WO2025019800A1

WO2025019800A1 - Novel prodrugs and conjugates of dimethyltryptamine and methods of using the same

Info

Publication number: WO2025019800A1
Application number: PCT/US2024/038804
Authority: WO
Inventors: Tanweer A. Khan
Original assignee: Atai Therapeutics Inc
Current assignee: Atai Therapeutics Inc
Priority date: 2023-07-19
Filing date: 2024-07-19
Publication date: 2025-01-23
Anticipated expiration: 2026-01-19

Abstract

Provided herein are compounds of Formula I, or pharmaceutically acceptable salt thereof, wherein R₁, R₂, R₃, R₄, R₅, R₈, R₉, X, Y, Z, W, and m are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula I or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipients, and methods of using the same, e.g., in the treatment of mental health diseases and/or disorders.

Description

NOVEL PRODRUGS AND CONJUGATES OF DIMETHYLTRYPTAMINE AND METHODS OF USING THE SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63/514,534, filed July 19, 2023, which is hereby incorporated by reference in its entirety for all purposes.

BACKGROUND

[0002] 7V,7V-dimethyltryptamine (DMT) is a naturally occurring compound found in numerous plant species and botanical preparations, such as the hallucinogenic infusion known as ayahuasca, and classified as a classic serotonergic psychedelic that induces intense modifications in perception, emotion, and cognition in humans. At higher doses, DMT has a rapid onset, intense psychedelic effects, and a relatively short duration of action with an estimated half-life of less than fifteen minutes. Like other hallucinogens in the tryptamine family, DMT binds to serotonin receptors to produce euphoria and psychedelic effects. Unfortunately, DMT is metabolically unstable and is readily converted by monoamine oxidases (MAO’s) to indoleacetic acid and N-oxidation metabolites resulting in poor oral bioavailability.

[0003] Serotonergic psychedelics have also demonstrated promising antidepressant, anxiolytic, and anti-addictive properties.

[0004] There remains a need for improved prodrugs of tryptamines, such as N,N- dimethyltryptamine (DMT).

SUMMARY

[0005] In embodiments, the present disclosure provides a compound of Formula I:

Formula I, or a pharmaceutically acceptable salt thereof; wherein,

Ri and R2 are each independently hydrogen, alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring;

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR7-, or - CH₂-;

R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, - (C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)- ORA(ORB);

W is oxygen, sulfur or NRe;

Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl- (C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇- O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH₂- heterocyclic ring, -(C=O)-alkyl, -(C=O)CR₇-NH2-(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)-alkyl-(NH)(C=NH)-NH₂;

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

R₉ is hydrogen, alkyl, or halogen;

RA, RB, and Re are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid; and m is an integer from 1-4, and wherein, when Rs is hydrogen or alkyl: at least one of R3, R4, and R5 is -(C=O)-alkyl, -(C=O)CR₇-NH2, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(ORB), or -(P=O)-OR_A(OR_B); or

W is NR₆ and Re is -CHR₇-(P=O)-ORA(OR_B), -CHR₇-O(C=O)-alkyl- (C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇- O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH₂- heterocyclic ring, -(C=O)-alkyl, -(C=O)CR₇-NH₂ -(C=O)CH(NH₂)-alkyl-NH₂, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)-alkyl-(NH)(C=NH)-NH₂.

[0006] In embodiments, the present disclosure provides compounds of Formula IV:

or a pharmaceutically acceptable salt thereof; wherein,

Ri and R2 are each independently hydrogen, alkyl, cycloalkyl, -or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring;

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR₇-, or - CH₂-;

R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, - (C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-OR_A(OR_B), or -(P=O)- ORA(ORB);

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

R₉is hydrogen, alkyl, or halogen; Rio is -CHR₇-O-(P=O)ORA(ORB), -CHR₇-O-aryl, -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid;

RA and RB are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or am amino acid; m is an integer from 1-4; and

A- is a pharmaceutically acceptable anion.

DEFINITIONS

[0007] Throughout this disclosure, various patents, patent applications and publications are referenced. The disclosures of these patents, patent applications and publications in their entireties are incorporated into this disclosure by reference for all purposes in order to more fully describe the state of the art as known to those skilled therein as of the date of this disclosure. This disclosure will govern in the instance that there is any inconsistency between the patents, patent applications and publications cited and this disclosure.

[0008] For convenience, certain terms employed in the specification, examples and claims are collected here. Unless defined otherwise, all technical and scientific terms used in this disclosure have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0009] The term “about” when immediately preceding a numerical value means a range (e.g., plus or minus 10% of that value). For example, “about 50” can mean 45 to 55, “about 25,000” can mean 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation. For example, in a list of numerical values such as “about 49, about 50, about 55, ...”, “about 50” means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g., more than 49.5 to less than 50.5. Furthermore, the phrases “less than about” a value or “greater than about” a value should be understood in view of the definition of the term “about” provided herein. Similarly, the term “about” when preceding a series of numerical values or a range of values (e.g., “about 10, 20, 30” or “about 10-30”) refers, respectively to all values in the series, or the endpoints of the range.

[0010] The terms “administer,” “administering” or “administration” as used herein refer to administering a compound or pharmaceutically acceptable salt of the compound or a composition or formulation comprising the compound or pharmaceutically acceptable salt of the compound to a patient. [0011] The term “pharmaceutically acceptable salts” includes both acid and base addition salts. Pharmaceutically acceptable salts include those obtained by reacting the active compound functioning as a base, with an inorganic or organic acid to form a salt, for example, salts of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, camphorsulfonic acid, oxalic acid, maleic acid, succinic acid, citric acid, formic acid, hydrobromic acid, benzoic acid, tartaric acid, fumaric acid, salicylic acid, mandelic acid, carbonic acid, etc. The acids that may be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds are those that form non-toxic acid addition salts, i.e., salts containing pharmaceutically acceptable anions, including but not limited to malate, oxalate, chloride, bromide, iodide, nitrate, acetate, tartrate, oleate, fumarate, formate, benzoate, glutamate, methanesulfonate, benzenesulfonate, and p-toluenesulfonate salts. Base addition salts include but are not limited to, ethylenediamine, N-methyl-glucamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, diethylamine, piperazine, tris-(hydroxymethyl)- aminomethane, tetramethylammonium hydroxide, triethylamine, dibenzylamine, ephenamine, dehydroabietylamine, N-ethylpiperidine, benzylamine, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, ethylamine, basic amino acids, e. g., lysine and arginine dicyclohexylamine and the like. Examples of metal salts include lithium, sodium, potassium, magnesium, calcium salts and the like. Examples of ammonium and alkylated ammonium salts include ammonium, methylammonium, dimethylammonium, trimethylammonium, ethylammonium, hydroxyethylammonium, diethylammonium, butylammonium, tetramethylammonium salts and the like. Examples of organic bases include lysine, arginine, guanidine, diethanolamine, choline and the like. Those skilled in the art will further recognize that acid addition salts may be prepared by reaction of the compounds with the appropriate inorganic or organic acid via any of a number of known methods.

