. 32 is independently halogen, alkyl, hydroxyl, or cyano.

[0088] In some embodiments, the compound is of formula (II-Ig), (II-Igb) or (II- Igc) [formation] 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring or a pharmaceutically acceptable salt thereof.

[0089] In some embodiments, the compound is of formula (II-Ieg), (II-Iegb) or (I I-Iegc) [formation] 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring or a pharmaceutically acceptable salt thereof.

[0090] In some embodiments, the compound has the formula (II-Ih), (II-Ihb) or (II- Ihc) [formation] or a pharmaceutically acceptable salt thereof, wherein R 35 each of the independently is logene, alkyl, hydroxyl, or cyano; r is 0, 1, 2, or 3 be.

[0091] In some embodiments, the compound is of formula (II-Ii), (II-Iib) or (II- IC) [formation] is a compound of 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 independently , hydrogen, substituted or unsubstituted C1-6 alkyl, C(=O)R GA , -C(=O) OR G A , -C(=O)N(RGA ) 2 , -S(=O) 2 R. GA , or -S(=O) 2 N(R GA ) 2 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring or a pharmaceutically acceptable salt thereof.

[0092] In some embodiments, the compound is of formula (II-IIa) or (II-IIab) [formation] or a pharmaceutically acceptable salt thereof.

[0093] In some embodiments, the compound is of formula (II-IIb) or (II-IIbb) [formation] or a pharmaceutically acceptable salt thereof.

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

[0095] In some embodiments, the compound has the formula (II-IIe) or (II-IIeb) [formation] is a compound of 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; or a pharmaceutically acceptable salt thereof.

[0096] In some embodiments, the compound has the formula (II-IIg) or (II-IIgb) [formation] 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring or a pharmaceutically acceptable salt thereof.

[0097] In some embodiments, the compound has the formula (II-IIh) or (II-IIhb) [formation] or a pharmaceutically acceptable salt thereof, where R 35 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) [formation] is a compound of where v is 0, 1, 2, or 3, n is 0, 1, or 2, and each X is unique. -C(R N )-, -C(R N ) 2 -, -O-, -S-, -N-, or N(R N )-, where R N is 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 is;

