Compounds, compositions, and methods thereof

Abstract

Among other things, this disclosure provides compounds of formula I or salts thereof. In some embodiments, the provided compounds can be used as Nav1.8 antagonists. In some embodiments, this disclosure provides methods for preventing or treating symptoms, disorders, or diseases associated with Nav1.8.

Description

Technical Field

[0001] In some embodiments, the compounds and compositions provided in this disclosure can be used to regulate the activity of voltage-gated sodium channel 1.8 (Nav1.8). In some embodiments, the provided compounds and compositions help prevent or treat conditions, disorders, or diseases associated with Nav1.8, such as migraines, post-ischemic neurodegeneration, epilepsy, inflammatory pain, spontaneous pain, acute pain, preoperative pain, perioperative pain, postoperative pain, and neuropathic pain. In some embodiments, this disclosure provides techniques for preparing said compounds and compositions. Background Technology

[0002] According to literature, pain is a way for the body to perceive stimuli. It is an important early warning signal that alerts the body to the presence of tissue damage or injury and triggers an appropriate response.

[0003] According to some literature reports, painful stimuli involve electrical impulses transmitted from noxious dorsal root ganglion neurons through ascending pathways in the spinal cord, ultimately reaching the central nervous system (CNS). Pain receptors are thought to express voltage-gated sodium channels (VGSCs), which selectively mediate the influx of sodium ions and play a crucial role in initiating and conducting action potentials (APs) (Yu et al., *Genome Biology* 4:207, 2003). VGSCs are reportedly composed of nine α subunits encoded by genes SCN1A to SCN11A, forming complexes with β subunits that modulate channel properties. The fourth transmembrane segment (S4) of the α subunits acts as a voltage sensor, mediating the different electrophysiological characteristics of the nine Nav channel subtypes (Nav1.1–Nav1.9), resulting in distinct voltage-dependent and kinetic properties. Tetrodotoxin (TTX) has been reported to bind to Nav channels on the neuronal cell membrane, inhibiting the firing of neuronal action potentials. Based on their response to tetrodotoxin, Nav channels can be divided into two categories: TTX-sensitive channels (TTXs) such as Nav1.1-1.4, Nav1.6, and Nav1.7, and TTX-resistant channels (TTXr) such as Nav1.5, Nav1.8, and Nav1.9. Furthermore, the expression patterns of Nav channels have been reported to be tissue-specific, with Nav1.1 and Nav1.6 primarily found in the central nervous system, while Nav1.7, Nav1.8, and Nav1.9 are mainly found in neurons of the peripheral nervous system (PNS).

[0004] Nav1.8, encoded by the SCN10A gene, is reportedly selectively expressed in specific pain receptors, with expression concentrated in small-diameter neurons of the dorsal root ganglia (DRG) in the peripheral nervous system. These neurons are typically less than 30 μm in diameter. These DRG neurons, as primary sensory neurons, are reported to play a crucial role in pain perception. They receive and process injury-related signals from peripheral nerve endings and transmit this information to the spinal cord for further processing and integration. Increased excitability of DRG neurons is reported to play a significant role in various types of peripheral pain. Nav1.8 is reportedly involved in the initial stages of action potential generation in pain receptors. Mutations or deletions in the Nav1.8 gene are reportedly frequently associated with neuropathic pain. For example, excitatory mutations in Nav1.8 have been found in patients diagnosed with painful small fiber neuropathy. On the other hand, Nav1.8 gene knockout leads to a reduction in the pain phenotype, particularly in inflammation-induced pain (AN Akopian et al., Nature Neuroscience, 1999; 2; 541-548). Furthermore, Nav1.8 gene knockout reduces pain-related behaviors, including in neuropathic pain (J. Lai et al., Pain, 2002; 95(1-2): 143-152). Additionally, according to some literature, a naturally occurring mutant, A1073V, can induce a shift in the activation voltage of the channel towards greater depolarization and, to some extent, improve pain symptoms. Summary of the Invention

[0005] Among other things, this disclosure includes the understanding that existing pain management drug treatments have limited effectiveness, often providing only partial relief, and in some cases even no effect at all. Furthermore, some existing treatments may be accompanied by significant adverse reactions. In some embodiments, this disclosure provides superior pain management techniques to address this pressing medical need.

[0006] In some embodiments, this disclosure provides techniques for targeting Nav1.8 voltage-gated sodium ion channels, such as using modulators, like inhibitors, to provide treatments for treating or preventing various symptoms, disorders, or diseases associated with Nav1.8. In some embodiments, the provided techniques, such as compounds having the structure of Formula I, Formula I', or Formula II, or salts thereof, selectively inhibit Nav1.8 channels. In some embodiments, the provided techniques selectively inhibit peripheral Nav1.8 channels, representing a strategy for non-addictive analgesics. In some embodiments, this disclosure provides non-addictive analgesics. In some embodiments, the symptoms, disorders, or diseases are migraines, post-ischemic neurodegeneration, epilepsy, inflammatory pain, spontaneous pain, acute pain, preoperative pain, perioperative pain, postoperative pain, neuropathic pain, chronic pruritus, or pruritus.

[0007] In some embodiments, this disclosure provides various compounds, such as compounds having the structure of Formula I or salts thereof, as well as compositions and methods thereof. In some embodiments, this disclosure provides a compound having the structure of Formula I:

[0008]

[0009] I

[0010] or its salt, wherein:

[0011] R 1 It is an optional substituted group selected from 6-10-membered aryl groups; 5-10-membered heteroaryl groups containing 1-4 heteroatoms, wherein the heteroatoms are independently nitrogen, oxygen, or sulfur; 3-10-membered alicyclic groups; 3-10-membered heterocyclic groups containing 1-4 heteroatoms, wherein the heteroatoms are independently nitrogen, oxygen, or sulfur; and bicyclic structures, wherein the first ring is attached to a nitrogen atom and is a benzene ring or a 5-6-membered heteroaryl ring containing 1-4 heteroatoms, wherein the heteroatoms are independently nitrogen, oxygen, or sulfur, and the second ring is a benzene ring, or a 5-10-membered heteroaryl ring containing 1-4 heteroatoms, wherein the heteroatoms are independently nitrogen, oxygen, or sulfur, or a 3-10-membered heterocyclic ring containing 1-4 heteroatoms, wherein the heteroatoms are independently nitrogen, oxygen, or sulfur; or R 1 yes

[0012] R 1' It is R', or R 1 and R 1' Together with the nitrogen atom it is attached to, it forms an optional substituted 3-10 membered ring, which has 0-6 heteroatoms in addition to the nitrogen atom.

[0013] Q is O, S, NR Q ;

[0014] R Q It is either -R' or -OR';

[0015] R 2 It is an optional substituted group, selected from phenyl, 3-10 membered aliphatic groups, and 5-10 membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 2 Yes -L R2 -R B ;

[0016] L R2 For a bond or -O-, -S-, or optionally substituted -CH2-;

[0017] R B yes ;

[0018] R 3 and R 4 Each can be independently hydrogen, -CN, or R;

[0019] Each X is independently -O-, -S-, -S(O)-, -S(O)2-, -S(O)(NR) QX ) -, -Se-, -Se(O)-, -Se(O)2-, -C(R x )2-, or optionally substituted -CH2-;

[0020] Each R x Independently defined as -R' or -N(R')2;

[0021] Each R QX Independently -R' or -OR';

[0022] x is 1 or 2;

[0023] W is N, C, C(R) w ) or alternatively, CH, where R w It is -R' or -N(R')2, and when W is C, Z is C;

[0024] Z is N, C, C(R) z ) or alternatively, CH, where R z It is -R' or -N(R')2, and when Z is C, W is C or Y is -C(R). y = or optional substitution -CH=;

[0025] Each Y is independently -O-, -S-, -N(R) y )-、-C(R y )2-、-C(Ry =, optional substitution of -CH2- or optional substitution of -CH=, where each R y Independently, it is either -R' or -N(R)2, and when the Y bonded to Z is -C(R)2. y When Z is C, or optionally substituted with -CH=, Z is C;

[0026] y is 1 or 2;

[0027] Ring A and ring B are independently optional substituted 3- to 10-membered rings, the rings containing 0-6 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0028] Each R s1 Independent of halogen, -CN, -L s1 - R s11 -OR s11 -NR s11 R s12 -C(O)R s11 -C(O)NR s11 R s12 -C(NR) s13 )NR s11 R s12 -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 , -C(O)N(R s13 )S(O)2NR s11 R s12 or -OS(O)2NR s11 R s12 ;

[0029] Each L s1 divalent C, which can be independently bonded or optionally substituted. 1-6 aliphatic chains or C 1-4 A heteroaliphatic chain, wherein the heteroaliphatic chain contains 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein C 1-6 aliphatic chains or C 1-4 One or more methylene units in the heteroaliphatic chain may be optionally and independently converted to -C(O)-, -C(O)N(R) Ls1 )-, -C(S)-, -C(S)N(R Ls1 )-,-C(=NR Ls2)-, -C(=NR Ls2 )N(R Ls1 )-, -O-, -S-, -S(O)-, -S(O)2-, -S(O)2N(R Ls1 )-, -OS(O)2N(R Ls1 )-, -S(O)(=NR Ls1 )-, -N(R Ls1 )-, -P(O)(R Ls1 )-, -P(O)(R Ls1 )O-, -P(S)(R Ls1 )-,-P(S)(R Ls1 O- or -Cy- substitution

[0030] Each -Cy- is independently a divalent 3- to 10-membered ring with optional substitution, the ring containing 0 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0031] Each R s2 Independent of halogen, -CN, -R s21 , -OR s21 , -NR s21 R s22 , -C(O)R s21 , -C(O)NR s21 R s22 , -SR s21 , -S(O)2NR s21 R s22 , -S(O)2R s21 , -S(O)R s21 , -S(O)(NR s22 )R s21 , -S(O)NR s21 R s22 -SF5 or -OS(O)2NR s21 R s22 ;

[0032] s1 and s2 are each independently 0, 1, 2, 3, 4 or 5;

[0033] R s11 R s12 R s13 R s21 R s22 R Ls1 and R Ls2 Each of them is independently R';

[0034] Each It can be a single bond or a double bond independently;

[0035] Each R' is independently R, -OR, -C(O)R, -C(O)OR, -S(O)R, or -S(O)2R;

[0036] Each R is independently hydrogen or an optionally substituted group selected from C1-C6 aliphatic groups, C1-C6 heteroaliphatic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 membered cycloaliphatic groups, 3-10 membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl groups, 5-10 membered heteroaryl groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl-C1-C6 aliphatic groups, and 5-10 membered heteroaryl-C1-C6 aliphatic groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0037] Two R groups on the same atom may optionally and independently form an optionally substituted 3-10 membered ring with the atom, the ring containing, in addition to the atom, 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0038] The two R groups on the two atoms can optionally and independently form optional substituted 3-10 membered rings together with the atoms between them, and have 0-4 heteroatoms in addition to the atoms between them.

[0039] In some implementations, when X is -O-, W is not -CH-, or Z is not -CH-, or Y is not -C(R) y )2-.

[0040] In some embodiments, the compound is a compound with the structure of formula I':

[0041]

[0042] I'

[0043] Or its salt.

[0044] In some embodiments, the compound is a compound with the structure of Formula II:

[0045] ,

[0046] II

[0047] Or its salts, wherein each variable is independent as described in this disclosure.

[0048] In some embodiments, the compound is a compound with the structure of formula II':

[0049] ,

[0050] II'

[0051] Or its salts, wherein each variable is independent as described in this disclosure.

[0052] In some embodiments, the compound is a compound with the structure of formula I' or II' or a salt thereof, wherein

[0053] R 1 The substituted group is selected from 6-10 aryl groups, 5-10 heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and bicyclic systems, wherein the first ring is connected to a nitrogen atom and is a benzene ring or a 5-6 heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the second ring is a benzene ring, a 5-10 heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10 heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 1 yes ;

[0054] R 1' It is R', or R 1 and R 1' Together with the nitrogen atoms to which they are attached, they form optional substituted 3-6 membered rings, which contain 0-3 heteroatoms in addition to nitrogen atoms;

[0055] R 2 The substituted group is optionally selected from phenyl and 5-6 membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or R 2 yes ;

[0056] R 3 and R 4 Each can be independently hydrogen, -CN, or R;

[0057] X is -O-, -S-, -S(O)-, -S(O)2-, or -C(R) x )2-, where each R x Independently hydrogen or optionally substituted C1-C6 aliphatic, OR, or -N(R)2;

[0058] W is N, C, or C(R) w ), where R w It is hydrogen or optionally substituted C1-C6 aliphatic, OR or -N(R)2, where Z is C when W is C;

[0059] Z is N, C, or C(R)z ), where R z It is hydrogen or optionally substituted C1-C6 aliphatic, OR, or -N(R)2, where W is C when Z is C or Y is -C(R)2. y =

[0060] Y is -O-, -S-, -N(R) y )-、-C(R y )2- or -C(R y =, where each R y Independently hydrogen or optionally substituted C1-C6 aliphatic, OR, or -N(R)2, where Y is -C(R)2. y When ) = , Z is C;

[0061] Ring A and ring B are independently optional substituted 5-6 membered aromatic rings, the rings containing 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0062] Each R s1 Independent of halogen, -CN, R s11 , -OR s11 , -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 , or -OS(O)2NR s11 R s12 ;

[0063] Each R s2 Independent of halogen, -CN, R s21 , -OR s21 , -NR s21 R s22 , -C(O)R s21 , -C(O)NR s21 R s22 , -S(O)2NR s21 R s22 , -S(O)2R s21 , -S(O)R s21 , -S(O)(NRs22 )R s21 , -S(O)NR s21 R s22 , or -OS(O)2NR s21 R s22 ;

[0064] s1 and s2 are each independently 0, 1, 2, 3, 4 or 5;

[0065] R s11 R s12 R s21 and R s22 Each of them is independently R';

[0066] Each They are all independent single or double bonds;

[0067] Each R' is independently R, -OR, -C(O)R, -C(O)OR, -S(O)R, or -S(O)2R;

[0068] Each R is independently hydrogen or an optionally substituted group selected from C1-C6 aliphatic groups, C1-C6 heteroaliphatic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 membered cycloaliphatic groups, 3-10 membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl groups, 5-10 membered heteroaryl groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl-C1-C6 aliphatic groups, and 5-10 membered heteroaryl-C1-C6 aliphatic groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0069] Two R groups on the same atom may optionally and independently form an optionally substituted 3-10 membered ring with the atom, the ring containing, in addition to the atom, 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0070] The two R groups optionally and independently form optional substituted 3-10-membered rings together with the atoms between them, having 0-4 heteroatoms in addition to the atoms between them; and

[0071] Where X is -O-, W is not -CH-, Z is not -CH-, or Y is not -C(R) y )2-.

[0072] In some embodiments, this disclosure provides a pharmaceutical composition of the compound. In some embodiments, this disclosure provides a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In some embodiments, this disclosure provides a pharmaceutical composition for delivering the provided compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0073] The provided technology can be used for a variety of purposes. In some embodiments, the compound can be used as a sodium channel modulator. In some embodiments, the compound is a Nav1.8 modulator. In some embodiments, the provided technology (such as compounds, compositions, methods, etc.) can be used to prevent or treat various symptoms, disorders, or diseases. In some embodiments, the symptoms, disorders, or diseases are Nav1.8-related symptoms, disorders, or diseases. In some embodiments, the symptoms, disorders, or diseases are or include migraine, post-ischemic neurodegeneration, epilepsy, inflammatory pain, spontaneous pain, acute pain, preoperative pain, perioperative pain, postoperative pain, neuropathic pain, chronic pruritus, and pruritus. In some embodiments, the symptoms, disorders, or diseases are associated with the administration of another therapeutic agent.

[0074] In some embodiments, this disclosure provides a method for preventing a condition, disorder, or disease, comprising administering or delivering an effective amount of the compound, such as a compound of formula I, I', or II, or a salt thereof, to a susceptible individual. In some embodiments, this disclosure provides a method for treating a condition, disorder, or disease, comprising administering or delivering an effective amount of the compound, such as a compound of formula I, I', or II, or a salt thereof, to an individual suffering from the condition, disorder, or disease. In some embodiments, the condition, disorder, or disease is a condition, disorder, or disease associated with Nav1.8. In some embodiments, the condition, disorder, or disease is associated with activation of Nav1.8. In some embodiments, the condition, disorder, or disease includes or relates to migraine, post-ischemic neurodegeneration, epilepsy, inflammatory pain, spontaneous pain, acute pain, preoperative pain, perioperative pain, postoperative pain, neuropathic pain, chronic pruritus, and pruritus.

[0075] In some embodiments, this disclosure provides a method for preventing a condition, disorder, or disease, comprising administering or delivering an effective amount of the compound and another agent to a subject susceptible to the condition, disorder, or disease. In some embodiments, this disclosure provides a method for treating a condition, disorder, or disease, comprising administering or delivering an effective amount of the compound and another agent to a subject suffering from the condition, disorder, or disease.

[0076] In some embodiments, this disclosure provides techniques, such as methods, reagents, etc., for preparing compounds of formula I, I', or II or pharmaceutically acceptable salts thereof. Attached Figure Description

[0077] Figure 1 The provided compound can alleviate inflammatory pain. The analgesic efficacy of the compound in a CFA model of inflammatory pain was confirmed. Compared with the model group, *p<0.05, ***p<0.001.

[0078] Figure 2. The provided compound can alleviate neuropathic pain. The analgesic efficacy of the compound in a CCI model of neuropathic pain was confirmed. Compared with the model group, *** p < 0.001; compared with the contralateral group, ### p < 0.001.

[0079] Figure 3. The provided compound can alleviate postoperative pain. The analgesic efficacy of the compound in a hind paw incision model simulating postoperative pain was confirmed. ***P<0.001 compared to the model group; ###P<0.001 compared to the placebo group. Detailed Implementation

[0080] The present disclosure can be more readily understood by referring to the following detailed description of certain embodiments.

[0081] definition

[0082] Unless otherwise stated, the definitions used herein are as follows. For the purposes of this disclosure, chemical elements are identified according to the CAS version of the periodic table, Handbook of Chemistry and Physics, 75th edition. Furthermore, the general principles of organic chemistry are described in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," 5th edition, Ed.: Smith, MB, and March, J., John Wiley & Sons, New York: 2001.

[0083] As used in this disclosure, in the absence of clear context, the following terms shall have the following meanings: (i) the term “a” may be understood as at least one; (ii) the term “or” may be understood as “and / or”; (iii) the terms “comprising,” “including” (whether or not used with “not limited to”) and “including” (whether or not used with “not limited to”) may be understood as including the listed components or steps, whether presented alone or together with one or more additional components or steps; (iv) the term “another” may be understood as at least one additional / second or more; (v) the terms “about” and “approximately” may be understood as allowing for standard variations as understood by a person skilled in the art; (vi) if a range is provided, the endpoints are included. Isomers of the compound are also included unless the context clearly indicates otherwise. Those skilled in the art will recognize that compounds can be provided, administered, or delivered in various forms, such as salts (e.g., pharmaceutically acceptable salts), solvates, hydrates, esters, prodrugs, tautomers, etc.

[0084] The prefix "rac-" used in this article, when referring to chiral compounds, indicates the racemic composition or formulation of that compound. With the "rac-" prefix, (R)- and (S) in the chemical name indicate relative stereochemistry.

[0085] The prefix "rel-" used in this article, when associated with chiral compounds, refers to a single enantiomer whose absolute configuration is unknown or unspecified. In compounds with the "rel-" prefix, the (R)- and (S)- symbols in the chemical name reflect the relative stereochemical structure of the compound, but not necessarily its absolute stereochemical structure. If the relative stereochemical properties of a given stereocenter are unknown, no stereochemical designation is provided. In some cases, the absolute configuration of some stereocenters is known, while the relative configuration of others is unknown.

[0086] Aliphatic: As used herein, "aliphatic" refers to a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more unsaturated units (but not aromatic), or a substituted or unsubstituted monocyclic, bicyclic, or polycyclic hydrocarbon ring, or a combination thereof, that is fully saturated or contains one or more unsaturated units (but not aromatic). In some embodiments, the aliphatic group contains 1-50 aliphatic carbon atoms. In some embodiments, the aliphatic group contains 1-20 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-10 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-9 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-8 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-7 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-6 aliphatic carbon atoms. In some embodiments, the aliphatic group contains 1-5 aliphatic carbon atoms, while in other embodiments, the aliphatic group contains 1, 2, 3, or 4 aliphatic carbon atoms. Suitable aliphatic groups include, but are not limited to, straight-chain or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl, and mixtures thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0087] Alkenyl: As used herein, the term "alkenyl" refers to an aliphatic group having one or more double bonds, as defined herein.

[0088] Alkyl: As used herein, the term "alkyl" has its common meaning in the art and can include saturated aliphatic groups, including straight-chain alkyl, branched alkyl, cycloalkyl (alicyclic), alkyl-substituted cycloalkyl, and cycloalkyl-substituted alkyl. In some embodiments, the alkyl group has 1-100 carbon atoms. In some embodiments, the backbone of the straight-chain or branched alkyl group contains about 1-20 carbon atoms (e.g., straight-chain C1-C1). 20 The branch is C2-C. 20 (e.g., about 1-10 carbon atoms). In some embodiments, the cycloalkyl ring has about 3-10 carbon atoms in its cyclic structure, wherein such ring is monocyclic, bicyclic, or polycyclic, and the number of carbon atoms in the cyclic structure is about 5, 6, or 7. In some embodiments, the alkyl group can be a lower alkyl group, wherein the lower alkyl group comprises 1-4 carbon atoms (e.g., straight-chain lower alkyl groups are C1-C4).

[0089] Alkyne group: As used herein, the term "alkynyl group" refers to an aliphatic group having one or more triple bonds, as defined herein.

[0090] Animal: As used herein, the term "animal" means any member of the animal kingdom. In some embodiments, "animal" means a human being at any developmental stage. In some embodiments, "animal" means a non-human animal at any developmental stage. In some embodiments, non-human animals are mammals (such as rodents, rats, rats, rabbits, monkeys, dogs, cats, sheep, cattle, primates, and / or pigs). In some embodiments, animals include, but are not limited to, mammals, birds, reptiles, amphibians, fish, and / or worms. In some embodiments, animals may be transgenic animals, genetically engineered animals, and / or cloned animals.

[0091] Aryl: As used herein, the term "aryl," whether used alone or as part of a larger molecule, such as "aralkyl," "aralkylkoxy," or "aryloxyalkyl," refers to a monocyclic, bicyclic, or polycyclic cyclic system having a total of five to thirty cyclic members, wherein at least one ring in the system is aromatic. In some embodiments, aryl refers to a monocyclic, bicyclic, or polycyclic cyclic system having a total of 5 to 14 cyclic members, wherein at least one ring in the system is an aromatic ring, and each ring in the system contains 3 to 7 cyclic members. In some embodiments, each monocyclic unit is aromatic. In some embodiments, the aryl is diaryl. The term "aryl" may be used interchangeably with the term "aryl ring." In certain embodiments of this disclosure, "aryl" refers to an aromatic ring system, including but not limited to phenyl, biphenyl, naphthyl, binaphthyl, anthracene, etc., which may have one or more substituents. The term "aryl" as used in this article also includes groups fused with one or more non-aromatic rings, such as indole, phthalimide, naphthalimide, or tetrahydronaphthyl.

[0092] Comparability: As used herein, the term "comparable" means that two sets (or more sets) of conditions or environments are sufficiently similar to each other that the results obtained or the phenomena observed can be compared. In some embodiments, comparable conditions or environments have several substantially identical features and one or a few different features. Those skilled in the art will understand that sets of conditions are comparable when they have a sufficient number and type of substantially identical features, so that it is reasonable to conclude that the differences in results obtained or observed under different conditions or environments are caused by, or indicate, changes in, these changing features.

[0093] The terms "cycloaliphatic," "carbocyclic," "carbon chain," "carbocyclic group," and "carbocyclic" are used interchangeably as described herein to refer to saturated or partially unsaturated, but non-aromatic, cyclic aliphatic monocyclic, bicyclic, or polycyclic ring systems, which, unless otherwise specified, have 3 to 30 cyclic members. Cycloaliphatic groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, norbornyl, adamantyl, and cyclooctadienyl. In some embodiments, the cycloaliphatic group has 3-6 carbon atoms. In some embodiments, the cycloaliphatic group is a saturated cycloalkyl group. The term "cycloaliphatic" may also include an alicyclic ring fused with one or more aromatic or non-aromatic rings, such as decahydronaphthyl or tetrahydronaphthyl. In some embodiments, the cycloaliphatic group is bicyclic. In some embodiments, the cycloaliphatic group is tricyclic. In some embodiments, the cyclic aliphatic group is polycyclic. In some embodiments, "cyclic aliphatic" refers to C3-C6 monocyclic hydrocarbons, or C8-C6 monocyclic hydrocarbons. 10 Bicyclic or polycyclic hydrocarbons, fully saturated or containing one or more unsaturated units, but not aromatic, or fully saturated or containing one or more unsaturated units but not aromatic C9-C hydrocarbons. 16 Polycyclic hydrocarbons are single-point connections to the rest of the molecule.

[0094] Heteroaliphatic: As used herein, the term "heteroaliphatic" has its common meaning in the art and refers to the aliphatic group described herein, wherein one or more carbon atoms are independently substituted by one or more heteroatoms (such as oxygen, nitrogen, sulfur, silicon, phosphorus, etc.). In some embodiments, one or more units selected from C, CH, CH2, and CH3 are independently substituted by one or more heteroatoms (including their oxidized and / or substituted forms). In some embodiments, the heteroaliphatic group is a heteroalkyl group. In some embodiments, the heteroaliphatic group is a heteroalkenyl group.

[0095] Heteroalkyl: As used herein, the term "heteroalkyl" has its common meaning in the art and refers to an alkyl group in which one or more carbon atoms are independently substituted by one or more heteroatoms (such as oxygen, nitrogen, sulfur, silicon, phosphorus, etc.). Examples of heteroalkyl groups include, but are not limited to, alkoxy, polyethylene glycol, alkyl-substituted amino, tetrahydrofuranyl, piperidinyl, morpholinyl, etc.

[0096] Heteroaryl: The terms "heteroaryl" and "heteroaryl-" as used herein may be used alone or as part of a larger molecule (such as "heteroalkyl" or "heteroalkoxy"), referring to a monocyclic, bicyclic, or polycyclic system having 5 to 30 ring members, wherein at least one ring is an aromatic ring and at least one aromatic ring atom is a heteroatom. In some embodiments, a heteroaryl is a group having 5 to 10 ring atoms (i.e., monocyclic, bicyclic, or polycyclic), and in some embodiments, a heteroaryl is a group having 5, 6, 9, or 10 ring atoms. In some embodiments, each monocyclic unit is aromatic. In some embodiments, a heteroaryl has 6, 10, or 14 shared π electrons arranged in a ring configuration; and in addition to a carbon atom, it has 1 to 5 heteroatoms. Heteroaryl groups include, but are not limited to, thiophene, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, indoleazinyl, purine, naphridinyl, and pteridinyl. In some embodiments, the heteroaryl group is a heterodiaryl group, such as bispyridinyl. The terms "heteroaryl" and "heteroaryl-" as used herein also include groups in which the heteroaryl ring is fused with one or more aryl rings, cycloalicyclic rings, or heterocyclic rings, wherein the group or connecting point is located on the heteroaryl ring. Non-limiting examples include indolyl, isoindolyl, benzothiophenyl, benzofuranyl, dibenzofuranyl, indazoleyl, benzimidazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, terpineyl, phthalazinyl, quinazolinyl, quinoxolinyl, 4H-quinoxolinyl, 4H-quinoxolinyl, carbazoleyl, acridineyl, pyridazinyl, phenothiazinyl, phenothiazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. Heteroaryl groups can be monocyclic, bicyclic, or polycyclic. The term "heteroaryl" is used interchangeably with the terms "heteroaryl ring," "heteroaryl," or "heteroaromatic," wherein any of these terms includes the optionally substituted ring. The term "heteroaryl" refers to an alkyl group substituted with a heteroaryl group, wherein the alkyl and heteroaryl portions are optionally substituted independently.

[0097] Heteroatom: As used herein, the term "heteroatom" refers to an atom that is not carbon or hydrogen. In some embodiments, the heteroatom is boron, oxygen, sulfur, nitrogen, phosphorus, or silicon (including oxidized forms of nitrogen, sulfur, phosphorus, or silicon; charged forms of nitrogen (such as quaternized forms, forms in imide groups, etc.), phosphorus, sulfur, oxygen, etc.). In some embodiments, the heteroatom is silicon, phosphorus, oxygen, sulfur, or nitrogen. In some embodiments, the heteroatom is silicon, oxygen, sulfur, or nitrogen. In some embodiments, the heteroatom is oxygen, sulfur, or nitrogen.

[0098] Heterocyclic: As used herein, the terms "heterocyclic," "heterocyclic group," "heterocyclic group," and "heterocyclic" are used interchangeably to refer to a monocyclic, bicyclic, or polycyclic cyclic molecule (e.g., 3-30 molecules) that is saturated or partially unsaturated and has one or more heteroatom ring atoms. In some embodiments, the heterocyclic group is a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic molecule that is saturated or partially unsaturated and has one or more, preferably one to four, heteroatoms in addition to a carbon atom, as defined above. When referring to the ring atom of a heterocycle, the term "nitrogen" includes substituted nitrogen. For example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur, and nitrogen, nitrogen can be N (e.g., 3,4-dihydro-2H-pyrrole), NH (e.g., pyrrolealkyl), or... + NR (such as N-substituted pyrrolidinyl). Heterocycles can be attached to their diacyclic groups on any heteroatom or carbon atom to form a stable structure, and any atom on the ring can be selectively substituted. Examples of such saturated or partially unsaturated heterocyclic groups include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, pyrrolidinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolyl, piperazine, dioxoheterocyclic, dioxoheteropentyl, diazaheterocyclic heptyl, oxonitroheterocyclic heptyl, thionitroheterocyclic heptyl, morpholinyl, and quinolinyl. The terms "heterocycle," "heterocyclic group," "heterocyclic ring," "heterocyclic group," "heterocyclic molecule," and "heterocyclic group" are used interchangeably herein and also include groups fused with one or more aryl, heteroaryl, or cycloaliphatic rings, such as indololinyl, 3H-indololinyl, chromyl, phenanthridine, or tetrahydroquinolinyl. Heterocyclic groups can be monocyclic, bicyclic, or polycyclic. The term "heterocyclic alkyl" refers to an alkyl group substituted with a heterocyclic alkyl group, wherein the alkyl group and the heterocyclic alkyl group are optionally substituted independently.

[0099] Optional Substitution: As described herein, the compounds disclosed may comprise optionally substituted, substituted, and / or unsubstituted molecules. Generally, the term "substituted" means that one or more hydrogen atoms of a specified molecule are independently substituted by a substituent. Unless otherwise stated, an "optionally substituted" group may independently have one substituent at each substituted position of the group, and the substituents at each position may be the same or different when more than one position in any given structure can be substituted by two or more substituents. In some embodiments, the optionally substituted group is unsubstituted. In some embodiments, the optionally substituted group is substituted. Various substituents are described below.