[0012] The term “treating” as used herein with regard to a patient, refers to improving at least one symptom of the patient's disorder. In some embodiments, treating can be improving, or at least partially ameliorating a disorder or one or more symptoms of a disorder.

[0013] The term “preventing” as used herein with regard to a patient or subject, refers to preventing the onset of disease development if none had occurred, preventing the disease or disorder from occurring in a subject or a patient that may be predisposed to the disorder or disease but has not yet been diagnosed as having the disorder or disease, and/or preventing further disease/disorder development if already present.

[0014] The term “therapeutically effective” applied to dose or amount refers to that quantity of a compound or pharmaceutical formulation that is sufficient to result in a desired clinical benefit after administration to a patient in need thereof.

[0015] When a range of values is listed, it is intended to encompass each value and sub-range within the range. For example, “Ci-Ce alkyl” is intended to encompass Ci, C2, C3, C4, C5, C₆, C1-6, Ci-5, C1-4, C1-3, C1-2, C2-6, C2-5, C2-4, C2-3, C3-6, C3.5, C3-4, C4-6, C4-5, and C_5.6 alkyl.

[0016] “Alkyl” or “alkyl group” refers to a fully saturated, straight or branched hydrocarbon chain having from one to twelve carbon atoms, and which is attached to the rest of the molecule by a single bond. Alkyls comprising any number of carbon atoms from 1 to 12 are included. An alkyl comprising up to 12 carbon atoms is a C1-C12 alkyl, an alkyl comprising up to 10 carbon atoms is a C1-C10 alkyl, an alkyl comprising up to 6 carbon atoms is a Ci-Ce alkyl and an alkyl comprising up to 5 carbon atoms is a C1-C5 alkyl. A C1-C5 alkyl includes C5 alkyls, C4 alkyls, C3 alkyls, C2 alkyls and Ci alkyl (i.e., methyl). A Ci-Ce alkyl includes all moieties described above for C1-C5 alkyls but also includes Ce alkyls. A C1-C10 alkyl includes all moieties described above for C1-C5 alkyls and Ci-Ce alkyls, but also includes C7, Cs, C9 and C10 alkyls. Similarly, a C1-C12 alkyl includes all the foregoing moieties, but also includes Cn and C12 alkyls. Non-limiting examples of Ci- C12 alkyl include methyl, ethyl, //-propyl, z-propyl, ec-propyl, //-butyl, z-butyl, sec-butyl, /-butyl, //-pentyl, /-amyl, //-hexyl, //-heptyl, //-octyl, //-nonyl, //-decyl, //-undecyl, and n- dodecyl. Unless stated otherwise specifically in the specification, an alkyl group can be optionally substituted.

[0017] “Aryl” refers to a hydrocarbon ring system comprising hydrogen, 6 to 18 carbon atoms and at least one aromatic ring, and which is attached to the rest of the molecule by a single bond. For purposes of this disclosure, the aryl can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused or bridged ring systems. Aryls include, but are not limited to, aryls derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as- indacene, -indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. Unless stated otherwise specifically in the specification, the “aryl” can be optionally substituted. [0018] “Cycloalkyl” refers to a stable non-aromatic monocyclic or polycyclic fully saturated hydrocarbon consisting solely of carbon and hydrogen atoms, which can include fused, bridged, or spirocyclic ring systems, having from three to twenty carbon atoms (e.g., having from three to ten carbon atoms) and which is attached to the rest of the molecule by a single bond. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbomyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Unless otherwise stated specifically in the specification, a cycloalkyl group can be optionally substituted.

[0019] “Heterocyclic ring” or “heterocycle” refers to a stable saturated, unsaturated, or aromatic 3- to 20-membered ring which consists of two to nineteen carbon atoms and from one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and which is attached to the rest of the molecule by a single bond. Heterocyclic rings include heteroaryls, heterocyclylalkyls, heterocyclylalkenyls, and hetercyclylalkynyls. Unless stated otherwise specifically in the specification, the heterocyclic ring can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused, bridged, or spirocyclic ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclic ring can be optionally oxidized; the nitrogen atom can be optionally quatemized; and the heterocyclic ring can be partially or fully saturated. Examples of such heterocyclic rings include, but are not limited to, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, a heterocyclic ring group can be optionally substituted.

[0020] “Heteroaryl” refers to a 5- to 20-membered ring system comprising hydrogen atoms, one to nineteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, at least one aromatic ring, and which is attached to the rest of the molecule by a single bond. For purposes of this disclosure, the heteroaryl can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heteroaryl can be optionally oxidized; the nitrogen atom can be optionally quaternized. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodi oxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[Z>][l,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodi oxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1 -oxi dopy ridazinyl, 1 -phenyl- 1 //-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e. thienyl). Unless stated otherwise specifically in the specification, a heteroaryl group can be optionally substituted.

[0021] The term “substituted” used herein means any of the groups described herein (e.g., alkyl, aryl, cycloalkyl, heterocyclic ring, and/or heteroaryl) wherein at least one hydrogen atom is replaced by a bond to a non-hydrogen atoms such as, but not limited to: a halogen atom such as F, Cl, Br, and I; an oxygen atom in groups such as hydroxyl groups, alkoxy groups, and ester groups; a sulfur atom in groups such as thiol groups, thioalkyl groups, sulfone groups, sulfonyl groups, and sulfoxide groups; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides, and enamines; a silicon atom in groups such as trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups, and triarylsilyl groups; and other heteroatoms in various other groups. “Substituted” also means any of the above groups in which one or more hydrogen atoms are replaced by a higher-order bond (e.g., a double- or triple-bond) to a heteroatom such as oxygen in oxo, carbonyl, carboxyl, and ester groups; and nitrogen in groups such as imines, oximes, hydrazones, and nitriles. For example, “substituted” includes any of the above groups in which one or more hydrogen atoms are replaced withNRgRh, -NR_gC(=O)Rh, -NR_gC(=O)NR_gRh, -NR_gC(=O)OR_h, -NR_gSO₂R_h, -OC(=O)N