[0099] R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring or a pharmaceutically acceptable salt thereof. [000100] In some embodiments, the compound is from the group consisting of compounds identified in Table II-1 below. Selected: [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, formula (III-I) [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, In formula (III-I), R. 5 is hydrogen or substituted or unsubstituted methyl (e.g., -CH 3 ) or [formation] is a double bond, then 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 rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl can be; 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 is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, 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 hydrogen, halogen, cyano, hydrated roxyl, 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 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or optionally substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, attached to a nitrogen atom is a nitrogen protecting group if two R D1 groups taken together to form a substituted or unsubstituted form a monocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a oh and R 2b , R 4a and R 4b , R 11a and R 11b , as well as R 18a and R 18b together form an oxo (=O) group; R. 7a , R 7b , R 7aa , and R 7bb is independently hydrogen, halogen, cyan no, 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 of is independently hydrogen, substituted or unsubstituted alkyl, substituted substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, oxygen protecting group when attached to oxygen atom, nitrogen atom is a nitrogen protecting group when attached, or two R D1 the groups together are substituted or forming an unsubstituted heterocyclic ring; or R 7a and R 7b and R 7aa and R 7bb together form an oxo (=O) group; R. 16a , R 16b , R 17a , and R 17b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -S R. A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(= O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O) SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O) OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O ) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 de , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carboxy cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted is an unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, sulfur protecting group when attached to a nitrogen atom, nitrogen protecting group when attached to a nitrogen atom, 2 R. A2 , -C(O)R A2 or two R A1 groups together form a substituted or unsubstituted heterocyclic ring or or form a 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 is unsubstituted heteroaryl, or R 17a and R 17b together oxo forming a group; here, [formation] represents a single or double bond, and if a double bond is present, R 5and R 6a or R 6b does not exist. [000102] In one aspect, formula (III-I) [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, In formula (III-I), R. 5 is hydrogen or substituted or unsubstituted methyl (e.g., -CH 3 ) or [formation] is a double bond, then 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 lyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R. 19 is substituted or unsubstituted alkyl (e.g., substituted or unsubstituted C 1 -C 6 Al alkyl), substituted or unsubstituted alkenyl (e.g. substituted or unsubstituted C 2 -C 6 Arche nyl), or substituted or unsubstituted alkynyl (e.g., substituted or unsubstituted C 2 -C 6 alkynyl); R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, 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 hydrogen, halogen, cyano, hydrated roxyl, 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 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or optionally substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, attached to a nitrogen atom is a nitrogen protecting group if two R D1 groups taken together to form a substituted or unsubstituted form a monocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a oh and R 2b , R 4a and R 4b , R 11a and R 11b , as well as R 18a and R 18b together form an oxo (=O) group; R. 7a , R 7b , R 7aa , and R 7bb is independently hydrogen, halogen, cyan no, 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 of is independently hydrogen, substituted or unsubstituted alkyl, substituted substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, oxygen protecting group when attached to oxygen atom, nitrogen atom is a nitrogen protecting group when attached, or two R D1 the groups together are substituted or forming an unsubstituted heterocyclic ring; or R 7a and R 7b and R 7aa and R 7bb together form an oxo (=O) group; R. 16a , R 16b , R 17a , and R 17b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -S R. A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(= O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O) SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O) OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O ) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 de , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carboxy cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted is an unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, sulfur protecting group when attached to a nitrogen atom, nitrogen protecting group when attached to a nitrogen atom, 2 R. A2 , -C(O)R A2 or two R A1 groups together form a substituted or unsubstituted heterocyclic ring or or form a 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 is unsubstituted heteroaryl, or R 17a and R 17btogether oxo forming a group; here, [formation] represents a single or double bond, and if a double bond is present, R 5 and R 6a or R 6b does not exist. [000103] In one aspect, formula (III-II) [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, In formula (III-II), R. 5 is hydrogen or substituted or unsubstituted methyl (e.g., -CH 3 ) or [formation] is a double bond, then 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 rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl can be; R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, 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 hydrogen, halogen, cyano, hydrated roxyl, 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 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or optionally substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, attached to a nitrogen atom is a nitrogen protecting group if two R D1 groups taken together to form a substituted or unsubstituted form a monocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a oh and R 2b , R 4a and R 4b , R 11a and R 11b , as well as R 18a and R 18b together form an oxo (=O) group; R. 7a , R 7b , R 7aa , and R 7bb is independently hydrogen, halogen, cyan no, 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 of is independently hydrogen, substituted or unsubstituted alkyl, substituted substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, oxygen protecting group when attached to oxygen atom, nitrogen atom is a nitrogen protecting group when attached, or two R D1 the groups together are substituted or forming an unsubstituted heterocyclic ring; or R 7a and R 7b and R 7aa and R 7bb together form an oxo (=O) group; R. 16a , R 16b , R 17a , and R 17b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -S R. A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(= O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O) SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O) OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O ) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 de , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carboxy cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted is an unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, sulfur protecting group when attached to a nitrogen atom, nitrogen protecting group when attached to a nitrogen atom, 2 R. A2 , -C(O)R A2 or two R A1 groups together form a substituted or unsubstituted heterocyclic ring or or form a 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 is an unsubstituted heteroaryl; here, [formation] represents a single or double bond, and if a double bond is present, R 5 and R 6a or R 6b does not exist. Formula (III-I) and Formula (III-II): Group R 1a and R 1b [000104] In some aspects, R 1a and R 1b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is 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 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000105] In some aspects, R 1a and R 1b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000106] In some aspects, R 1a and R 1b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl . [000107] In some aspects, R 1a and R 1b are both hydrogen. [000108] In some embodiments, R 1a and R 1b are each independently hydrogen or substituted or It is 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 -O is H. [000110] In some