[0100] The monovalent substituent is independently halogen; -(CH2) 0-4 R°; -(CH (2) ) 0-4 OR°; -O(CH2) 0-4 Ro , -O-(CH2) 0-4 C(O)OR°; -(CH2) 0-4 CH(OR°)2; -(CH2) 0-4 Ph can be replaced by R°; -(CH2) 0- 4 O(CH2) 0-1 Ph can be substituted by R°; -CH=CHPh can be substituted by R°; -(CH2) 0-4 O(CH2) 0-1 -Pyridyl group, which can be substituted by R°; –NO2; –CN; –N3; -(CH2) 0–4 N(R°)2; –(CH2) 0–4 N(R°)C(O)R°; –N(R°)C(S)R°; –(CH2) 0–4 N(R°)C(O)N(R°)2; -N(R°)C(S)N(R°)2; –(CH2) 0–4 N(R°)C(O)OR°; –N(R°)N(R°)C(O)R°; -N(R°)N(R°)C(O)N(R°)2; -N(R°)N(R°)C(O)OR°; –(CH2) 0–4 C(O)R°; –C(S)R°; –(CH2) 0–4 C(O)OR°; –(CH2) 0–4 C(O)SR°; -(CH2) 0–4 C(O)OSi(R°)3; –(CH2) 0–4 OC(O)R°; –OC(O)(CH2) 0–4 SR°, -SC(S)SR°; -(CH2) 0–4 SC(O)R°; –(CH2) 0–4 C(O)N(R°)2; –C(S)N(R°)2; –C(S)SR°; -SC(S)SR°, -(CH2) 0–4 OC(O)N(R°)2; -C(O)N(OR°)R°; –C(O)C(O)R°; –C(O)CH2C(O)R°; -C(NOR°)R°; -(CH2) 0–4 SSR°; –(CH2) 0–4 S(O)₂R°; –(CH₂) 0–4 S(O)₂OR°; –(CH₂) 0–4 OS(O)2R°; -S(O)2N(R°)2;-(CH2) 0–4S(O)R°; –N(R°)S(O)2N(R°)2; –N(R°)S(O)2R°; –N(OR°)R°; -C(NH)N(R°)2; –Si(R°)3; –OSi(R°)3; –P(R°)2; -N(R°)P(R°)2; -B(R°)2;-OB(R°)2; -P(O)(R°)2; -OP(O)(R°)2; -N(R°)P(O)(R°)2; -(C 1-4 Straight-chain or branched alkyl)ON(R°)2; or -(C 1-4 Straight-chain or branched alkyl)C(O)ON(R°)2, wherein each R° can be independently substituted by the following as defined below, and is independently hydrogen, C 1-10 (e.g., C) 1-6 C 1-4 (etc.) aliphatic, C 1-10 (e.g., C) 1-6 C 1-4 (etc.) heteroaliphatic compounds, possessing 1-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus, C 6-10 (e.g., C6, C) 10 (etc.) aryl, having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur at the 5-10 (e.g. 5-9, 5-6, 5, 6, 9, 10, etc.) positions, -CH2-(C 6-10 (e.g., C6, C) 10 Aryl group, -O(CH2) 0-1 (C 6-10 (e.g., C6, C) 10 -(aryl), -CH2- (5-10 (e.g., 5-9, 5-6, 5, 6, 9, 10, etc.) heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), -O(CH2) 0-1(5-10 (e.g., 5-9, 5-6, 5, 6, 9, 10, etc.) heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur); 3-10 (e.g., 3-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) monocyclic, bicyclic, or polycyclic, saturated or partially unsaturated rings having 0-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus; or, despite the above definitions, two independently occurring R° groups together with the atoms between them form a 3-10 (e.g., 3-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroaryl group, or a 3-10 (e.g., 3-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heteroaryl group having 0-4 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus; or, notwithstanding the above definitions, two independently occurring R° groups together with the atoms between them form ... A monocyclic, bicyclic, or polycyclic, saturated, partially unsaturated, or aromatic ring (for aromatic rings, 5-10 (e.g., 5-9, 5-6, 5, 6, 7, 8, 9, 10, etc.) ring, in addition to an intermediate atom, has 0-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus, which may be substituted as defined below.

[0101] The monovalent substituents on R° (or the ring formed by two independently occurring R° atoms together) are independently halogens,

[0102] or Each of them It is either unsubstituted, or, in the case of "halogen," substituted by only one or more halogens, and is independently selected from C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or 3-6 (e.g., 3-5, 5-6, etc.) saturated ring, partially unsaturated ring, or aromatic ring (aromatic ring is a 5 or 6-membered ring), having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. The divalent substituents on the R° saturated carbon atom are independently =O or =S.

[0103] The divalent substituents can be independently of the following types: =O, =S, =NNR * 2, =NNHC(O)R * =NNHC(O)OR * =NNHS(O)2R * =NR * =NOR * , -O(C(R * 2)) 2–3 O- or -S(C(R) * 2))2–3 S-, where each independently occurring R * Selected from hydrogen, C 1-6 An aliphatic (substitutable as defined below) or unsubstituted 3-6 (e.g., 3-5, 5-6, etc.) saturated ring, partially unsaturated ring, or aromatic ring (aromatic ring is a 5 or 6-membered ring) having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. The divalent substituent bonded to the adjacent substituted carbon atom of the "optionally substituted" group is independently -O(CR). * 2) 2–3 O-, where each independently occurring R * All are selected from hydrogen, and the C that can be substituted can be defined as follows. 1-6 Aliphatic or unsubstituted 3-6 (e.g., 3-5, 5-6, etc.) saturated rings, partially unsaturated rings, or aromatic rings (aromatic rings are 5 or 6-membered rings) having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0104] R * The substituents on the aliphatic group are independently halogens.

[0105] Each of them It is unsubstituted, or, if preceded by "halogen", substituted by only one or more halogens, and is independently C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or 3-6 (e.g., 3-5, 5-6, etc.) saturated rings, partially unsaturated rings, or aromatic rings (aromatic rings are 5 or 6-membered rings) with 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0106] The substituents on the substituted nitrogen are independently -R † -NR † 2. -C(O)R † -C(O)OR † -C(O)C(O)R † -C(O)CH2C(O)R † , -S(O)2R † , -S(O)2NR † 2, -C(S)NR † 2, -C(NH)NR † 2, or -N(R) † )S(O)2R † ; where each R † Independently hydrogen, C 1-6Aliphatic (substitutable as defined below), unsubstituted -OPh, or unsubstituted 3-6 (e.g., 3-5, 5-6, etc.) saturated ring, partially unsaturated ring, or aromatic ring (aromatic ring is 5 or 6-membered ring) having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or, despite the above definition, two independently occurring R atoms. † Together with the atoms between them, they form unsubstituted 3-12 (e.g., 3-10, 3-6, 5-10, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) saturated, partially unsaturated, or aryl monocyclic or bicyclic rings having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0107] R † The substituents on the aliphatic group are independently halogens.

[0108] Each of them It is unsubstituted, or, if preceded by "halogen", substituted by only one or more halogens, and is independently C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or 3-6 (e.g., 3-5, 5-6, etc.) saturated rings, partially unsaturated rings, or aromatic rings (aromatic rings are 5 or 6-membered rings) with 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0109] Partially Unsaturated: As used herein, the term "partially unsaturated" refers to a cyclic molecule containing at least one double or triple bond. The term "partially unsaturated" is intended to include rings with multiple unsaturated sites, but excludes aryl or heteroaryl groups as defined herein.

[0110] Pharmaceutical Composition: As used herein, the term "pharmaceutical composition" refers to an active pharmaceutical ingredient formulated together with one or more pharmaceutically acceptable carriers. In some embodiments, the unit dose of the active pharmaceutical ingredient is suitable for administration in a treatment regimen and, when administered to the relevant population, has a statistically significant probability of achieving the intended therapeutic effect. In some embodiments, the pharmaceutical composition may be specifically formulated for administration in solid or liquid form, including compositions suitable for: oral administration, e.g., infusions (aqueous or non-aqueous solutions or suspensions), tablets, e.g., tablets, suppositories, powders, granules, or ointments for oral, sublingual, and systemic absorption; parenteral administration, such as subcutaneous, intramuscular, intravenous, or epidural injections, such as sterile solutions, suspensions, or sustained-release formulations; topical administration, e.g., as creams, ointments, controlled-release patches, or sprays applied to the skin, lungs, or mouth; vaginal or rectal administration, e.g., as suppositories, creams, or foams; sublingual administration; ophthalmic administration; transdermal administration; or administration to the nasal cavity, lungs, and other mucosal surfaces.

[0111] Pharmaceutically acceptable: As used herein, "pharmaceutically acceptable" means, to a reasonable extent of medical judgment, a compound, material, composition, and / or dosage form that is suitable for use in contact with human and animal tissues without causing excessive toxicity, irritation, allergic reactions, or other problems or complications, and is commensurate with a reasonable benefit / risk ratio.

[0112] Pharmaceutically acceptable carrier: As used herein, "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition, or carrier, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, for carrying or transporting a test compound from one organ or site of the body to another. Each carrier must be "acceptable," meaning it is compatible with other components in the formulation and will not cause harm to the patient. Materials that can serve as pharmaceutically acceptable carriers include sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; sea buckthorn powder; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; ethylene glycols such as propylene glycol; polyols such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; pH buffer solutions; polyesters, polycarbonates, and / or polyanhydrides; and other non-toxic and compatible substances used in pharmaceutical formulations.

[0113] Pharmaceutically Acceptable Salts: As used herein, the term "pharmaceutically acceptable salt" refers to a salt of such compounds suitable for use in a pharmaceutical setting, i.e., a salt suitable for contact with human and lower animal tissues without excessive toxicity, irritation, allergic reactions, etc., within reasonable medical judgment, and in proportion to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, SMBerge et al. described pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66:1-19 (1977). In some embodiments, pharmaceutically acceptable salts include, but are not limited to, non-toxic acid addition salts, which are salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by using other methods used in the art, such as ion exchange. In some implementations, pharmaceutically acceptable salts include, but are not limited to, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, hydrogen sulfate, borate, butyrate, camphorate, camphor sulfonate, citrate, cyclopentylpropionate, diglucuronate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucohepate, glycerophosphate, gluconate, hemisulfate, heptasulfate, hydroiodide, 2-hydroxyethanesulfonate, lactobionate, lactate, laurate, dodecyl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, picrate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. In some embodiments, the provided compound comprises one or more acidic groups, and the pharmaceutically acceptable salt is an alkali, alkaline earth metal, or ammonium salt (e.g., an ammonium salt of N(R)3, wherein each R is independently defined and described in this disclosure). Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. In some embodiments, the pharmaceutically acceptable salt is a sodium salt. In some embodiments, the pharmaceutically acceptable salt is a potassium salt. In some embodiments, the pharmaceutically acceptable salt is a calcium salt. In some embodiments, the pharmaceutically acceptable salt, where appropriate, includes non-toxic ammonium, quaternary ammonium, and amine cations that resist counterion formation, such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, alkyl groups having 1-6 carbon atoms, sulfonates, and aryl sulfonates. In some embodiments, the provided compound comprises two or more acidic groups. In some embodiments, the pharmaceutically acceptable salt or common salt of this compound comprises two or more cations, which may be the same or different.In some embodiments, in pharmaceutically acceptable salts (or conventional salts), all ionizable hydrogen atoms in the acidic group (e.g., in aqueous solutions with pKa not greater than about 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2; in some embodiments, pKa not greater than about 7; in some embodiments, pKa not greater than about 6; in some embodiments, pKa not greater than about 5; in some embodiments, pKa not greater than about 4; in some embodiments, pKa not greater than about 3) are replaced by cations.

[0114] Protecting Groups: The term "protecting group" as used herein is well-known in the art, including the protecting groups described in detail in *Protecting Groups in Organic Synthesis*, T.W. Greene and P.G. W. M. Uts, 3rd edition, John Willy & Son, 1999, the entire text of which is incorporated herein by reference. Additionally, it includes the protecting groups specifically for nucleoside and nucleotide chemistry described in *Current Protocols in Nucleic Acid Chemistry*, edited by Serge L. Beaucage et al. Suitable amino protecting groups include methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfonyl)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-[9-(10,10- Dioxo-10,10,10,10-tetrahydrothionyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenylacetyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1-(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenyl)ethyl carbamate (Bpoc), 1-(3,5-di-tert-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2'- And 4'-pyridyl)carbamate ethyl ester (Pyoc), 2-(N,N-dicyclohexylcarbamate)carbamate ethyl ester, tert-butyl carbamate (BOC), 1-adamantylcarbamate ethyl ester (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl tert-butyl carbamate (Coc), 4-nitrocininol carbamate (Noc), 8-quinolinyl carbamate, N-hydroxypiperidine carbamate, alkyl dithiocarbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitrobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-Dichlorobenzylcarbamate, 4-Methylsulfinylbenzylcarbamate (Msz), 9-Anthrylmethylcarbamate, 2-Methylthioethylcarbamate, 2-(p-toluenesulfonyl)ethylcarbamate, [2-(1,3-dithiayl)]methylcarbamate (Dmoc), 4-Methylthiophenylcarbamate (Mtpc), 2,2-phosphonoethylcarbamate (Peoc), 2-triphenylphosphonoisopropylcarbamate (Ppoc), 1,1-dimethyl-2-cyanoethylcarbamate, m-chloro-p-acetoxybenzylcarbamate, p-(dihydroxybenzyl)carbamate, 5-benzisoxazolemethylcarbamate, 2-(trifluoromethyl)-6-bromomethylcarbamate (Tcroc), m-nitrocarbamate, 3,5- Dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, benzothiazinyl-(10)-carbonyl derivative, N'-p-toluenesulfonic acid aminocarbonyl derivative, N'-phenylaminothiocarbonyl derivative, tert-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decoxybenzyl carbamate, 2,2-dimethoxycarbonyl vinyl carbamate, o-(N,N-dimethylformamido)benzyl carbamate, 1,1-dimethyl-3-(N,N-dimethylformamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2- Pyridyl)methyl carbamate, 2-furanmethyl carbamate, 2-iodoethyl carbamate, isobutyl carbamate, isobutyl carbamate, isonicocarbamate, p-(p'-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, ethyl 1-methylcyclohexyl carbamate, ethyl 1-methyl-1-cyclopropylmethyl carbamate, ethyl 1-methyl-1-(3,5-dimethoxyphenyl)carbamate, ethyl 1-methyl-1-(p-phenylazophenyl)carbamate, ethyl 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-phenylazobenzyl carbamate, 2,4,6-tributylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, 2,4. Formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropionamide, pyridine amide, 3-pyridine carboxamide, N-benzoylphenylpropanamide derivative, benzamide, p-phenylbenzamide, o-nitrophenylacetamide, o-nitrophenoxyacetamide, acetylacetamide, (N'-dithiobenzyloxycarbonylamino)acetamide, 3-(p-hydroxyphenyl)propionamide, 3-(o-nitrophenyl)propionamide, 2-methyl-2-(o-nitrophenoxy)propionamide, 2-methyl-2-(o-phenylacetophenoxy)propionamide (N-phenyloxy)propionamide, 4-chlorobutyramide, 3-methyl-3-nitrobutyramide, o-nitrocinnamamide, N-acetylmethionine derivatives, o-nitrobenzamide, o-benzoyloxymethylbenzamide, 4,5-diphenyl-3-oxazoline-2-one, N-phthalimide, N-dithiosuccinimide (DTS), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4-tetramethyldisilazane adduct (STABASE), 5-substituted 1 3-Dimethyl-1,3,5-triazacyclohexane-2-one, 5-substituted 1,3-dibenzyl-1,3,5-triazacyclohexane-2-one, 1-substituted 3,5-dinitro-4-pyridinone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4-nitro-2-oxo-3-pyrrololin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4-methoxyphenyl)methylamine, N-5-diphenyl And furanylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluoreneamine (PhF), N-2,7-dichloro-9-fluorenemethylamine, N-ferrocenemethylamine (Fcm), N-2-cyclopentanamine N'-oxide, N-1,1-dimethylthiomethyleneamine, N-benzylamine, N-(N',N'-dimethylaminomethylene)amine, N,N'-isopropylideneamine, N-p-nitrobenzylamine, N-(5,5-dimethyl-3-oxo-1- Cyclohexenyl amine, N-borane derivatives, N-diphenylboronic acid derivatives, N-[phenyl(pentacarbonylchromium or tungsten)carbonyl]amine, N-copper chelate, N-zinc chelate, N-nitrosamine, N-nitrosoamine, amine N-oxide, diphenylphosphamide (Dpp), dimethylthiophosphamide (Mpt), diphenylthiophosphamide (Ppt), dialkylphosphamide, dibenzylphosphamide, diphenylphosphamide, benzylsulfonamide, o-nitrobenzenesulfonamide (Nps), 2,2,3,6,-triphenylmethylsulfonamide, 3-nitropyridinesulfonamide (Npys), p-toluenesulfonamide (Ts), benzylsulfonamide, 2,3,6,-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-Tetramethyl-4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylbenzopyran-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilyl ethanesulfonamide (SES), 9-anthracitesulfonamide, 4-(4',8'-dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and benzenesulfonamide.

[0115] Suitable protected carboxylic acids also include, but are not limited to, silyl, alkyl, alkenyl, aryl, and aralkyl-protected carboxylic acids. Suitable silyl groups include trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triisopropylsilyl, etc. Suitable alkyl groups include methyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, tributyl, tetrabutyl, tetrahydropyran-2-yl, etc. Suitable alkenyl groups include allyl. Suitable aryl groups include optionally substituted phenyl, biphenyl, or naphthyl groups. Examples of suitable aralkyl groups include optionally substituted benzyl groups (such as p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl), and 2- and 4-pinyl groups.

[0116] Suitable hydroxyl protecting groups include methyl, methoxymethyl (MOM), methylthiomethyl (MTM), tert-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacol methyl (GUM), t-butoxymethyl, 4-pentenoxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2-(trimethylsilyl) ) ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiaranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiaranyl, 4-methoxytetrahydrothiaranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxanepent-2-yl, tetrahydrofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-tolyzofuran-2-yl, 1- Ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, tert-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl-p-cyanobenzyl, p-phenylbenzyl, 2-pyridyl, 4-pyridyl, 3-methyl-2-pyridin N-oxo, diphenylmethyl, p,p'-dinitrophenyl, 5-diphenyl Furanyl, triphenylmethyl, α-naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p-methoxyphenyl)phenylmethyl, 4,4',4''-tris(4,5-dichlorophthaliminophenyl)methyl, 4,4',4''-tris(levo-benzoyloxyphenyl)methyl, 4,4',4''-tris(benzoyloxyphenyl)methyl, 3-(imidazol-1-yl)bis(4',4''-dimethoxyphenyl)methyl, 1,1-bis(4-methoxyphenyl)-1'-pyrenemethyl, 9-anthrayl, 9-(9-phenyl)xanthonyl, 9-(9-phenyl-10-oxo)anthrayl, 1,3-benzodithiol-2-yl, benzisothiazolyl S,S-dioxo, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylhexylsilyl, tert-butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-oxysilyl, triphenylsilyl, formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenyl Propionate, 4-oxovalerate (L-valerate), 4,4-(ethylene dithio)valerate (L-dithioacetaldehyde), pteropenate, adamantinate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (formamidinate), alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), ethylalkyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(benzenesulfonyl)ethyl carbonate (Psec), 2-(triphenylphosphono)ethyl carbonate (Peoc) Isobutylalkyl carbonate, vinylalkyl carbonate, allylalkyl carbonate, p-nitrophenylalkyl carbonate, benzylalkyl carbonate, p-methoxybenzylalkyl carbonate, 3,4-dimethoxybenzylalkyl carbonate, o-nitrobenzylalkyl carbonate, p-nitrobenzylalkyl carbonate, S-benzylalkyl thiocarbonate, 4-ethoxy-1-naphthyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylvalerate, o-(dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2-(meththiomethoxy)ethyl, 4-(meththiomethoxy)butyrate, 2-(meththiomethoxymethyl)benzene Formate, 2,6-dichloro-4-methylphenoxyacetic acid, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetic acid, 2,4-bis(1,1-dimethylpropyl)phenoxyacetic acid, dichlorophenylacetic acid, isobutyrate, monosuccinate, (E)-2-methyl-2-butenoate, o-methoxycarbonylbenzoate, α-naphthalate, nitrate, N,N,N',N'-tetramethylphosphodiamide alkyl ester, N-phenylcarbamate alkyl ester, borate, dimethyl thiophosphate, alkyl 2,4-dinitrobenzenesulfonate, sulfate, methanesulfonate (methanesulfonate), benzyl sulfonate and p-sulfonate (Ts). Protecting groups used to protect 1,2- or 1,3-diols include methylene acetal, ethylene acetal, 1-t-butyl ethylene ketal, 1-phenyl ethylene ketal, (4-methoxyphenyl)ethylene acetal, 2,2-diol, etc.2-Trichloroethylene acetal, acetone, cyclopentyl ketal, cyclohexyl ketal, cycloheptyl ketal, benzylidene acetal, p-methoxybenzylidene acetal, 2,4-dimethoxybenzylidene acetal, 3,4-dimethoxybenzylidene acetal, 2-nitrobenzylidene acetal, methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene ester, 1-methoxyethylidene ester, 1-ethoxyethylidene ester, 1,2-dimethoxyethylidene ester, α-methoxybenzylidene Protoesters, 1-(N,N-dimethylamino)ethylidene derivatives, α-(N,N'-dimethylamino)benzylidene derivatives, 2-oxocyclopentyl protoesters, di-tert-butylsilyl groups (DTBS), 1,3-(1,1,3,3-tetraisopropyldisiloxanemethylene) derivatives (TIPDS), tetra-tert-butoxydisiloxane-1,3-dimethylene derivatives (TBDS), cyclic carbonates, cyclic borates, ethyl borate, and phenyl borate.

[0117] In some embodiments, the hydroxyl protecting group includes acetyl, tert-butyl, tert-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, benzoyl, p-phenylbenzoyl, 2,6-dichlorophenyl, diphenylmethyl, p-nitrophenylmethyl, triphenylmethyl (triphenylmethyl), 4,4'-dimethoxytriphenylmethyl, trimethylsilyl, tri... Ethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, triphenylsilyl, triisopropylsilyl, benzoylcarbamate, chloroacetyl, trichloroacetyl, trifluoroacetyl, tertvalyl, 9-fluorenemethyl carbonate, methanesulfonate, toluenesulfonate, trifluoromethanesulfonate, triphenylmethyl, monomethoxytriphenylmethyl (MMTr), 4,4'-dimethoxytriphenylmethyl (DMTr) and 4,4',4''-trimethoxytriphenylmethyl (TMTr), 2-cyanoethyl (CE) Or Cne), 2-(trimethylsilyl)ethyl (TSE), 2-(2-nitrophenyl)ethyl, 2-(4-cyanophenyl)ethyl, 2-(4-nitrophenyl)ethyl (NPE), 2-(4-nitrophenylsulfonyl)ethyl, 3,5-dichlorophenyl, 2,4-dimethylphenyl, 2-nitrophenyl, 4-nitrophenyl, 2,4,6-trimethylphenyl, 2-(2-nitrophenyl)ethyl, butylthiocarbonyl, 4,4',4''-tris(benzoyloxy)trimethylmethyl, diphenylcarbamoyl, vinyl, 2-(dibromomethyl)benzoyl (Dbmb), 2-(isopropylthiomethoxymethyl)benzoyl (Ptmt), 9-phenyloxanthracene-9-yl (pixyl) or 9-(p-methoxyphenyl)xanthine-9-yl (MOX). In some embodiments, the hydroxyl protecting groups are each independently selected from acetyl, benzyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, and 4,4'-dimethoxytriphenylmethyl. In some embodiments, the hydroxyl protecting groups are selected from the group consisting of triphenylmethyl, monomethoxytriphenylmethyl, and 4,4'-dimethoxytriphenylmethyl.In some embodiments, the protecting group is 2-cyanoethyl (CE or Cne), 2-trimethylsilylethyl, 2-nitroethyl, 2-sulfonylethyl, methyl, benzyl, o-nitrobenzyl, 2-(p-nitrophenyl)ethyl (NPE) Or Npe), 2-phenylethyl, 3-(N-tert-butylcarboxamido)-1-propyl, 4-oxopentyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-methylphenylethyl, 4-oxopentyl, 4-methylthio-1-butyl, 2-cyano-1,1-dimethylethyl, 4-N-methylaminobutyl, 3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, 2-(N-formyl,N-methyl)aminoethyl or 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl.

[0118] Test Subject: As used herein, the terms "subject" or "test subject" refer to any organism to which a compound or composition is administered, for example, for experimental, diagnostic, preventive, and / or therapeutic purposes, in accordance with this disclosure. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and humans; insects; worms, etc.) and plants. In some embodiments, the test subject is a human. In some embodiments, the subject may have and / or be susceptible to a disease, disorder, and / or condition.

[0119] Substantively: As used herein, the term "substantively" refers to a qualitative condition of the full or near full range or extent of the characteristic or property of interest. Those skilled in the art of biology and / or chemistry will understand that biological and chemical phenomena rarely (if at all) achieve completeness and / or wholeness, or reach or avoid absolute results. Therefore, this article uses the term "substantively" to encompass the potential incompleteness inherent in many biological and / or chemical phenomena.

[0120] Susceptible Population: A "susceptible person" for a disease, disorder, and / or condition is someone who has a higher risk of developing a disease, disorder, and / or condition than the general public. In some implementations, an individual susceptible to a disease, disorder, and / or condition has a predisposition to develop that disease, disorder, and / or condition. In some implementations, an individual susceptible to a disease, disorder, and / or condition may not have been diagnosed with that disease, disorder, and / or condition. In some implementations, an individual susceptible to a disease, disorder, and / or condition may exhibit symptoms of the disease, disorder, and / or condition. In some implementations, an individual susceptible to a disease, disorder, and / or condition may not exhibit symptoms of the disease, disorder, and / or condition. In some implementations, an individual susceptible to a disease, disorder, and / or condition will develop the disease, disorder, and / or condition. In some implementations, an individual susceptible to a disease, disorder, and / or condition will not develop the disease, disorder, and / or condition.

[0121] Therapeutic agent: As used herein, the term "therapeutic agent" broadly refers to any pharmaceutical agent that, when administered to a subject, produces a desired effect (such as a desired biological, clinical, or pharmacological effect). In some embodiments, an agent is considered a therapeutic agent if it demonstrates a statistically significant effect in an appropriate population. In some embodiments, an appropriate population refers to a group of subjects who have and / or are susceptible to a disease, disorder, or condition. In some embodiments, an appropriate population is a model biological population. In some embodiments, an appropriate population may be defined by one or more criteria, such as age group, sex, genetic background, pre-existing clinical condition, prior treatment, etc. In some embodiments, a therapeutic agent is a substance that, when administered to a subject in an effective amount, reduces, improves, alleviates, inhibits, prevents, delays the onset, reduces the severity, and / or decreases the incidence of one or more symptoms or features of a disease, disorder, and / or condition. In some embodiments, a "therapeutic agent" means an agent that has been or requires approval from a government agency before being marketed for human use. In some embodiments, a "therapeutic agent" is an agent that requires a medical prescription for human use. In some embodiments, a therapeutic agent is a provided compound.

[0122] Therapeutic Effective Amount: As used herein, the term "therapeutic effective amount" refers to the amount of a substance (such as a therapeutic agent, composition, and / or formulation) that, when administered as part of a treatment regimen, elicits the expected biological response. In some embodiments, a therapeutically effective amount of a substance refers to an amount sufficient to treat, diagnose, prevent, and / or delay the onset of a disease, disorder, and / or condition when administered to a subject who has or is susceptible to such a disease, disorder, and / or condition. As will be understood by those skilled in the art, the effective amount of a substance can vary depending on factors such as the desired biological endpoint, the substance to be delivered, and the target cells or tissues. For example, an effective amount of a compound in a formulation for treating a disease, disorder, and / or condition refers to an amount that can reduce, improve, alleviate, inhibit, prevent, delay the onset, reduce the severity, and / or decrease the incidence of one or more symptoms or features of the disease, disorder, and / or condition. In some embodiments, the therapeutically effective amount is administered in a single dose; in other embodiments, multiple unit doses are required to achieve the therapeutically effective amount.

[0123] Treatment: As used herein, the term treatment refers to any method used to partially or completely alleviate, improve, relieve, suppress, prevent, delay the onset of, reduce the severity of, and / or decrease the incidence of one or more symptoms or features of a disease, disorder, and / or condition. Treatment may be administered to subjects who do not exhibit disease, disorder, and / or symptoms. In some implementations, treatment may be administered to subjects who only exhibit early symptoms of a disease, disorder, and / or condition, for example, to reduce the risk of pathological development associated with the disease, disorder, and / or condition.

[0124] Unsaturated: The term "unsaturated" as used here refers to a molecule having one or more unsaturated units.

[0125] In some embodiments, the compound or composition comprises enrichment levels of one or more isotopes. For example, in some embodiments, the provided compound or composition comprises enrichment levels of deuterium (D). Various techniques can be used to incorporate various isotope enrichment levels according to this disclosure. In some embodiments, one or more isotopes at one or more sites in the compound are independently enriched, e.g., relative to native abundance. In some embodiments, the enrichment fold is about or at least about 2, 5, 10, 20, 50, 100, 200, 500, 1000, 2000, 5000, or 10000 times. In some embodiments, the enrichment is about or at least about 1%, 2%, 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, or 95% of the compound molecules having a specific isotope at a particular site, wherein the percentage is higher than a reference value (e.g., percentage in an unenriched compound, native abundance, percentage at one or more unenriched sites, etc.). In some embodiments, the isotopic purity of the compound is about 5%-100% (e.g., about 5%, 10%, 20%, 50%), 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or higher, or about 5%-100%, 10%-100%, 20%-100%, 30%-100%, 50%-100%, 80%-100%, 90%-100%, 95%-100%, 96%-100%, 97%-100%, 98%-100%, 99%-100%, 95-99%, 95%-99.5%, 95%-99.9%, etc.). In some implementations, the isotope purity is approximately 5%-100% (e.g., approximately 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or more, or approximately 5%-100%, 10%-100%, 20%-100%, 30%-100%, 50%-100%, 80%-100%, 90%-100%, 95%-100%, 96%-100%, 97%-100%, 98%-100%, 99%-100%, 95-99%, 95%-99.5%, 95%-99.9%, etc., relative to the isotope at a certain position).For example, in some embodiments, the compound contains one or more D atoms at one or more positions, and for each D a particular position, its isotopic purity is independently about 5%-100% (e.g., about 5%, 10%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9% or more, or about 5%-100%, 10%-100%, 20%-100%, 30%-100%, 50%-100%, 80%-100%, 90%-100%, 95%-100%, 96%-100%, 97%-100%, 98%-100%, 99%-100%, 95-99%, 95%-99.5%, 95%-99.9%, etc.). In some embodiments, the isotopic purity is about 5% or higher. In some embodiments, the isotopic purity is about 10% or higher. In some embodiments, the isotopic purity is about 20% or higher. In some embodiments, the isotopic purity is about 30% or higher. In some embodiments, the isotopic purity is about 40% or higher. In some embodiments, the isotopic purity is about 50% or higher. In some embodiments, the isotopic purity is about 60% or higher. In some embodiments, the isotopic purity is about 70% or higher. In some embodiments, the isotopic purity is about 80% or higher. In some embodiments, the isotopic purity is about 90% or higher. For example, in some embodiments, R is -CD3, and the isotopic purity of each D in the compound or composition is independent of what is described herein.