R_gRh, -OR_g, -SR_g, -SOR_g, -SO₂R_g, -OSO₂R_g, -SO₂OR_g, =NSO₂R_g, and -SO₂NR_gR_h. “Substituted” also means any of the above groups in which one or more hydrogen atoms are replaced with -C(=O)R_g, -C(=O)OR_g, -C(=O)NR_gR_h, -CH₂SO₂R_g, -CH₂SO₂NR_gR_h. In the foregoing, R_g and Rh are the same or different and independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic ring, A-heterocyclic ring, heterocyclylalkyl, heteroaryl, /f-heteroaryl and/or heteroarylalkyl. “Substituted” further means any of the above groups in which one or more hydrogen atoms are replaced by a bond to an amino, cyano, hydroxyl, imino, nitro, oxo, thioxo, halo, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclic ring, A-heterocyclyl, heterocyclylalkyl, heteroaryl, 7V-heteroaryl and/or heteroarylalkyl group. In addition, each of the foregoing substituents can also be optionally substituted with one or more of the above substituents.

DETAILED DESCRPTION

[0022] The present disclosure provides compounds that are prodrugs of tryptamines and related scaffolds, for example /f-dimethyltryptarnine (DMT) as well as pharmaceutical compositions thereof.

[0023] DMT is metabolically unstable and is readily converted by monoamine oxidases (MAO’s) to indoleacetic acid and A-oxidation metabolites resulting in poor oral bioavailability. In embodiments, the compounds of the present disclosure allow for the controlled release of DMT. Advantages of compounds of the present disclosure may include increased metabolic stability, increased absorption, decreased maximal plasma concentrations of parent drug DMT over time, and less frequent dosing. In embodiments, compounds of the present disclosure prevent or inhibit A -oxidation to promote oral bioavailability and increased exposure.

[0024] In embodiments, compounds of the present disclosure comprise an enacarbil moiety. Without being bound by theory such compounds may for example, increase bioavailability by virtue of active transport of the prodrug in the small intestine by high-capacity nutrient transporters, including mono-carboxylate transporter-1 (MCT-1). DMT-enacarbil prodrugs may also reduce abuse potential by preventing absorption by snorting or insufflation. Compounds

[0025] In one aspect, the present disclosure provides prodrugs of tryptamines (e.g., DMT) and derivatives thereof. In embodiments, the present disclosure provides compounds of Formulas I, II, III, and IV.

Compounds of Formula I:

[0026] In embodiments, the present disclosure provides a compound of Formula I:

Formula I, or a pharmaceutically acceptable salt thereof; wherein,

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR7-, or -CH2-;

R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, - (C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B);

W is oxygen, sulfur or NRe;

Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl- (C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇- O(C=O) -alkyl-N(alkyl)2, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH2-heterocyclic ring, -(C=O)-alkyl, -(C=O)CR₇-NH₂ -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)- alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂;

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc; R₉ is hydrogen, alkyl, or halogen;

RA, RB, and Re are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid; and m is an integer from 1-4, and wherein, when Rs is hydrogen or alkyl: at least one of R₃, R₄, and Rs is -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(ORB), or -(P=O)-OR_A(OR_B); or

W is NR₆ and Re is -CHR₇-(P=O)-OR_A(OR_B), -CHR₇-O(C=O)-alkyl-(C=O)OR_c, - CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH₂-heterocyclic ring, -(C=O)- alkyl, -(C=O)CR₇-NH₂ -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂.

[0027] In embodiments, the present disclosure provides compounds of Formula (la):

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R₂ are each both are methyl;

X, Y, and Z are each either absent or -O-;

R₃, R₄, and Rs are each independently absent, hydrogen, Ci-C₃ alkyl, or - CH₂-(P=O)-(OH)₂, wherein when R₃ is present X is -O-, when R₄ is present Y is -O-, and when Rs is present Z is -O-;

Re is hydrogen, -CHR₇-(P=O)-OR_A(OR_B), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)2, -CHR7-0(C=0)-aryl, or -CH2-O(C=O)-aryl-CH2-heterocyclic ring, wherein R7 is hydrogen or methyl, and RA, RB, and Re are each independently hydrogen or methyl; and wherein at least one of R3, R4, Rs, and Re are present and non-hydrogen, and wherein Re is H, at least one of R4 and Rs are -CHR7-(P=0)-0RA(0RB), and R3 is not -CH₂-(P=O)-OH(OH).

[0028] In embodiments, Ri and R2 are each independently alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or cycloalkyl.

[0029] In embodiments, Ri and R2 are each independently hydrogen or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently cycloalkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or alkyl.

[0030] In embodiments, Ri and R2 are each alkyl. In embodiments, Ri and R2 are each hydrogen. In embodiments, one of Ri and R2 is hydrogen and one of Ri and R2 is alkyl.

[0031] In embodiments, Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, the heterocyclic ring is a monocyclic, bicyclic, tricyclic, or tetracyclic ring. In embodiments, the heterocyclic ring is a monocyclic ring. In embodiments, the heterocyclic ring is a bicyclic ring. In embodiments, the heterocyclic ring is a tricyclic ring. In embodiments, the heterocyclic ring is a tetracyclic ring.

[0032] In embodiments, X, Y and Z are each independently halogen, -O-, -S-, -NR?-,or - CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, - NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -NR7-.

[0033] In embodiments, X, Y and Z are each independently -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently halogen, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or - CH2-. In embodiments, halogen, -O-, -S-, or -CH2-. In embodiments, halogen, -O-, - S-, or -NR7-.

[0034] In embodiments, X, Y and Z are each independently hydrogen, -S-, -NR7-, or -CH2- In embodiments, X, Y and Z are each independently hydrogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, or -S-.

[0035] In embodiments, X, Y and Z are each independently -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently -O-, -NR7-, or-CH2- In embodiments, X, Y and Z are each independently -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently -O-, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, or -CH2-. X, Y and Z are each independently hydrogen, halogen, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, or -O-.

[0036] In embodiments, X, Y and Z are each independently hydrogen or halogen. In embodiments, X, Y, and Z are each independently hydrogen or -O-. In embodiments, X, Y, and Z are each independently hydrogen or -S-. In embodiments, X, Y, and Z are each independently hydrogen or -NR7-. In embodiments, X, Y, and Z are each independently hydrogen or -CH2-.

[0037] In embodiments, X, Y and Z are each independently halogen or -O-. In embodiments,

X, Y and Z are each independently halogen or -S-. In embodiments, X, Y and Z are each independently halogen or -NR7-. In embodiments, X, Y and Z are each independently halogen or -CH2-.