embodiments, R 1a and R 1b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (III-I) and Formula (III-II): Group R 2a and R 2b [000111] In some aspects, R 2a and R 2b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is 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 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000112] In some aspects, R 2a and R 2b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000113] In some aspects, R 2a and R 2b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl . [000114] In some aspects, R 2a and R 2b are both hydrogen. [000115] In some embodiments, R 2a and R 2b are each independently hydrogen or substituted or It is unsubstituted alkyl. [000116] In some embodiments, R 2a and R 2b are each independently hydrogen, C 1 ~C 6 Archi L, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, also is -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 is. Formula (III-I) and Formula (III-II): Group R 4a and R 4b [000118] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is 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 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000119] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000120] In some aspects, R 4a and R 4b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl . [000121] In some aspects, R 4a and R 4b are both hydrogen. In a further embodiment, R 4a and R 4b are each independently hydrogen or substituted or unsubstituted alkyl. [000122] In some aspects, 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 with alkoxyhalo, or -OH be. In some other aspects, R 4a and R 4b but -CH 3 , -CH 2 CH 3 , -OH , -OCH 3 , or -CH(CH 3 ) 2 is. Formula (III-I) and Formula (III-II): Group R 11a and R 11b [000123] In some embodiments, R 11a and R 11b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl. [000124] In some further embodiments, R 11a and R 11b are each independently hydrogen, halo gen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk nil, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl. [000125] In some aspects, R 11a and R 11b are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be. In some aspects, R 11a and R 11b are both hydrogen. [000126] In some aspects, R 11a and R 11b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 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 Arco xyhalo, or -OH. [000127] In some aspects, R 11a and R 11b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. [000128] In some embodiments, R 11a and R 11b together form oxo (=O) be. Formula (III-I) and Formula (III-II): Group R 16a and R 16b [000129] In some aspects, R 16a and R 16b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl. [000130] In some embodiments, R 16a and R 16b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl. [000131] In some embodiments, R 16a and R 16b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le. [000132] In some further embodiments, R 16a and R 16b are both hydrogen. [000133] In some aspects, R 16a and R 16b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 16a and R 16b each of the water independently elementary, 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 aspects, R 16a and R 16b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (III-I) and Formula (III-II): Group R 7a , R 7b , R 7aa , and R 7 bb [000135] In some embodiments, R 7a , R 7b , R 7aa , and R 7bb but each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted substituted alkenyl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted alkyl nil, -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 is unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted is substituted 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 but each independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N( R. D1 ) 2 , where 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 aspects, R 7a , R 7b , R 7aa , and R 7bb are each independently 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 existence is unique hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted substituted heteroaryl. [000138] In some aspects, R 7a , R 7b , R 7aa , and R 7bb are all hydrogen. [000139] In some aspects, R 7a , R 7b , R 7aa , and R 7bb are each independently hydrogen or substituted or unsubstituted alkyl. In some aspects, R 7a , R 7b , R 7aa , and R 7bb are each independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkie L, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, or -OH. [000140] In some aspects, R 7a , R 7b , R 7aa , and R 7bb but -CH 3 , -CH 2 CH 3 , -OH, -OCH 3 , or -CH(CH 3 ) 2 is. [000141] In some embodiments, R 7a and R 7b or R 7aa and R 7bb is either Together they form oxo (=O). Formula (III-I) and Formula (III-II): Group R 5 [000142] In some aspects, R 5 is a cis hydrogen. In some other aspects, R 5 but hydrogen at the position. In some embodiments, R 5 is cis-methyl. some more In an embodiment where R 5 is methyl in 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 substituted alkenyl, or substituted or unsubstituted alkynyl; [000144] In some embodiments, R 3 is substituted or unsubstituted carbocyclyl, substituted or unsubstituted substituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl is a rule. [000145] In some embodiments, R 3 is a substituted or unsubstituted alkyl. [000146] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a substituted alkyl is le. In some embodiments, R 3 is an unsubstituted alkyl. In some embodiments R. 3 is methyl. Formula (III-I): Group R 19 [000147] In some aspects, R 19 is hydrogen. [000148] In some embodiments, R 19 is a substituted alkyl. In some embodiments, R 19 but , is an unsubstituted alkyl. [000149] In some embodiments, R 19 is methyl. In some embodiments, R 19 but -O CH 3 is. In some aspects, 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 is. [000151] In some aspects, R 6a and R 6b is independently hydrogen or substituted or unsubstituted Kill. [000152] In some aspects, R 6a and R 6b is independently hydrogen or substituted alkyl. one In some embodiments, R 6a and R 6b is independently hydrogen or unsubstituted alkyl. [000153] In some aspects, R 6a and R 6b are both hydrogen. In some aspects, R 6a but , halo or alkyl, and R 6b is hydrogen. In some embodiments, R 6a and and R 6b are both halos. [000154] In some aspects, 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 are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl. [000157] In some aspects, R 12a and R 12b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl. [000158] In some embodiments, R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le. [000159] In some embodiments, R 12a and R 12b are both hydrogen. [000160] In some further embodiments, R 12a and R 12b are each independently hydrogen or is substituted or unsubstituted alkyl. [000161] In some embodiments, R 12a and R 12b together form an oxo group (=O) do. Formula (III-I) and Formula (III-II): Group R 17a and R 17b [000162] In some aspects, R 17a and R 17b is substituted or unsubstituted alkyl, substituted if or unsubstituted alkenyl, 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 A1 each occurrence of is independently hydrogen, substituted or is unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted substituted 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 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 substituted heteroaryl. [000164] In some aspects, R 17a and R 17b is -C(O)R A1 , where R A1 is substituted alkyl. [000165] In some embodiments, alkyl is substituted with 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 are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl. [000168] In some aspects, R 18a and R 18b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl. [000169] In some embodiments, R 18a and R 18b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le. [000170] In some embodiments, R 18a and R 18b are both hydrogen. [000171] In some further embodiments, R 18a and R 18b are each independently hydrogen or It is substituted or unsubstituted alkyl. [000172] In some embodiments, R 18a and R 18b together form an oxo group (=O) do. Formula (III-I) [000173] In some embodiments, the compound is of Formula (III-Ia) [formation] or a pharmaceutically acceptable salt thereof. [000174] In some embodiments, the compound is of Formula (III-Ib) [formation] or a pharmaceutically acceptable salt thereof. [000175] In some embodiments, the compound is of formula (III-Ic) [formation] or a pharmaceutically acceptable salt thereof. [000176] In some embodiments, the compound has the formula (III-Id) [formation] or a pharmaceutically acceptable salt thereof. [000177] In some embodiments, the compound is of formula (III-Ie) [formation] or a pharmaceutically acceptable salt thereof. [000178] In some embodiments, the compound has the formula (III-If) [formation] or a pharmaceutically 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 le, -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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, or 