[0126] As will be understood by those skilled in the art, the methods and compositions described herein relating to the provided compounds are generally also applicable to pharmaceutically acceptable salts of such compounds.

[0127] Some implementation schemes of the compound

[0128] Among other things, this disclosure provides compounds with a variety of uses. In some embodiments, the provided compounds are those represented by Formula I:

[0129] ,

[0130] I

[0131] Or its salts, wherein each variable is independent as described in this disclosure.

[0132] In some embodiments, the provided compound is the compound represented by Formula II:

[0133] ,

[0134] II

[0135] Or its salts, wherein each variable is independent as described in this disclosure.

[0136] In some embodiments, the provided compound is the compound represented by formula II':

[0137] ,

[0138] II'

[0139] Or its salts, wherein each variable is independent as described in this disclosure.

[0140] Examples of various variables in various formulas (such as Formula I, Formula I', Formula II, etc.) are described in this disclosure. Those skilled in the art who read this disclosure will be able to select embodiments for each variable and combine them; such combinations fall within the scope of this disclosure. Those skilled in the art will also understand that embodiments described for one variable (e.g., R) can be used for other variables that may be that variable (e.g., R', R'). s11 R s12 R s21 R s22 R s31 R s32 R s41 R s42 "etc." can be variables of R.

[0141] R 1

[0142] As stated in this disclosure, R 1 It is an optional substituted group selected from 6-10-membered aryl groups, 5-10-membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10-membered cycloaliphatic groups, 3-10-membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and bicyclic groups, wherein the first ring is connected to a nitrogen atom and is a phenyl ring or a 5-6-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the second ring is a phenyl ring, a 5-10-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10-membered heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 1 yes In some implementations, R 1It is an optional substituted group selected from 6-10 aryl groups, 5-10 heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and bicyclic groups, wherein the first ring is connected to a nitrogen atom and is a phenyl ring or a 5-6 heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the second ring is a phenyl ring, a 5-10 heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10 heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 yes .

[0143] In some implementation schemes, R 1 It is an optional 6-10 aryl group. In some embodiments, R 1 It is an optional substituted phenyl group. In some embodiments, R 1 It is phenyl. In some embodiments, R 1 It is an optionally substituted naphthyl group. In some embodiments, R 1 It is a naphthyl group.

[0144] In some implementation schemes, R 1 It is an optional substituted 5-10-membered heteroaryl group having 1-4 heteroatoms. In some embodiments, R 1 It is a 5-10 membered heteroaryl group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optionally substituted bicyclic 9-membered heteroaryl group having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is a 10-membered bicyclic heteroaryl group with optional substitutions of 1-4 heteroatoms (e.g., 1-2, 1, 2, 3, 4, etc.) independently selected from nitrogen, oxygen and sulfur.

[0145] In some implementation schemes, R 1 It is an optional substituted 5-6-membered heteroaryl group having 1-4 heteroatoms. In some embodiments, R 1 It is a 5-6 membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0146] In some implementation schemes, R 1 It is a 5-membered heteroaryl ring with 1-4 heteroatoms that can be optionally substituted. In some embodiments, R 1 It is an optional substituted five-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1It is an optional substituted 5-membered heteroaromatic ring with 1-3 heteroatoms. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with 1-2 heteroatoms. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring having 1-2 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with 2 heteroatoms. In some embodiments, R 1 It is an optional substituted 5-membered heteroaryl ring with one heteroatom. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with one oxygen atom. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with one nitrogen atom. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with one sulfur atom. In some embodiments, R 1 It is an optional substituted five-membered heteroaromatic ring having two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with two heteroatoms, one of which is nitrogen. In some embodiments, R 1 It is a 5-membered heteroaryl ring with two independently selected heteroatoms chosen from N and S, which can be optionally substituted. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring having two independently selected heteroatoms chosen from nitrogen and oxygen. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring having two independently selected heteroatoms chosen from oxygen and sulfur. In some embodiments, R 1 It is an optional substituted 5-membered heteroaromatic ring with 3 heteroatoms. In some embodiments, R 1 The ring is a 5-membered heteroaryl ring with three independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, the ring has a single heteroatom. In some embodiments, the ring has two or more heteroatoms, at least one of which is nitrogen. In some embodiments, each heteroatom is nitrogen. In some embodiments, all heteroatoms are identical. In some embodiments, at least one heteroatom is different from the other heteroatoms.

[0147] In some implementation schemes, R 1 It is an optional substituted 6-membered heteroaromatic ring having 1-4 heteroatoms. In some embodiments, R 1 It is an optional substituted 6-membered heteroaromatic ring having 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R1 It is an optional substituted 6-membered heteroaryl ring with 1-3 heteroatoms. In some embodiments, R 1 It is an optional substituted 6-membered heteroaromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 6-membered heteroaromatic ring with 1-2 heteroatoms. In some embodiments, R 1 It is an optionally substituted 6-membered heteroaromatic ring having 1-2 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 6-membered heteroaromatic ring with 2 heteroatoms. In some embodiments, R 1 It is an optionally substituted 6-membered heteroaromatic ring having one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 6-membered heteroaromatic ring with one nitrogen atom. In some embodiments, R 1 It is an optional substituted six-membered heteroaromatic ring having two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optionally substituted 6-membered heteroaromatic ring with two heteroatoms, each of which is nitrogen. In some embodiments, R 1 It is an optional substituted 6-membered heteroaromatic ring with 3 heteroatoms. In some embodiments, R 1 It is an optional substituted six-membered heteroaromatic ring having three independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is a 6-membered heteroaryl ring with three heteroatoms, one of which is nitrogen.

[0148] In some implementation schemes, R 1 It is an optional substituted 9-membered heteroaryl group having 1-4 heteroatoms. In some embodiments, R 1 It is a 9-membered heteroaryl group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 9-membered heteroaryl group having 1-2 heteroatoms. In some embodiments, R 1 It is a 9-membered heteroaryl group with 1-2 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0149] In some implementation schemes, R 1 It is an optional substituted 10-membered heteroaryl ring having 1-4 heteroatoms. In some embodiments, R 1 It is an optional substituted 10-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1It is an optional substituted 10-membered heteroaryl ring with 1-2 heteroatoms. In some embodiments, R 1 It is a 10-membered heteroaryl ring with 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, which can be optionally substituted.

[0150] In some implementation schemes, R 1 It is an optional substituted 3-10 membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 3-7 membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 3-6 membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 3-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 4-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 5-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 6-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 7-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 8-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 9-membered cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 10-membered cyclic aliphatic group.

[0151] In some implementation schemes, R 1 It is an optional substituted 3-10-membered partially unsaturated cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 3-7-membered partially unsaturated cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 3-6 partially unsaturated alicyclic compound. In some embodiments, R 1 It is an optional substituted 3-membered partially unsaturated cyclic aliphatic group. In some embodiments, R 1 It is an optional 4-membered partially unsaturated alicyclic compound. In some embodiments, R 1 It is an optional substituted 5-membered partially unsaturated cyclic aliphatic group. In some embodiments, R 1 It is an optional substituted 6-membered partially unsaturated alicyclic compound. In some embodiments, R 1 It is an optional 7-membered partially unsaturated alicyclic compound. In some embodiments, R 1 It is an optional 8-membered partially unsaturated alicyclic compound. In some embodiments, R 1 It is an optional 9-membered partially unsaturated alicyclic compound. In some embodiments, R 1It is an optional substituted decameric partially unsaturated cyclic aliphatic group. For example, in some embodiments, R 1 It is an optional replacement In some implementations, R 1 yes .

[0152] In some implementation schemes, R 1 It is an optional substituted 3-10 membered heterocyclic group having 1-4 heteroatoms. In some embodiments, R 1 It is an optional substituted 3-10 membered heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 3-10 membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 3-7 membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 3-membered heterocyclic group having one heteroatom independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 4-membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 5-membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is an optional substituted 6-membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 It is a 7-membered heterocyclic group with 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, which can be optionally substituted.

[0153] In some implementation schemes, R 1The system is an optionally substituted bicyclic system, wherein the first ring is connected to a nitrogen atom and is a benzene ring or a 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; the second ring is a benzene ring, a 5-10 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10 membered heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the first ring is an optionally substituted benzene ring. In some embodiments, the first ring is a benzene ring. In some embodiments, the first ring is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the first ring is an optionally substituted 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted benzene ring. In some embodiments, the second ring is a benzene ring. In some embodiments, the second ring is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 3-10 membered heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 3-10 membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 5-6 membered heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 5-membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 5-membered heterocyclic group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the second ring is an optionally substituted 6-membered heterocyclic group having 1-2 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, the first and second rings are fused.

[0154] In some implementation schemes, R 1 It is an optional substituted pyridinyl group. In some embodiments, R 1 It is pyridyl. In some embodiments, R 1 It is an optional replacement In some implementations, R 1 yes In some implementations, R 1 It is an optional replacement In some implementations, R 1 yes In some implementations, R 1 It is an optional replacement In some implementations, R1 yes In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some embodiments, the nitrogen atom is in an oxidized form. For example, in some embodiments, R... 1 It is an optional replacement .

[0155] Ring A

[0156] In some implementation schemes, R 1 yes Each variable is independent as described in this disclosure.

[0157] In some embodiments, ring A is an optionally substituted 3-10 membered ring (e.g., 4-10 membered, 1 membered, 2 membered, 3 membered, 4 membered, 5 membered, 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, etc.), said ring having 0-6 (e.g., 0, 1-6, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 3-10 membered ring (e.g., 4-10 membered, 1 membered, 2 membered, 3 membered, 4 membered, 5 membered, 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, etc.), said ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 4-10 membered ring. In some embodiments, ring A is a 4-9 membered ring. In some implementations, ring A is a 4-8 element ring. In some implementations, ring A is a 4-7 element ring. In some implementations, ring A is a 4-6 element ring.

[0158] In some embodiments, ring A is an aryl group. In some embodiments, ring A is not an aryl group. In some embodiments, ring A is saturated. In some embodiments, ring A is partially unsaturated.

[0159] In some embodiments, ring A has one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A has no heteroatoms.

[0160] In some embodiments, ring A is a monocyclic ring. In some embodiments, ring A is a bicyclic ring. In some embodiments, ring A is a bicyclic ring, and each monocyclic unit is independently a 3-9 member (e.g., 3-7, 4-7, 4-6, 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring. In some embodiments, each monocyclic unit is independently a 3-7 member ring. In some embodiments, each monocyclic unit is independently a 4-7 member ring. In some embodiments, each monocyclic unit is independently a 5-7 member ring. In some embodiments, each monocyclic unit is independently a 5- or 6-membered ring. In some embodiments, at least one monocyclic unit is a 6-membered ring. In some embodiments, at least one monocyclic unit is a 5-membered ring. In some embodiments, at least one monocyclic unit is an aromatic ring. In some embodiments, at least one monocyclic unit is an aromatic ring, a 6-membered ring, and does not contain heteroatoms. In some embodiments, at least one monocyclic unit is a heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 5-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 6-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a non-aromatic ring.

[0161] In some embodiments, ring A is an optionally substituted phenyl group. In some embodiments, ring A is a benzene ring. In some embodiments, ring A is an optionally substituted 10-membered aromatic ring without heteroatoms.

[0162] In some embodiments, ring A is an optional substituted 9-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optional 10-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0163] In some embodiments, ring A is an optionally substituted 5-6 membered aromatic ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted benzene ring. In some embodiments, ring A is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 5-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 5-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms, one heteroatom being nitrogen and the other heteroatom independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 5-membered heteroaromatic ring having 1 heteroatom independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 6-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 6-membered heteroaromatic ring having 1 nitrogen atom. In some embodiments, ring A is a 6-membered heteroaromatic ring having one nitrogen atom. In some embodiments, ring A is an optionally substituted pyridyl group. In some embodiments, ring A is a pyridyl group. In some embodiments, ring A is an optionally substituted 6-membered heteroaromatic ring having two nitrogen atoms.

[0164] In some embodiments, ring A is an optionally substituted 3- to 10-membered heterocyclic base ring (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 3- to 10-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 4-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 5-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted 6-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optional substituted 7-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0165] In some embodiments, ring A is optionally substituted with a pyridyl group. In some implementations, ring A is In some implementations, ring A is an optional replacement. In some implementations, ring A is In some implementations, ring A is an optional replacement. In some implementations, ring A is In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is optional. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some implementations, ring A is an optional replacement. In some embodiments, the nitrogen atom is in an oxidized form. For example, in some embodiments, ring A is optionally substituted. .

[0166] In some implementations, one or more R s1 (Maximum s1) are connected to the ring A.

[0167] R s1

[0168] In some implementations, each Rs1 Independent of halogen, -CN, -L s1 -R s11 , -OR s11 , -NR s11 R s12 ,-C(O)R s11 , -C(O)NR s11 R s12 , -C(NR')NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 , -C(O)N(R s13 )S(O)2NR s11 R s12 or -OS(O)2NR s11 R s12 In some implementations, each R s1 Independent of halogen, -CN, R s11 , -OR s11 , -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 or -OS(O)2NR s11 R s12 .

[0169] In some implementations, each R s1 Independently selected from halogens, -CN, R s11 , -OR s11 , -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NRs11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 or -OS(O)2NR s11 R s12 , where each R s11 and R s12 Independently -H or optionally substituted groups, said groups are selected from C1-C6 aliphatic groups or 5-6 membered rings having 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, said groups may optionally be substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH or =O. In some embodiments, each R s1 Independently selected from halogens, -CN, R s11 , -OR s11 , -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 and -OS(O)2NR s11 R s12 , where each R s11 and R s12 Independently -H or optionally substituted groups, said groups are selected from C1-C6 aliphatic groups or 5-6 membered rings having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, said groups may optionally be substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH or =O. In some embodiments, each R s1 Independently selected from halogens, -CN, R s11 , -OR s11 , -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NR s11 Rs12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 and -OS(O)2NR s11 R s12 , where each R s11 and R s12 Independently, it is a -H or optionally substituted group, said group being selected from C1-C6 aliphatic groups or 5-6 membered saturated rings having 0-4 nitrogen atoms, said group being optionally substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH, or =O. In some embodiments, each R s1 Independently selected from halogens, -CN, R s11 , -OR s11 , -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 and -OS(O)2NR s11 R s12 , where each R s11 and R s12 The substituent is independently -H or optionally substituted, the substituent being selected from C1-C6 aliphatic groups or 5-6 membered saturated rings having 1-2 nitrogen atoms, wherein the substituent may optionally be substituted by one or more substituents (e.g., 1-3), the substituents being independently selected from halogens, -OH, or =O. In some embodiments, each halogen is -F.

[0170] In some implementation schemes, R s1 It is a halogen. In some implementations, R s1 It is F. In some implementations, R s1 It is Br.

[0171] In some implementation schemes, R s1 It's CN.

[0172] In some implementation schemes, Rs1 Yes -L s1 -R s11 Each variable is independent as described in this disclosure.

[0173] In some implementation schemes, R s1 It is R s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is R, where R is as described in this disclosure. In some embodiments, R s1 Yes - OR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 Yes -NR s11 R s12 Each variable is independent as described in this disclosure. In some implementations, R s1 Yes - NHR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 Yes - NHR s11 , where R s11 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s1 It is -C(O)R s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -C(O)R s11 , where R s11 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s1 It is -C(O)NR s11 R s12 Each variable is independent as described in this disclosure. In some implementations, R s1 It is -C(O)NHR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -C(O)NHR s11 , where R s11 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s1 It is -C(NR) s13 )NR s11 R s12 , where R s11 R s12 and R s13Independently as described in this disclosure. In some embodiments, R s1 It is -C(NH)NR s11 R s12 , where R s11 and R s12 Independently as described in this disclosure. In some embodiments, R s1 It is -C(NH)NR s11 R s12 , where R s11 It is hydrogen. In some implementations, R s1 It is -S(O)2NR s11 R s12 , where each variable is independent as described in this disclosure. In some embodiments, R s1 It is -S(O)2NHR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -S(O)2NHR s11 , where R s11 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s1 Yes-S(O)2R s11 , where each variable is independent as described in this disclosure. In some embodiments, R s1 It is -S(O)R s11 Each variable is independent as described in this disclosure. In some implementations, R s1 It is -S(O)(NR) s12 )R s11 Each variable is independent as described in this disclosure. In some implementations, R s1 It is -S(O)(NH)R s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -S(O)NR s11 R s12 Each variable is independent as described in this disclosure. In some embodiments, R s1 It is -S(O)NHR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -S(O)NHR s11 , where R s11 It is C 1-6 Aliphatic. In some implementations, R s1 It is -C(O)N(R) s13 )S(O)2NR s11 Rs12 , where R s11 R s12 and R s13 Each is independent as described in this disclosure. In some embodiments, R s1 It is -C(O)NHS(O)2NR s11 R s12 , where R s11 and R s12 Each is independent as described in this disclosure. In some embodiments, R s1 It is -C(O)NHS(O)2NHR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -OS(O)2NR s11 R s12 Each variable is independent as described in this disclosure. In some implementations, R s1 It is -OS(O)2NHR s11 , where R s11 As described in this disclosure. In some embodiments, R s1 It is -OS(O)2NHR s11 , where R s11 It is C 1-6 Aliphatic.

[0174] R s11

[0175] In some implementation schemes, R s11 It is R', where R' is as described in this disclosure. In some embodiments, R s11 R is R, where R is as described in this disclosure.

[0176] In some implementation schemes, R s11 It's H.

[0177] In some implementation schemes, R s11 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s11 It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R s11 It is a C1-C6 aliphatic compound optionally substituted with one or more (e.g., 1-3) ions, independently selected from halogens, -OH, or =O. In some embodiments, R s11 It is a C1-C6 alkyl group that is optionally substituted by one or more (e.g., 1-3) independently selected from halogens or -OH. In some embodiments, R s11It is a C1-C4 alkyl group that is optionally substituted by one or more (e.g., 1-3) independently selected from halogens, -OH, or =O. In some embodiments, R s11 It is a C1-C6 alkyl group. In some embodiments, R s11 It is a C1-C3 alkyl group. In some embodiments, R s11 It is methyl. In some embodiments, R s11 It is -CH2OH. In some implementations, R s11 It is -CHF2. In some implementations, R s11 It is -CH(OH)CH2OH. In some implementations, R s11 It is -C(OH)(Me)2. In some implementations, R s11 It is an optional replacement for C 3-6 Cyclic aliphatic group. In some embodiments, R s11 It is an optional substituted cyclopropyl group.

[0178] In some implementation schemes, R s11 It is a C1-C6 heteroaliphatic compound with 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which can be optionally substituted.

[0179] In some implementation schemes, R s11 It is an optional substituted 3-10 (such as 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10 etc.) membered cycloaliphatic group.

[0180] In some implementation schemes, R s11 It is a 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered heterocycle with 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s11 It is a 5-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s11 It is a 6-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s11 It is an optional replacement In some implementations, R s11 yes In some implementations, R s11 It is an optional replacement In some implementations, R s11 It is an optional replacement In some implementations, Rs11 It is an optional replacement In some implementations, R s11 yes .

[0181] In some implementation schemes, R s11 It is an optional 6-10 aryl group. In some embodiments, R s11 It is an optional substituted phenyl group. In some embodiments, R s11 It is a phenyl group.

[0182] In some embodiments, Rs11 is an optionally substituted 5-10 membered heteroaryl group (e.g., 5-6, 9-10, 5, 6, 9, 10, etc.) having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Rs11 is an optionally substituted 5-6 membered heteroaryl group (e.g., 1-2, 1, 2, 3, 4, etc.) having 1 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Rs11 is an optionally substituted 9-10 membered bicyclic heteroaryl group (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) having 1 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Rs11 is an optionally substituted 5-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Rs11 is an optionally substituted 6-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s11 It is an optional replacement In some implementations, R s11 It is an optional replacement .

[0183] In some implementation schemes, R s11 It is an optionally substituted 6-10 aryl-C1-C6 aliphatic group, wherein the aryl and aliphatic groups are each independently optionally substituted as described herein.

[0184] In some implementation schemes, R s11 It is a 5-10-membered heteroaryl group having optional substitutions of 1-6 heteroatoms -C1-C6 aliphatic groups, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur, and each heteroaryl group and aliphatic group is independently optional substituted, as described in this disclosure.

[0185] R s12

[0186] In some implementation schemes, R s12It is R', where R' is as described in this disclosure. In some embodiments, R s12 R is R, where R is as described in this disclosure.

[0187] In some implementation schemes, R s12 It's H.

[0188] In some implementation schemes, R s12 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s12 It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R s12 It is a C1-C6 aliphatic compound optionally substituted with one or more (e.g., 1-3) substituents independently selected from halogens, -OH, or =O. In some embodiments, R s12 It is a C that is optionally substituted by one or more (e.g., 1-3) substituents independently selected from halogens or -OH. 1 -C (6 Alkyl group. In some embodiments, R s12 It is a C1-C4 alkyl group optionally substituted with one or more (e.g., 1-3) substituents independently selected from halogens, -OH, or =O. In some embodiments, R s12 It is a C1-C6 alkyl group. In some embodiments, R s12 It is a C1-C3 alkyl group. In some embodiments, R s12 It is methyl. In some embodiments, R s12 It is -CH2OH. In some implementations, R s12 It is -CHF2. In some implementations, R s12 It is -CH(OH)CH2OH. In some implementations, R s12 It is -C(OH)(Me)2. In some implementations, R s12 It is -C(OH)(Me)2. In some implementations, R s12 It is an optional replacement for C 3-6 Cyclic aliphatic group. In some embodiments, R s12 It is an optional substituted cyclopropyl group.

[0189] In some implementation schemes, R s12 It is a C1-C6 heteroaliphatic compound with 1-3 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0190] In some implementation schemes, R s12It is an optional substituted 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered cycloaliphatic group.

[0191] In some implementation schemes, R s12 It is a 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heterocycle with optional substitutions of 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12 It is a 5-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12 It is a six-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12 It is an optional replacement In some implementations, R s12 yes In some implementations, R s12 It is an optional replacement In some implementations, R s12 It is an optional replacement In some implementations, R s12 It is an optional replacement In some implementations, R s12 yes .

[0192] In some implementation schemes, R s12 It is an optional 6-10 aryl group. In some embodiments, R s12 It is an optional substituted phenyl group. In some embodiments, R s12 It is a phenyl group.

[0193] In some implementation schemes, R s12 It is a 5-10 membered (e.g., 5-6, 9-10, 5, 6, etc.) heteroaryl group with optional substitutions of 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, 9, 10, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12 It is a 5-6 membered heteroaryl group with optional substitutions having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12It is a 9-10 membered bicyclic heteroaryl group with optional substitutions having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12 It is a 5-membered heteroaryl group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s12 It is an optional replacement In some implementations, R s12 It is an optional replacement .

[0194] In some implementation schemes, R s12 It is optionally substituted with 6-10 aryl-C1-C6 aliphatic groups, and each heteroaryl and aliphatic group is independently optionally substituted as described in this disclosure.

[0195] In some implementation schemes, R s12 It is a 5-10 membered heteroaryl-C1-C6 aliphatic group having 1-6 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur, and each heteroaryl and aliphatic group is independently optionally substituted as described in this disclosure.

[0196] In some implementation schemes, R s11 and R s12 One of them is -H. In some implementations, both are -H. In some implementations, one is -H and the other is not.

[0197] In some implementation schemes, R s1 and Rs 12All are R, and together with the atoms therebetween, form optional substituted 3-10 member rings (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) as described herein, wherein the rings, in addition to the aforementioned atoms, also have 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the formed rings are substituted. In some embodiments, the formed rings are not substituted. In some embodiments, the formed rings are 3-membered rings. In some embodiments, the formed rings are 4-membered rings. In some embodiments, the formed rings are 5-membered rings. In some embodiments, the formed rings are 6-membered rings. In some embodiments, the formed rings are 7-membered rings. In some embodiments, the formed rings are 8-membered rings. In some embodiments, the formed rings are monocyclic. In some embodiments, the formed rings are saturated rings. In some embodiments, the formed rings are partially unsaturated rings. In some embodiments, the formed ring is an aromatic ring. In some embodiments, the formed ring has no additional heteroatoms. In some embodiments, the formed ring has one or more additional heteroatoms. In some embodiments, the number of additional heteroatoms is one. In some embodiments, the number of additional heteroatoms is two. In some embodiments, the additional heteroatom is nitrogen. In some embodiments, the additional heteroatom is oxygen.

[0198] R s13

[0199] In some implementation schemes, R s13 It is R' as described in this disclosure. In some embodiments, R s13 It is R as described in this disclosure.

[0200] In some implementation schemes, R s13 Yes, it's -H.

[0201] In some implementation schemes, R s13 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s13 It is C 1-6 Alkyl group. In some embodiments, R s13 It is methyl. In some embodiments, R s13 It is ethyl. In some embodiments, R s13 Yes - CN.

[0202] In some implementation schemes, R s13 Yes - OR, where R is as described in this disclosure. In some embodiments, R s13 It is -OR, where R is the alternative C. 1-6Aliphatic. In some implementations, R s13 It is -OR, where R is the alternative C. 1-6 Alkyl group. For example, in some embodiments, R s13 It is -OR, where R is methyl; in some embodiments, R s13 It is -OR, where R is cyclopropyl.

[0203] L s1

[0204] In some implementations, each L s1 divalent C, which can be independently bonded or optionally substituted. 1-6 Aliphatic chains or C atoms having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1-4 Heterolipotic chains, of which C 1-6 Fatty acid chain or C 1-4 One or more methylene units in the heteroaliphatic chain may be optionally and independently modified by -C(O)-, -C(O)N(R) Ls1 )-, -C(S)-, -C(S)N(R Ls1 )-, -C(=NR Ls2 )-, -C(=NR Ls2 )N(R Ls1 )-, -O-, -S-, -S(O)-, -S(O)2-, -S(O)2N(R Ls1 )-, -OS(O)2N(R Ls1 )-, -S(O)(=NR Ls1 )-, -N(R Ls1 )-, -P(O)(R Ls1 )-, -P(O)(R Ls1 )O-, -P(S)(R Ls1 )-, -P(S)(R Ls1 O- or -Cy- are used as substitutes. In some implementations, each L s1 Independently, it is a combination of 1-6 units (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.), each unit being independently selected from optional substituted -CH2-, optional substituted -CH=CH-, -C≡C-, optional substituted -CH=N-, -C(O)-, -C(O)N(R). Ls1 )-, -C(S)-, -C(S)N(R Ls1 )-, -C(=NR Ls2 )-, -C(=NR Ls2 )N(R Ls1)-, -O-, -S-, -S(O)-, -S(O)2-, -S(O)2N(R Ls1 )-, -OS(O)2N(R Ls1 )-, -S(O)(=NR Ls1 )-, -N(R Ls1 )-, -P(O)(R Ls1 )-, -P(O)(R Ls1 )O-, -P(S)(R Ls1 )-, -P(S)(R Ls1 )O-, -N=N- or -Cy-.

[0205] In some implementations, L s1 It is or contains -C(O)-. In some implementations, L s1 It is or contains -C(O)N(R) Ls1 In some implementations, L s1 It is or contains -C(O)NH-. In some implementations, L s1 It is or contains -C(S)-. In some implementations, L s1 It is or contains -C(S)N(R) Ls1 In some implementations, L s1 It is or contains -C(S)NH-. In some implementations, L s1 Yes or contain -C (=NR) Ls2 In some implementations, L s1 It is or contains -C (=NH)-. In some implementations, L s1 Yes or contain -C (=NR) Ls2 )N(R Ls1 In some implementations, L s1 It is or contains -C(=NH)NH-. In some implementations, L s1 Yes or contains -O-. In some implementations, L s1 Yes or contains -S-. In some implementations, L s1 It is or contains -S(O)-. In some implementations, L s1 It is or contains -S(O)2-. In some implementations, L s1 It is or contains -S(O)2N(R) Ls1 In some implementations, L s1 It is or contains -S(O)2NH-. In some implementations, L s1 Yes or contains -OS(O)2N(R) Ls1 In some implementations, L s1It is or contains -OS(O)2NH-. In some implementations, L s1 Is or contains -S(O)(=NR) Ls1 In some implementations, L s1 It is or contains -S(O)(=NH)-. In some implementations, L s1 Yes or contains -N(R) Ls1 In some implementations, L s1 It is or contains -NH-. In some implementations, L s1 Is or contains -P(O)(R Ls1 In some implementations, L s1 Is or contains -P(O)(R Ls1 )-, where R Ls1 Not -H. In some implementations, L s1 Is or contains -P(O)(R Ls1 )-, where R Ls1 It is an optional replacement for C 1-6 Fatty base. In some implementations, L s1 It is or contains -P(O)(CH3)-. In some implementations, L s1 It is or contains -P(O)(Et)-. In some implementations, L s1 Yes or contains -N(R) Ls1 )-P(O)(R Ls1 )-, where each R Ls1 Independently as described in this disclosure. In some embodiments, L s1 It is or contains -NH-P(O)(R Ls1 )-, where R Ls1 As described in this disclosure. In some embodiments, L s1 It is or contains -NH-P(O)(Et)-. In some implementations, L s1 Is or contains -P(O)(R Ls1 In some implementations, L s1 Is or contains -P(O)(R Ls1 )O-, where R Ls1 Not -H. In some implementations, L s1 Is or contains -P(O)(R Ls1 )O-, where R Ls1 ) is -OR, where R is as described in this disclosure. In some embodiments, L s1 Is or contains -P(O)(R Ls1 )O-, where R Ls1 It is -OR, where R is the alternative C. 1-6Fatty base. In some implementations, L s1 It is or contains -P(O)(OEt)O-. In some implementations, L s1 Yes or contains -N(R) Ls1 )-P(O)(R Ls1 )O-, where each R Ls1 Independently as described in this disclosure. In some embodiments, L s1 It is or contains -NH-P(O)(R Ls1 )O-, where R Ls1 As described in this disclosure. In some embodiments, L s1 It is or contains -NH-P(O)(OEt)O-. In some implementations, L s1 Yes or contains -P(S)(R Ls1 In some implementations, L s1 Yes or contains -P(S)(R Ls1 )-, where R Ls1 Not -H. In some implementations, L s1 Yes or contains -P(S)(R Ls1 )-, where R Ls1 It is an optional replacement for C 1-6 Fatty base. In some implementations, L s1 It is or contains -P(S)(CH3)-. In some implementations, L s1 It is or contains -P(S)(Et)-. In some implementations, L s1 Yes or contains -P(S)(R Ls1 In some implementations, L s1 Yes or contains -P(S)(R Ls1 )O-, where R Ls1 Not -H. In some implementations, L s1 Yes or contains -P(S)(R Ls1 )O-, where R Ls1 Yes - OR, where R is as described in this disclosure. In some embodiments, L s1 Yes or contains -P(S)(R Ls1 )O-, where R Ls1 It is -OR, where R is the alternative C. 1-6 Fatty base. In some implementations, L s1 It is or contains -P(S)(OEt)O-. In some implementations, L s1 It is or contains -C(O)-Cy-. In some implementations, L s1 Yes or contains -N(R) Ls1)S(O)2Cy-. In some implementations, L s1 It is or contains -NHS(O)2Cy-. In some implementations, L s1 It is or contains -S(O)2N(R) Ls1 Cy-. In some implementations, L s1 It is or contains -S(O)2NHCy-. In some implementations, L s1 It is or contains -C(O)N(R) Ls1 In some implementations, L s1 It is or contains -C(O)NH-O-. In some embodiments, L s1 Is or contains -Cy-N(R) Ls1 In some implementations, L s1 It is or contains -Cy-NH-. In some implementations, L s1 Yes or contains -N(R) Ls1 )-Cy-N(R Ls1 In some implementations, L s1 It is or contains -NH-Cy-NH-. In some implementations, L s1 Is or contains -Cy-N(R) Ls1 )-Cy-. In some implementations, L s1 It is or contains -Cy-NH-Cy-. For example, in some embodiments, L s1 yes In some implementations, -C(O)- is related to R. s11 Bonding. In some implementations, -Cy- is bonded to R. s11 Bonding. In some implementations, -N(R) Ls1 ) and R s11 Bonding.