[0038] In embodiments, X, Y, and Z are each independently -O- or -S-, In embodiments, X,

Y, and Z are each independently -O- or -NR7-. In embodiments, Z, Y, and Z are each independently -O- or -CH -. In embodiments, X, Y, and Z are each independently -S- or -NR7-. In embodiments, Z, Y, and Z are each independently -S- or -CH2-.

[0039] In embodiments, X is hydrogen. In embodiments, X is halogen. In embodiments, X is -O-. In embodiments, X is -S-. In embodiments, X is -NR7-. In embodiments, X is - CH2-.

[0040] In embodiments, Y is hydrogen. In embodiments, Y is halogen. In embodiments, Y is -O-. In embodiments, Y is -S-. In embodiments, Y is -NR7-. In embodiments, Y is - CH2-.

[0041] In embodiments, Y is hydrogen. In embodiments, Z is halogen. In embodiments, Z is -O-. In embodiments, Z is -S-. In embodiments, Z is -NR7-. In embodiments, Z is - CH2-.

[0042] In embodiments, R3, R4, and R5 are each independently hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)- ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, alkyl, -(C=O)- alkyl, -(C=O)CR7-NH2,-(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-OR_A(OR_B), or - (P=O)-ORA(OR_B). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, -(C=O)-alkyl, -(C=O)CR7-NH₂,-(C=O)CH(NH₂)-alkyl-NH2, (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CR?-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=0)-0RA(0RB), or -(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CHR7-NH2, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH₂, -CHR₇(P=O)-OR_A(ORB), or -(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR?- NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, - CHR7(P=0)-0RA(0RB), or -(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=0)CR?-NH2, -

(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)- ORA(ORB), or-(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=0)CR?-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or - (P=O)-ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=0)CR?-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or - CHR₇(P=O)-OR_A(ORB).

[0043] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)- alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH2, or -CHR7(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH2, or -CHR7(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH2, or -CHR7(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-NH2, -(C=O)CH(NH2)- alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or -CHR₇(P=O)- ORA(ORB).

[0044] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -(C=O)CR7-NH2. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)CH(NH2)-alkyl-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or - (C=O)CH(NH2)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)-alkyl-(NH)(C=NH)- NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -CHR₇(P=O)-OR_A(OR_B).

[0045] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, or -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH2)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or -(C=O)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(ORB).

[0046] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, - (C=O)-alkyl.

[0047] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)CR₇-NH₂.

[0048] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH₂)-alkyl-NH2.

[0049] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)-alkyl-(NH)(C=NH)-NH₂.

[0050] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-OR_A(ORB).

[0051] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (P=O)-ORA(ORB).

[0052] In embodiments, R3 and R4 are hydrogen and Rs is -CHR₇(P=O)-ORA(ORB).

[0053] In embodiments, R3 and Rs are hydrogen and R4 is -CHR₇(P=O)-ORA(ORB).

[0054] In embodiments, R4 and Rs are hydrogen and R3 is -CHR₇(P=O)-ORA(ORB).

[0055] In embodiments, R3 and R4 are hydrogen and Rs is alkyl.

[0056] In embodiments, R3 and Rs are hydrogen and R4 is alkyl.

[0057] In embodiments, R4 and Rs are hydrogen and R3 is alkyl. [0058] In embodiments, R3, R4, and R5 are each hydrogen.

[0059] In embodiments, R3 and R4 are hydrogen, R5 is -CHR7(P=O)-ORA(ORB), X and Y are absent, and Z is -O-.

[0060] In embodiments, R3 and R4 are hydrogen, R5 is -CH2(P=O)-ORA(ORB), X and Y are absent, and Z is -O-.

[0061] In embodiments, R3 and R5 are hydrogen, R4 is -CHR7(P=O)-ORA(ORB), X and Z are absent, and Y is -O-.

[0062] In embodiments, R3 and R5 are hydrogen, R4 is -CH2(P=O)-ORA(ORB), X and Z are absent, and Y is -O-.

[0063] In embodiments, R4 and R5 are hydrogen, R3 is -CHR7(P=O)-ORA(ORB), Y and Z are absent, and X is -O-.

[0064] In embodiments, R4 and R5 are hydrogen, R3 is -CH2(P=O)-ORA(ORB), Y and Z are absent, and X is -O-.

[0065] In embodiments, R3 and R4 are hydrogen, R5 is hydrogen, X and Y are absent, and Z is -O-.

[0066] In embodiments, R3 and R4 are hydrogen, R5 is alkyl, X and Y are absent, and Z is -O-

[0067] In embodiments, R3 and R5 are hydrogen, R4 is hydrogen, X and Z are absent, and Y is -O-.

[0068] In embodiments, R3 and R5 are hydrogen, R4 is alkyl, X and Z are absent, and Y is -O-

[0069] In embodiments, R4 and R5 are hydrogen, R3 is hydrogen, Y and Z are absent, and X is -O-.

[0070] In embodiments, R4 and R5 are hydrogen, R3 is alkyl, Y and Z are absent, and X is -O-

[0071] In embodiments, W is oxygen or sulfur. In embodiments, W is oxygen or NRe. In embodiments, W is sulfur or NRe. In embodiments, W is oxygen. In embodiments, W is sulfur. In embodiments, W is NRe. [0072] In embodiments, Re is hydrogen, alkyl, -CHR7-(P=O)-ORA(ORB), -CHR7-O(C=O)- alkyl-(C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, - CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇- NH₂. -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or - (C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, alkyl, -CHR7-(P=O)- ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, - CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl - (C=O)-alkyl, -(C=O)CHR₇-NH₂-(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, -CHR₇-(P=O)-OR_A(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-

O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR7-O(C=O)-alkyl-(C=O)OR_c, - CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR7-(P=O)-ORA(ORB), -CHR7- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR7-(P=O)-ORA(ORB), -CHR7- O(C=O)-alkyl-(C=O)ORc,-CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR7-(P=O)-ORA(ORB), -CHR7- O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃,-CHR₇-O(C=O)-aryl, - (C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(OR_B), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O)-alkyl- N(alkyl)₂,-(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR7-(P=O)-ORA(ORB), -CHR7-O(C=O)- alkyl-(C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, - CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)CHR₇-NH₂, - (C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)- alkyl-(NH)(C=NH)-NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-(P=O)- ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, - CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, - (C=O)-alkyl,-(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, alkyl, - CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)OR_c, -CHR₇-O(C=O)-alkyl- N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇- O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl- N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇- O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, or- (C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇- (P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl- N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O)-alkyl-N(alkyl)₂, -CHR₇- O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, or - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂.