2. [000179] In some embodiments, the compound has the formula (III-Ig) [formation] or a pharmaceutically 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 le, -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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3. [000180] In some embodiments, the compound has the formula (III-Ih) [formation] or a pharmaceutically 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do. [000181] In some embodiments, the compound is of formula (III-Ii) [formation] or a pharmaceutically 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do. [000182] In some embodiments, the compound has formula (III-Ij) [formation] or a pharmaceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; 21 is independently halogen, alkyl, hydroxyl, or cyano. [000183] In some embodiments, the compound has the formula (III-Ik) [formation] or a pharmaceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, or 2; 21 is independently halogen, alkyl, hydroxyl, or cyano. [000184] In some embodiments, R 21 is -CN. In some embodiments, m is 1 and n is 1. [000185] In some embodiments, the compound has the formula (III-IL) [formation] or a pharmaceutically acceptable salt thereof. [000186] In some embodiments, the compound has the formula (III-Im) [formation] or a pharmaceutically acceptable salt thereof. [000187] In some embodiments, the compound of formula (III-I) is a compound of formula (III-In) or formula (I II-Io) [formation] or a pharmaceutically 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 independently , hydrogen, substituted or unsubstituted C 1~6 Alkyl, C(=O)R GA , -C(=O) OR G A , -C(=O)N(R GA ) 2 , -S(=O) 2 R. GA , or -S(=O) 2 N(R GA ) 2 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do. Formula (III-II) [000188] In some embodiments, the compound is of formula (III-IIa) [formation] or a pharmaceutically acceptable salt thereof. [000189] In some embodiments, the compound is of Formula (III-IIb) [formation] or a pharmaceutically acceptable salt thereof. [000190] In some embodiments, the compound is of formula (III-IIc) [formation] or a pharmaceutically acceptable salt thereof. [000191] In some embodiments, the compound is of formula (III-IId) [formation] or a pharmaceutically acceptable salt thereof. [000192] In some embodiments, the compound is of formula (III-IIe) [formation] or a pharmaceutically acceptable salt thereof. [000193] In some embodiments, the compound has the formula (III-IIf) [formation] or a pharmaceutically acceptable salt thereof, where 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 Roaryl, -OR A1 , -SR A1 , -N(R A1 ) 2 , -OC(=O)R A1 , -O C(=O)OR A1 , -OC(=O)SR A1 , -OC(=O)N(R A1 ) 2 , -SC (=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 , -SC(=O)N (R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 , -NHC(=O) SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid Oxygen protecting group when bonding to a nitrogen atom, sulfur protecting group when bonding to a sulfur atom, nitrogen atom is a nitrogen protecting group when attached, or two R A1 the groups together are substituted or forming an unsubstituted heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3 be. [000194] In some embodiments, the compound has the formula (III-IIg) [formation] or a pharmaceutically 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 le, -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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3. [000195] In some embodiments, the compound has the formula (III-IIh) [formation] or a pharmaceutically 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do. [000196] In some embodiments, the compound has the formula (III-IIi) [formation] or a pharmaceutically 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do. [000197] In some embodiments, the compound has the formula (III-IIj) [formation] or a pharmaceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, or 2; 21 is independently halogen, alkyl, hydroxyl, or cyano. [000198] In some embodiments, the compound has the formula (III-IIk) [formation] or a pharmaceutically acceptable salt thereof, where m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; 21 is independently halogen, alkyl, hydroxyl, or cyano. [000199] In some embodiments, R 21 is -CN. In some embodiments, m is 1 and n is 1. [000200] In some embodiments, the compound has the formula (III-IIL) [formation] or a pharmaceutically acceptable salt thereof. [000201] In some embodiments, the compound is of formula (III-IIm) [formation] or a pharmaceutically acceptable salt thereof. [000202] In some embodiments, the compound is of Formula (III-IIn) or Formula (III-IIo) [formation] or a pharmaceutically 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 independently , hydrogen, substituted or unsubstituted C1-6 alkyl, C(=O)R GA , -C(=O) OR G A , -C(=O)N(R GA ) 2 , -S(=O) 2 R. GA , or -S(=O) 2 N(R GA ) 2 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, acid when attached to oxygen a nitrogen protecting group, a nitrogen protecting group when attached to a nitrogen, or two R GA group is an intervening atom together form a substituted or unsubstituted heterocyclyl or heteroaryl ring do. [000203] In some embodiments, R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted kenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl is the reel. [000204] In some embodiments, R 1 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; 0, 1, 2, 3, 4, or 5. [000205] In some embodiments, R 1 but, [formation] and where R 20 each occurrence of is independently 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 G A , -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 G A ) 2 , or -N(R GA )S(=O) 2 R. GA ;substituted or unsubstituted C 1~6 Archi le, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~4 carbocyclyl, substituted or unsubstituted 3- or 4-membered heterocyclyl Ril or two Rs as appropriate GA together with the intervening atoms, either substituted or forms an unsubstituted 3-4 membered carbocyclic or heterocyclic ring; where R GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 alkyl, substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or unsubstituted C 3~6 carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, when attached to oxygen an oxygen protecting group when attached to a nitrogen, a nitrogen protecting group when attached to a nitrogen, or two R GA base is intervening together with the remaining atoms form a substituted or unsubstituted carbocyclic or heterocyclic ring; e or is 0, 1, 2, 3, 4, or 5. [000206] In one aspect, formula (IV-I): [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, In formula (IV-I), R. 5 is hydrogen or substituted or unsubstituted methyl, or [formation] is a double bond, then 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 rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl can be; R. 19 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or is substituted or unsubstituted alkynyl; R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, 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 hydrogen, halogen, cyano, hydrated roxyl, 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 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or optionally substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, attached to a nitrogen atom is a nitrogen protecting group if two R D1 groups taken together to form a substituted or unsubstituted form a monocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a oh and R 2b , R 4a and R 4b , R 11a and R 11b , as well as R 18a and R 18b together form an oxo (=O) group; R. 16a , R 16b , R 17a , and R 17b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -S R. A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(= O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O) SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O) OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O ) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 de , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carboxy cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted is an unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, sulfur protecting group when attached to a nitrogen atom, nitrogen protecting group when attached to a nitrogen atom, 2 R. A2 , -C(O)R A2 or two R A1 groups together form a substituted or unsubstituted heterocyclic ring or or form a 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 is an unsubstituted heteroaryl; here, [formation] represents a single or double bond, and if a double bond is present, R 5 and R 6a or R 6b does not exist. [000207] In one aspect, Formula (IV-I): [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, In formula (IV-I), R. 5 is hydrogen or substituted or unsubstituted methyl, or [formation] is a double bond, then 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 lyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R. 19 is substituted or unsubstituted alkyl (e.g., substituted or unsubstituted C 1 -C 6 Al alkyl), substituted or unsubstituted alkenyl (e.g. substituted or unsubstituted C 2 -C 6 Arche nyl), or substituted or unsubstituted alkynyl; R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, 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 hydrogen, halogen, cyano, hydrated roxyl, 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 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or optionally substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, attached to a nitrogen atom is a nitrogen protecting group if two R D1 groups taken together to form a substituted or unsubstituted form a monocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a oh and R 2b , R 4a and R 4b , R 11a and R 11b , as well as R 18a and R 18b together form an oxo (=O) group; R. 16a , R 16b , R 17a , and R 17b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -ORA1 , -S R. A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(= O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O) SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O) OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O ) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 de , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carboxy cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted is an unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, sulfur protecting group when attached to a nitrogen atom, nitrogen protecting group when attached to a nitrogen atom, 2 R. A2 , -C(O)R A2 or two R A1 groups together form a substituted or unsubstituted heterocyclic ring or or form a 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 is an unsubstituted heteroaryl; here, [formation] represents a single or double bond, and if a double bond is present, R 5 and R 6a or R 6b does not exist. [000208] In one aspect, Formula (IV-II): [formation] Provided herein is a compound of or a pharmaceutically acceptable salt thereof, In formula (IV-II), R. 5 is hydrogen or substituted or unsubstituted methyl (e.g., -CH 3 ) or [formation] is a double bond, then 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 rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl can be; R. 6a and R 6b is independently hydrogen, halogen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted is lukynyl, 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 hydrogen, halogen, cyano, hydrated roxyl, 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 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or optionally substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, attached to a nitrogen atom is a nitrogen protecting group if two R D1 groups taken together to form a substituted or unsubstituted form a monocyclic ring; or R 1a and R 1b , R 12a and R 12b , R 2a oh and R 2b , R 4a and R 4b , R 11a and R 11b , as well as R 18a and R 18b together form an oxo (=O) group; R. 16a , R 16b , R 17a , and R 17b are each independently hydrogen, halo gen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl , substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -OR A1 , -S R. A1 , -N(R A1 ) 2 , -N(R A1 ), -CN(R A1 ) 2 , -C(O)R A1 , -OC(=O)R A1 , -OC(=O)OR A1 , -OC(=O)SR A1 , -OC(= O)N(R A1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O) SR A1 , -SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O) OR A1 , -NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O ) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 de , where R A1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carboxy cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted is an unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, sulfur protecting group when attached to a nitrogen atom, nitrogen protecting group when attached to a nitrogen atom, 2 R. A2 , -C(O)R A2 or two R A1 groups together form a substituted or unsubstituted heterocyclic ring or or form a 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 is an unsubstituted heteroaryl; here, [formation] represents a single or double bond, and if a double bond is present, R 5 and R 6a or R 6b does not exist. [000209] In one aspect, formulas (IV-III) [formation] Provided herein are compounds of In formula (IV-III), R. 1 is hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted C, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbo cyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or 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 A 1 ) 2 , -SC(=O)R A2 , -SC(=O)OR A1 , -SC(=O)SR A1 ,- SC(=O)N(R A1 ) 2 , -NHC(=O)R A1 , -NHC(=O)OR A1 ,- NHC(=O)SR A1 , -NHC(=O)N(R A1 ) 2 , -OS(=O) 2 R. A2 , -OS(=O) 2 OR A1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 , -SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 each occurrence 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, substituted or unsubstituted Loaryl, oxygen protecting group when attached to an oxygen atom, sulfur protection when attached to a sulfur atom group, a nitrogen protecting group when attached to a nitrogen atom, or two R A1 base together to form a substituted or unsubstituted heterocyclic or heteroaryl ring; R A2 also replace or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl , substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or is unsubstituted aryl, or substituted or unsubstituted heteroaryl; R. 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl can be; 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). Formula (IV-I) and Formula (IV-II): Group R 1a and R 1b [000210] In some aspects, R 1a and R 1b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is 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 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000211] In some aspects, R 1a and R 1b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000212] In some aspects, R 1a and R 1b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl . [000213] In some aspects, R 1a and R 1b are both hydrogen. [000214] In some embodiments, R 1a and R 1b are each independently hydrogen or substituted or It is unsubstituted alkyl. [000215] In some embodiments, R 1a and R 1b are independently hydrogen, C 1 ~C 6 Alkyl, C 1 ~C6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, or -O is H. [000216] In some embodiments, R 1a and R 1b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (IV-I) and Formula (IV-II): Group R 2a and R 2b [000217] In some aspects, R 2a and R 2b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is 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 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000218] In some aspects, R 2a and R 2b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000219] In some aspects, R 2a and R 2b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl . [000220] In some aspects, R 2a and R 2b are both hydrogen. [000221] In some embodiments, R 2a and R 2b are each independently hydrogen or substituted or It is unsubstituted alkyl. [000222] In some embodiments, R 2a and R 2b are each independently hydrogen, C 1 ~C 6 Archi L, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, also is -OH. [000223] In some embodiments, R 2a and R 2b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (IV-I) and Formula (IV-II): Group R 4a and R 4b [000224] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, doloxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is 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 is , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbosyl lyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000225] In some aspects, R 4a and R 4b are each independently hydrogen, halogen, cyano, droxyl, 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 of each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000226] In some aspects, R 4a and R 4b are each independently hydrogen, substituted or unsubstituted Rukir, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -N R. D1 C(=O)R D1 , where R D1 each occurrence of is independently hydrogen, substituted if or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl is cryl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl . [000227] In some aspects, R 4a and R 4b are both hydrogen. In a further embodiment, R 4a and R 4b are each independently hydrogen or substituted or unsubstituted alkyl. [000228] In some aspects, 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 with alkoxyhalo, or -OH be. In some other aspects, R 4a and R 4b but -CH 3 , -CH 2 CH 3 , -OH , -OCH 3 , or -CH(CH 3 ) 2 is. Formula (IV-I) and Formula (IV-II): Group R 11a and R 11b [000229] In some embodiments, R 11a and R 11b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl. [000230] In some further embodiments, R 11a and R 11b are each independently hydrogen, halo gen, cyano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alk nil, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 and