[0206] R Ls1

[0207] In some implementation schemes, R Ls1 It is R' as described in this disclosure. In some embodiments, R Ls1 It is R as described in this disclosure. For example, in some embodiments, R Ls1 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R Ls1 It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R Ls1 It is an optional 6-10 aryl group. In some embodiments, R Ls1It is a 5-10 (e.g., 5-6, 9-10, 5, 6, 9, 10, etc.) heteroaryl group with 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0208] In some implementation schemes, R Ls1 Yes, it's -H.

[0209] In some implementation schemes, R Ls1 The R described in this disclosure s11 .

[0210] R Ls2

[0211] In some implementation schemes, R Ls2 It is R' as described in this disclosure. In some embodiments, R Ls2 It is R as described in this disclosure.

[0212] In some implementation schemes, R Ls2 Yes, it's -H.

[0213] In some implementation schemes, R Ls2 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R Ls2 It is C 1-6 Alkyl group. In some embodiments, R Ls2 It is methyl. In some embodiments, R Ls2 It is ethyl. In some embodiments, R Ls2 Yes - CN.

[0214] In some implementation schemes, R Ls2 Yes - OR, where R is as described in this disclosure. In some embodiments, R Ls2 It is -OR, where R is the alternative C. 1-6 Aliphatic. In some implementations, R Ls2 It is -OR, where R is the alternative C. 1-6 Alkyl group. For example, in some embodiments, R Ls2 It is -OR, where R is methyl; in some embodiments, R Ls2 It is -OR, where R is cyclopropyl.

[0215] In some implementation schemes, R Ls2 The R described in this disclosure s13 .

[0216] -Cy-

[0217] In some embodiments, each -Cy- is independently a 3-10 (e.g., 4-10, 1, 2, 3, 4, etc.) divalent ring with optional substitutions of 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is a 4-10 membered ring. In some embodiments, it is a 4-9 membered ring. In some embodiments, it is a 4-8 membered ring. In some embodiments, it is a 4-7 membered ring. In some embodiments, it is a 4-6 membered ring.

[0218] In some embodiments, -Cy- is an aromatic group. In some embodiments, -Cy- is not an aromatic group. In some embodiments, -Cy- is saturated. In some embodiments, -Cy- is partially unsaturated.

[0219] In some embodiments, -Cy- has one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- has no heteroatoms.

[0220] In some embodiments, the ring is a monocyclic ring. In some embodiments, the ring is a bicyclic ring. In some embodiments, the ring is a bicyclic ring, and each monocyclic unit is independently a 3-9 member (e.g., 3-7, 4-7, 4-6, 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring. In some embodiments, each monocyclic unit is independently a 3-7 member ring. In some embodiments, each monocyclic unit is independently a 4-7 member ring. In some embodiments, each monocyclic unit is independently a 5-7 member ring. In some embodiments, each monocyclic unit is independently a 5- or 6-membered ring. In some embodiments, at least one monocyclic unit is a 6-membered ring. In some embodiments, at least one monocyclic unit is a 5-membered ring. In some embodiments, at least one monocyclic unit is an aromatic ring. In some embodiments, at least one monocyclic unit is an aromatic ring, a 6-membered ring, and does not contain heteroatoms. In some embodiments, at least one monocyclic unit is a heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 5-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 6-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a non-aromatic ring.

[0221] In some embodiments, the ring is an optionally substituted phenyl group. In some embodiments, the ring is a benzene ring. In some embodiments, the ring is an optionally substituted 10-membered bicyclic aromatic ring without heteroatoms.

[0222] In some embodiments, the ring is an optionally substituted 9-membered bicyclic heteroaryl group having 1-6 heteroatoms (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 10-membered bicyclic heteroaryl group having 1-6 heteroatoms (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) independently selected from nitrogen, oxygen, and sulfur. In some embodiments, at least one heteroatom is nitrogen. In some embodiments, each heteroatom is nitrogen.

[0223] In some embodiments, the ring is an optionally substituted 5-6 membered aromatic ring having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is a 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is a 5-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms, one heteroatom being nitrogen and the other heteroatom being independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-membered heteroaromatic ring having 1 heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is a 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 6-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is a 6-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 6-membered heteroaromatic ring having 1 nitrogen atom. In some embodiments, the ring is a 6-membered heteroaromatic ring having 1 nitrogen atom. In some embodiments, the ring is an optionally substituted pyridyl group. In some embodiments, the ring is a pyridyl group. In some embodiments, the ring is an optionally substituted six-membered heteroaromatic ring having two nitrogen atoms.

[0224] In some embodiments, the ring is an optional substituted 3-10 membered heterocyclic base ring (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optional substituted 3-10 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optional substituted 4 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optional substituted 5 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optional substituted 6 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 7-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0225] For example, in some implementations, -Cy- is an optional replacement. In some implementations, -Cy- is .

[0226] Among other things, this disclosure describes and provides various R... s1 Examples of implementation schemes, including those containing R s11 R s12 R s13 L s1 Various implementation schemes, etc. In some implementation schemes, R s1 It is -C(O)NH2. In some implementations, R s1 It is -C(O)NHCH3. In some implementations, R s1 It is -CH2OH. In some implementations, R s1 It is -CHF2. In some implementations, R s1 It is -S(O)2NH2. In some implementations, R s1 It is a halogen. In some implementations, R s1 Yes -F. In some implementations, R s1 Yes -Cl. In some implementations, R s1 It is -C(NH)NH2. In some implementations, R s1 It is -S(O)2Me. In some implementations, R s1 It is -S(O)Me. In some implementations, R s1 It is -CH(OH)CH2(OH). In some implementations, R s1 It is an optional replacement In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 yes In some implementation schemes, Rs1 yes In some implementations, R s1 It is -S(NH)(O)Me. In some implementations, R s1 It is -S(NMe)(O)Me. In some implementations, R s1 Yes -CHO. In some implementations, R s1 It is -C(CH3)2OH. In some embodiments, R s1 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s1 It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R s1 It is C 1-6 Alkyl group. In some embodiments, R s1 It is methyl. In some embodiments, R s1 It is -NH2. In some implementations, R s1 It is a 5-6 membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R s1 yes In some implementations, R s1 Yes - OR, where R is as described in this disclosure. In some embodiments, R s1 It is -OH. In some implementations, R s1 It is -OR, where R is the alternative C. 1-6 Aliphatic. In some implementations, R s1 It is -OR, where R is the alternative C. 1-6 Alkyl group. In some embodiments, R s1 Yes -OMe. In some implementations, R s1 It is -NH2. In some implementations, R s1 It is -OCH2CH(OH)CH2(OH). In some implementations, R s1It is (S)-OCH2CH(OH)CH2(OH). In some embodiments, R s1 It is (R)-OCH2CH(OH)CH2(OH). In some embodiments, R s1 Yes -H. In some implementations, R s1 It is -CH(CF3)NH2. In some implementations, R s1 Yes -CN. In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 It is -C(S)NH2. In some implementations, R s1 It is -C(NMe)NH2. In some implementations, R s1 It is -C(NEt)NH2. In some implementations, R s1 It is -C(NOMe)NH2. In some implementations, R s1 It is -C(NO-cyclopropyl)NH2. In some embodiments, R s1 It is -C(N-CN)NH2. In some implementations, R s1 It is -C(O)NHOMe. In some implementations, R s1 It is -CH(NH2)CH2OH. In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 yes In some implementations, R s1 yes. In some implementations, R s1 It is -NH(4-pyridyl).

[0227] In some implementations, two R s1 The group, together with the atoms interposed therein, forms an optionally substituted ring as described herein. In some embodiments, the two R groups... s1 The group, together with the atoms interposed therein, forms an optionally substituted 5-6 membered ring, which, in addition to the interposed atoms, has 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R groups... s1The group, together with the atoms interposed therein, forms an optionally substituted 5-membered ring, which, in addition to the interposed atoms, has 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R groups... s1 The group, together with the atoms interposed therein, forms an optionally substituted 6-membered ring, which, in addition to the interposed atoms, has 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0228] s1

[0229] In some implementations, s1 is 0, 1, 2, 3, 4, or 5. In some implementations, s1 is 0. In some implementations, s1 is 1. In some implementations, s1 is 2. In some implementations, s1 is 3. In some implementations, s1 is 4. In some implementations, s1 is 5. In some implementations, s1 is 1 or 2.

[0230] In some implementation schemes, R 1 It has not been replaced.

[0231] In some implementation schemes, R 1 For 1-5 R s1 Optional substituted phenyl groups. In some embodiments, R 1 Is it by 1 or 2 Rs s1 Optional substituted phenyl groups. In some embodiments, R 1 It is by 2 or more R s1 Substituted phenyl groups. In some embodiments, R 1 It was by an R s1 Substituted phenyl groups.

[0232] In some implementation schemes, R 1 It is a 5-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 1-4 R atoms. s1 Optional replacement. In some implementations, R 1 It is a 5-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 1-4 R atoms. s1 Optional replacement. In some implementations, R 1 It is a 5-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is bonded by two or more R atoms. s1 Replacement. In some implementations, R 1 It is a 5-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is separated by an R s1 replace.

[0233] In some implementation schemes, R 1 It is a 6-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 1-5 R atoms. s1 Optional replacement. In some implementations, R 1 It is a 6-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 1-5 R atoms. s1 Optional replacement. In some implementations, R 1 It is a 6-membered heteroaryl group having 1-4 independent heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by two or more R atoms. s1 Replacement. In some implementations, R 1 It is a 6-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is separated by an R s1 replace.

[0234] In some implementation schemes, R 1 It was by an R s1 Substituted 2-pyridyl. In some embodiments, R 1 It was by an R s1 Substituted 3-pyridyl. In some embodiments, R 1 It was by an R s1 Substituted 4-pyridyl. In some embodiments, R 1 It was by two Rs s1 Substituted 2-pyridyl. In some embodiments, R 1 It was by two Rs s1 Substituted 3-pyridyl. In some embodiments, R 1 It was by two Rs s1 Substituted 4-pyridyl. In some embodiments, R 1 It is by two or more R s1 Substituted 2-pyridyl. In some embodiments, R 1 It is by two or more R s1 Substituted 3-pyridine. In some embodiments, R 1 It is by two or more R s1 Substituted 4-pyridyl group.

[0235] In some implementation schemes, R 1 The substituted group. In some embodiments, R 1 There is a substituent on it. In some implementations, R 1 It has two substituents. In some implementations, R1 It has three or more substituents. In some embodiments, the substituents are located at position 2 (R). 1 The atom bonded to the nitrogen atom is at position 1. In some embodiments, the substituent is located at position 3 (R). 1 The atom bonded to the nitrogen atom is located at position 1. In some embodiments, the substituent is located at position 4 (R). 1 The atom attached to the nitrogen atom is located at position 1. In some embodiments, the substituent is located at position 2, and the substituent is located at position 3, where R... 1 It is attached to the nitrogen atom at position 1. In some embodiments, one substituent is located at position 3 and one substituent is located at position 4, where R 1 It is attached to the nitrogen atom at position 1. In some embodiments, each substituent is independently R as described in this disclosure. s1 In some implementations, R 1 There is a substituent on it. In some implementations, R 1 It has two substituents. In some implementations, R 1 It has three or more substituents. In some embodiments, the substituents are located at position 2 (R). 1 The atom attached to the nitrogen atom is at position 1. In some embodiments, the substituent is located at position 3 (R). 1 The atom attached to the nitrogen atom is at position 1. In some embodiments, the substituent is located at position 4 (R). 1 The atom attached to the nitrogen atom is at position 1. In some embodiments, the substituent is located at position 2 and position 3, where R 1 A nitrogen atom is attached at position 1. In some embodiments, the substituent is located at position 3 and position 4, where R... 1 A nitrogen atom is attached at position 1. In some embodiments, each substituent is independently R as described herein. s1 .

[0236] In some implementation schemes, R 1 yes , where R a1 R b1 R c1 R d1 and R e1 Each of them is R independently. s1 In some implementations, R a1 R b1 R c1 R d1 and R e1 Each is independently selected from halogen, -CN, -OR s11 -NRs11 R s12 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 and , where each R s11 and R s12 Independently -H or optionally substituted C1-C6 aliphatic compounds. In some embodiments, R a1 R b1 R c1 R d1 and R e1 Each is independently selected from halogen, -CN, -OR s11 -NR s11 R s12 -CONR s11 R s12 -SO2NR s11 R s12 and , where R s11 and R s12 Each is independently -H or optionally substituted C1-C6 aliphatic.

[0237] In some implementation schemes, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R 1 yes R b1 Yes - CONR s11 R s12 -SO2NR s11 R s12 or , where R s11 It is -H or optionally substituted C1-C6 aliphatic, R s12 As described in this disclosure. In some embodiments, R 1 yes R b1 Is it -CONH2, -SO2NH2 or In some implementations, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R 1yes , where R e1 Yes - OR s11 Each of the other variables is independent as described in this disclosure. In some implementations, R 1 yes R b1 As described in this disclosure. In some embodiments, R b1 Selected from halogens, -CN, -OMe, -CONH2, and -SO2NH2. In some embodiments, R 1 yes Each variable is independent as described in this disclosure. In some embodiments, R 1 yes And R b1 and R c1 Each of these is independently selected from halogens, -CN, -OMe, -C(O)NH2, and -SO2NH2. In some embodiments, R 1 yes R b1 Selected from halogens, -CN, -OMe, -C(O)NH2 and -SO2NH2, R c1 Selected from -F and -CN.

[0238] In some implementation schemes, R 1 Selected from the following structures:

[0239] , , , , , , , , , , , , , and .

[0240] In some implementation schemes, R 1 yes R f1 R g1 R h1 and R i1 Each of them is R independently. s1 Each variable is independent as described in this disclosure. In some implementations, R 1 yes And R f1 R g1 R h1 and R i1Each of them is R independently. s1 , where each R s1 Independently selected from halogen, -CN, -OR s11 -NR s11 R s12 -C(O)NR s11 R s12 -SO2NR s11 R s12 and , where each R s11 Independently -H or optionally substituted C1-C6 aliphatic. In some embodiments, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R g1 It is halogen, -CN, -OR s11 -NR s11 R s12 or , where each R s11 and R s12 Independently -H or optionally substituted C1-C6 aliphatic, R s12 As described in this disclosure. In some embodiments, R g1 It is halogen, -CN, -OR s11 -NR s11 R s12 or , where each R s11 and R s12 Independently -H or optionally substituted with halogen or -OH, it is a C1-C6 aliphatic compound, and R s12 As described in this disclosure. In some embodiments, R g1 It is -C(O)N(R) s1 )2、-S(O)2N(R s1 )2、-S(O)R s1 -S(O)2R s1 -S(O)(=NR) s1 )R s2 or -OS(O)2N(R) s1 )2, where each R s1 Independently, it is -H or optionally substituted C1-C6 aliphatic. In some embodiments, R g1 It is a 3-10 membered heterocyclic group with optional substitution of 1-4 heteroatoms. In some embodiments, R g1It is an optional substituted 3-6 membered heterocyclic group having 1-3 heteroatoms. In some embodiments, R g1 It is an optional substituted 6-membered heterocyclic group having 1-3 heteroatoms. In some embodiments, R i1 It is halogen, -CN, -OR s11 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 or , where R s11 It is -H or optionally substituted C1-C6 aliphatic, R s12 Independently as described in this disclosure. In some embodiments, R i1 It is a halogen. In some implementations, R i1 It is F.

[0241] In some implementation schemes, R 1 Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0242] In some implementation schemes, R 1 yes And R j1 R k1 R l1 and R m1 Each of them is R independently. s1 Each variable is independent as described in this disclosure. In some implementations, R 1 yes R j1R k1 R l1 and R m1 Each of them is R independently. s1 , where each R s1 Independently selected from halogen, -CN, -OR s11 -NR s11 R s12 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 and , where each R s11 and R s12 Independently -H or optionally substituted C1-C6 aliphatic, R s12 As described in this disclosure. In some embodiments, R 1 yes Each variable is independent as described in this disclosure. In some implementations, R k1 It is halogen, -CN, -OR s1 -N(R) s1 )2、 -C(O)N(R s1 ) 2 、 -S(O)2N(R s1 )2 or , where each R s1 Independently, it is -H or optionally substituted C1-C6 aliphatic. In some embodiments, R k1 It is a halogen, -CN, -OH, -C(O)NH2, -S(O)2NH2 or .

[0243] In some implementation schemes, R 1 yes In some implementations, R 1 yes .

[0244] In some implementation schemes, R 1 It is an optionally substituted pyridine N-oxide. In some embodiments, R 1 It is an optional replacement In some implementations, R 1 yes In some implementations, R 1 It is an optional replacement In some implementations, R 1 yes In some implementations, R 1 It is an optional replacement In some implementations, R 1 yes In some implementations, R 1 yes .

[0245] In some implementation schemes, R 1 It is an optional replacement , , , , , , , and In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement , , , , , , , and The substituents are selected from halogens, -CN, and -OR. s1 -N(R) s1 )2、-C(O)N(R s1 )2、-S(O)2N ( R s1 )2 and , where each R s1 Independently -H or optionally substituted C1-C6 aliphatic compounds. In some embodiments, R 1It is an optional replacement , , , , , , , and The substituents are selected from halogens, -CN, and -OR. s1 -N(R) s1 )2、-C(O)N(R s1 )2、-S(O)2N ( R s1 )2 and , where each R s1 Independently -H or optionally substituted C1-C6 aliphatic compounds. In some embodiments, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes .

[0246] In some implementation schemes, R 1 It is an optional replacement , , , , , , , , , , , , , , , and In some implementations, R 1 It is an optional replacement In some implementations, R 1It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement , , , , , , , , , , , , , , and The substituents are selected from halogens, -CN, and -OR. s1 -N(R) s1 )2、-C(O)N(R s1 )2、-S(O)2N(R s1 )2 and , where each R s1 Independently -H or optionally substituted C1-C6 aliphatic compounds. In some embodiments, R 1 It is an optional replacement , , , , , , , , , , , , , , and The substituents are selected from halogens, -CN, and -OR. s1 -N(R) s1 )2、-C(O)N(R s1 )2、-S(O)2N(R s1 )2 and , where each R s1 Independently -H or optionally substituted C1-C6 aliphatic compounds. In some embodiments, R 1 yes In some implementations, R 1 Optional replacement In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes.

[0247] In some implementation schemes, R 1 It is an optional replacement , , , ,and In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some embodiments, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement In some implementations, R 1 It is an optional replacement.

[0248] In some implementations, ring A is an optional replacement. , , , , , , and In some implementations, each substituent of ring A is independently R. s1 And R s1 As described in this disclosure, in some embodiments, ring A is optionally replaced. , , , , , , and In some embodiments, each substituent of ring A is independently selected from halogens, -CN, -OR. s11 -NR s11 R s12 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 and , where R s11 and R s12 Each is independently -H or optionally substituted C1-C6 aliphatic. In some embodiments, ring A is optionally substituted. , , , , , , and In some embodiments, each substituent of ring A is independently selected from halogens, -CN, -OR. s11 -NR s11 R s12 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 and , where R s11 and R s12 Each is independently -H or optionally substituted C1-C ( 6) Aliphatic. In some implementations, ring A is optionally substituted. , , and In some implementations, each substituent of ring A is independently R. s1 And R s1 As described in this disclosure, in some embodiments, ring A is optionally replaced. , , , and In some embodiments, each substituent of ring A is independently selected from halogens, -CN, -OR. s11 -NR s11 R s12 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 and , where R s11and R s12 Each is independently -H or optionally substituted C1-C6 aliphatic. In some embodiments, ring A is optionally substituted. , , , and In some embodiments, each substituent of ring A is independently selected from halogens, -CN, -OR. s11 -NR s11 R s12 -C(O)NR s11 R s12 -S(O)2NR s11 R s12 and , where R s11 and R s12 Each is independently -H or optionally substituted C1-C6 aliphatic.

[0249] In some implementation schemes, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes In some implementations, R 1 yes .

[0250] In some implementation schemes, R 1 Selected from

[0251] .

[0252] In some implementation schemes, R 1 yes , , , , or In some implementations, each R Ls1 and R s11 Independently -H, or optionally substituted groups, said groups are selected from C 1-6 Aliphatic group, 6-membered or 10-membered aryl group, or 5-10-membered (e.g., 5-membered, 6-membered, 9-membered, 10-membered, etc.) heteroaryl group having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0253] In some implementation schemes, R 1 Selected from

[0254]

[0255] In some implementations, R 1 yes , , , , , , , , , , , or .

[0256] R 1'

[0257] In some implementation schemes, R 1' It is R' as described in this disclosure. In some embodiments, R 1' It is R as described in this disclosure. In some embodiments, R 1' It is hydrogen. In some implementations, R 1 and R 1' Together with the nitrogen atom to which they are attached, they form optional substituted 3-6 membered rings, which in addition to the nitrogen atom, have 0-3 heteroatoms.

[0258] In some implementation schemes, R 1' It is hydrogen.

[0259] In some implementation schemes, R 1 and R 1'Together with the nitrogen atom to which it is attached, it forms optional substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) rings, said rings having, in addition to the nitrogen atom, 0-6 (e.g., 0, 1-6, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 and R 1' Together with the nitrogen atom to which it is attached, it forms optionally substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) rings, said rings having, in addition to the nitrogen atom, 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 and R 1' Together with the nitrogen atom it is attached to, it forms an optionally substituted 3-6 membered ring, which has 0-3 heteroatoms in addition to the nitrogen atom. In some embodiments, R 1 and R 1' Together with the nitrogen atom it is attached to, it forms an optionally substituted 3-6 membered ring, which, in addition to the nitrogen atom, has 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 and R 1' Together with the nitrogen atom to which it is attached, it forms an optionally substituted 5-6 membered heterocycle, said heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 and R 1' Together with the nitrogen atom to which it is attached, it forms an optionally substituted 6-membered heterocycle, said heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1 and R 1' Together with the nitrogen atoms to which they are attached, they form optional substitutions. In some implementations, R 1 and R 1' Together with the nitrogen atoms they are attached to, they form In some implementations, R 1 and R 1' Together with the nitrogen atoms they are attached to, they form .

[0260] Q

[0261] In some implementations, Q is O. In some implementations, Q is S. In some implementations, R... Q It is -R' as described in this disclosure. In some embodiments, RQ Yes - OR, where R is as described in this disclosure. In some embodiments, R Q It is -OR, where R is not -H. In some implementations, Q is NH. In some implementations, Q is NR. Q , where R Q It is an optional replacement for C 1-6 Fatty base. In some implementations, Q is NR. Q , where R Q It is an optional replacement for C 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is C 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is -OR, where R is the alternative C. 1-6 Aliphatic. In some implementations, Q is NR. Q , where R Q It is -OR, where R is the alternative C. 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is -OR, where R is C 1-6 alkyl.

[0262] R 2

[0263] In some implementation schemes, R 2 It is an optional substituent group selected from phenyl, 3-10 membered cyclic aliphatic groups, and 5-6 membered heteroaryl groups having 1-4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; or R2 is -L (R2 )-R B Each variable is independent as described in this disclosure. In some embodiments, R 2 It is an optional substituent group selected from phenyl and having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or R 2 yes Each variable is independent as described in this disclosure.

[0264] In some implementation schemes, R 2 It is an optional substituted phenyl group. In some embodiments, R 2 It is a phenyl group.

[0265] In some implementation schemes, R 2 It is an optional substituted 3-10 membered cyclic aliphatic group. In some embodiments, R2 It is an optional substituted 3-7 membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 3-6 membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 3-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 4-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 5-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 6-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 7-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 8-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 9-membered cyclic aliphatic group. In some embodiments, R 2 It is an optional substituted 10-membered cyclic aliphatic group.

[0266] In some implementation schemes, R 2 It is an optional substituted 5-6-membered heteroaryl group having 1-4 heteroatoms. In some embodiments, R 2 It is a 5-6 membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0267] In some implementation schemes, R 2 It is an optional substituted 5-membered heteroaryl group having 1-4 heteroatoms. In some embodiments, R 2 It is a 5-membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group having 1-3 heteroatoms. In some embodiments, R 2 It is a optionally substituted five-membered heteroaryl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group having 1-2 heteroatoms. In some embodiments, R 2 It is an optional substituted five-membered heteroaryl group having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group with 2 heteroatoms. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group having one heteroatom. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group having one oxygen atom. In some embodiments, R2 It is an optional substituted 5-membered heteroaryl group having one nitrogen atom. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group with a sulfur atom. In some embodiments, R 2 It is a 5-membered heteroaryl group with two independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2 R2 is an optionally substituted 5-membered heteroaryl group, wherein the ring has two heteroatoms, one of which is a nitrogen atom. In some embodiments, R2 is an optionally substituted 5-membered heteroaryl group, wherein the ring has two heteroatoms independently selected from N and S. In some embodiments, R... 2 It is an optional substituted 5-membered heteroaryl group, wherein the ring has two heteroatoms independently selected from oxygen and sulfur. In some embodiments, R 2 It is an optional substituted 5-membered heteroaryl group with 3 heteroatoms. In some embodiments, R 2 It is an optionally substituted 5-membered heteroaryl group, the ring having three independent heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring has one heteroatom. In some embodiments, the ring has two or more heteroatoms, at least one of which is a nitrogen atom. In some embodiments, each heteroatom is nitrogen. In some embodiments, all heteroatoms are identical. In some embodiments, at least one heteroatom is different from the other heteroatoms.

[0268] In some implementation schemes, R 2 It is an optional substituted 6-membered heteroaryl group having 1-4 heteroatoms. In some embodiments, R 2 It is a 6-membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optional substituted 6-membered heteroaryl group having 1-3 heteroatoms. In some embodiments, R 2 It is a 6-membered heteroaryl group with 1-3 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optional substituted 6-membered heteroaryl group having 1-2 heteroatoms. In some embodiments, R 2 It is a 6-membered heteroaryl group with 1-2 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optional substituted 6-membered heteroaryl group having two heteroatoms. In some embodiments, R2 is an optional substituted 6-membered heteroaryl group having one heteroatom selected from O, N, and S. In some embodiments, R... 2It is an optionally substituted 6-membered heteroaryl group, wherein the ring has two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is an optionally substituted 6-membered heteroaryl group, wherein the ring has 2 heteroatoms, each of which is nitrogen. In some embodiments, R 2 It is an optional substituted 6-membered heteroaryl group with 3 heteroatoms. In some embodiments, R 2 It is an optional substituted 6-membered heteroaryl group having three heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2 It is a 6-membered heteroaryl group with optional substitution of 3 heteroatoms, one of which is nitrogen.

[0269] In some implementation schemes, R 2 yes Each variable is independent as described in this disclosure. In some implementations, R 2 yes Each variable is independent as described in this disclosure.

[0270] Ring B

[0271] In some embodiments, ring B is an optionally substituted 3-10 membered ring (e.g., 4-10 membered, 1 membered, 2 membered, 3 membered, 4 membered, 5 membered, 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, etc.) having 0-6 heteroatoms (e.g., 0, 1-6, 1-4, 1, 2, 3, 4, 5, 6, etc.) independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 3-10 membered ring (e.g., 4-10 membered, 1 membered, 2 membered, 3 membered, 4 membered, 5 membered, 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, etc.) having 0-4 heteroatoms (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is a 4-10 membered ring. In some embodiments, ring B is a 4-9 membered ring. In some implementations, ring B is a 4-8 element ring. In some implementations, ring B is a 4-7 element ring. In some implementations, ring B is a 4-6 element ring.

[0272] In some embodiments, ring B is an aromatic ring. In some embodiments, ring B is a non-aromatic ring. In some embodiments, ring B is a saturated ring. In some embodiments, ring B is a partially unsaturated ring.

[0273] In some embodiments, ring B has one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B has no heteroatoms.

[0274] In some embodiments, ring B is a monocyclic ring. In some embodiments, ring B is a bicyclic ring. In some embodiments, ring B is a bicyclic ring, and each monocyclic unit is independently a 3-9 member (e.g., 3-7, 4-7, 4-6, 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring. In some embodiments, each monocyclic unit is independently a 3-7 member ring. In some embodiments, each monocyclic unit is independently a 4-7 member ring. In some embodiments, each monocyclic unit is independently a 5-7 member ring. In some embodiments, each monocyclic unit is independently a 5- or 6-membered ring. In some embodiments, at least one monocyclic unit is a 6-membered ring. In some embodiments, at least one monocyclic unit is a 5-membered ring. In some embodiments, at least one monocyclic unit is an aromatic ring. In some embodiments, at least one monocyclic unit is an aromatic ring, a 6-membered ring, and does not contain heteroatoms. In some embodiments, at least one monocyclic unit is a heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 5-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 6-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a non-aromatic ring.

[0275] In some embodiments, ring B is an optionally substituted phenyl group. In some embodiments, ring B is a benzene ring. In some embodiments, ring B is an optionally substituted 10-membered aromatic ring without heteroatoms.

[0276] In some embodiments, ring B is an optional substituted 9-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optional substituted 10-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0277] In some embodiments, ring B is an optionally substituted 5-6 membered aromatic ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted benzene ring. In some embodiments, ring B is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 5-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is a 5-membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms, one heteroatom being nitrogen and the other heteroatom independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 5-membered heteroaromatic ring having 1 heteroatom independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is a 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 6-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is an optionally substituted 6-membered heteroaromatic ring having 1 nitrogen atom. In some embodiments, ring B is a 6-membered heteroaromatic ring having one nitrogen atom. In some embodiments, ring B is an optionally substituted pyridyl group. In some embodiments, ring B is a pyridyl group. In some embodiments, ring B is an optionally substituted 6-membered heteroaromatic ring having two nitrogen atoms.