[0073] In embodiments, Re is absent. In embodiments, Re is hydrogen. In embodiments, Re is alkyl. In embodiments, Re is -CHR₇-(P=O)-ORA(ORB). In embodiments, Re is -CHR₇- O(C=O)-alkyl-(C=O)ORc. In embodiments, Re is -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃. In embodiments, Re is -CHR₇-O(C=O)-alkyl-NH₂. In embodiments, Re is -CHR₇-O(C=O) -alkyl-N(alkyl)₂. In embodiments, Re is -CHR₇-O(C=O)-aryl. In embodiments, Re is - (C=O)-alkyl. In embodiments, Re is -(C=O)CHR₇-NH₂. In embodiments, Re is - (C=O)CH(NH₂)-alkyl-NH₂. In embodiments, Re is -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂. In embodiments, Reis -(C=O)-alkyl-(NH)(C=NH)-NH₂.

[0074] In embodiments, R₇ is hydrogen. In embodiments, R₇ is alkyl. In embodiments, R₇ is a Ci-Ce alkyl. In embodiments, R₇ is a Ci alkyl. In embodiments, R₇ is a C₂ alkyl. In embodiments, R₇ is a C₃ alkyl.

[0075] In embodiments, RA, RB, and R_c are each independently alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and Re are each independently hydrogen, alkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or ketal.

[0076] In embodiments, RA, RB, and Rc are each hydrogen. In embodiments, RA and R_c are each hydrogen. In embodiments, RA and RB are each hydrogen. In embodiments, RB and Rc are each hydrogen.

[0077] In embodiments, RA, RB, and R_c are each alkyl. In embodiments, RA and Rc are each alkyl. In embodiments, RA and RB are each alkyl. In embodiments, RB and R_c are each alkyl.

[0078] In embodiments, RA is hydrogen. In embodiments, RB is hydrogen. In embodiments, Rc is hydrogen.

[0079] In embodiments, RA is hydrogen and RB is alkyl. In embodiments, RA is alkyl and RB is hydrogen.

[0080] In embodiments, Rc is hydrogen. In embodiments Rc is alkyl.

[0081] In embodiments, Re is -CHR?-(P=O)-ORA(ORB), and RA and RB hydrogen.

[0082] In embodiments, Re is -CHR?-(P=O)-ORA(ORB), and RA, RB, and R? are hydrogen.

[0083] In embodiments, Re is -CHR7-O(C=O)-alkyl-(C=O)ORc, and Rc is hydrogen.

[0084] In embodiments, Re is -CHR7-O(C=O)-alkyl-(C=O)ORc, and Rc and R? are hydrogen.

[0085] In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a Ci-Ce alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a Ci alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C2 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C3 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C4 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C5 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a Ce alkyl.

[0086] In embodiments, Re is -CHR7-O(C=O)-aryl, and R7 is hydrogen. In embodiments, Re is -CHR7-O(C=O)-aryl, and R7 is alkyl.

[0087] In embodiments, Rs is hydrogen, alkyl, or -(C=O)ORc.

[0088] In embodiments, Rs is hydrogen. In embodiments, Rs is alkyl. In embodiments, Rs is Ci-Ce alkyl. In embodiments, Rs is Ci alkyl. In embodiments, Rs is C2 alkyl. In embodiments, Rs is C3 alkyl. In embodiments, Rs is a C4 alkyl. In embodiments, Rs is C5 alkyl. In embodiments, Rs is Ce alkyl.

[0089] In embodiments, Rs is -(C=O)OR_c. In embodiments, Rs is -(C=O)ORc and Re is hydrogen. In embodiments, Rs is -(C=O)ORc and Re is alkyl. In embodiments, Rs is - (C=O)OR_c and R_c is heteroalkyl. In embodiments, Rs is -(C=O)ORc and R_c is cycloalkyl. In embodiments, Rs is -(C=O)OR_c and Rc is alkoxy. In embodiments, Rs is -(C=O)ORc and Rc is hemiacetal. In embodiments, Rs is -(C=O)OR_c and Rc is ketal. In embodiments, Rs is -(C=O)OR_c and Rc is amino acid.

[0090] In embodiments, R9 is hydrogen, alkyl, or halogen. In embodiments, R9 is hydrogen. In embodiments, R9 is alkyl. In embodiments, R9 is halogen.

[0091] In embodiments, m is an integer from 1-4. In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3. In embodiments, m is 4.

[0092] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is -(P=O)- ORA(ORB), and R3 and Rs are absent.

[0093] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is -(P=O)- ORA(ORB), R3 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0094] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is -(P=O)- ORA(ORB), and R4 and Rs are absent.

[0095] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is -(P=O)- ORA(ORB), R4 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen. [0096] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is -(P=O)- ORA(ORB), and R3 and R4 are absent.

[0097] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is -(P=O)- ORA(ORB), R3 and R4 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0098] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, and R3 and Rs are absent.

[0099] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0100] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, and R4 and Rs are absent.

[0101] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0102] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, and R3 and R4 are absent.

[0103] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0104] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, and R3 and Rs are absent.

[0105] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and Rs are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0106] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, and R4 and Rs are absent.

[0107] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and Rs are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0108] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, and R3 and R4 are absent.

[0109] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, R3 and R4 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen. [0110] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, and R3, R4, and R5 are absent.

[OlH] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, and R3, R4, and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, and R9 is hydrogen.

[0112] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, and Re is -CHR₇-O(C=O)-alkyl-(C=O)OR_c.

[0113] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-(C=O)ORc, Rs is hydrogen, and R9 is hydrogen.

[0114] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3.

[0115] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, Rs is hydrogen, and R9 is hydrogen.

[0116] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-N(alkyl)2.

[0117] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-N(alkyl)2, Rs is hydrogen, and R9 is hydrogen.

[0118] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, and Re is -CHR₇-O(C=O)-aryl.

[0119] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, Re is -CHR₇-O(C=O)-aryl, Rs is hydrogen, and R9 is hydrogen.

[0120] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, and Re is -CHR7-O(C=O)-CH2-heterocyclic ring.

[0121] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, W is NRe, Re is -CHR7-O(C=O)-CH2-heterocyclic ring, Rs is hydrogen, and R9 is hydrogen.

[0122] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, and R3 and R5 are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c. [0123] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and R5 are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c, Rs is hydrogen, and R9 is hydrogen.

[0124] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, and R4 and R5 are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c.

[0125] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and Rs are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c, Rs is hydrogen, and R9 is hydrogen.

[0126] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, and R3 and R4 are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c.