where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or is unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl aryl, or substituted or unsubstituted heteroaryl. [000231] In some aspects, R 11a and R 11b are each independently hydrogen, substituted or unsubstituted substituted 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 hetero rocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl be. In some aspects, R 11a and R 11b are both hydrogen. [000232] In some aspects, R 11a and R 11b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 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 Arco xyhalo, or -OH. [000233] In some aspects, R 11a and R 11b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. [000234] In some embodiments, R 11a and R 11b together form oxo (=O) be. Formula (IV-I) and Formula (IV-II): Group R 16a and R 16b [000235] In some aspects, R 16a and R 16b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted also or unsubstituted heterocyclyl, or substituted or unsubstituted alkynyl, -OR D1 , -O C(=O)R D1 , -NH 2 , -N(R D1 ) 2 , or -NR D1 C(=O)R D1 in Yes, where R D1 each occurrence of is independently 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 It is substituted or unsubstituted heteroaryl. [000236] In some embodiments, R 16a and R 16b are each independently hydrogen, halogen, ano, 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 or substituted or unsubstituted heteroaryl. [000237] In some embodiments, R 16a and R 16b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le. [000238] In some further embodiments, R 16a and R 16b are both hydrogen. [000239] In some aspects, R 16a and R 16b are each independently hydrogen or substituted or It is unsubstituted alkyl. In some aspects, R 16a and R 16b each of the water independently elementary, C 1 ~C 6 Alkyl, C 1 ~C 6 haloalkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 alkoxyhalo, or -OH. [000240] In some aspects, R 16a and R 16b but -CH 3 , -CH 2 CH 3 , -OH, - OCH 3 , or -CH(CH 3 ) 2 is. Formula (IV-I) and Formula (IV-II): Group R 5 [000241] In some aspects, R 5 is a cis hydrogen. In some other aspects, R 5 but hydrogen at the position. In some embodiments, R 5 is cis-methyl. some more In an embodiment where R 5 is methyl in trans position. Formula (IV-I), Formula (IV-II) and Formula (IV-III): Group R 3 [000242] In some embodiments, R 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted substituted alkenyl, or substituted or unsubstituted alkynyl; [000243] In some embodiments, R 3 is substituted or unsubstituted carbocyclyl, substituted or unsubstituted substituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl is a rule. [000244] In some embodiments, R 3 is a substituted or unsubstituted alkyl. [000245] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is a substituted alkyl is le. In some embodiments, R 3 is an unsubstituted alkyl. In some embodiments R. 3 is methyl. Formula (IV-I) and Formula (IV-III): Group R 19 [000246] In some aspects, R 19 is hydrogen. [000247] In some embodiments, R 19 is a substituted alkyl. In some embodiments, R 19 but , is an unsubstituted alkyl. [000248] In some embodiments, R 19 is methyl. In some embodiments, R 19 but -O CH 3 is. In some aspects, R 19 is ethyl. Formula (IV-I) and Formula (IV-II): Group R 6a and R 6b [000249] 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 is. [000250] In some aspects, R 6a and R 6b is independently hydrogen or substituted or unsubstituted Kill. [000251] In some aspects, R 6a and R 6b is independently hydrogen or substituted alkyl. one In some embodiments, R 6a and R 6b is independently hydrogen or unsubstituted alkyl. [000252] In some aspects, R 6a and R 6b are both hydrogen. In some aspects, R 6a but , halo or alkyl, and R 6b is hydrogen. In some embodiments, R 6a and and R 6b are both halos. [000253] In some aspects, R 6a and R 6b are both alkyl. [000254] In some embodiments, R 6a and R 6b together form an oxo group. Formula (IV-I) and Formula (IV-II): Group R 12a and R 12b [000255] In some embodiments, R 12a and R 12b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl. [000256] In some aspects, R 12a and R 12b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl. [000257] In some embodiments, R 12a and R 12b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le. [000258] In some embodiments, R 12a and R 12b are both hydrogen. [000259] In some further embodiments, R 12a and R 12b are each independently hydrogen or is substituted or unsubstituted alkyl. [000260] In some embodiments, R 12a and R 12b together form an oxo group (=O) do. Formula (IV-I) and Formula (IV-II): Group R 17a and R 17b [000261] In some aspects, R 17a and R 17b is substituted or unsubstituted alkyl, substituted if or unsubstituted alkenyl, 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)OR A1 , -C(=O)N(R A1 ) 2 , -OC(=O)SR A1 , or -OC(=O)N(R A1 ) 2 , where R A1 each existence of is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl lyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. [000262] 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 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 substituted heteroaryl. [000263] In some aspects, R 17a and R 17b is -C(O)R A1 , where R A1 is substituted alkyl. [000264] In some embodiments, alkyl is substituted with heteroaryl. [000265] In some further embodiments, the alkyl is substituted with a 5-membered heteroaryl. Formula (IV-I) and Formula (IV-II): Group R 18a and R 18b [000266] In some embodiments, R 18a and R 18b are each independently hydrogen, halogen, ano, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted 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 D 1 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl. [000267] In some aspects, R 18a and R 18b are each independently hydrogen, halogen, cyano , hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -OR D1 , -OC(=O)R D1 , -NH 2 , or -N(R D1 ) 2 , where R D1 each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted bocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or It is substituted or unsubstituted heteroaryl. [000268] In some embodiments, R 18a and R 18b are each independently hydrogen, substituted or unsubstituted alkyl, -OR D1 , -OC(=O)R D1 , -NH 2 , -N(R D1 ) 2 ,Ma 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 is le. [000269] In some embodiments, R 18a and R 18b are both hydrogen. [000270] In some further embodiments, R 18a and R 18b are each independently hydrogen or It is substituted or unsubstituted alkyl. [000271] In some embodiments, R 18a and R 18b together form an oxo group (=O) do. Formula (IV-I) [000272] In some embodiments, the compound is of Formula (IV-Ia) [formation] or a pharmaceutically acceptable salt thereof. [000273] In some embodiments, the compound is of Formula (IV-Ib) [formation] or a pharmaceutically acceptable salt thereof. [000274] In some embodiments, the compound is of formula (IV-Ic) [formation] or a pharmaceutically acceptable salt thereof. [000275] In some embodiments, the compound has the formula (IV-Id) [formation] or a pharmaceutically acceptable salt thereof. [000276] In some embodiments, the compound is of formula (IV-Ie) [formation] or a pharmaceutically acceptable salt thereof. [000277] In some embodiments, the compound has the formula (IV-If) [formation] or a pharmaceutically 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 le, -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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, 2 or 3. [000278] In some embodiments, the compound has the formula (IV-Ig) [formation] or a pharmaceutically 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 le, -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 A 1 , -S-S(=O) 2 R. A2 , -S-S(=O) 2 OR A1 , -S(=O)R A2 ,- SO 2 R. A2 , or -S(=O) 2 OR A1 , where R A1 existence of each is independent is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or is unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl acryl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, oxygen atom Oxygen protecting group when binding, sulfur protecting group when binding to a sulfur atom, binding to a nitrogen atom is a nitrogen protecting group if two R A1 groups together are substituted or unsubstituted forming a heterocyclic or heteroaryl ring; R A2 is a substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted rubocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or is substituted or unsubstituted heteroaryl; n is 0, 1, 2, or 3. [000279] In some embodiments, the compound has the formula (IV-Ih) [formation] or a pharmaceutically 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 is 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 is; R. GA each occurrence of is independently hydrogen, substituted or unsubstituted C 1~6 Alkyl, also substituted or unsubstituted C 2~6 alkenyl, substituted or unsubstituted C 2~6 alkynyl, substituted or is unsubstituted C 3~6 carbocyclyl, substituted or unsub...