[0278] L R2

[0279] In some implementations, L R2 As a key. In some implementations, L R2 Yes -O-. In some implementations, L R2 Yes -S-. In some implementations, L R2 It is an optional substitution of -CH2-. In some implementations, L R2 It is -CH2-.

[0280] Rs2

[0281] In some implementations, each R s2 Independent of halogen, -CN, -R s21 , -OR s21 , -NR s21 R s22 , -C(O)R s21 , -C(O)NR s21 R s22 , -SR s21 , -S(O)2NR s21 R s22 , -S(O)2R s21 , -S(O)R s21 , -S(O)(NR s22 )R s21 ,-S(O)NR s21 R s22 -SF5 or -OS(O)2NR s21 R s22 In some implementations, each R s2 Independently selected from halogens, -CN, -R s21 , -OR s21 , -NR s21 R s22 , -C(O)R s21 , -C(O)NR s21 R s22 , -S(O)2NR s21 R s22 , -S(O)2R s21 , -S(O)R s21 , -S(O)(NR s22 )R s21 , -S(O)NR s21 R s22 and -OS(O)2NR s21 R s22 , where each R s21 and R s22 Independently -H or optionally substituted groups, said groups are selected from C1-C6 aliphatic groups or 5-6 membered rings having 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, said groups may optionally be substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH or =O, wherein each other variable is independently as described herein. In some embodiments, each R s2 Independently selected from halogens, -CN, R s21 -OR s21 -NRs21 R s22 -C(O)R s21 -C(O)NR s21 R s22 -S(O)2NR s21 R s22 -S(O)2R s21 -S(O)R s21 -S(O)(NR) s22 )R s21 -S(O)NR s21 R s22 and -OS(O)2NR s21 R s22 , where each R s21 and R s22 Independently -H or optionally substituted groups, said groups are selected from C1-C6 aliphatic groups or 5-6 membered saturated rings having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, said groups may optionally be substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH or =O, wherein each other variable is independently as described herein. In some embodiments, each R s2 Independently selected from halogens, -CN, R s21 -OR s21 -NR s21 R s22 -C(O)R s21 -C(O)NR s21 R s22 -S(O)2NR s21 R s22 -S(O)2R s21 -S(O)R s21 -S(O)(NR) s22 )R s21 -S(O)NR s21 R s22 and -OS(O)2NR s21 R s22 , where each R s21 and R s22 Independently -H or optionally substituted groups, said groups are selected from C1-C6 aliphatic groups or 5-6 membered saturated rings having 0-4 nitrogen atoms, said groups may optionally be substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH or =O, wherein each other variable is independently as described herein. In some embodiments, each R s2 Independently selected from halogens, -CN, R s21 -OR s21 -NR s21 Rs22 -C(O)R s21 -C(O)NR s21 R s22 -S(O)2NR s21 R s22 -S(O)2R s21 -S(O)R s21 -S(O)(NR) s22 )R s21 -S(O)NR s21 R s22 and -OS(O)2NR s21 R s22 , where each R s21 and R s22 Independently -H or optionally substituted groups, said groups are selected from C1-C6 aliphatic groups or 5-6 membered saturated rings having 1-2 nitrogen atoms, said groups may optionally be substituted by one or more substituents (e.g., 1-3), said substituents being independently selected from halogens, -OH or =O, wherein each other variable is independently as described herein. In some embodiments, each R s2 Independent of halogen and -OR s21 , where R s21 As described in this article. In some implementations, each R s2 Independent of halogen and -OR s21 , where R s21 C is an optional replacement 1-6 Aliphatic groups. In some implementations, each R s2 Independent of halogen and -OR s21 , where R s21 C is an optional replacement 1-6 Aliphatic groups, wherein the C 1-6 The aliphatic group may be replaced by a halogen, -OH, or =O. In some embodiments, each R s2 Independent of halogen and -OR s21 , where R s21 It is a C1-6 aliphatic group. In some embodiments, each R s2 Independent of halogen and -OR s21 , where R s21 C 1-6 Alkyl group. In some embodiments, each R s2 Independently halogenated and -OMe. In some embodiments, each halogen is independently -F or -Cl. In some embodiments, each halogen is -F. In some embodiments, each R... s2 Independently -F, -Cl, or -OMe. In some implementations, each R s2Independently -F or -OMe.

[0282] In some implementation schemes, R s2 It is a halogen. In some implementations, R s2 It is F. In some implementations, R s2 It is Br.

[0283] In some implementation schemes, R s2 It's CN.

[0284] In some implementation schemes, R s2 It is R s21 , where R s21 As described in this disclosure. In some embodiments, R s2 Yes - OR s21 , where R s21 As described in this disclosure. In some embodiments, R s2 Yes -NR s21 R s2 2, where each variable is independent as described in this disclosure. In some embodiments, R s2 It is -C(O)R s21 , where R s21 As described in this disclosure. In some embodiments, R s2 It is -C(O)NR s21 R s22 Each variable is independent as described in this disclosure. In some implementations, R s2 It is -SR s21 Each variable is independent as described in this disclosure. In some implementations, R s2 It is -S(O)2NR s21 R s22 Each variable is independent as described in this disclosure. In some embodiments, R s2 Yes-S(O)2R s21 Each variable is independent as described in this disclosure. In some implementations, R s2 It is -S(O)R s21 Each variable is independent as described in this disclosure. In some implementations, R s2 It is -S(O)(NR) s22 )R s21 Each variable is independent as described in this disclosure. In some embodiments, R s2 It is -S(O)NR s21 R s22 Each variable is independent as described in this disclosure. In some implementations, R s2 Yes -SF5. In some implementations, R s2It is -OS(O)2NR s21 R s22 Each variable is independent as described in this disclosure.

[0285] R s21

[0286] In some implementation schemes, R s21 It is R', where R' is as described in this disclosure. In some embodiments, R s21 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s21 It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R s21 It is a C1-C6 aliphatic compound optionally substituted with one or more substituents (e.g., 1-3) independently selected from halogens, -OH, or =O. In some embodiments, R s21 It is a C1-C6 alkyl group optionally substituted by one or more (e.g., 1-3) substituents independently selected from halogens or -OH. In some embodiments, R s21 It is a C1-C4 alkyl group optionally substituted with one or more (e.g., 1-3) substituents independently selected from halogens, -OH, or =O. In some embodiments, R s21 It is a C1-C6 alkyl group. In some embodiments, R s21 It is a C1-C3 alkyl group. In some embodiments, R s21 It is methyl. In some embodiments, R s21 It is -CH2OH. In some implementations, R s21 It is -CHF2. In some implementations, R s21 It is -CH(OH)CH2OH. In some implementations, R s21 It is -C(OH)(Me)2.

[0287] In some implementation schemes, R s21 It is a 5-membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R s21 It is a optionally substituted six-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s21 It is an optional replacement .

[0288] In some implementation schemes, R s21 It is a 5-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s21It is a 6-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s21 It is an optional replacement In some implementations, R s21 yes In some implementations, R s21 It is an optional replacement .

[0289] In some implementation schemes, R s21 It's H.

[0290] R s22

[0291] In some implementation schemes, R s22 It is R', where R' is as described in this disclosure. In some embodiments, R s22 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s22 It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R s22 It is a C1-C6 aliphatic compound optionally substituted with one or more substituents (e.g., 1-3) independently selected from halogens, -OH, or =O. In some embodiments, R s22 It is a C1-C6 alkyl group optionally substituted by one or more (e.g., 1-3) substituents independently selected from halogens or -OH. In some embodiments, R s22 It is a C1-C4 alkyl group optionally substituted with one or more (e.g., 1-3) substituents independently selected from halogens, -OH, or =O. In some embodiments, R s22 It is a C1-C6 alkyl group. In some embodiments, R s22 It is a C1-C3 alkyl group. In some embodiments, R s22 It is methyl. In some embodiments, R s22 It is -CH2OH. In some implementations, R s22 It is -CHF2. In some implementations, R s22 It is -CH(OH)CH2OH. In some implementations, R s22 It is -C(OH)(Me)2.

[0292] In some implementation schemes, R s22 It is a 5-membered heteroaryl group with 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R s22It is a optionally substituted six-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R s22 It is an optional replacement .

[0293] In some implementation schemes, R s22 It is a 5-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s22 It is a 6-membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R s22 It is an optional replacement In some implementations, R s22 yes In some implementations, R s22 It is an optional replacement .

[0294] In some implementation schemes, R s22 It's H.

[0295] In some implementation schemes, R s2 Yes - OR s21 , where R s21 As described in this disclosure. In some embodiments, R s2 It is -OR, where R is as described in this disclosure. For example, in some embodiments, R is an optional alternative to C. 1-6 Fatty base. In some embodiments, R is C 1-6 Alkyl group. In some embodiments, R s2 Yes -OMe. In some implementations, R s2 Yes -OCHF2. In some implementations, R s2 Yes - OCD3. In some implementations, R s2 Yes -OCF3. In some implementations, R s2 Yes -OEt. In some implementations, R s2 It is -O-cyclopropyl.

[0296] In some implementation schemes, R s2 It is R' as described in this disclosure. In some embodiments, R s2 It is R as described in this disclosure. In some embodiments, R s2 Yes -H. In some implementations, R s2 It is an optional replacement for C 1-6 Aliphatic. In some implementations, R s2 It is an optional replacement for C 1-6Alkyl group. In some embodiments, R s2 It is an optional substituted 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered cyclic aliphatic group. In some embodiments, R s2 It is an optional substituted 3-10 membered cycloalkyl group. In some embodiments, R s2 It is -C≡CH. In some implementations, R s2 It is --C≡C-CH3. In some implementations, R s2 It is cyclopropyl.

[0297] In some implementation schemes, R s2 It is -SR s21 , where R s21 As described in this disclosure. In some embodiments, R s2 It is -SR, where R is as described in this disclosure. For example, in some embodiments, R is an optional alternative to C. 1-6 Fatty base. In some embodiments, R is C 1-6 Alkyl group. In some embodiments, R s2 Yes -SMe. In some implementations, R s2 It is -SCF3.

[0298] In some implementation schemes, R s2 Yes -CONH2. In some implementations, R s2 It is -CONHCH3. In some implementations, R s2 It is -S(O)2NH2. In some implementations, R s2 It is -S(O)2Me. In some implementations, R s2 It is -S(O)Me. In some implementations, R s2 It is -S(NH)(O)Me. In some implementations, R s2 It is -S(NMe)(O)Me. In some implementations, R s2 It is -OH. In some implementations, R s2 Yes -OMe. In some implementations, R s2 It is -NH2. In some implementations, R s2 It is -OCH2CH(OH)CH2(OH).

[0299] In some implementations, two R s2 The group and its spacer atoms together form an optionally substituted 5-6 membered ring, which, in addition to the spacer atoms, has 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R groups... s2The group and its spacer atoms together form an optionally substituted 5-membered ring, wherein the ring, in addition to the spacer atoms, has 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R groups... s2 The group and its spacer atoms together form an optionally substituted 6-membered ring, wherein, in addition to the spacer atoms, the ring has 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0300] s2

[0301] In some implementations, s2 is 0, 1, 2, 3, 4, or 5. In some implementations, s2 is 0. In some implementations, s2 is 1. In some implementations, s2 is 2. In some implementations, s2 is 3. In some implementations, s2 is 4. In some implementations, s2 is 5. In some implementations, s2 is 1 or 2.

[0302] In some implementation schemes, R 2 It is not replaced.

[0303] In some implementation schemes, R 2 It is by 1-5 R s2 Optional substituted phenyl groups. In some embodiments, R2 is replaced by one or two R groups. s2 Optional substituted phenyl groups. In some embodiments, R2 is substituted with two or more R groups. s2 Substituted phenyl groups. In some embodiments, R2 is replaced by three R groups. s2 Substituted phenyl groups, each R s2 All are independent as described in this disclosure.

[0304] In some implementation schemes, R 2 It is a 5-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 1-5 R atoms. s2 Optional replacement, R s2 As described in this disclosure. In some embodiments, R 2 It is a 5-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, said heteroaryl group being surrounded by 1-5 R atoms. s2 Optional replacement, R s2 As described in this disclosure. In some embodiments, R 2 It is a 5-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 2 or more R atoms. s2 Replace, R s2 As stated in this disclosure.

[0305] In some implementation schemes, R 2 It is a 6-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 1-5 R atoms. s2 Optional replacement, R s2 As described in this disclosure. In some embodiments, R 2 It is a 6-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, said heteroaryl group being surrounded by 1-5 R atoms. s2 Optional replacement, R s2 As described in this disclosure. In some embodiments, R 2 It is a 6-membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl group is surrounded by 2 or more R atoms. s2 Replace, and R s2 As stated in this disclosure.

[0306] In some implementation schemes, R 2 It is by two or more R s2 Substituted 2-pyridyl, wherein R s2 As described in this disclosure. In some embodiments, R 2 It is by two or more R s2 Substituted 3-pyridyl, wherein R s2 As described in this disclosure. In some embodiments, R 2 It is by two or more R s2 Substituted 4-pyridyl, wherein R s2 As stated in this disclosure.

[0307] In some implementation schemes, R 2 Substituted. In some embodiments, the substituent is located at position 2 (R). 2 The atom attached to the nitrogen atom is at position 1. In some embodiments, the substituent is located at position 3 (R). 2 The atom attached to the nitrogen atom is at position 1. In some embodiments, the substituent is located at position 4 (R). 2 The atom attached to the nitrogen atom is at position 1. In some implementations, an R s2 The group is located at position 2 and has one R s2 The group is located at position 3, where R 2 A nitrogen atom is attached at position 1. In some implementations, an R... s2 The group is located at position 3 and has one R s2 The group is located at position 4, where R 2 It is connected to a nitrogen atom at position 1.

[0308] In some implementation schemes, R 2 yes R a2 R b2 R c2 R d2 and R e2 Each of them is independently R s2 ,and R s2 As described in this disclosure. In some embodiments, R 2 yes R a2 R b2 and R c2 Each of them is independently R s2 , and R s2 As described in this disclosure. In some embodiments, each R s2 Independently selected from halogen, -CN, -OR s21 -NR s21 R s22 -C(O)R s21 -C(O)NR s21 R s22 or -S(O)2NR s21 R s22 Each variable is independent as described in this disclosure. In some implementations, R s21 and R s22 Each of them is independently -H or an optional substituted C. 1-6 Aliphatic. In some implementations, R s21 and R s22 Each is independently -H or optionally substituted C. 1-6 Fatty base. In some implementations, R s22 Yes, it's -H.

[0309] In some implementation schemes, R 2 yes R a2 R b2 R c2 R d2 and R e2 Each of them is independently R s2 And R s2 As described in this disclosure. In some embodiments, R 2 yes R a2 R b2 and R c2 Each of them is independently R s2 , and R s2 As described in this disclosure. In some embodiments, each R s2Independently selected from halogen, -CN, -OR s21 -NR s21 R s22 -C(O)R s21 -C(O)NR s21 R s22 or -S(O)2NR s21 R s22 Each variable is independent as described in this disclosure. In some implementations, R s21 and R s22 Each of them is independently -H or an optional substituted C. 1-6 Aliphatic. In some implementations, R s21 and R s22 Each is independently -H or optionally substituted C. 1-6 Fatty base. In some implementations, R s22 Yes, it's -H.

[0310] In some implementation schemes, R a2 Yes - OR s21 R s21 It is an optional substituted C1-6 alkyl group. In some embodiments, R a2 Yes-OMe.

[0311] In some implementation schemes, R b2 It is a halogen. In some implementations, R b2 It is F. In some implementations, R b2 It is Br.

[0312] In some implementation schemes, R c2 It is a halogen. In some implementations, R c2 It is F. In some implementations, R c2 It is Br.

[0313] In some implementation schemes, R 2 yes. In some implementations, R2 yes In some implementations, R2 is... In some implementations, R2 is... In some embodiments, R2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R2 is... In some implementations, R2 Selected from:

[0314] In some implementations, R 2 yes or .

[0315] R 3

[0316] In some implementation schemes, R 3 and R 4 Each can be independently hydrogen, -CN, or R. In some implementations, R 3 and R 4 Each group is independently hydrogen, -CN, or optionally substituted, selected from C1-C6 aliphatic, phenyl, 5-6 membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 3-10 membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 3 and R 4 Together with the carbon atoms to which they are attached, they form optional substituted 3-6 membered rings, which have 0-3 independent heteroatoms selected from nitrogen, oxygen and sulfur.

[0317] In some implementation schemes, R 3 It is a hydrogen, -CN, or optionally substituted group, said group being selected from C1-C6 aliphatic, phenyl, 5-6-membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 3-10-membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 3 and R 4 Together with the carbon atoms to which they are attached, they form optional substituted 3-6 membered rings, which have 0-3 independent heteroatoms selected from nitrogen, oxygen and sulfur.

[0318] In some implementation schemes, R 3 It is hydrogen.

[0319] In some implementation schemes, R 3 Yes - CN.

[0320] In some implementation schemes, R 3 It is R as described in this disclosure.

[0321] In some implementation schemes, R 3 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R 3 It is an optional substituted C1-C6 alkyl group. In some embodiments, R 3 It is an optional substituted C1-C3 alkyl group. In some embodiments, R 3 It is a C1-C3 alkyl group that can be optionally substituted with a halogen. In some embodiments, R 3 It is a C1-C3 alkyl group substituted with a halogen. In some embodiments, R 3 It is a C1-C3 alkyl group. In some embodiments, R 3 It is an optional substituted methyl group. In some embodiments, R 3 It is methyl. In some embodiments, R 3 It is a halogen-substituted methyl group. In some embodiments, R3 is -CF3. In some embodiments, R 3 It is -CHF2. In some implementations, R 3 It is an optional substituted ethyl group. In some embodiments, R 3 It is an ethyl group substituted with a halogen. In some embodiments, R (3 ) It is -CH2CF3. In some implementations, R 3 It is optionally substituted with n-propyl. In some embodiments, R 3 It is a halogen-substituted n-propyl group. In some embodiments, R 3 It is an optional substituted isopropyl group. In some embodiments, R 3 It is an isopropyl group substituted with a halogen. In some embodiments, R 3 It is isopropyl.

[0322] In some implementation schemes, R 3 It is an optional substituted phenyl group. In some embodiments, R 3 It is phenyl. In some embodiments, R 3 It is 2-trifluoromethylphenyl. In some embodiments, R 3 It is 3-trifluoromethylphenyl. In some embodiments, R 3 It is 4-trifluoromethylphenyl.

[0323] Those skilled in the art will understand upon reading this disclosure that, in some embodiments, R 3 Can have The structural group is substituted, and R a3 R b3 R c3 R d3 and R e3Each of them is independently R s3 , where R s3 It is the substituent described in this disclosure. In some embodiments, R 3 yes And R a3 R b3 R c3 R d3 and R e3 Each of them is R independently. s3 , where R s3 It is R s31 Halogen, -CN, -OR s31 -NR s31 R s32 -C(O)NR s31 R s32 and -S(O)2R s31 R s32 , where each R s31 and R s32 Independently -H or optionally halogenated C1-C6 aliphatic. In some embodiments, R 3 yes R a3 It is R s3 , where R s3 It is R s31 Halogen, -CN, -OR s31 -NR s31 R s32 -C(O)NR s31 R s32 , and -S(O)2R s31 R s32 , where each R s31 and R s32 Independently -H or optionally halogenated C1-C6 aliphatic. In some embodiments, R 3 yes R b3 It is R s3 , where R s3 It is R s31 Halogen, -CN, -OR s31 -NR s31 R s32 -C(O)NR s31 R s32 , and -S(O)2R s31 R s32 , where each R s31 and R s32Independently -H or optionally halogenated C1-C6 aliphatic. In some embodiments, R 3 yes R c3 It is R s3 , where R s3 It is R s31 Halogen, -CN, -OR s31 -NR s31 R s32 -C(O)NR s31 R s32 , and -S(O)2R s31 R s32 , where each R s31 and R s32 Independent of -H or optionally halogenated C1-C6 aliphatic.

[0324] In some implementation schemes, R a3 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R a3 It is an optional substituted C1-C6 alkyl group. In some embodiments, R a3 It is an optional substituted C1-C3 alkyl group. In some embodiments, R a3 It is a C1-C3 alkyl group. In some embodiments, R a3 It is an optional substituted methyl group. In some embodiments, R a3 It is methyl. In some embodiments, R a3 It is -CF3. In some implementations, R a3 It is -CHF2. In some implementations, R a3 It is a halogen. In some implementations, R a3 It is F. In some implementations, R a3 It is Br. In some implementations, R a3 It is I. In some implementations, R a3 Yes - OR s31 , where R s31 As described in this disclosure. In some embodiments, R a3 Yes - OR s31 , where R s31 It is a -H or optionally substituted C1-C6 alkyl group. In some embodiments, R a3 It is -OH. In some implementations, R a3 Yes - OR s31 , where R s31 It is an optional substituted C1-C6 alkyl group. In some embodiments, R a3 Yes-OMe.

[0325] In some implementation schemes, R b3 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R b3 It is an optional substituted C1-C6 alkyl group. In some embodiments, R b3 It is an optional substituted C1-C3 alkyl group. In some embodiments, R b3 It is a C1-C3 alkyl group. In some embodiments, R b3 It is an optional substituted methyl group. In some embodiments, R b3 It is methyl. In some embodiments, R b3 It is -CF3. In some implementations, R b3 It is -CHF2. In some implementations, R b3 It is a halogen. In some implementations, R b3 It is F. In some implementations, R b3 It is Br. In some implementations, R b3 It is I. In some implementations, R b3 Yes - OR s31 , where R s31 It is a -H or optionally substituted C1-C6 alkyl group. In some embodiments, R b3 It is -OH. In some implementations, R b3 Yes - OR s31 , where R s31 It is an optional substituted C1-C6 alkyl group. In some embodiments, R b3 Yes-OMe.

[0326] In some implementation schemes, R c3 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R c3 It is an optional substituted C1-C6 alkyl group. In some embodiments, R c3 It is an optional substituted C1-C3 alkyl group. In some embodiments, R c3 It is a C1-C3 alkyl group. In some embodiments, R c3 It is an optional substituted methyl group. In some embodiments, R c3 It is methyl. In some embodiments, R c3 It is -CF3. In some implementations, R c3 It is -CHF2. In some implementations, R c3 It is a halogen. In some implementations, R c3 It is F. In some implementations, R c3 It is Br. In some implementations, R c3It is I. In some implementations, R c3 Yes - OR s31 , where R s31 It is a -H or optionally substituted C1-C6 alkyl group. In some embodiments, R c3 It is -OH. In some implementations, R c3 Yes - OR s31 , where R s31 It is an optional substituted C1-C6 alkyl group. In some embodiments, R c3 Yes-OMe.

[0327] In some implementation schemes, R 3 It is an optional substituted 5-6 membered heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optional substituted 5-membered heteroaryl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optional substituted 5-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optional substituted 6-membered heteroaryl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optional substituted 6-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0328] In some implementation schemes, R 3 It is an optional substituted pyridinyl group. In some embodiments, R 3 It is pyridyl. In some embodiments, R 3 It is an optional replacement In some implementations, R 3 yes In some implementations, R 3 It is an optional replacement In some implementations, R 3 yes In some implementations, R 3 It is an optional replacement In some implementations, R 3 yes In some implementations, R 3 It is an optional substituted pyrazole. In some embodiments, R 3 It is pyrazole. In some implementations, R 3 It is an optional replacement n. In some implementations, R 3 yes In some implementations, R 3 yes .

[0329] In some implementation schemes, R 3 It is an optionally substituted 3-10-membered heterocyclic alkyl group having 1-4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optionally substituted 3-6 membered heterocyclic alkyl group having 1-3 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optionally substituted 5-6 membered heterocyclic alkyl group having 1-2 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 3 It is an optional substituted 3-6 membered cycloalkyl group. In some embodiments, R 3 It is an optional replacement In some implementations, R 3 yes In some implementations, R 3 It is an optional replacement In some implementations, R 3 yes In some implementations, R 3 It is an optional replacement In some implementations, R 3 yes In some implementations, R 3 It is an optional replacement In some implementations, R 3 yes .

[0330] In some implementation schemes, R 3 It is R as described in this disclosure. For example, in some embodiments, R 3 R is an optional substituted 6-10 aryl-C1-C6 aliphatic compound. In some embodiments, R... 3 It is R, where R is optionally substituted -CH2-Ph. In some embodiments, R 3 R is an optional substituted 5-10-membered heteroaryl group having 1-6 heteroatoms (-C1-C6 aliphatic groups), wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R... 3 R is an optional substituted 5-10 heteroaryl group with 1-6 heteroatoms -CH2-, wherein each heteroatom is independently chosen to be nitrogen, oxygen, or sulfur.

[0331] R 4

[0332] In some implementation schemes, R 4 It is hydrogen, -CN, or optionally substituted groups selected from C1-C6 aliphatic, phenyl, 5-6 membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 3-10 membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 3 and R 4 Together with the carbon atoms to which they are attached, they form optional substituted 3-6 membered rings, which have 0-3 independent heteroatoms selected from nitrogen, oxygen and sulfur.

[0333] In some implementation schemes, R 4 It is hydrogen.

[0334] In some implementation schemes, R 4 Yes - CN.

[0335] In some implementation schemes, R 4 It is R as described in this disclosure.

[0336] In some implementation schemes, R 4 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R 4 It is an optional substituted C1-C6 alkyl group. In some embodiments, R 4 It is an optional substituted C1-C3 alkyl group. In some embodiments, R 4 It is a C1-C3 alkyl group that can be optionally substituted with a halogen. In some embodiments, R 4 It is a C1-C3 alkyl group substituted with a halogen. In some embodiments, R 4 It is a C1-C3 alkyl group. In some embodiments, R 4 It is an optional substituted methyl group. In some embodiments, R 4 It is methyl. In some embodiments, R 4 It is a methyl group substituted with a halogen. In some embodiments, R 4 It is -CF3. In some implementations, R 4 It is -CHF2. In some implementations, R 4 It is an optional substituted ethyl group. In some embodiments, R 4 It is an ethyl group substituted with a halogen. In some embodiments, R 4 It is -CH2CF3. In some implementations, R 4 It is optionally substituted with n-propyl. In some embodiments, R 4 It is a halogen-substituted n-propyl group. In some embodiments, R 4 It is an optional substituted isopropyl group. In some embodiments, R4 It is an isopropyl group substituted with a halogen. In some embodiments, R 4 It is isopropyl.

[0337] In some implementation schemes, R 4 It is an optional substituted phenyl group. In some embodiments, R 4 It is a phenyl group.

[0338] Those skilled in the art will understand upon reading this disclosure that, in some embodiments, R 4 Can have The structural group is substituted, and R a4 R b4 R c4 R d4 and R e4 Each of them is independently R s4 , where R s4 The substituents described in this disclosure. In some embodiments, R 4 yes And R a4 R b4 R c4 R d4 and R e4 Each of them is R independently. s4 , where R s4 It is R s41 Halogen, -CN, -OR s41 -NR s41 R s42 -C(O)NR s41 R s42 and -S(O)2R s41 R s42 , where each R s41 and R s42 Independently -H or optionally halogenated C1-C6 aliphatic. In some embodiments, R 4 yes R a4 It is R s4 , where R s4 It is R s41 Halogen, -CN, -OR s41 -NR s41 R s42 -C(O)NR s41 R s42 , and -S(O)2R s41 R s42 , where each R s41 and R s42Independently -H or optionally halogenated C1-C6 aliphatic. In some embodiments, R 4 yes R b4 It is R s4 , where R s4 It is R s41 Halogen, -CN, -OR s41 -NR s41 R s42 -C(O)NR s41 R s42 , and -S(O)2R s41 R s42 , where each R s41 and R s42 Independently -H or optionally halogenated C1-C6 aliphatic. In some embodiments, R 4 yes R c4 It is R s4 , where R s4 It is R s41 Halogen, -CN, -OR s41 -NR s41 R s42 -C(O)NR s41 R s42 , and -S(O)2R s41 R s42 , where each R s41 and R s42 Independently -H or optionally halogenated C1-C6 aliphatic.

[0339] In some implementation schemes, R a4 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R a4 It is an optional substituted C1-C6 alkyl group. In some embodiments, R a4 It is an optional substituted C1-C3 alkyl group. In some embodiments, R a4 It is a C1-C3 alkyl group. In some embodiments, R a4 It is an optional substituted methyl group. In some embodiments, R a4 It is methyl. In some embodiments, R a4 It is -CF3. In some implementations, R a4 It is -CHF2. In some implementations, R a4 It is a halogen. In some implementations, R a4 It is F. In some implementations, R a4 Yes - OR s41 , where Rs41 As described in this disclosure. In some embodiments, R a4 Yes - OR s41 , where R s41 It is a -H or optionally substituted C1-C6 alkyl group. In some embodiments, R a4 It is -OH. In some implementations, R a4 Yes - OR s41 , where R s41 It is an optional substituted C1-C6 alkyl group. In some embodiments, R a4 Yes-OMe.

[0340] In some implementation schemes, R b4 It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R b4 It is an optional substituted C1-C6 alkyl group. In some embodiments, R b4 It is an optional substituted C1-C3 alkyl group. In some embodiments, R b4 It is a C1-C3 alkyl group. In some embodiments, R b4 It is an optional substituted methyl group. In some embodiments, R b4 It is methyl. In some embodiments, R b4 It is -CF3. In some implementations, R b4 It is -CHF2. In some implementations, R b4 It is a halogen. In some implementations, R b4 It is F. In some implementations, R b4 It is Cl. In some implementations, R b4 It is Br. In some implementations, R b4 It is I. In some implementations, R b4 Yes - OR s41 , where R s41 As described in this disclosure. In some embodiments, R b4 Yes - OR s41 , where R s41 It is a -H or optionally substituted C1-C6 alkyl group. In some embodiments, R b4 It is -OH. In some implementations, R b4 Yes - OR s41 , where R s41 It is an optional substituted C1-C6 alkyl group. In some embodiments, R b4 Yes-OMe.

[0341] In some implementation schemes, R c4It is an optional replacement for C1-C6 aliphatic compounds. In some embodiments, R c4 It is an optional substituted C1-C6 alkyl group. In some embodiments, R c4 It is an optional substituted C1-C3 alkyl group. In some embodiments, R c4 It is a C1-C3 alkyl group. In some embodiments, R c4 It is an optional substituted methyl group. In some embodiments, R c4 It is methyl. In some embodiments, R c4 It is -CF3. In some implementations, R c4 It is -CHF2. In some implementations, R c4 It is a halogen. In some implementations, R c4 It is F. In some implementations, R c4 It is Br. In some implementations, R c4 It is I. In some implementations, R c4 Yes - OR s41 , where R s41 It is a -H or optionally substituted C1-C6 alkyl group. In some embodiments, R c4 It is -OH. In some implementations, R c4 Yes - OR s41 , where R s41 It is an optional substituted C1-C6 alkyl group. In some embodiments, R c4 Yes-OMe.