[0127] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, R3 and R4 are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c, Rs is hydrogen, and R9 is hydrogen.

[0128] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, and R3 and Rs are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-(C=O)OR_c W is NRe, and Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3.

[0129] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and Rs are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, Rs is hydrogen, and R9 is hydrogen.

[0130] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, and R4 and Rs are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3.

[0131] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and Rs are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, Rs is hydrogen, and R9 is hydrogen.

[0132] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, and R3 and R4 are absent, W is NRe, and Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3.

[0133] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, R3 and R4 are absent, W is NRe, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, Rs is hydrogen, and R9 is hydrogen. [0134] In embodiments, the present disclosure provides a compound of Formula I or pharmaceutically acceptable salts thereof selected from Table 1.

Table 1. Compounds of Formula I of the Present Disclosure

Compounds of Formula II:

[0135] In embodiments, provided herein is a compound of Formula II:

Formula II or a pharmaceutically acceptable salt thereof; wherein,

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR7-, or -CH2-; R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, - (C=O)CR₇-NH₇, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B);

W is oxygen, sulfur or NRe;

R₇ is hydrogen or alkyl;

RA, RB, and Re are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid; and m is an integer from 1-4.

[0136] In embodiments, the present disclosure provides compounds having the structure of Formula Ila:

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, or C1-C3 alkyl, wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is - O-;

Re is hydrogen or C1-C3 alkyl, wherein at least one of R3, R4, and R5 are present and non-hydrogen, and wherein when Re is H, at least one of XR3 and ZRs are -O-(Ci-C3 alkyl).

[0137] In embodiments, Ri and R2 are each independently alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or cycloalkyl.

[0138] In embodiments, Ri and R2 are each independently hydrogen or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently cycloalkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or alkyl.

[0139] In embodiments, Ri and R2 are each alkyl. In embodiments, Ri and R2 are each hydrogen. In embodiments, one of Ri and R2 is hydrogen and one of Ri and R2 is alkyl.

[0140] In embodiments, Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, the heterocyclic ring is a monocyclic, bicyclic, tricyclic, or tetracyclic ring. In embodiments, the heterocyclic ring is a monocyclic ring. In embodiments, the heterocyclic ring is a bicyclic ring. In embodiments, the heterocyclic ring is a tricyclic ring. In embodiments, the heterocyclic ring is a tetracyclic ring.

[0141] In embodiments, X, Y and Z are each independently halogen, -O-, -S-, -NR?-,or - CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, - NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -NR7-.

[0142] In embodiments, X, Y and Z are each independently -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently halogen, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or - CH2-. In embodiments, halogen, -O-, -S-, or -CH2-. In embodiments, halogen, -O-, - S-, or -NR7-. [0143] In embodiments, X, Y and Z are each independently hydrogen, -S-, -NR7-, or -CH2- In embodiments, X, Y and Z are each independently hydrogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, or -S-.

[0144] In embodiments, X, Y and Z are each independently -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently -O-, -NR7-, or-CH2- In embodiments,

X, Y and Z are each independently -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently -O-, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, or -CH2-. X, Y and Z are each independently hydrogen, halogen, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, or -O-.

[0145] In embodiments, X, Y and Z are each independently hydrogen or halogen. In embodiments, X, Y, and Z are each independently hydrogen or -O-. In embodiments, X,

Y, and Z are each independently hydrogen or -S-. In embodiments, X, Y, and Z are each independently hydrogen or -NR7-. In embodiments, X, Y, and Z are each independently hydrogen or -CH2-.

[0146] In embodiments, X, Y and Z are each independently halogen or -O-. In embodiments,

[0147] In embodiments, X, Y, and Z are each independently -O- or -S-. In embodiments, X,

Y, and Z are each independently -O- or -NR7-. In embodiments, Z, Y, and Z are each independently -O- or -CH2-. In embodiments, X, Y, and Z are each independently -S- or -NR7- In embodiments, Z, Y, and Z are each independently -S- or -CH2-. [0148] In embodiments, X is hydrogen. In embodiments, X is halogen. In embodiments, X is -O-. In embodiments, X is -S-. In embodiments, X is -NR7-. In embodiments, X is - CH₂-.

[0149] In embodiments, Y is hydrogen. In embodiments, Y is halogen. In embodiments, Y is -O-. In embodiments, Y is -S-. In embodiments, Y is -NR7-. In embodiments, Y is - CH2-.

[0150] In embodiments, Y is hydrogen. In embodiments, Z is halogen. In embodiments, Z is -O-. In embodiments, Z is -S-. In embodiments, Z is -NR7-. In embodiments, Z is - CH2-.

[0151] In embodiments, R3, R4, and R5 are each independently hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)- ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, alkyl, -(C=O)- alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-OR_A(OR_B), or - (P=O)-ORA(OR_B). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CR?-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CHR7-NH2, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR?- NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, - CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR?-NH2, -

(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)- ORA(ORB), or-(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or - (P=O)-ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or - CHR₇(P=O)-OR_A(ORB).

[0152] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)- alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH2, or -CHR?(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH2, or -CHR?(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH2, or -CHR?(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-NH2, -(C=O)CH(NH2)- alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or -CHR₇(P=O)- ORA(ORB).

[0153] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -(C=O)CR₇-NH2. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)CH(NH2)-alkyl-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or - (C=O)CH(NH2)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)-alkyl-(NH)(C=NH)- NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -CHR₇(P=O)-OR_A(OR_B).

[0154] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, or -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)- alkyl-NH2, or -(C=O)CH(NH2)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or -(C=O)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(OR_B).

[0155] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl.

[0156] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (C=O)CR₇-NH₂.

[0157] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH₂)-alkyl-NH₂.

[0158] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (C=O)-alkyl-(NH)(C=NH)-NH₂.

[0159] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(ORB).

[0160] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (P=O)-ORA(ORB).

[0161] In embodiments, R3 and R4 are hydrogen and R5 is -CHR₇(P=O)-ORA(ORB).

[0162] In embodiments, R3 and R5 are hydrogen and R4 is -CHR₇(P=O)-ORA(ORB).

[0163] In embodiments, R4 and R5 are hydrogen and R3 is -CHR₇(P=O)-ORA(ORB).

[0164] In embodiments, R3 and R4 are hydrogen and R5 is alkyl.

[0165] In embodiments, R3 and R5 are hydrogen and R4 is alkyl.

[0166] In embodiments, R4 and R5 are hydrogen and R3 is alkyl.

[0167] In embodiments, R3, R4, and R5 are each hydrogen.