Claims

1. Formula (I-I): 【Chemistry 424】 or a pharma- ceutically acceptable salt thereof, In formula (II), t is 1; R ７ is hydrogen; R ３ is a substituted or unsubstituted C １～３ is alkyl; R ９ is hydrogen or unsubstituted C １～３ is alkyl; R ５ａ , R ５ｂ , R ６ａ , R ６ｂ , R １１ａ , R １１ｂ , R １５ａ , R １５ｂ , R １６ａ , R １６ｂ , R １７ａ , R １７ｂ , R １８ａ , R １８ｂ , R １９ａ , or R １９ｂ each is hydrogen; R ８ and R １３ each 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, -SR Ａ１ , -N(R Ａ１ ) ２ , -C(O)R Ａ１ , -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 , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ where R Ａ１ each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, an oxygen protecting group when attached to an oxygen atom, 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; Here, 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, -SR Ａ１ , -N(R Ａ１ ) ２ , -C(O)R Ａ１ , -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 , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ Must be; or R ８ and R １３ together form an oxo (=O) group, Here, R ８ and R １３ and cannot both be methyl; and Where: 【Chemistry 426】 represents a single bond, a compound or a pharma- ceutically acceptable salt thereof.

2. R ７ But, R ９ 2. The compound or pharma- ceutically acceptable salt of claim 1, wherein:

3. R ７ But, R ９ 2. The compound or pharma- ceutically acceptable salt of claim 1, wherein:

4. R ３ is unsubstituted C １～３ Alkyl or unsubstituted C １～３ Alkoxy-C １～３ 4. The compound or a pharma- ceutically acceptable salt according to any one of claims 1 to 3, wherein: R is an alkyl group;

5. R ３ The compound or pharma- ceutically acceptable salt of any one of claims 1 to 4, wherein is methyl, ethyl, methoxymethyl, or ethoxymethyl.

6. R ３ 6. The compound or pharma- ceutically acceptable salt according to any one of claims 1 to 5, wherein is methyl or ethoxymethyl.

7. R ９ The compound or pharma- ceutically acceptable salt of any one of claims 1 to 6, wherein is hydrogen, methyl, or ethyl.

8. The compound or pharma- ceutically acceptable salt according to any one of claims 1 to 7, wherein R9 is hydrogen.

9. The compound or pharma- ceutically acceptable salt according to any one of claims 1 to 7, wherein R9 is methyl.

10. R ８ is hydrogen and R １３ is a substituted or unsubstituted alkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, -SR Ａ１ , -N(R Ａ１ ) ２ , -C(O)R Ａ１ , -C(=O)N(R Ａ１ ) ２ , -OC(=O)R Ａ１ , -OC(=O)OR Ａ１ , -OC(=O)SR Ａ１ or -OC(=O)N(R Ａ１ ) ２ where R Ａ１ 10. The compound of any one of claims 1-9, or a pharma- ceutically acceptable salt thereof, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

11. R ８ Or R １３ is a substituted or unsubstituted alkyl, —C(O)R Ａ１ , -C(=O)N(R Ａ１ ) ２ , -OC(=O)R Ａ１ or -OC(=O)OR Ａ１ where R Ａ１ 10. The compound of any one of claims 1-9, or a pharma- ceutically acceptable salt thereof, wherein each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

12. R ８ Or R １３ But -C(O)R Ａ１ where R Ａ１ 12. The compound or pharma- ceutically acceptable salt of any one of claims 1 to 9 or 11, wherein is alkyl substituted with a substituted or unsubstituted heteroaryl.