[0342] In some implementation schemes, R 4 It is a 5-6 membered heteroaryl group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is a optionally substituted 5-membered heteroaryl group having 1-3 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is an optional substituted 5-membered heteroaryl group having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is a substituted 6-membered heteroaryl group having 1-3 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is a 6-membered heteroaryl group with 1-2 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0343] In some implementation schemes, R 4 It is an optional substituted pyridinyl group. In some embodiments, R 4 It is pyridyl. In some embodiments, R 4 It is an optional replacement In some implementations, R 4 yes In some implementations, R 4 It is an optional replacement In some implementations, R 4 yes In some implementations, R 4 It is an optional replacement In some implementations, R 4 yes In some implementations, R 4 It is an optional substituted pyrazole. In some embodiments, R 4 It is pyrazole. In some implementations, R 4 It is an optional replacement n. In some implementations, R 4 yes In some implementations, R 4 yes .

[0344] In some implementation schemes, R 4 It is a 3-10 membered heterocyclic group with 1-4 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is a 3-6 membered heterocyclic group with optional substitutions of 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is a 5-6 membered heterocyclic group with 1-2 independently substituted heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R 4 It is an optional substituted 3-6 membered cycloalkyl group. In some embodiments, R 4 It is an optional replacement In some implementations, R 4 yes In some implementations, R 4 It is an optional replacement In some implementations, R 4 yes In some implementations, R 4 It is an optional replacement In some implementations, R 4 yes In some implementations, R 4 It is an optional replacement In some implementations, R 4 yes .

[0345] In some implementation schemes, R4 It is R as described in this disclosure. For example, in some embodiments, R 4 R is an optional substituted 6-10 aryl-C1-C6 aliphatic compound. In some embodiments, R... 4 It is R, where R is optionally substituted -CH2-Ph. In some embodiments, R 4 R is an optionally substituted -C1-C6 aliphatic 5-10 membered heteroaryl group having 1-6 heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 4 R is an optional substituted 5-10 heteroaryl group with 1-6 heteroatoms -CH2-, wherein each heteroatom is independently chosen to be nitrogen, oxygen, or sulfur.

[0346] In some implementation schemes, R 3 and R 4 All are optional substituted C1-C3 alkyl groups. In some embodiments, R 3 and R 4 All are C1-C3 alkyl groups that can be optionally substituted with halogens. In some embodiments, R 3 and R 4 All are C1-C3 alkyl groups. In some embodiments, R 3 and R 4 All are methyl groups.

[0347] In some implementation schemes, R 3 It is a C1-C3 alkyl group substituted with halogen, R 4 It is not a C1-C3 alkyl group substituted with a halogen. In some embodiments, R 3 It is a C1-C3 alkyl group substituted with halogen, R 4 It is a C1-C3 alkyl group. In some embodiments, R 3 It is a C1-C3 alkyl group substituted with halogen, R 4 It is hydrogen. In some implementations, R 3 and R 4 Each of them is independently a C1-C3 alkyl group substituted with a halogen. In some embodiments, R 3 and R 3 One of them is -CF3, and the other is -CH3. In some implementations, R 3 It is -CF3.

[0348] In some implementation schemes, R 3 and R 4 One of them is the optional replacement C 1-6One is an aliphatic phenyl group (such as -CH3, -CF3, etc.), and the other is an optionally substituted phenyl group (such as 2-, 3-, or 4-trifluoromethylphenyl). In some embodiments, R 3 and R 4 One of them is the optional replacement C 1-6 Aliphatic (e.g., -CH3, -CF3, etc.), another is -CN. In some implementations, R 3 and R 4 One of them is hydrogen, and the other is an optionally substituted phenyl group (such as 2-, 3-, or 4-trifluoromethylphenyl). In some embodiments, R 3 It is an optional replacement for C 1-6 Aliphatic (e.g., -CH3, -CF3, etc.). In some implementations, R 3 Yes, it's -H.

[0349] In some implementation schemes, R 3 and R 4 One of them is the optional replacement C 1-6 One type is an aliphatic group (such as -CH3, -CF3, etc.), and the other is an optional substituted 5-6 heteroaryl group (such as 2-, 3-, or 4-pyridyl) having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 and R 4 One of them is hydrogen, and the other is an optionally substituted phenyl group (such as 2-, 3-, or 4-trifluoromethylphenyl). In some embodiments, R 3 It is an optional replacement for C 1-6 Aliphatic (e.g., -CH3, -CF3, etc.). In some implementations, R 3 Yes, it's -H.

[0350] In some implementation schemes, R 3 and R 4 All are R, and together with the carbon atom to which they are attached, they form optional substituted 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) rings, which, in addition to the attached atom, have 0-4 (0, 1-4, 1-2, 1, 2, 3, 4) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0351] In some implementation schemes, R 3 and R 4 Together with the carbon atoms to which they are attached, they form optionally substituted 3-6 membered rings with 0-3 heteroatoms. In some embodiments, R 3 and R 4Together with the carbon atoms they are attached to, they form optionally substituted 3-6 membered rings, said rings having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 and R 4 Together with the carbon atoms to which they are attached, they form optional substituted 5-6 membered rings, which have 1-2 independent heteroatoms selected from nitrogen, oxygen and sulfur.

[0352] In some implementation schemes, R 3 and R 4 Together with the carbon atoms to which they are attached, they form optionally substituted 3-6 membered cyclic aliphatic groups. In some embodiments, R 3 and R 4 Together with the carbon atoms to which they are attached, they form optionally substituted 3-6 membered cycloalkyl groups. In some embodiments, R 3 and R 4 Together with the carbon atoms they are attached to, they form 3-6 membered cycloalkyl groups. In some embodiments, R 3 and R 4 Together with the attached carbon atom, it forms a halogen-substituted 3-6 membered cycloalkyl group. In some embodiments, R 3 and R 4 Together with the carbon atoms they are attached to, they form -F-substituted 3-6 membered cycloalkyl groups. In some embodiments, R 3 and R 4 Together with the carbon atoms they are attached to, they form optional substitutions. In some implementations, R 3 and R 4 Together with the carbon atoms they are attached to, they form optional substitutions. In some implementations, R 3 and R 4 With the carbon atoms they are attached to, optional substitutions are formed. In some implementations, R 3 and R 4 Together with the carbon atoms they are attached to, they form optional substitutions. .

[0353] In some implementation schemes, R 3 and R 4 Together with the carbon atoms they are attached to, they form halogen-substituted compounds. In some implementations, R 3 and R 4 Together with the carbon atoms they are attached to, they form -F-substituted atoms. In some implementations, R 3 and R4 Together with the carbon atoms they are attached to, they form .

[0354] In some implementations, connecting R 3 and R 4 The carbon in R is achiral. In some implementations, R 3 and R 4 The attached carbon atom is chiral, with a configuration of R. In some embodiments, R... 3 and R 4 The attached carbon atom is chiral and has an S configuration. In some embodiments, R... 3 With -C(O)N(R) 1 (R) 1 ') is in cis. In some implementations, R 3 It is an optional replacement for C 1-6 Aliphatic, with -C(O)N(R) 1 (R) 1 ') is in sequence, and R 4 C is not an optional replacement 1-6 Aliphatic. In some implementations, R3 is -CF3, similar to -C(O)N(R 1 (R) 1 ') is in sequence, and R 4 Not -CF3. In some implementations, -CR 3 R 4 - yes ,in x Indicates connection with X. y This indicates a connection to Y. In some implementations, -CR 3 R 4 - yes ,in x Indicates connection with X. y This indicates a connection to Y. In some implementations, -CR 3 R 4 - yes ,in x Indicates connection with X. y This indicates a connection to Y. In some implementations, -CR 3 R 4 - yes ,in x Indicates connection with X. y This indicates a connection to Y.

[0355] In some implementations, -CR 3 R 4- Selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and , where x represents a connection to X, and y represents a connection to Y. In some implementations, " "Indicates that -C(=Q)- (e.g., -C(O)-) is cis-bonded to W.

[0356] X

[0357] In some implementations, each X is independently -O-, -S-, -S(O)-, -S(O)2-, -S(O)(NR) QX )-, -Se-, -Se(O)-, -Se(O)2-, -C(R x )2- or optionally replaced by -CH2-.

[0358] In some implementations, X is -O-, -S-, -S(O)-, -S(O)2-, or -C(R) x )2-, where each R xIndependently, it is hydrogen or optionally substituted C1-C6 aliphatic, OR, or -N(R)2. In some embodiments, X is -O-. In some embodiments, X is -S-. In some embodiments, X is -S(O)-. In some embodiments, X is -S(O)2-. In some embodiments, X is -S(O)(NR)2-. QX )-, where R QX As described in this disclosure. In some embodiments, X is -S(O)(NH)-. In some embodiments, X is -Se-. In some embodiments, X is -Se(O)-. In some embodiments, X is -Se(O)2-.

[0359] In some embodiments, X is an optional substituted -CH2-. In some embodiments, X is -CH2-. In some embodiments, each X is independently an optional substituted -CH2-. In some embodiments, each X is -CH2-.

[0360] In some implementations, X is -C(R) x )2-, where each R x Independently as described in this disclosure. In some embodiments, X is -C(R x )2-, where each R x Independently as described in this disclosure. In some embodiments, X is -C(R x )2-, and each R x Independent of -OR, R as described in this disclosure. In some embodiments, X is -C(R) x )2-, and each R x X is independent as -N(R)2, and each R is independent as described in this disclosure. In some embodiments, X is -C(R)2. x )2-, and each R x X is independently -N(R)2, and each R is independently as described in this disclosure. In some embodiments, each R is independently -H or optionally substituted C1-C6 aliphatic. In some embodiments, X is -CH2.

[0361] R QX

[0362] In some implementation schemes, R QX It is R' as described in this disclosure. In some embodiments, R QX It is R as described in this disclosure. In some embodiments, R QX Yes -H. In some implementations, R QX Not -H. In some implementations, R QXIt is an optional replacement for C 1-6 Fatty base. In some implementations, R QX It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R QX It is an optional 6-10 aryl group. In some embodiments, R QX It is a 5-10 substituted heteroaryl group having 1-6 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0363] In some implementation schemes, R QX It is -OR', where R' is as described in this disclosure. For example, in some embodiments, R' is the R described in this disclosure. In some embodiments, R' is -H. In some embodiments, R' is not -H. In some embodiments, R' is an optional alternative C. 1-6 Aliphatic group. In some embodiments, R' is optionally substituted C. 1-6 Alkyl group. In some embodiments, R' is an optional substituted 6-10 aryl group. In some embodiments, R' is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0364] R x

[0365] In some implementation schemes, R x It is R' as described in this disclosure. In some embodiments, R x It is R as described in this disclosure. In some embodiments, R x Yes -H. In some implementations, R x Not -H. In some implementations, R x It is an optional replacement for C 1-6 Fatty base. In some implementations, R x It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R x It is an optional 6-10 aryl group. In some embodiments, R x It is a 5-10 substituted heteroaryl group having 1-6 independently selected heteroatoms chosen from nitrogen, oxygen and sulfur.

[0366] In some implementation schemes, R x It is -OR, where R is as described in this disclosure. In some embodiments, R is -H. In some embodiments, R is not -H.

[0367] In some implementation schemes, R x It is -N(R') 2，Each R' is independent as described in this disclosure. In some embodiments, R x It is -NHR', where R' is as described in this disclosure. In some embodiments, each R' is independently R as described in this disclosure. In some embodiments, R x It is -N(R) 2， Each R is independently the R described in this disclosure. In some embodiments, R x It is -NHR, where R is as described in this disclosure. In some embodiments, it is -H. In some embodiments, it is not -H. In some embodiments, it is optionally replaced by C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6 Alkyl group. In some embodiments, it is an optionally substituted 6-10 aryl group. In some embodiments, it is an optionally substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R's are R, and together with the nitrogen atom to which they are attached, form an optionally substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom. Embodiments and examples of various rings are as described herein.

[0368] x

[0369] In some implementations, x is 1. In some implementations, x is 2. In some implementations, when x is 2, each X is independently an optional substituted -CH2-. In some implementations, when x is 2, each X is independently -C(R) x )2-.

[0370] W

[0371] In some implementations, W is N, C, C(R) w ) or alternatively, CH, where R w It is -R' or -N(R')2, and Z is C when W is C.

[0372] In some implementations, the bond between W and Z is a single bond. In other implementations, the bond between W and Z is a double bond.

[0373] In some implementations, W is N.

[0374] In some implementations, W is C and Z is C. In some implementations, W is C and Z is C, and the bond between W and Z is a double bond.

[0375] In some implementations, W is C(R) w ), where R w As described in this disclosure, in some embodiments, W is C(R) w ), where R w It is hydrogen or optionally substituted C1-C6 aliphatic, -R', -OR, or -N(R)2, and each other variable is independent as described in this disclosure. In some embodiments, W is CH. In some embodiments, W is C(R)2. w ), where R w It is - R'. In some implementations, W is C(R) w ), where R w It is an optional C1-C6 aliphatic compound. In some embodiments, W is C(R) w ), where R w It is an optional substituted C1-C6 alkyl group. In some embodiments, W is a C(R) alkyl group. w ), where R w It is an optional substituted C1-C3 alkyl group. In some embodiments, W is a C(R) alkyl group. w ), where R w It is an optional substituted methyl group. In some embodiments, W is C(R) w ), where R w It is a methyl group. In some embodiments, W is C(R) w ), where R w It is a methyl group substituted with a halogen. In some embodiments, W is C(R) w ), where R w It is -CF3. In some implementations, W is C(R) w ), where R w It is -CHF2.

[0376] In some implementations, W is C(R) w ), where R w It is an optional replacement for - OR, R as described in this disclosure. In some embodiments, W is C(R) w ), where R w Yes - OR, R is H or an alternatively substituted C1-C6 aliphatic compound. In some embodiments, W is C(R) w ), where R wIt is an optional substitution of -N(R)2, and each R exists independently as described in this disclosure. In some embodiments, W is C(R)2. w ), where R w It is -N(R)2, where each R is independently H or optionally substituted C1-C6 aliphatic. In some embodiments, R w and R 3 It is the reverse form. In some implementations, R w and R 3 It is in sequence.

[0377] In some implementations, W is an optional substitute for CH.

[0378] R w

[0379] In some implementation schemes, R w It is R' as described in this disclosure. In some embodiments, R w It is R as described in this disclosure. In some embodiments, R w It is -H. In some implementations, it is not -H. In some implementations, it is an optional replacement for C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6 Alkyl group. In some embodiments, it is an optional substituted 6-10 aryl group. In some embodiments, it is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0380] In some implementation schemes, R w It is -OR, where R is as described in this disclosure. In some embodiments, R is -H. In some embodiments, R is not -H.

[0381] In some implementation schemes, R w It is -N(R')2, where each R' is independent as described in this disclosure. In some embodiments, R w It is -NHR', where R' is as described in this disclosure. In some embodiments, each R' is independently R as described in this disclosure. In some embodiments, R w It is -N(R)2, where each R is independently R as described in this disclosure. In some embodiments, R w It is -NHR, where R is as described in this disclosure. In some embodiments, it is -H. In some embodiments, it is not -H. In some embodiments, it is optionally replaced by C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6Alkyl group. In some embodiments, it is an optionally substituted 6-10 aryl group. In some embodiments, it is an optionally substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R's are R, and together with the nitrogen atom to which they are attached, form an optionally substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom. Embodiments and examples of various rings are as described herein.

[0382] Z

[0383] In some implementations, Z is N, C, C(R) z ) or optionally, CH, where R z It is -R' or -N(R')2, when Z is C, W is C or Y is -C(R). y )= or optional alternative -CH=.

[0384] In some implementations, the bond between Y and Z is a single bond. In other implementations, the bond between Y and Z is a double bond.

[0385] In some implementations, Z is N.

[0386] In some implementations, Z is C. In some implementations, Z is C, W is C, or Y is -C(R). y )=, where R y As described in this disclosure. In some embodiments, Z is C and W is C. In some embodiments, Z is C and Y is -C(R) y ) = , where R y As stated in this disclosure.

[0387] In some implementations, Z is C, W is C, and the bond between Z and W is a double bond. In some implementations, Z is C, Y is -C(R) y )=, where R y As stated in this disclosure.

[0388] In some implementations, Z is C(R) z ), where R z As described in this disclosure, in some embodiments, Z is C(R) z ), where R zIt is hydrogen or optionally substituted C1-C6 aliphatic, -R', -OR, or -N(R)2. In some embodiments, Z is -CH-. In some embodiments, Z is C(R)2. z ), where R z It is - R'. In some implementations, Z is C(R) z ), where R z It is an optional C1-C6 aliphatic compound. In some embodiments, Z is C(R z ), where R z It is an optional substituted C1-C6 alkyl group. In some embodiments, Z is a C(R) alkyl group. z ), where R z It is an optional substituted C1-C3 alkyl group. In some embodiments, Z is a C(R) alkyl group. z ), where R z Z is an optional substituted methyl group. In some embodiments, Z is C(R) z ), where R z It is a methyl group. In some embodiments, Z is C. ( R z ), where R z It is -CF3. In some implementations, Z is C(R) z ), where R z It is -CHF2.

[0389] In some implementations, Z is C(R) z ), where R z It is an optional alternative to -OR, and R is as described in this disclosure. In some embodiments, W is C(R) z ), where R z Yes - OR, and R is H or an alternatively substituted C1-C6 aliphatic compound. In some embodiments, W is C(R) z ), where R w It is an optional alternative to -N(R)2, where each R is independent as described in this disclosure. In some embodiments, W is C(R)2. z ), where R z It is -N(R)2, where each R is independently H or optionally substituted C1-C6 aliphatic. In some embodiments, R z and R 3 It is the reverse form. In some implementations, R z and R 3 It is in sequence.

[0390] In some implementation schemes, R zCH is an optional replacement.

[0391] R z

[0392] In some implementation schemes, R z It is R' as described in this disclosure. In some embodiments, R z It is R as described in this disclosure. In some embodiments, R z It is -H. In some implementations, it is not -H. In some implementations, it is an optional replacement for C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6 Alkyl group. In some embodiments, it is an optionally substituted 6-10 aryl group. In some embodiments, it is an optionally substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0393] In some implementation schemes, R z It is -OR, where R is as described in this disclosure. In some embodiments, R is -H. In some embodiments, R is not -H.

[0394] In some implementation schemes, R z It is -N(R') 2， Each R' is independent as described in this disclosure. In some embodiments, R z It is -NHR', where R' is as described in this disclosure. In some embodiments, each R' is independently R as described in this disclosure. In some embodiments, R z It is -N(R)2, where each R is independently described in this disclosure. In some embodiments, R z It is -NHR, where R is as described in this disclosure. In some embodiments, it is -H. In some embodiments, it is not -H. In some embodiments, it is optionally replaced by C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6Alkyl group. In some embodiments, it is an optionally substituted 6-10 aryl group. In some embodiments, it is an optionally substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R's are R, and together with the nitrogen atom to which they are attached, form an optionally substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom. Embodiments and examples of various rings are as described herein.

[0395] Y

[0396] In some implementations, each Y is independently -O-, -S-, -N(R) y )-、-C(R y )2-、-C(R y =, optional substitution of -CH2- or optional substitution of -CH=, where each R y Independently, it is -R' or -N(R)2, when the Y bonded to Z is -C(R)2. y When Z is C, or when Z is the alternative substitution -CH=, Z is C.

[0397] In some implementations, Y is -O-, -S-, -N(R) y )-、-C(R y )2- or -C(R y =, where each R y Independently hydrogen or optionally substituted C1-C6 aliphatic, -OR, or -N(R)2; when Y is -C(R)2 y When )=, Z is C. In some implementations, Y is -O-. In some implementations, Y is -S-. In some implementations, Y is -N(R) y )-, R y It is independently hydrogen or optionally substituted C1-C6 aliphatic. In some embodiments, Y is -N(R y )-, R y It is hydrogen. In some implementations, Y is -N(R) y )-, R y It is an optional C1-C6 aliphatic compound. In some embodiments, Y is -N(R y )-, R y It is an optional substituted C1-C6 alkyl group. In some embodiments, Y is -N(R y )-, Ry It is an optional substituted C1-C3 alkyl group. In some embodiments, Y is -N(R y )-, R y It is a methyl group. In some embodiments, Y is -NH-.

[0398] In some implementations, Y is -C(R) y )2-, each R y Independently, it is hydrogen or optionally substituted C1-C6 aliphatic, -OR, or -N(R)2. In some embodiments, Y is -CH2-. In some embodiments, Y is -CH(R)2-. y )-, R y It is an optional C1-C6 aliphatic compound. In some embodiments, Y is -CH(R) y )-, R y It is an optional substituted C1-C6 alkyl group. In some embodiments, Y is -CH(R) y )-, R y It is an optional substituted C1-C3 alkyl group. In some embodiments, Y is -CH(R) y )-, R y It is a methyl group. In some embodiments, Y is -C(R) y )2-, and each R y Independently defined as -OR, where R is as described in this disclosure. In some embodiments, Y is -C(R) y )2-, and each R y Independently, Y is -OR, where R is hydrogen or an optionally substituted C1-C6 aliphatic compound. In some embodiments, Y is -CHR. y -, R y Independently, Y is -OR, where R is an optional substituted C1-C6 aliphatic compound. In some embodiments, Y is -CHR. y -, R y It is -OMe. In some implementations, Y is -C(R) y )2-, each R y Independently, it is -N(R)2, where each R is independently as described in this disclosure. In some embodiments, Y is -C(R)2. y )2-, each R y Independently, it is -N(R)2, where each R is independently hydrogen or optionally substituted C1-C6 aliphatic. In some embodiments, R 3 and R y It is the reverse form. In some implementations, R 3 and R y It is in sequence.

[0399] In some implementations, Y is -C(R) y =, Z is C, the bond between Y and Z is a double bond, where R y It is hydrogen or optionally substituted C1-C6 aliphatic. In some embodiments, Y is -CH=, Z is C, and the bond between Y and Z is a double bond. In some embodiments, Y is -C(R) y =, Z is C, the bond between Y and Z is a double bond, where R y It is an optional C1-C6 aliphatic compound. In some embodiments, Y is -C(R y =, Z is C, the bond between Y and Z is a double bond, where R y It is an optional substituted C1-C6 alkyl group. In some embodiments, Y is -C(R) y =, Z is C, the bond between Y and Z is a double bond, where R y It is an optional substituted C1-C3 alkyl group.

[0400] In some implementations, Y is optionally substituted with -CH2-. In some implementations, Y is optionally substituted with -CH=.

[0401] R y

[0402] In some implementation schemes, R y It is R' as described in this disclosure. In some embodiments, R y It is R as described in this disclosure. In some embodiments, R y It is -H. In some implementations, it is not -H. In some implementations, it is an optional replacement for C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6 Alkyl group. In some embodiments, it is an optional substituted 6-10 aryl group. In some embodiments, it is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0403] In some implementation schemes, R y It is -OR, where R is as described in this disclosure. In some embodiments, R is -H. In some embodiments, R is not -H.

[0404] In some implementation schemes, R y It is -N(R') 2， Each R' is independent as described in this disclosure. In some embodiments, Ry It is -NHR', where R' is as described in this disclosure. In some embodiments, each R' is independently R as described in this disclosure. In some embodiments, R y It is -N(R) 2， Each R is independently the R described in this disclosure. In some embodiments, R y It is -NHR, where R is as described in this disclosure. In some embodiments, it is -H. In some embodiments, it is not -H. In some embodiments, it is optionally replaced by C. 1-6 Fatty group. In some embodiments, it is optionally replaced by C 1-6 Alkyl group. In some embodiments, it is an optionally substituted 6-10 aryl group. In some embodiments, it is an optionally substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the two R's are R, and together with the nitrogen atom to which they are attached, form an optionally substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom. Embodiments and examples of various rings are as described herein.

[0405] y

[0406] In some implementations, y is 1 or 2. In some implementations, y is 1. In some implementations, y is 2. In some implementations, y is 2, and each y is independently -C(R) y )2- , where each R y Independently as described in this disclosure. In some embodiments, y is 2, and each Y is independently an optional substituted -CH2-. In some embodiments, y is 2, and each Y is -CH2-.

[0407] In some implementation schemes, or Selected from:

[0408] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0409] In some implementation schemes, yes

[0410] , , , , , , , , , , , , , , , or .

[0411] In some implementation schemes, Selected from Each **R is independently Q as described in this disclosure, and each R" (if present) is independently R' as described in this disclosure. In some embodiments, Selected from Each **R is independently Q as described in this disclosure, and each T is independently O or NR as described in this disclosure. QX Each R" (if present) is independently R as described in this disclosure. In some embodiments, Q is O. In some embodiments, Q is S. In some embodiments, Q is NR. Q , where R Q As described in this disclosure. In some embodiments, R QIt is R as described in this disclosure. In some embodiments, R Q It is -H, optional substitution of C 1-6 Alkyl or -OR, where R is an optional substituted C 1-6 Alkyl group. In some embodiments, R Q It is -H, C 1-6 Alkyl or -OR, where R is C 1-6 Alkyl group. In some embodiments, R w Yes -H. In some implementations, R w The group is an optional substituted group, which is selected from C 1-6 Alkyl, 6-10 aryl, or 5-10 aryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w Selected from C 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is -H or an optional substitute selected from C. 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y Yes -H or selected from C 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is bonded to a nitrogen atom and is -H or an optional substituted group selected from C. 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is bonded to a nitrogen atom and is -H or selected from C. 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is a group that bonds to a carbon atom and is optionally substituted; this group is selected from C. 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y Bonded to carbon atoms, selected from C 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y with sp 3 Carbon atom bonding, with optional substituted groups selected from C.1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y with sp 3 Carbon atoms are bonded and selected from C 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y with sp 2 Carbon atoms are bonded, and the group is -H or optionally substituted, selected from C. 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y with sp 2 Carbon atoms are bonded, and the atom is -H or selected from C. 1-6 Alkyl, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, T is O. In some embodiments, T is NR. QX In some implementations, T is NR. QX , where R QX It is -H or an optional C substitution 1-6 Aliphatic. In some implementations, T is NR. QX , where R QX It is -H or an optional C substitution 1-6 Alkyl group. In some embodiments, Q is O. In some embodiments, Q is S. In some embodiments, Q is NH. In some embodiments, Q is NR. Q , where R Q It is an optional replacement for C 1-6 Aliphatic. In some implementations, Q is NR. Q , where R Q It is an optional replacement for C 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is C 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is -OR, where R is the alternative C. 1-6 Aliphatic. In some implementations, Q is NR. Q , where R Q It is -OR, where R is the alternative C. 1-6Alkyl group. In some embodiments, Q is NR. Q , where R Q It is -OR, where R is C 1-6 alkyl.

[0412] In some implementation schemes, yes , or In some implementation schemes, yes , or In some implementations, R w Not -H. In some implementations, R w It is an optional substituted group, selected from C 1-6 Aliphatic, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R w It is C 1-6 Alkyl group. In some embodiments, R w It is an optional 6-10 aryl group. In some embodiments, R w It is a 6-10 aryl group. In some implementations, R w It is an optional substituted 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is a 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0413] In some implementation schemes, yes , , , , , or In some implementation schemes, yes , , , , or In some implementations, R w Yes -H. In some implementations, R w These are optional substituents selected from C groups having 1 to 6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1-6Aliphatic, 6-10 aryl, and 5-10 heteroaryl. In some embodiments, R w It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R w It is C 1-6 Alkyl group. In some embodiments, R w It is an optional 6-10 aryl group. In some embodiments, R w It is a 6-10 aryl group. In some implementations, R w It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is a 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0414] In some implementation schemes, yes , , , , , , , , , , or In some implementation schemes, yes , , , , , , , , , , or In some implementations, R y Yes -H. In some implementations, R y It is selected from C 1-6 Optional substituents include aliphatic, 6-10 aryl, and 5-10 heteroaryl groups, said groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R y It is C 1-6 Alkyl group. In some embodiments, R y It is an optional 6-10 aryl group. In some embodiments, R yIt is a 6-10 aryl group. In some implementations, R y It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is a 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Q is O. In some embodiments, Q is S. In some embodiments, Q is NH. In some embodiments, Q is NR. Q , where R Q It is an optional replacement for C 1-6 Aliphatic. In some implementations, Q is NR. Q , where R Q It is an optional replacement for C 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is C 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is -OR, where R is the alternative C. 1-6 Aliphatic. In some implementations, Q is NR. Q , where R Q It is -OR, where R is the alternative C. 1-6 Alkyl group. In some embodiments, Q is NR. Q , where R Q It is -OR, where R is C 1-6 alkyl.

[0415] In some implementation schemes, yes In some implementation schemes, yes In some implementations, R y Not -H. In some implementations, R y It is an optional substituted group, selected from C 1-6 Aliphatic, 6-10 aryl groups, and 5-10 heteroaryl groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R y It is C 1-6 Alkyl group. In some embodiments, R y It is an optional 6-10 aryl group. In some embodiments, R yIt is a 6-10 aryl group. In some implementations, R y It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is a 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0416] In some implementation schemes, yes , , , , , , , or In some implementation schemes, yes , , , , , , , or In some implementations, R z Yes -H. In some implementations, R z It is an optional substituted group, selected from C 1-6 Aliphatic, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R z It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R z It is C 1-6 Alkyl group. In some embodiments, R z It is an optional substituted 6-10 aryl group. In some embodiments, R z It is a 6-10 aryl group. In some implementations, R z It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R z It is a 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0417] In some implementation schemes, yes , , , , or In some implementation schemes, yes , , , , or In some implementations, R y Not -H. In some implementations, R y It is an optional substituted group, selected from C 1-6 Aliphatic, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R y It is C 1-6 Alkyl group. In some embodiments, R y It is an optional 6-10 aryl group. In some embodiments, R y It is a 6-10 aryl group. In some implementations, R y It is an optional substituted 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is a 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w Yes -H. In some implementations, R w It is selected from C 1-6 Aliphatic, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R w It is C 1-6 Alkyl group. In some embodiments, R w It is an optional 6-10 aryl group. In some embodiments, R w It is a 6-10 aryl group. In some implementations, R w It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is a 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0418] In some implementation schemes, yes In some implementation schemes, yes In some implementations, R y Yes -H. In some implementations, R yIt is an optional substituted group, said group being selected from C 1-6 Aliphatic, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R y It is C 1-6 Alkyl group. In some embodiments, R y It is an optional 6-10 aryl group. In some embodiments, R y It is a 6-10 aryl group. In some implementations, R y It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is a 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w Not -H. In some implementations, R w These are optional substituents selected from C groups having 1 to 6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1-6 Aliphatic, 6-10 aryl, and 5-10 heteroaryl. In some embodiments, R w It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R w It is C 1-6 Alkyl group. In some embodiments, R w It is an optional 6-10 aryl group. In some embodiments, R w It is a 6-10 aryl group. In some implementations, R w It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is a 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0419] In some implementation schemes, yes , or In some implementation schemes, yes , or In some implementations, R y Yes -H. In some implementations, R y These are optional substituents selected from C groups having 1 to 6 heteroatoms independently selected from nitrogen, oxygen, and sulfur.1-6 Aliphatic, 6-10 aryl, and 5-10 heteroaryl. In some embodiments, R y It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R y It is C 1-6 Alkyl group. In some embodiments, R y It is an optional 6-10 aryl group. In some embodiments, R y It is a 6-10 aryl group. In some implementations, R y It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R y It is a 5-10 membered heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w Yes -H. In some implementations, R w It is selected from C 1-6 Aliphatic, 6-10 aryl, or 5-10 heteroaryl having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is an optional replacement for C 1-6 Alkyl group. In some embodiments, R w It is C 1-6 Alkyl group. In some embodiments, R w It is an optional 6-10 aryl group. In some embodiments, R w It is a 6-10 aryl group. In some implementations, R w It is an optional substituted 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R w It is a 5-10 heteroaryl group having 1-6 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0420] ring

[0421] In some embodiments, the compound comprises an optionally substituted ring. In some embodiments, an embodiment of the variable is or includes an optionally substituted ring. In some embodiments, the ring is substituted. In some embodiments, the ring is unsubstituted. In some embodiments, the compound comprises an optionally substituted ring. In some embodiments, an embodiment of the variable is or includes an optionally substituted ring. In some embodiments, the ring is substituted. In some embodiments, the ring is unsubstituted.