[0168] In embodiments, R3 and R4 are hydrogen, R5 is -CH₂(P=O)-ORA(ORB), X and Y are absent, and Z is -O-.

[0169] In embodiments, R3 and R5 are hydrogen, R4 is -CHR₇(P=O)-ORA(ORB), X and Z are absent, and Y is -O-.

[0170] In embodiments, R3 and R5 are hydrogen, R4 is -CH₂(P=O)-ORA(ORB), X and Z are absent, and Y is -O-.

[0171] In embodiments, R4 and R5 are hydrogen, R3 is -CHR₇(P=O)-ORA(ORB), Y and Z are absent, and X is -O-. [0172] In embodiments, R4 and R5 are hydrogen, R3 is -CH2(P=O)-ORA(ORB), Y and Z are absent, and X is -O-.

[0173] In embodiments, R3 and R4 are hydrogen, R5 is hydrogen, X and Y are absent, and Z is -O-.

[0174] In embodiments, R3 and R4 are hydrogen, R5 is alkyl, X and Y are absent, and Z is -O-

[0175] In embodiments, R3 and R5 are hydrogen, R4 is hydrogen, X and Z are absent, and Y is -O-.

[0176] In embodiments, R3 and R5 are hydrogen, R4 is alkyl, X and Z are absent, and Y is -O-

[0177] In embodiments, R4 and R5 are hydrogen, R3 is hydrogen, Y and Z are absent, and X is -O-.

[0178] In embodiments, R4 and R5 are hydrogen, R3 is alkyl, Y and Z are absent, and X is -O-

[0179] In embodiments, R7 is hydrogen. In embodiments, R7 is alkyl. In embodiments, R7 is a Ci-Ce alkyl. In embodiments, R7 is a Ci alkyl. In embodiments, R7 is a C2 alkyl. In embodiments, R7 is a C3 alkyl.

[0180] In embodiments, RA, RB, and R_c are each independently alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or ketal. [0181] In embodiments, RA, RB, and Re are each hydrogen. In embodiments, RA and R_c are each hydrogen. In embodiments, RA and RB are each hydrogen. In embodiments, RB and Re are each hydrogen.

[0182] In embodiments, RA, RB, and R_c are each alkyl. In embodiments, RA and Re are each alkyl. In embodiments, RA and RB are each alkyl. In embodiments, RB and R_c are each alkyl.

[0183] In embodiments, RA is hydrogen. In embodiments, RB is hydrogen. In embodiments, Rc is hydrogen.

[0184] In embodiments, RA is hydrogen and RB is alkyl. In embodiments, RA is alkyl and RB is hydrogen.

[0185] In embodiments, Rc is hydrogen. In embodiments Rc is alkyl.

[0186] In embodiments, m is an integer from 1-4. In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3. In embodiments, m is 4.

[0187] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, and R4 and Rs are absent.

[0188] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, and Rc is hydrogen.

[0189] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, and Rc is alkyl.

[0190] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, and R3 and Rs are absent.

[0191] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and R5 are absent, and Rc is hydrogen.

[0192] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and R5 are absent, and Rc is alkyl.

[0193] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, and R3 and R4 are absent.

[0194] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, and Rc is hydrogen. [0195] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, and Rc is alkyl.

[0196] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, and R4 and Rs are absent.

[0197] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and Rs are absent, and Rc is hydrogen.

[0198] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and Rs are absent, and Rc is alkyl.

[0199] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, and R3 and Rs are absent.

[0200] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and Rs are absent, and Rc is hydrogen.

[0201] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and Rs are absent, and Rc is alkyl.

[0202] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, and R3 and R4 are absent.

[0203] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, R3 and R4 are absent, and Rc is hydrogen.

[0204] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, Rs is hydrogen, R3 and R4 are absent, and Rc is alkyl.

[0205] In embodiments, the present disclosure provides a compound of Formula II or pharmaceutically acceptable salts thereof selected from Table 2.

Table 2, Compounds of Formula II of the Present Disclosure

Compounds of Formula III:

[0206] In embodiments, provided herein is a compound of Formula III:

Formula III, or a pharmaceutically acceptable salt thereof; wherein, Ri and R2 are each independently hydrogen, alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring;

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR7-, or -CH2-;

W is oxygen, sulfur or NRe;

Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl- (C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇- O(C=O) -alkyl-N(alkyl)2, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH2-heterocyclic ring, -(C=O)-alkyl, -(C=O)CHR₇-NH2,-(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)- alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂;

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

R₉ is hydrogen, alkyl, or halogen;

Rio is hydrogen, alkyl, -CHR₇-O-(P=O)ORA(ORB), -CHR₇-O-aryl, -CHR₇-aryl- 0(C=0)-CH2-NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid,

RA, RB, and Re are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid;

A- is a pharmaceutically acceptable anion; and m is an integer from 1-4.

[0207] In embodiments of Formula III:

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR₇-, or -CH2-;

R3, R4, and R5 are each independently absent, hydrogen, or alkyl;

W is oxygen, sulfur or NRe;

Re is absent, hydrogen, or alkyl; R7 is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

Ro is hydrogen, alkyl, or halogen;

Rio is hydrogen, alkyl, -CHR7-0-(P=0)0RA(0RB), -CHR₇-O-aryl, -CHR?-aryl- O(C=O)-CH₂-NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid,

A- is a pharmaceutically acceptable anion; and m is an integer from 1-4.

[0208] In embodiments, the present disclosure provides compounds having the structure of

Formula Illa:

(Illa), or a pharmaceutically acceptable salt thereof, wherein:

Ri and R₂ are methyl;

X, Y, and Z are each either absent or -O-;

Rio is -CHR₇-O-(P=O)ORA(OR_B), -CH₂-O-aryl, -CH₂-aryl-O(C=O)-CH₂- NH(alkyl), wherein RA and RB are each independently hydrogen or methyl;

R7 is hydrogen or alkyl; and

A' is a pharmaceutically acceptable anion, wherein when Rio is -CHR7-O-(P=O)OH(OH), at least one of R3, R4, and R5 are present, and XR3 and ZR5 are not -OH, and YR4 is not -OCH3.

[0209] In embodiments, Ri and R2 are each independently alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or cycloalkyl.

[0210] In embodiments, Ri and R2 are each independently hydrogen or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently cycloalkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or alkyl.

[0211] In embodiments, Ri and R2 are each alkyl. In embodiments, Ri and R2 are each hydrogen. In embodiments, one of Ri and R2 is hydrogen and one of Ri and R2 is alkyl.