13. The compound according to claim 1, wherein R 8 is hydrogen, R 13 is -C(O)R A1 , -C(=O)N(R A1 ) 2 , or -C(=O)NH(R A1 ), and each occurrence of R A1 is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, 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, wherein said heterocyclic or heteroaryl has at least one nitrogen atom; and R A2 or a pharma- ceutically acceptable salt thereof. The compound of any one of claims 1 to 9, wherein is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

14. The compound according to claim 14, wherein R 8 is hydrogen and R 13 is -N(R A1 ) 2 , where each occurrence of R A1 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, wherein said heterocyclic or heteroaryl has at least one nitrogen atom; and R A2 or a pharma- ceutically acceptable salt thereof. The compound of any one of claims 1 to 9, wherein is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

15. The compound of formula (II) is represented by formula (I-Ia) 【Chemistry 610】 or a pharma- ceutically acceptable salt thereof, Here, R １ is a substituted or unsubstituted alkyl, a substituted or unsubstituted carbocyclyl, a substituted or unsubstituted heterocyclyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, -OR Ａ１ , -SR Ａ１ , -N(R Ａ１ ) ２ , -N(R Ａ１ ), -OC(=O)R Ａ１ , -OC(=O)OR Ａ１ , -OC(=O)SR Ａ１ , -OC(=O)N(R Ａ１ ) ２ , -SC(=O)R Ａ２ , -SC(=O)OR Ａ１ , -SC(=O)SR Ａ１ , -SC(=O)N(R Ａ１ ) ２ , -NHC(=O)R Ａ１ , -NHC(=O)OR Ａ１ , -NHC(=O)SR Ａ１ , -NHC(=O)N(R Ａ１ ) ２ , -OS(=O) ２ R Ａ２ , -OS(=O) ２ OR Ａ１ , -S-S(=O) ２ R Ａ２ , -S-S(=O) ２ OR Ａ１ , -S(=O)R Ａ２ , -SO ２ R Ａ２ Or -S(=O) ２ OR Ａ１ where R Ａ１ Each occurrence of is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, 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 carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; 2. The compound or pharma- ceutically acceptable salt of claim 1, wherein n is 0, 1, 2, or 3.

16. The compound of formula (I-Ia) is represented by formula (I-Ib) 【Chemistry 611】 16. The compound or pharma- ceutically acceptable salt of claim 15, which is the compound or a pharma- ceutically acceptable salt thereof:

17. R １ but, 【Chemistry 430】 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 ３～４ carbocyclyl, or a substituted or unsubstituted 3- to 4-membered heterocyclyl; Here, R ＧＡ Each occurrence is independently hydrogen, substituted or unsubstituted C １～６ Alkyl, substituted or unsubstituted C ３～６ carbocyclyl, substituted or unsubstituted 3- to 6-membered heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or two R ＧＡ the groups, together with the intervening atoms, form a substituted or unsubstituted carbocyclic or heterocyclic ring; 17. The compound or pharma- ceutically acceptable salt of claim 15 or claim 16, wherein each of n and e is independently 0, 1, 2, 3, 4, or 5.

18. The compound of formula (II) is represented by formula (I-Id): 【Chemistry 612】 or a pharma- ceutically acceptable salt thereof, Here, R １０ 2. The compound or pharma- ceutically acceptable salt of claim 1, wherein is independently hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano.

19. The compound of formula (II) is represented by formula (I-Ie): 【Chemistry 613】 or a pharma- ceutically acceptable salt thereof, where e is 0, 1, 2, or 3; p is 0, 1, or 3; R ５ 2. The compound or pharma- ceutically acceptable salt of claim 1, wherein each of is independently halogen, alkyl, hydroxyl, or cyano.

20. The compound of formula (II) is represented by formula (I-If) 【Chemistry 614】 or a pharma- ceutically acceptable salt thereof, Here, R １０ 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein is hydrogen, halogen, substituted or unsubstituted alkyl, hydroxyl, or cyano. 【Request 21】 【Table 21-1】 【Table 21-2】 【Table 21-3】 【Table 21-4】 【Table 21-5】 【Table 21-6】 【Table 21-7】 【Table 21-8】 【Table 21-9】 【Table 21-10A】 【Table 21-11】 【Table 21-12】 or a pharma- ceutically acceptable salt thereof.

22. The compound, 【Chemistry 22-1】 【Chemistry 22-2】 【Chemistry 22-3】 【Chemistry 22-4】 【Chemistry 22-5】 【Chemistry 22-6】 【Chemistry 22-7】 or a pharma- ceutically acceptable salt thereof.

22. The compound of claim 21, wherein said compound is selected from:

23. The compound, 【Chemistry 23-1】 【Chemistry 23-2】 【Chemistry 23-3】 or a pharma- ceutically acceptable salt thereof.

22. The compound of claim 21, wherein said compound is selected from:

24. A pharmaceutical composition comprising a compound according to any one of claims 1 to 23 or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable excipient.

25. 24. A composition for use in treating a CNS-related disorder in a subject in need thereof, comprising a compound according to any one of claims 1 to 23 or a pharma- ceutically acceptable salt thereof, wherein the CNS-related disorder is a sleep disorder, a mood disorder, a schizophrenia spectrum disorder, a seizure disorder, a disorder of memory and / or cognition, a movement disorder, a personality disorder, an autism spectrum disorder, pain, a traumatic brain injury, a vascular disease, a substance abuse disorder and / or withdrawal syndrome, tinnitus, or status epilepticus.

26. 26. The composition of claim 25, wherein the CNS-related disorder is depression.

27. 27. The composition of claim 26, wherein the depression is postpartum depression.

28. 26. The composition of claim 25, wherein the CNS-related disorder is major depressive disorder.

29. 29. The composition of claim 28, wherein the major depressive disorder is moderate major depressive disorder.

30. 29. The composition of claim 28, wherein the major depressive disorder is severe major depressive disorder.

31. 26. The composition of claim 25, wherein the CNS-related disorder is seizures.

32. 26. The composition of claim 25, wherein the CNS-related disorder is epilepsy or status epilepticus.

33. 26. The composition of claim 25, wherein the CNS-related disorder is tremor.

34. 34. The composition of claim 33, wherein the tremor is essential tremor.

35. 26. The composition of claim 25, wherein the composition is administered chronically or acutely.

36. 36. The composition of claim 35, wherein the composition is administered orally, intravenously, transdermally, intranasally, or subcutaneously.

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