[0422] The ring can be monovalent, divalent, or polyvalent. In some embodiments, the ring is monovalent. In some embodiments, the ring is divalent. In some embodiments, the ring is polyvalent. As will be understood by those skilled in the art, optional substituents may be appropriately excluded when calculating the valence of the ring.

[0423] In some embodiments, the ring is an optionally substituted divalent 3-10 member ring (e.g., 4-10 member, 1 member, 2 member, 3 member, 4 member, 5 member, 6 member, 7 member, 8 member, 9 member, 10 member, etc.), said ring having 0-4 heteroatoms (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is a 4-10 member ring. In some embodiments, it is a 4-9 member ring. In some embodiments, it is a 4-8 member ring. In some embodiments, it is a 4-7 member ring. In some embodiments, it is a 4-6 member ring.

[0424] In some embodiments, the ring is an aromatic ring. In some embodiments, it is a non-aromatic ring. In some embodiments, it is a saturated ring. In some embodiments, it is a partially unsaturated ring. In some embodiments, the ring comprises a saturated monocyclic unit. In some embodiments, the ring comprises a partially unsaturated monocyclic unit. In some embodiments, the ring comprises an aromatic monocyclic unit. In some embodiments, the ring comprises a heteroaromatic monocyclic unit.

[0425] In some embodiments, the ring has one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it has no heteroatoms. In some embodiments, the ring has one nitrogen atom. In some embodiments, the ring has one oxygen atom. In some embodiments, the ring has one sulfur atom.

[0426] In some embodiments, the ring is a monocyclic ring. In some embodiments, it is a bicyclic ring. In some embodiments, the ring is a polycyclic ring. In some embodiments, each monocyclic unit is independently a 3-9 member (e.g., 3-7, 4-7, 4-6, 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) ring. In some embodiments, each monocyclic unit is independently a 3-7 member ring. In some embodiments, each monocyclic unit is independently a 4-7 member ring. In some embodiments, each monocyclic unit is independently a 5-7 member ring. In some embodiments, each monocyclic unit is independently a 5- or 6-membered ring. In some embodiments, at least one monocyclic unit is a 6-membered ring. In some embodiments, at least one monocyclic unit is a 5-membered ring. In some embodiments, at least one monocyclic unit is an aromatic ring. In some embodiments, at least one monocyclic unit is an aromatic ring, a 6-membered ring, and does not contain heteroatoms. In some embodiments, at least one monocyclic unit is a heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 5-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a 6-membered heteroaromatic ring. In some embodiments, at least one monocyclic unit is a non-aromatic ring.

[0427] In some embodiments, the ring is an optional substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) cycloalkyl ring. In some embodiments, it is an optional substituted 3-10 member (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) cycloalkyl ring. In some embodiments, it is an optional substituted 3-membered saturated aliphatic ring. In some embodiments, it is an optional substituted 4-membered saturated aliphatic ring. In some embodiments, it is an optional substituted 5-membered saturated aliphatic ring. In some embodiments, it is an optional substituted 6-membered saturated aliphatic ring. In some embodiments, it is an optional substituted 7-membered saturated aliphatic ring.

[0428] In some embodiments, the ring is an optionally substituted benzene ring. In some embodiments, it is a benzene ring. In some embodiments, the ring is an optionally substituted 10-membered bicyclic aromatic ring and does not contain heteroatoms.

[0429] In some embodiments, the ring is an optionally substituted 3-10 membered heterocyclic base ring (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.), the ring having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 3-10 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 4 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 6 membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optional substituted 7-membered heterocyclic base ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0430] In some embodiments, the ring is an optionally substituted 9- or 10-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 9-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 10-membered bicyclic heteroaromatic ring having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring is an optionally substituted 5-6 membered aromatic ring having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5-6 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is a 5-6 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is a 5 membered heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5 membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5-membered heteroaromatic ring having 1-2 heteroatoms, one of which is nitrogen and the other is independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 5-membered heteroaromatic ring having 1 heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is a 6-membered heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 6-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is a 6-membered heteroaromatic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, it is an optionally substituted 6-membered heteroaromatic ring having 1 nitrogen atom. In some embodiments, it is a 6-membered heteroaromatic ring having 1 nitrogen atom. In some embodiments, it is an optionally substituted pyridyl group. In some embodiments, it is a pyridyl group. In some embodiments, it is an optional substituted 6-membered heteroaryl ring having two nitrogen atoms.

[0431] R'

[0432] R' can be any of the various variables described in this disclosure. In some embodiments, R' is hydrogen.

[0433] In some embodiments, R' is the R described in this disclosure. In some embodiments, R' is -OR, where R is as described in this disclosure. In some embodiments, R' is -C(O)R, where R is as described in this disclosure. In some embodiments, R' is -C(O)OR, where R is as described in this disclosure. In some embodiments, R' is -S(O)R, where R is as described in this disclosure. In some embodiments, R' is -S(O)2R, where R is as described in this disclosure.

[0434] R

[0435] R can be any of the various variables described in this disclosure. This disclosure broadly describes various implementations of R, including those applicable to other variables that can be R (such as R0). ' R s1 R s2 R s11 R s12 R s21 R s22 R s31 R s32 R s41 R s42 The various parts of (etc.).

[0436] In some implementations, R is -H. In other implementations, R is not -H.

[0437] In some embodiments, each R is independently hydrogen or an optional substituted C1-C6 aliphatic group, a C1-C6 heteroaliphatic group having 1-3 heteroatoms, a 3-10 membered cyclic aliphatic group, a 3-10 membered heterocyclic group having 1-4 heteroatoms, a 6-10 membered aryl group, a 5-10 membered heteroaryl group having 1-6 heteroatoms, a 6-10 membered aryl-C1-C6 aliphatic group, and a 5-10 membered heteroaryl-C1-C6 aliphatic group having 1-6 heteroatoms.

[0438] In some implementations, R is an optional replacement for C. 1-6 Aliphatic. In some implementations, R is optionally replaced by C. 1-6 Alkyl group. In some embodiments, R is an optional substituted methyl group. In some embodiments, R is an optional substituted ethyl group. In some embodiments, R is an optional substituted n-propyl group. In some embodiments, R is an optional substituted isopropyl group. In some embodiments, R is n-butyl group. In some embodiments, R is tert-butyl group. In some embodiments, R is pentyl group. In some embodiments, R is hexyl group.

[0439] In some embodiments, R is an optionally substituted C having 1-3 (e.g., 1, 2, or 3) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. 1-6 Heteroaliphatic group. In some embodiments, R is an optionally substituted C having 1-3 (e.g., 1, 2, or 3) heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1-6 Heteroaliphatic group. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0440] In some implementations, R is an optional replacement for C. 3-10 (e.g., C) 4-10 C 3-9 C 3-7 Or 3, 4, 5, 6, 7, 8, 9, or 10 cyclic aliphatic groups. In some embodiments, the cyclic aliphatic group is cycloalkyl. In some embodiments, the cyclic aliphatic group is monocyclic. In some embodiments, the cyclic aliphatic group is bicyclic. In some embodiments, it is polycyclic. In some embodiments, each monocyclic unit is independently 3-10 (e.g., C10, C20, C30, C40, C50, C60, C70, C1 ... 4-10 C 3-9 C 3-7 The cyclic aliphatic ring may have 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides. In some embodiments, the cyclic aliphatic group is saturated. In some embodiments, the cyclic aliphatic group is partially unsaturated. In some embodiments, R is an optionally substituted cyclopropyl group. In some embodiments, R is an optionally substituted cyclobutyl group. In some embodiments, R is an optionally substituted cyclopentyl group. In some embodiments, R is an optionally substituted cyclohexyl group. In some embodiments, R is an optionally substituted cycloheptyl group. In some embodiments, R is a cyclopropyl group. In some embodiments, R is a cyclobutyl group. In some embodiments, R is a cyclopentyl group. In some embodiments, R is a cyclohexyl group. In some embodiments, R is a cycloheptyl group.

[0441] In some embodiments, R is a 3-10 (e.g., 3-9, 3-6, 3-5, or 3, 4, 5, 6, 7, 8, 9, or 10) membered heterocycle with 1-4 (e.g., 1, 2, 3, or 4) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, respectively. In some embodiments, the heterocyclic group is monocyclic. In some embodiments, the heterocyclic group is bicyclic. In some embodiments, the heterocyclic group is polycyclic. In some embodiments, each monocyclic unit is independently a 3-10 (e.g., 3, 4, 5, 6, 7, 8, 9, or 10) heterocyclic ring having 1-4 (e.g., 1, 2, 3, or 4) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heterocyclic group is saturated. In some embodiments, the heterocyclic group is partially unsaturated. In some embodiments, the heterocyclic ring has one heteroatom. In some embodiments, the heterocyclic ring has two or more heteroatoms. In some embodiments, the heterocyclic ring has three or more heteroatoms. In some embodiments, the heterocyclic ring has four or more heteroatoms. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0442] In some implementations, R is an optional replacement for C. 6-10 (e.g., C6, C) 10 (etc.) aryl. In some embodiments, the aryl ring is monocyclic. In some embodiments, the aryl ring is bicyclic. In some embodiments, the aryl ring is polycyclic. In some embodiments, each monocyclic unit is an independent 6-membered aromatic ring. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is a phenyl. In some embodiments, R is an optionally substituted 10-membered aryl. In some embodiments, R is an optionally substituted naphthyl. In some embodiments, R is naphthyl.

[0443] In some embodiments, R is a 5-10 (e.g., 5-9, or 5, 6, 7, 8, 9, or 10) heteroaryl group having 1-6 (e.g., 1-6, 1-5, 1-4, or 1, 2, 3, 4, 5, or 6, etc.) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, with optional substitution. In some embodiments, R is a 5-10 (e.g., 5-9, or 5, 6, 9, or 10, etc.) heteroaryl group having 1-4 (e.g., 1, 2, 3, or 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur, with optional substitution. In some embodiments, the heteroaryl group is monocyclic. In some embodiments, the heteroaryl group is bicyclic. In some embodiments, the heteroaryl group is polycyclic. In some embodiments, each monocyclic unit is independently a 5 or 6-membered aromatic ring having 0-4 heteroatoms (e.g., independently selected from nitrogen, oxygen, and sulfur), wherein at least one monocyclic unit contains 1-4 heteroatoms. In some embodiments, R is an optionally substituted 5-membered monocyclic heteroaryl group, the ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 6-membered monocyclic heteroaryl group, the ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 8-membered bicyclic heteroaryl group, the ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 9-membered bicyclic heteroaryl group, the ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 10-membered bicyclic heteroaryl group, the ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl group has one heteroatom. In some embodiments, the heteroaryl group has two or more heteroatoms. In some embodiments, the heteroaryl group has three or more heteroatoms. In some embodiments, the heteroaryl group has four or more heteroatoms. In some embodiments, the heteroatom is nitrogen. In some embodiments, the heteroatom is oxygen. In some embodiments, the heteroatom is sulfur.

[0444] In some implementations, R is an optional replacement for C. 6-10 (e.g., C6, C) 10 Aryl-C, etc. 1-6 Aliphatic group, wherein the aryl and aliphatic groups are independent as described in this disclosure. In some embodiments, R is optionally substituted C. 6-10 Aryl-C 1-6 alkyl.

[0445] In some embodiments, R is an optionally substituted 5-10 (e.g., 5-9, or 5, 6, 7, 8, 9, or 10, etc.) heteroaryl-C having 1-6 (e.g., 1, 2, 3, 4, 5, or 6) heteroatoms.1-6 Aliphatic, the heteroaryl and aliphatic are independently as described in this disclosure. In some embodiments, R is an optionally substituted 5-10 member heteroaryl-C having 1-5 heteroatoms. 1-6 Aliphatic. In some embodiments, R is an optionally substituted 5-6 membered heteroaryl-C having 1-4 heteroatoms. 1-6 Aliphatic. In some embodiments, R is an optionally substituted 5-10 membered heteroaryl-C having 1-6 (e.g., 1, 2, 3, 4, 5, or 6) heteroatoms. 1-6 Alkyl groups, the heteroaryl groups and alkyl groups being independently as described in this disclosure. In some embodiments, R is an optionally substituted 5-10 membered heteroaryl-C having 1-5 heteroatoms. 1-6 Alkyl group. In some embodiments, R is an optionally substituted 5-6-membered heteroaryl-C having 1-4 heteroatoms. 1-6 Alkyl groups. Various suitable heteroaryl and aliphatic groups are as described in this disclosure.

[0446] In some embodiments, two R groups on the same atom may optionally and independently form, together with the atom, an optionally substituted 3-10 fused (e.g., 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered) ring, the ring having 0-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms in addition to the atom. In some embodiments, two R groups on two atoms may optionally and independently form, together with the atom between them, an optionally substituted 3-10 fused (e.g., 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered) ring, the ring having 0-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms in addition to the atom between them.

[0447] As described herein, in various cases, two R groups, or two groups that are or may be R (e.g., R', R'), 2 , R 3(etc.), can form optionally substituted rings with the atoms therebetween as described herein. In some embodiments, the formed ring is substituted (except for groups attached to the atoms therebetween). In some embodiments, the formed ring is unsubstituted. In some embodiments, the formed ring is a 3-membered ring. In some embodiments, the formed ring is a 4-membered ring. In some embodiments, the formed ring is a 5-membered ring. In some embodiments, the formed ring is a 6-membered ring. In some embodiments, the formed ring is a 7-membered ring. In some embodiments, the formed ring is an 8-membered ring. In some embodiments, the formed ring is a 9-membered ring. In some embodiments, the formed ring is a 10-membered ring. In some embodiments, the formed ring is a saturated ring. In some embodiments, the formed ring is a partially unsaturated ring. In some embodiments, the formed ring is an aromatic ring. In some embodiments, the formed ring is a monocyclic ring. In some embodiments, it is a bicyclic ring. In some embodiments, it is a polycyclic ring. In some embodiments, each monocyclic unit is independently a 3-10 member (e.g., 3-8, 3-6, 5-6, or 3, 4, 5, 6, 7, 8, 9, or 10 member ring, etc.), said ring being independently a saturated, partially unsaturated, or aromatic ring, and having 0-4 (e.g., 0, 1, 2, 3, or 4) heteroatoms. In some embodiments, each monocyclic unit is independently a 3-10 member (e.g., 3-10, 3-8, 3-6, 5-6, or 3, 4, 5, 6, 7, 8, 9, or 10 member ring, etc.), said ring being independently a saturated, partially unsaturated, or aromatic ring, and having 0-4 (e.g., 0, 1, 2, 3, or 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each monocyclic unit is independently a 3-7 member ring. In some embodiments, each monocyclic unit is independently a 3-6 membered ring. In some embodiments, each monocyclic unit is independently a 5-7 membered ring. In some embodiments, each monocyclic unit is independently a saturated or partially unsaturated ring. In some embodiments, at least one monocyclic unit is a saturated ring. In some embodiments, at least one monocyclic unit is a partially unsaturated ring. In some embodiments, at least one monocyclic unit is an aromatic ring. In some embodiments, the formed ring, in addition to the atoms between it, has 0-4 (e.g., 0, 1, 2, 3, or 4, etc.) heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, there are no additional heteroatoms. In some embodiments, there is one additional heteroatom. In some embodiments, there are two additional heteroatoms. In some embodiments, there are three additional heteroatoms. In some embodiments, there are four additional heteroatoms. In some embodiments, there are five additional heteroatoms. In some embodiments, there are six or more additional heteroatoms. In some embodiments, the additional heteroatom is nitrogen. In some embodiments, the additional heteroatom is oxygen.In some implementations, the additional heteroatom is sulfur.

[0448] As described in this disclosure, various substituents may be optionally substituted. Substitution is widely used in the chemical field, including in the development of various pharmaceuticals. According to this disclosure, various substituents may be used. In some embodiments, the optionally substituted group is unsubstituted. In some embodiments, the optionally substituted group is substituted. As described in this disclosure, preferred substituents are those capable of forming compounds having the desired properties, activities, uses, etc. In some embodiments, the compound is stable for the therapeutic uses described in this disclosure. The term "stable" as used in this disclosure means that the compound does not undergo substantial change when subjected to conditions permissible for its production, testing, and (in some embodiments) its recovery, purification, and use for one or more purposes disclosed in this disclosure. In some embodiments, the substituent is a hydrocarbon group. In some embodiments, the substituent includes a heteroatom. In some embodiments, the substituent includes multiple heteroatoms. In some embodiments, each atom in the substituent is independently selected from hydrogen, carbon, halogen, nitrogen, oxygen, sulfur, phosphorus, and silicon. In some embodiments, each atom in the substituent is independently selected from hydrogen, carbon, halogen, nitrogen, oxygen, and sulfur. In some embodiments, each atom in the substituent is independently selected from hydrogen, carbon, fluorine, chlorine, bromine, iodine, nitrogen, oxygen, and sulfur. In some embodiments, the total number of carbon and non-halogen heteroatoms in the substituent is about or no more than about 1; in some embodiments, no more than about 2; in some embodiments, no more than about 3; in some embodiments, no more than about 4; in some embodiments, no more than about 5; in some embodiments, no more than about 6; in some embodiments, no more than about 7; in some embodiments, no more than about 8; in some embodiments, no more than about 9; in some embodiments, no more than about 10; in some embodiments, no more than about 11; in some embodiments, no more than about 12; in some embodiments, no more than about 13; in some embodiments, no more than about 14; in some embodiments, no more than about 15; in some embodiments, no more than about 20. In some embodiments, the total number of carbon and non-halogen heteroatoms in each substituent independently does not exceed about 20. In some embodiments, the total number of carbon and non-halogen heteroatoms in each substituent independently does not exceed about 15. In some embodiments, the total number of carbon and non-halogen heteroatoms in each substituent independently does not exceed about 10. In some embodiments, the total number of carbon and non-halogen heteroatoms in each substituent independently does not exceed about 6. In some embodiments, each optional substituent on the substituent group (e.g., ring A, ring B, R, etc.) is independently halogenated, C... 1-4Alkyl, -OH, -CN, -NO2, C 1-4 Halogenated alkyl groups (e.g., -CF3), -OR SB -N(R) SB )2、-C(O)OR SB -C(O)N(R) SB ))2 or -S(O)2N(R SB )2, where each R SB Independent as -H, C 1-4 Alkyl or optionally substituted C 1-4 Haloalkyl. In some embodiments, each optional substituent on the substituent group (such as ring A, ring B, R, etc.) is independently a halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl or -OH. In some embodiments, each optional substituent on the substituent group (such as ring A, ring B, R, etc.) is independently halogenated or optionally substituted C. 1-4 Alkyl groups. As examples, many substituents are illustrated in the compounds described herein, such as those in Table 1.

[0449] In some embodiments, this disclosure provides compounds having the structures listed in Table 1 (or salts thereof). In some embodiments, this disclosure provides stereoisomers of compounds having the structures listed in Table 1 (or salts thereof). In some embodiments, this disclosure provides enantiomers of compounds having the structures listed in Table 1 (or salts thereof). In some embodiments, the salt is a pharmaceutically acceptable salt. In some embodiments, the compounds may optionally be present in the form of a solvate. As will be understood by those skilled in the art upon reading this disclosure, the compounds described herein may exist in various forms, such as acids, bases, salts, solvates (e.g., solvates in the form of various acids, bases, or salts).

[0450] Table 1. Some compounds are shown as examples.

[0451] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0452] Preparation method

[0453] In some embodiments, this disclosure provides various techniques, such as reagents, intermediates, conditions, etc., for preparing compounds and compositions as described herein. Those skilled in the art will understand that many of these techniques are available and can be used in accordance with this disclosure.

[0454] As those skilled in the art will understand, in chemical reactions, various groups (e.g., hydroxyl, amino, carboxyl, etc.) may be protected to prevent undesirable reactions. Many protecting / deprotecting techniques are available to those skilled in the art and can be used according to this disclosure. Some of these techniques are described herein, including examples in the embodiments.

[0455] Various chemical reactions are typically carried out in solvents. In some embodiments, the reaction is carried out in a single solvent, such as DCM, THF, Et₂O, EtOH, toluene, etc. In some embodiments, the reaction is carried out in a mixture of two or more solvents. In some embodiments, the solvent is a polar solvent. In some embodiments, the solvent is a nonpolar solvent. In some embodiments, the solvent is a protic solvent. In some embodiments, the solvent is aprotic solvent. In some embodiments, the solvent is a polar but aprotic solvent. Solvents suitable for various reactions are available to those skilled in the art and can be used in accordance with this disclosure.

[0456] In some embodiments, the reaction is carried out under an inert atmosphere, such as N2, Ar, etc. In some embodiments, the reaction is carried out in air. In some embodiments, the reaction is carried out under anhydrous conditions, such as after reagents, solvents, containers, etc., have been properly dried. In some embodiments, the reaction is carried out in the presence of a significant amount of water (e.g., about 0.1, 0.5, or more than about 1 equivalent).

[0457] In some embodiments, the reaction is carried out or continued at a temperature above, below, or close to standard ambient temperature (25 °C). In some embodiments, the reaction temperature is below standard ambient temperature. In some embodiments, the temperature is about or does not exceed about -78, -60, -50, -40, -30, -20, -10, 0, or 10 °C. In some embodiments, the temperature is about or does not exceed about 10 °C. In some embodiments, the temperature is about or does not exceed about 15 °C. In some embodiments, the temperature is about or does not exceed about 20 °C. In some embodiments, the reaction temperature is about standard ambient temperature. In some embodiments, the reaction temperature is above standard ambient temperature. In some embodiments, the reaction temperature is about or at least about 35, 40, 50, 60, 70, 80, 90, 100, or 100 °C. In some embodiments, the reaction includes reflux in a boiling solvent system, such as in a solvent system like diethyl ether or toluene. In some embodiments, the temperature changes during the reaction, for example, from a lower temperature to a higher temperature, from a higher temperature to a lower temperature, or both.

[0458] In some embodiments, a particular product may be synthesized selectively relative to other potential products. In some embodiments, the production of a product exhibits chemoselectivity, stereoselectivity, and / or regioselectivity. In some embodiments, selectivity is expressed as a ratio, such as the ratio of one product to another. In some embodiments, the ratio is about or at least about 1.5:1, 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 25:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, 200:1, 500:1, or more.

[0459] The reaction can proceed over varying time periods. In some embodiments, the reaction is instantaneous. In other embodiments, the reaction time varies from minutes to hours to days, for example, 5, 10, 15, 20, 30, or 45 minutes, or 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 20, or 22 hours, or one or two days or longer. Those skilled in the art can use various techniques to determine when to terminate the reaction, for example, based on the consumption of starting materials, the formation of products, the formation of byproducts, etc.

[0460] In some embodiments, this disclosure provides compounds of high purity. In some embodiments, the purity of the compound is greater than or equal to about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.7%, or 99.9%. In some embodiments, the purity of the compound is or greater than about 80%. In some embodiments, the purity of the compound is or greater than about 85%. In some embodiments, the purity of the compound is greater than or equal to about 90%. In some embodiments, the purity of the compound is greater than or equal to about 95%. In some embodiments, the purity of the compound is greater than or equal to about 96%. In some embodiments, the purity of the compound is greater than or equal to about 97%. In some embodiments, the purity of the compound is greater than or equal to about 98%. In some embodiments, the purity of the compound is greater than or equal to about 99%. In some embodiments, the purity of the compound is greater than or equal to about 99.5%. In some embodiments, the purity of the compound is greater than or equal to about 99.7%. In some embodiments, the purity of the compound is greater than or equal to about 99.9%. In some implementations, such as those commonly used in the art, the purity for solid compositions is wt%.

[0461] In some embodiments, this disclosure provides compounds with high stereochemical purity. In some embodiments, the stereochemical purity of the compound is greater than or equal to about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.7%, or 99.9%. In some embodiments, the stereochemical purity of the compound is or greater than about 80%. In some embodiments, the stereochemical purity of the compound is or greater than about 85%. In some embodiments, the stereochemical purity of the compound is or greater than about 90%. In some embodiments, the stereochemical purity of the compound is or greater than about 95%. In some embodiments, the stereochemical purity of the compound is or greater than about 96%. In some embodiments, the stereochemical purity of the compound is or greater than about 97%. In some embodiments, the stereochemical purity of the compound is or greater than about 98%. In some embodiments, the stereochemical purity of the compound is greater than or equal to about 99%. In some embodiments, the stereochemical purity of the compound is greater than or equal to about 99.5%. In some embodiments, the stereochemical purity of the compound is greater than or equal to about 99.7%. In some embodiments, the stereochemical purity of the compound is greater than or equal to about 99.9%.

[0462] In some embodiments, this disclosure provides compounds with high enantiomeric purity. In some embodiments, the enantiomeric purity of the compound is greater than or equal to about 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.7%, or 99.9%. In some embodiments, the enantiomeric purity of the compound is or greater than about 80%. In some embodiments, the enantiomeric purity of the compound is or greater than about 85%. In some embodiments, the enantiomeric purity of the compound is or greater than about 90%. In some embodiments, the enantiomeric purity of the compound is or greater than about 95%. In some embodiments, the enantiomeric purity of the compound is or greater than about 96%. In some embodiments, the enantiomeric purity of the compound is or greater than about 97%. In some embodiments, the enantiomeric purity of the compound is or greater than about 98%. In some embodiments, the enantiomeric purity of the compound is or greater than about 99%. In some embodiments, the enantiomeric purity of the compound is or greater than about 99.5%. In some embodiments, the enantiomeric purity of the compound is greater than or equal to about 99.7%. In some embodiments, the enantiomeric purity of the compound is greater than or equal to about 99.9%. In some embodiments, the configuration of the stereocenter is shown next to the stereocenter in the chemical structure, for example, shown as "R", "S", "(R)", "(S)", etc., and this configuration is typically determined by commercial software such as ChemDraw when describing the chemical structure. In some embodiments, the configuration of the stereocenter is not shown. Those skilled in the art can easily determine the configuration of the stereocenter according to common practices in the art.

[0463] This disclosure provides various techniques for preparing stereochemically pure (e.g., enantiomeric) compounds and compositions. For example, in some embodiments, they can be prepared by separation (including chiral separation); in some embodiments, they can be prepared by stereoselective synthesis.

[0464] In some embodiments, this disclosure describes a method comprising one or more steps as described below, wherein each variable is independent as described in this disclosure. In some embodiments, one of the methods described below is provided as an example. In some embodiments, this disclosure provides a compound having a selected structure or a salt thereof.

[0465] In some implementations, this disclosure provides a method comprising:

[0466] Compounds having the structure of formula III-a or salts thereof are reacted with R 3 -C(O)-R 4 Compounds of a certain structure or their salts undergo chemical reactions:

[0467] ,

[0468] III-a

[0469] To provide compounds having the structure of formula IV-a or salts thereof:

[0470] ,

[0471] IV-a

[0472] Where R m1 As described in this disclosure, R' is used, and the other variables are independent as described in this disclosure.

[0473] In some implementations, this disclosure provides a method comprising:

[0474] Compounds having the structure of formula III-b or their salts are reacted with R 3 -C(O)-R 4 Compounds of the structure or their salts react:

[0475] ,

[0476] III-b

[0477] To provide compounds having the structure of formula IV-b or salts thereof:

[0478] ,

[0479] IV-b

[0480] Where R m1 As described in this disclosure, R' is used, and the other variables are independent as described in this disclosure.

[0481] In some implementations, this disclosure provides a method including

[0482] Compounds having the structure of formula III-c or their salts are reacted with R 3 -C(O)-R 4 Compounds of the structure or their salts react:

[0483] ,

[0484] III-c

[0485] To provide compounds having the structure of formula IV-c or salts thereof:

[0486] ,

[0487] IV-c

[0488] Where R m1 As described in this disclosure, R' is used, and the other variables are independent as described in this disclosure.

[0489] In some implementations, this disclosure provides a method including

[0490] Compounds having the structure of formula III-d or their salts having HC(O)C(O)OR m1 Compounds of the structure or their salts react:

[0491] R2-NH-C(R y )2-C(R 3 (R) 4 )-OH、

[0492] III-d

[0493] To provide compounds having the structure of formula IV-d or salts thereof:

[0494] ,

[0495] IV-d

[0496] Where R m1 As described in this disclosure, R' is used, and the other variables are independent as described in this disclosure.

[0497] In some embodiments, the method is carried out in the presence of acid. In some embodiments, the method is performed in... The method is carried out in the presence of H₂SO₄. In some embodiments, the method is carried out in the presence of concentrated H₂SO₄. In some embodiments, the method is carried out in the presence of TsOH, pyridinium p-toluenesulfonate (PPTS), and BF₃-Et₂O. In some embodiments, the method is carried out in the presence of pyridine p-toluenesulfonate (PPTS). In some embodiments, the method is carried out in the presence of BF₃-Et₂O. In some embodiments, the method is carried out in the presence of TsOH. In some embodiments, the method is carried out in the presence of TsOH. In some embodiments, the method is carried out in the presence of TsOH.

[0498] In some implementations, this disclosure provides a method including

[0499] Compounds having the structure of formula III-e or their salts are reacted with R 3 -C(O)-R 4 Compounds of the structure or their salts react:

[0500] ,

[0501] III-e

[0502] To provide compounds having the structure of formula IV-a or salts thereof:

[0503] ,

[0504] IV-a

[0505] Where R m1 R' is R', LG is a leaving group (such as -Br, -OTs, etc.), and the other variables are independent as described in this disclosure.

[0506] In some implementations, this disclosure provides a method including

[0507] Compounds having the structure of formula III-f or their salts are reacted with R 3 -C(O)-R 4 Compounds of the structure or their salts react:

[0508] ,

[0509] III-f

[0510] To provide compounds having the structure of formula IV-a or salts thereof:

[0511] ,

[0512] IV-a

[0513] Where R m1 R' is R', LG is a leaving group (such as -Br, -OTs, etc.), and the other variables are independent as described in this disclosure.

[0514] In some implementations, this disclosure provides a method including

[0515] Compounds having the structure of formula III-g or their salts are reacted with R w -C(O)-C(O)OR m1 Compounds of the structure or their salts react:

[0516] ,

[0517] III-g

[0518] To provide compounds having the structure of formula IV-g or salts thereof:

[0519] ,

[0520] IV-g

[0521] Where R m1 R' is the variable, and the other variables are independent as described in this disclosure.

[0522] In some implementations, this disclosure provides a method including

[0523] Compounds having the structure of formula III-h or their salts are reacted with R w -CH(SH)-C(O)OR m1 Compounds of the structure or their salts react:

[0524] C(R( 3 ))(R 4 )=C(R y )-C(O)-R2、

[0525] III-h

[0526] To provide compounds having the structure of formula IV-h or salts thereof:

[0527] ,

[0528] IV-h

[0529] To convert compounds having the structure of formula IV-h or their salts into compounds having the structure of formula IV-h-2 or IV-h-3 or their salts:

[0530] ,

[0531] IV-h-2

[0532] ,

[0533] IV-h-3

[0534] To convert a compound having the structure of formula IV-h-2 or a salt thereof into a compound ...

Claims

1. A compound of formula I or a salt thereof: ， I in R 1 It is an optional substituted group selected from the following structures: 6-10 aryl, 5-10 heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 cyclic aliphatic, 3-10 heterocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and bicyclic, wherein the first ring is attached to a nitrogen atom and is a benzene ring or a 5-6 heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the second ring is a benzene ring, a 5-10 heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10 heterocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 1 yes ; R 1' It is R', or R 1 and R 1' Together with the nitrogen atoms to which they are attached, they form optional substituted 3-10 membered rings, which may contain 0-6 heteroatoms in addition to the nitrogen atom; Q is O, S, NR Q ; R Q It is either -R' or -OR'; R 2 It is an optional substituted group selected from phenyl, 3-10 membered cyclic aliphatic groups, and 5-10 membered heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 2 Yes -L R2 -R B ; L R2 It can be a bond or -O-, -S-, or optionally substituted -CH2-; R B yes ; R 3 and R 4 Each can be independently hydrogen, -CN, or R; Each X is independently -O-, -S-, -S(O)-, -S(O)2-, -S(O)(NR) QX )-, -Se-, -Se(O)-, -Se(O)2-, -C(R x )2- or optionally substituted -CH2-; Each R x Independently -R' or -N(R')2; Each R QX Independently -R' or -OR'; x is 1 or 2; W is N, C, C(R) w ) or alternatively, CH, where R w It is -R' or -N(R')2, and Z is C when W is C; Z is N, C, C(R) z ) or alternatively, CH, where R z It is -R' or -N(R')2, when Z is C, W is C or Y is -C(R)2. y = or optional substitution -CH=; Each Y is independently -O-, -S-, -N(R) y )-、-C(R y )2-、-C(R y =, optionally substituted -CH2-, or optionally substituted -CH=, where each R y Independently, it is -R' or -N(R)2, when the Y bonded to Z is -C(R)2. y When Z is C, or optionally substituted with -CH=, Z is C; y is 1 or 2; Ring A and ring B are each independently substituted 3- to 10-membered rings, each ring containing 0-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R s1 Independent of halogen, -CN, -L s1 -R s11 -OR s11 -NR s11 R s12 -C(O)R s11 -C(O)NR s11 R s12 -C(NR) s13 )NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12) R s11 , -S(O)NR s11 R s12 , -C(O)N(R s13 )S(O)2NR s11 R s12 , or -OS(O)2NR s11 R s12 ; Each L s1 A C-type carbon atom that is independently bonded or optionally substituted, having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1-6 aliphatic chains or C 1-4 heterochain, in which C 1-6 aliphatic chains or C 1-4 One or more methylene units of the heteroester chain are independently and optionally separated by -C(O)-, -C(O)N(R) Ls1 )-,-C(S)-,-C(S)N(R Ls1 )-,-C(=NR Ls2 )-,-C(=NR Ls2 )N(R Ls1 )-, -O-, -S-, -S(O)-, -S(O)2-, -S(O)2N(R Ls1 )-、-OS(O)2N(R Ls1 )-、-S(O)(=NR Ls1 )-、-N(R Ls1 )-、-P(O)(R Ls1 )-、-P(O)(R Ls1 )O-、-P(S)(R Ls1 )-、-P(S)(R Ls1 O- or -Cy- substitution; Each -Cy- is independently a divalent 3- to 10-membered ring with optional substitution, the ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each R s2 Independent of halogen, -CN, -R s21 -OR s21 -NR s21 R s22 -C(O)R s21 -C(O)NR s21 R s22 -SR s21 -、S(O)2NR s21 R s22 -S(O)2R s21 -S(O)R s21 -S(O)(NR) s22 )R s21 -S(O)NR s21 R s22 -SF5 or -OS(O)2NR s21 R s22 ; s1 and s2 are each independently 0, 1, 2, 3, 4 or 5; R s11 R s12 R s13 R s21 R s22 R Ls1 and R Ls2 Each of them is independently R'; Each They are all independent single or double bonds; Each R' is independently R, -OR, -C(O)R, -C(O)OR, -S(O)R, or -S(O)2R; Each R is independently hydrogen or an optionally substituted group selected from: C1-C6 aliphatic groups, C1-C6 heteroaliphatic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 membered cycloaliphatic groups, 3-10 membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl groups, 5-10 membered heteroaryl groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl-C1-C6 aliphatic groups, and 5-10 membered heteroaryl-C1-C6 aliphatic groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or Two R groups on the same atom may optionally and independently form an optionally substituted 3-10 membered ring with the atom, the ring further comprising 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the atom; or The two R groups on the two atoms may optionally and independently form optional substituted 3-10 membered rings together with the spacer atoms between them, the rings may also contain 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur in addition to the spacer atoms.

2. A compound of formula I' or a salt thereof: ， I' in R 1 It is an optional substituted group selected from the following structures: 6-10 aryl, 5-10 heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 cyclic aliphatic, 3-10 heterocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and bicyclic, wherein the first ring is attached to a nitrogen atom and is a benzene ring or a 5-6 heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and the second ring is a benzene ring, a 5-10 heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 3-10 heterocyclic having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R 1 yes ; R 1' It is R', or R 1 and R 1' Together with the nitrogen atoms to which they are attached, they form optional substituted 3-6 membered rings, which may contain 0-3 heteroatoms in addition to the nitrogen atom; R 2 It is an optional substituted group selected from phenyl and 5-6 heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or R 2 yes ; R 3 and R 4 Each can be independently hydrogen, -CN, or R; X is -O-, -S-, -S(O)-, -S(O)2-, or -C(R) x )2-, where each R x Independently hydrogen or optionally substituted C1-C6 aliphatic groups, -OR or -N(R)2; W is N, C, or C(R) w ), where R w It is hydrogen or an optional substituted C1-C6 aliphatic group, -OR or -N(R)2, wherein when W is C, Z is C; Z is N, C, or C(R) z ), where R z It is hydrogen or an optional substituted C1-C6 aliphatic group, -OR or -N(R)2, wherein when Z is C, W is C or Y is -C(R)2. y = Y is -O-, -S-, -N(R) y )-、-C(R y )2- or -C(R y =, where each R y Independently hydrogen or optionally substituted C1-C6 aliphatic groups, -OR or -N(R)2, when Y is -C(R)2. y When ) = , Z is C; Ring A and ring B are independently substituted 5-6 membered aromatic groups, each having 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each R s1 Independent of halogen, -CN,R s11 ,,-OR s11 -NR s11 R s12 , -C(O)R s11 , -C(O)NR s11 R s12 , -S(O)2NR s11 R s12 , -S(O)2R s11 , -S(O)R s11 , -S(O)(NR s12 )R s11 , -S(O)NR s11 R s12 or -OS(O)2NR s11 R s12 ; Each R s2 Independent of halogen, -CN,R s21 , -OR s21 -NR s21 R s22 , -C(O)R s21 , -C(O)NR s21 R s22 , -S(O)2NR s21 R s22 , -S(O)2R s21 , -S(O)R s21 , -S(O)(NR s22 )R s21 , -S(O)NR s21 R s22 or -OS(O)2NR s21 R s22 ; s1 and s2 are each independently 0, 1, 2, 3, 4 or 5; R s11 R s12 R s21 and R s22 Each of them is independently R'; Each They are all independent single or double bonds; Each R' is independently R, -OR, -C(O)R, -C(O)OR, -S(O)R, or -S(O)2R; and Each R is independently hydrogen or an optionally substituted group selected from: C1-C6 aliphatic groups, C1-C6 heteroaliphatic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 3-10 membered cycloaliphatic groups, 3-10 membered heterocyclic groups having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl groups, 5-10 membered heteroaryl groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 6-10 membered aryl-C1-C6 aliphatic groups, and 5-10 membered heteroaryl-C1-C6 aliphatic groups having 1-6 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or The two R groups on the same atom may optionally and independently form an optionally substituted 3-10 membered ring with the atom, the ring further comprising 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the atom; or The two R groups on the two atoms may optionally and independently form optional substituted 3-10 membered rings together with the spacer atoms between them, the rings may also contain 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur in addition to the spacer atoms.

3. The compound of any one of the preceding claims, wherein when X is -O-, W is not -CH-, or Z is not -CH-, or Y is not -C(R) y )2-.

4. The compound of claim 1 or 3, wherein x is 1 and y is 1.

5. The compound of claim 1, wherein the compound has the structure of formula Ia: ， Ia Or its salt.

6. The compound of any one of claims 1-5, wherein R 1 It is an optional substituted group, selected from 6-10 aryl groups, 5-10 heteroaryl groups (e.g., 5-6, 9-10, 5, 6, 9, 10, etc.) having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 3-10 heteroaryl groups (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, etc.). Cyclic aliphatic groups of 4, 5, 6, 7, 8, 9, 10, etc., and heterocyclic groups of 3 to 10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) having 1-4 (e.g., 1-2, 1, 2, 3, 4, etc.) heterocyclic groups independently selected from nitrogen, oxygen and sulfur.

7. The compound of any one of claims 1-5, wherein R 1 yes .

8. The compound of claim 7, wherein ring A is an optionally substituted phenyl group.

9. The compound of claim 7, wherein ring A is an optionally substituted 5-6 heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

10. The compound of claim 7, wherein ring A is an optionally substituted 9-10 membered bicyclic system, said ring having 0-6 heteroatoms (e.g., 0, 1-6, 1-4, 1, 2, 3, 4, 5, 6, etc.) independently selected from nitrogen, oxygen, and sulfur.

11. The compound of claim 10, wherein at least one monocyclic unit is aromatic or heteroaromatic.

12. The compound of any one of claims 7-11, wherein s1 is 1-2.

13. The compound of any one of the preceding claims, wherein R s1 It is a halogen or -CN.

14. The compound of any one of the preceding claims, wherein R s1 -L s1 -R s11 .

15. The compound of any one of the preceding claims, wherein L s1 It is or contains -C(O)-, -C(O)N(R) Ls1 )-, -C(O)NH-, -C(S)-, -C(S)N(R Ls1 -, -C(S)NH-, -C(=NR Ls2 -, -C(=NH)-, -C(=NR) Ls2 )N(R Ls1 )-, -C(=NH)NH-, -O-, -S-, -S(O)-, -S(O)2-, -S(O)2N(R Ls1 -S(O)2NH-, -OS(O)2N RLs1 -, -OS(O)2NH-, -S(O)(=NR Ls1 )-, -S(O)(=NH)-, -N(R Ls1 )-, -NH-, -P(O)(R Ls1 )-, -P(O)(R Ls1 )-, where R Ls1 It is an optional replacement for C 1-6 aliphatic group, -N(R) Ls1 )-P(O)(R Ls1 )-,-NH-P(O)(R Ls1 )-,-P(O)(R Ls1 )O-、-P(O)(R Ls1 )O− , where R Ls1 It is -OR, where R is the alternative C. 1-6 aliphatic group, -N(R) Ls1 )-P(O)(R Ls1 )O-,-NH-P(O)(R Ls1 )O-,-P(S)(R Ls1 )-、-P(S)(R Ls1 )-, where R Ls1 It is an optional replacement for C 1-6 Aliphatic group, -P(S)(CH3)-, -P(S)(R Ls1 )O− ,-P(S)(R Ls1 )O− , where R Ls1 It is -OR, where R is the alternative C. 1-6 aliphatic group, -Cy-, -C(O)-Cy-, -N(R) Ls1 )S(O)2Cy-, -NHS(O)2Cy-, S(O)2N(R Ls1 Cy-, -S(O)2NHCy-, -C(O)N(R) Ls1 )-O-, -C(O)NH-O-, -Cy-N(R Ls1 )-, -Cy-NH-, -N(R Ls1 )-Cy-N(R Ls1 )-, -NH-Cy-NH-, -Cy-N(R Ls1 )-Cy- or -Cy-NH-Cy-.

16. The compound of any of the preceding claims, wherein -Cy- is an optionally substituted 3-8 (e.g., 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, etc.) divalent ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

17. The compound of any of the preceding claims, wherein -Cy- is an optionally substituted divalent 9-10 membered ring having 0-4 heteroatoms (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) independently selected from nitrogen, oxygen, and sulfur.

18. A compound of any of the preceding claims, wherein at least one monocyclic unit of -Cy- is aromatic or heteroaromatic.

19. The compound of any one of claims 1-14, L s1 yes .

20. The compound of any one of the preceding claims, wherein R s12 It is -H or an optional C substitution 1-6 Fatty base.

21. The compound of any one of the preceding claims, wherein R s11 It is a -H or optionally substituted group, said group being selected from: C1-C6 aliphatic, 6-10 aryl, 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) cyclic aliphatic groups, having 1-6 (e.g., 1-5, 1-4, 1, 2, 3, 4, 5, 6, etc.) independently selected from nitrogen, oxygen, and sulfur. Heteroaryl groups consisting of 5-10 members (e.g., 5-6, 9-10, 5, 6, 9, 10, etc.) and heterocyclic groups consisting of 1-4 members (e.g., 1-2, 1, 2, 3, 4, etc.) independently selected from nitrogen, oxygen and sulfur (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.).

22. The compound of any one of claims 1-20, wherein R s11 It is an optional replacement .

23. The compound of any one of claims 1-5, wherein R 1 Selected from ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， ， 。 24. The compound of any one of the preceding claims, wherein R 1' It is hydrogen.

25. The compound of any one of claims 1-5, wherein R 1 and R 1' Together with the nitrogen atoms to which they are attached, they form optional substituted 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) rings, which, in addition to the nitrogen atoms, also have 0-6 (e.g., 0, 1-6, 1-4, 1, 2, 3, 4, 5, 6, etc.) heteroatoms.

26. The compound of any one of the preceding claims, wherein Q is O.

27. The compound of any one of claims 1-25, wherein Q is S.

28. The compound of any one of claims 1-25, wherein Q is NR Q .

29. A compound of formula II or a salt thereof: ， II Each variable is independent as described in claim 1.

30. The compound of claim 29, wherein x is 1 and y is 1.

31. A compound of formula II' or a salt thereof: ， II' Each variable is independent as described in claim 2.

32. The compound of any one of the preceding claims, wherein when X is -O-, W is not -CH- or Z is not -CH- or Y is not -C(R) y )2-.

33. The compound of any one of claims 1-32, wherein R 2 It is an optional substituted phenyl, or R 2 It is an optional substituted 3-10 (e.g., 3-8, 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, 9, 10, etc.) membered cycloaliphatic group.

34. The compound of any one of claims 1-32, wherein R 2 yes or .

35. The compound of any of the preceding claims, wherein ring B is a 9-10 membered bicyclic system having 0-6 heteroatoms (e.g., 0, 1-6, 1-4, 1, 2, 3, 4, 5, 6, etc.) independently selected from nitrogen, oxygen and sulfur.

36. The compound of any one of claims 1-34, wherein ring B is an optionally substituted 3-8 (e.g., 3-6, 3-5, 4-6, 5-6, 3, 4, 5, 6, 7, 8, etc.) membered ring having 0-4 (e.g., 0, 1-4, 1-2, 1, 2, 3, 4, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

37. The compound of any of the preceding claims, wherein at least one monocyclic unit of ring B is a partially unsaturated ring or an aromatic group.

38. The compound of any one of claims 1-34, wherein ring B is an optionally substituted phenyl group.

39. The compound of any one of claims 1-34, wherein ring B is a 5-6 heteroaryl group having 1-5 heteroatoms (e.g., 1-4, 1-3, 1-2, 1, 2, 3, 4, 5, etc.) independently selected from nitrogen, oxygen and sulfur.

40. The compound of any one of claims 34-39, wherein s2 is 1-5.

41. The compound of any one of claims 1-32, wherein R 2 Selected from ， ， ， ， ， ， ， ， ， ， ， 。 42. The compound of any one of the preceding claims, wherein R 3 Yes - CN.

43. The compound of any one of claims 1-41, wherein R 3 It is an optional C1-C6 aliphatic group.

44. The compound of any one of claims 1-41, wherein R 3 It is an optional substituted group, which is selected from phenyl, 3-10 membered (e.g., 3-8 membered, 3-6 membered, 3-5 membered, 4-6 membered, 5-6 membered, 3 membered, 4 membered, 5 membered, 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, etc.) heterocyclic group having 1-4 (e.g., 1-2 membered, 1 membered, 2 membered, 3 membered, 4 membered, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-6 membered heteroaryl group having 1-4 (e.g., 1-2 membered, 1 membered, 2 membered, 3 membered, 4 membered, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

45. The compound of any one of the preceding claims, wherein R 4 Yes - CN.

46. ​​The compound of any one of claims 1-44, wherein R 4 It is an optional substituted group, which is selected from phenyl, 3-10 membered (e.g., 3-8 membered, 3-6 membered, 3-5 membered, 4-6 membered, 5-6 membered, 3 membered, 4 membered, 5 membered, 6 membered, 7 membered, 8 membered, 9 membered, 10 membered, etc.) heterocyclic group having 1-4 (e.g., 1-2 membered, 1 membered, 2 membered, 3 membered, 4 membered, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-6 membered heteroaryl group having 1-4 (e.g., 1-2 membered, 1 membered, 2 membered, 3 membered, 4 membered, etc.) heteroatoms independently selected from nitrogen, oxygen, and sulfur.

47. The compound of any one of claims 1-41, wherein -CR 3 R 4 -Selected from: 。 48. The compound of any one of claims 1-47, wherein X is -O-.

49. The compound of any one of claims 1-47, wherein X is -S-.

50. The compound of any one of claims 1-47, wherein X is -S(O)2−.

51. The compound of any one of claims 1-50, wherein W is C(R) w ).

52. The compound of any one of claims 1-51, wherein R w and R 3 It's the reverse form.

53. The compound of any one of claims 1-52, wherein Z is N.

54. The compound of any one of claims 1-52, wherein Z is C(R) z ).

55. The compound of claim 54, wherein R z and R 3 It is in sequence.

56. The compound of any one of claims 1-55, wherein Y is -O- or -S-.

57. The compound of any one of claims 1-55, wherein Y is -CH(R) y )-, R y It is an optional C1-C6 aliphatic group.

58. The compound of claim 57, wherein R 3 and R y It is the reverse form. 。 59. The compound of any one of claims 1-31, wherein Selected from ， ， ， ， ， ， 。 60. A compound selected from Table 1 or a salt thereof.

61. The compound of any of the preceding claims, wherein the compound is a pharmaceutically usable salt.

62. A compound, wherein the compound is a complex of the compound of any one of claims 29 to 59 and a chiral amine.

63. A compound, wherein the compound is or .

64. The compound of any of the preceding claims, wherein the enantiomeric purity of the compound is about or at least about 95%, and / or the purity is about or at least about 95%.

65. A pharmaceutical composition comprising a compound of any one of the preceding claims and a pharmaceutically acceptable carrier.

66. A method of treating a symptom, disorder, or disease, comprising administering or delivering to a patient an effective amount of a compound or pharmaceutical composition of any one of claims 1-65.

67. A method of preventing symptoms, disorders, or diseases, comprising administering or delivering to a susceptible population an effective amount of a compound or pharmaceutical composition of any one of claims 1-65.

68. The method according to any one of claims 66-67, wherein the symptom, disorder, or disease is related to Nav1.8 activation; and / or The symptoms, disorders, or diseases described herein are or include pain; and / or The symptoms, disorders, or diseases mentioned herein are or include chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain, visceral pain, multiple sclerosis, peroneal muscular dystrophy, urinary or fecal incontinence, pathological cough, or arrhythmia; and / or The symptoms, disorders, or diseases described herein are or include neuropathic pain, musculoskeletal pain, osteoarthritis pain, acute pain, acute postoperative pain, postoperative pain, hallux valgus pain, abdominoplasty pain, hernia pain, or visceral pain; and / or The symptoms, disorders, or diseases mentioned herein are or include postherpetic neuralgia, small fiber neuropathy, idiopathic small fiber neuropathy, diabetic neuropathy, or diabetic peripheral neuropathy; and / or The symptoms, disorders, or diseases mentioned above are or include migraines, post-ischemic neurodegeneration, epilepsy, arthralgia, cardiogenic pain due to ischemic myocardium, acute pain, chronic pain, angina, neuropathic pain, postoperative pain, pain caused by neuralgia (e.g., postherpetic neuralgia, traumatic neuralgia, fibromyalgia, trigeminal neuralgia), pain caused by diabetic neuropathy, toothache, cancer pain, or inflammatory pain (such as arthritis and osteoarthritis); and / or The symptoms, disorders, or diseases described herein are or include spontaneous pain, acute pain, preoperative pain, perioperative pain, or postoperative pain; and / or The symptoms, disorders, or diseases described herein are or include inflammatory pain; and / or The symptoms, disorders, or diseases mentioned herein are or include neuropathic pain; and / or The symptoms, disorders, or diseases mentioned herein are or include postoperative pain; and / or in, The symptoms, disorders, or diseases described are or include neuropathic pain, pain sensation, toothache, AIDS pain, cardiac pain caused by ischemic myocarditis, pain caused by migraines, joint pain, neuropathy, neurodegeneration, retinopathy, neurodermatitis, stroke, bladder hypersensitivity, urinary incontinence, vulvitis, gastrointestinal diseases such as irritable bowel syndrome, enteritis, ileitis, gastroduodenal reflux disease, gastrointestinal diseases such as irritable bowel syndrome, gastroesophageal reflux disease, enteritis, ileitis, peptic ulcer, inflammatory bowel disease, Crohn's disease, celiac disease, and pancreatitis. Inflammatory diseases, respiratory diseases such as allergic and non-allergic rhinitis, asthma, or chronic obstructive pulmonary disease; skin, eye, or mucous membrane irritation; atopic dermatitis, eczema, pruritus, fever, muscle spasms, hiccups, movement disorders, depression, Huntington's disease, memory impairment, limited brain function, amyotrophic lateral sclerosis (ALS), dementia, arthritis, osteoarthritis, diabetes, obesity, urticaria, actinic keratosis, keratoacanthoma, alopecia, Meniere's disease, tinnitus, hyperacusis, anxiety, or benign prostatic hyperplasia; and / or The symptoms, disorders, or diseases mentioned include or include acute pain, chronic pain, spontaneous pain, essential pain, neuropathic pain, peripheral neuropathy, migraine, post-ischemic neurodegeneration, multiple sclerosis, epilepsy, peroneal muscular dystrophy, post-ischemic neurodegeneration, epilepsy, trigeminal neuralgia, trigeminal automatic headache, diabetic neuropathy, sciatica, optic neuritis, HIV-associated sensory neuropathy, burning mouth syndrome, spinal stenosis, carpal tunnel syndrome, chemotherapy-induced peripheral neuropathy, radicular pain, nerve avulsion injury, brachial plexus injury, antiretroviral therapy-induced neuralgia, and spinal cord injury. Trauma, primary small fiber neuropathy, primary sensory neuropathy, inflammatory pain, rheumatoid arthritis pain, cancer pain, intestinal pain, visceral pain, musculoskeletal pain, acute pain from fractures, musculoskeletal injuries, chronic low back pain, phantom limb pain, chronic pelvic pain, intestinal pain, pancreatitis, renal colic, burn pain, preoperative pain, perioperative pain, postoperative pain, osteoarthritis, toothache, vulvar pain, fibromyalgia, urinary incontinence, pathological cough, arrhythmia, hereditary urticaria, asthma, pruritus, allergic or contact dermatitis, renal failure, cholestasis or arrhythmia; and / or The symptoms, disorders, or diseases mentioned herein are or include atopic dermatitis, eczema, seborrheic eczema, pruritus, skin inflammation, or psoriasis; and / or The symptoms, disorders, or diseases mentioned are skin inflammations.

69. A method for inhibiting voltage-gated sodium channels in a subject, comprising: Administering or delivering to a subject an effective amount of any one of the compounds or pharmaceutical compositions of claims 1-65; Optional: The voltage-gated sodium channel is or includes Nav1.8; and / or Wherein, the compound or composition is administered or delivered orally; and / or Wherein the compound or composition is administered intravenously or by delivery; and / or Wherein, the compound or composition is administered via subcutaneous injection or delivery; and / or Wherein, the compound or composition is administered or delivered topically; and / or Wherein, the compound or pharmaceutical composition is administered in combination with one or more additional therapeutic agents, each additional therapeutic agent being independently administered or delivered simultaneously, prior to, or after the compound or composition; and / or Wherein, the compound or pharmaceutical composition is delivered in combination with one or more additional therapeutic agents, each of which may be independently administered or delivered simultaneously, prior to, or after the compound or composition; or A method for inhibiting voltage-gated sodium channels in a system, comprising: administering or delivering an effective amount of the compound or pharmaceutical composition of any one of claims 1-65 to the system; optionally: The voltage-gated sodium channel is or includes Nav1.8; and / or The system is or includes cells; and / or The system is or includes an organization; and / or Wherein the system is or includes an organ; and / or Where the system is an organism; and / or The system is the subject.

70. A method comprising: Compounds having the structure of formula III-a or their salts are reacted with compounds having the structure of formula III-a. The compound or its salt of the structure reacts. , III-a To prepare compounds having the structure of formula IV-a: , IV-a or its salt, wherein R m1 R', and the other variables are independent as described in any of the preceding claims; or One method includes: Compounds having the structure of formula III-b or their salts are reacted with compounds having the structure of formula III-b. The compound or its salt of the structure reacts. , III-b To prepare compounds having the structure of formula IV-b: , IV-b or its salt, wherein R m1 R', and the other variables are independent as described in any of the preceding claims; or One method includes: To react a compound having the structure of formula III-c or a salt thereof with a compound having the structure of formula III-c or a salt thereof, , III-c To prepare compounds having the structure of formula IV-c: , IV-c or its salt, wherein R m1 R', and the other variables are independent as described in any of the preceding claims; or One method includes: Compounds having the structure of formula III-k or their salts are reacted with R 3 -C(O)-R 4 The compound or its salt of the structure reacts. , III-k To prepare compounds having the structure of formula IV-j: , IV-j or its salt, wherein R m1 R', and the other variables are independent as described in any of the preceding claims; or One method includes: Compounds having the structure of formula III-d or their salts having HC(O)C(O)OR m1 The compound or its salt of the structure reacts. R 2 −NH−C(R y )2−C(R 3 )(R 4 )−OH, III-d To prepare compounds having the structure of formula IV-d: , IV-d or its salt, wherein R m1 R', and the other variables are independent as described in any of the preceding claims; or One method includes: To react a compound having the structure of formula III-e or a salt thereof with a compound having the structure of III-e or a salt thereof, , III-e To prepare compounds having the structure of formula IV-a: , IV-a or its salt, wherein R m1 R' is a leaving group (such as -Br, -OTs, etc.), and the other variables are independently as described in any of the preceding claims; or One method includes: Compounds having the structure of formula III-f or their salts are reacted with compounds having the structure of formula III-f. The compound or its salt of the structure reacts. , III-f To prepare compounds having the structure of formula IV-a: , IV-a or its salt, wherein R m1 R' is a leaving group (such as -Br, -OTs, etc.), and the other variables are independently as described in any of the preceding claims; or One method includes: Compounds having the structure of formula III-g or their salts, having R w -C(O)-C(O)OR m1 The compound or its salt of the structure reacts. , III-g To prepare compounds having the structure of formula IV-g: , IV-g or its salt, wherein R m1 R', and the other variables are independent as described in any of the preceding claims; or One method, including Compounds having the structure of formula III-h or their salts, having R w -CH(SH)-C(O)OR m1 The compound or its salt of the structure reacts. C(R 3 )(R 4 )=C(R y )−C(O)−R 2 , III-h To prepare compounds having the structure of formula IV-h: , IV-h or its salt; Optionally, compounds of formula IV-h or their salts may be converted into compounds of formula IV-h-2 or IV-h-3: , IV-h-2 , IV-h-3 or its salt; Optionally, a compound of formula IV-h-2 or a salt thereof may be converted into a compound of formula IV-h-3 or a salt thereof; and To convert compounds of formula IV-h-2 or IV-h-3, or their salts, into compounds of formula IV-h-4: , IV-h-4 or its salt; Where R m1 R', and the other variables are independent as described in any of the preceding claims; or One method, including Compounds having the structure of formula III-i or their salts are reacted with C(R) 3 (R) 4 )=C(R y Compounds with a structure of )2 or their salts react to form 2. O - -N + (PG)=C(R z )(R 2 ), III-i To prepare compounds having the structure of formula IV-i: , IV-i or its salt; Optionally, a compound of formula IV-i or a salt thereof may be converted into a compound of formula IV-i-2: , IV-i-2 or its salt; Optionally, a compound of formula IV-i-2 or a salt thereof may be converted into a compound of formula IV-i-3: , IV-i-3 Or its salt (e.g., by means of having O=C=NR) 1 (reaction of compounds or their salts with the structure). Wherein PG is R' or a suitable protecting group (such as -CH2-optionally substituted aromatic group (such as phenyl)), and each other variable is independently as described in any of the preceding claims.

71. A method for preparing a compound according to any one of claims 1-61 and 64, comprising preparing a compound according to any one of claims 62-64.

72. The compound or composition according to any one of the preceding claims, used for treating a disease, symptom, or disorder; or The compound or composition of any one of the preceding claims is used to carry out the method of any one of claims 66-69; or The compound or composition according to any one of the preceding claims is used to manufacture a medicament for treating a certain symptom, disease, or disorder; or The compound or composition of any one of the preceding claims is used to manufacture the medicament according to any one of the methods of claims 66-69.

73. Use of the compound or composition according to any one of the preceding claims for the treatment of a certain symptom, disease, or disorder; or Use of the compound or composition according to any one of the preceding claims, for carrying out the method of any one of claims 66-69; or The use of the compound or composition according to any one of the preceding claims for the manufacture of a medicament for treating a certain condition, disease, or disorder; or The use of any compound or composition according to any one of the preceding claims for manufacturing the medicament according to any one of claims 66-69.

74. The compound, composition, method, or use of any one of the embodiments 1-817.

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