[0212] In embodiments, Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, the heterocyclic ring is a monocyclic, bicyclic, tricyclic, or tetracyclic ring. In embodiments, the heterocyclic ring is a monocyclic ring. In embodiments, the heterocyclic ring is a bicyclic ring. In embodiments, the heterocyclic ring is a tricyclic ring. In embodiments, the heterocyclic ring is a tetracyclic ring.

[0213] In embodiments, X, Y and Z are each independently halogen, -O-, -S-, -NR?-,or - CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, - NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -NR7-. [0214] In embodiments, X, Y and Z are each independently -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently halogen, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or - CH2-. In embodiments, halogen, -O-, -S-, or -CH2-. In embodiments, halogen, -O-, - S-, or -NR7-.

[0215] In embodiments, X, Y and Z are each independently hydrogen, -S-, -NR7-, or -CH2- . In embodiments, X, Y and Z are each independently hydrogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, or -S-.

[0216] In embodiments, X, Y and Z are each independently -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently -O-, -NR7-, or-CH2- In embodiments,

[0217] In embodiments, X, Y and Z are each independently hydrogen or halogen. In embodiments, X, Y, and Z are each independently hydrogen or -O-. In embodiments, X,

[0218] In embodiments, X, Y and Z are each independently halogen or -O-. In embodiments, X, Y and Z are each independently halogen or -S-. In embodiments, X, Y and Z are each independently halogen or -NR7-. In embodiments, X, Y and Z are each independently halogen or -CH2-. [0219] In embodiments, X, Y, and Z are each independently -O- or -S-. In embodiments, X, Y, and Z are each independently -O- or -NR7-. In embodiments, Z, Y, and Z are each independently -O- or -CH2-. In embodiments, X, Y, and Z are each independently -S- or -NR7-. In embodiments, Z, Y, and Z are each independently -S- or -CH2-.

[0220] In embodiments, X is hydrogen. In embodiments, X is halogen. In embodiments, X is -O-. In embodiments, X is -S-. In embodiments, X is -NR7-. In embodiments, X is - CH2-.

[0221] In embodiments, Y is hydrogen. In embodiments, Y is halogen. In embodiments, Y is -O-. In embodiments, Y is -S-. In embodiments, Y is -NR7-. In embodiments, Y is - CH2-.

[0222] In embodiments, Y is hydrogen. In embodiments, Z is halogen. In embodiments, Z is -O-. In embodiments, Z is -S-. In embodiments, Z is -NR7-. In embodiments, Z is - CH2-.

[0223] In embodiments, R3, R4, and R5 are each independently hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)- ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, alkyl, -(C=O)- alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-OR_A(OR_B), or - (P=O)-ORA(OR_B). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CR?-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CHR7-NH2, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇- NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, - CHR7(P=0)-0RA(0RB), or -(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH2, -

(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)- ORA(ORB), or-(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH2, -(C=O)CH(NH₂)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or - (P=O)-ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH2, -(C=O)CH(NH₂)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or - CHR₇(P=O)-OR_A(ORB).

[0224] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)- alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, or -CHR₇(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or -CHR₇(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl- (NH)(C=NH)-NH₂, or -CHR₇(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH2)- alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or -CHR₇(P=O)- ORA(ORB).

[0225] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -(C=O)CR₇-NH₂. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)CH(NH2)-alkyl-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)-alkyl-(NH)(C=NH)- NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -CHR₇(P=O)-OR_A(OR_B). [0226] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, or -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(OR_B).

[0227] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, - (C=O)-alkyl.

[0228] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)CR7-NH₂.

[0229] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH₂)-alkyl-NH2.

[0230] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)-alkyl-(NH)(C=NH)-NH₂.

[0231] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(ORB).

[0232] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (P=O)-ORA(ORB).

[0233] In embodiments, R3 and R4 are hydrogen and Rs is -CHR₇(P=O)-ORA(ORB).

[0234] In embodiments, R3 and Rs are hydrogen and R4 is -CHR₇(P=O)-ORA(ORB).

[0235] In embodiments, R4 and Rs are hydrogen and R3 is -CHR₇(P=O)-ORA(ORB).

[0236] In embodiments, R3 and R4 are hydrogen and Rs is alkyl.

[0237] In embodiments, R3 and Rs are hydrogen and R4 is alkyl.

[0238] In embodiments, R4 and Rs are hydrogen and R3 is alkyl.

[0239] In embodiments, R3, R4, and Rs are each hydrogen.

[0240] In embodiments, R3 and R4 are hydrogen, Rs is hydrogen, X and Y are absent, and Z is

-O-. [0241] In embodiments, R3 and R4 are hydrogen, R5 is alkyl, X and Y are absent, and Z is -O-

[0242] In embodiments, R3 and R5 are hydrogen, R4 is hydrogen, X and Z are absent, and Y is -O-.

[0243] In embodiments, R3 and R5 are hydrogen, R4 is alkyl, X and Z are absent, and Y is -O-

[0244] In embodiments, R4 and R5 are hydrogen, R3 is hydrogen, Y and Z are absent, and X is -O-.

[0245] In embodiments, R4 and R5 are hydrogen, R3 is alkyl, Y and Z are absent, and X is -O-

[0246] In embodiments, W is oxygen or sulfur. In embodiments, W is oxygen or NRe. In embodiments, W is sulfur or NRe. In embodiments, W is oxygen. In embodiments, W is sulfur. In embodiments, W is NRe.

[0247] In embodiments, Re is hydrogen, alkyl, -CHR7-(P=O)-ORA(ORB), -CHR₇-O(C=O)- alkyl-(C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, - CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇- NH₂. -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or - (C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, alkyl, -CHR₇-(P=O)- ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, - CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl - (C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, -CHR₇-(P=O)-OR_A(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-

O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-O(C=O)-alkyl-(C=O)OR_c, - CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇- O(C=O)-alkyl-(C=O)ORc,-CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)- alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)- NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇- O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃,-CHR₇-O(C=O)-aryl, - (C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-OR_A(OR_B), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O)-alkyl- N(alkyl)₂,-(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)- alkyl-(C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, - CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -(C=O)CHR₇-NH₂, - (C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)- alkyl-(NH)(C=NH)-NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇-(P=O)- ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, - CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, - (C=O)-alkyl,-(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, alkyl, - CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)OR_c, -CHR₇-O(C=O)-alkyl- N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇- O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl- N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇- O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, or- (C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, Reis absent, hydrogen, alkyl, -CHR₇- (P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇-O(C=O)-alkyl- N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O)-alkyl-N(alkyl)₂, -CHR₇- O(C=O)-aryl, -(C=O)-alkyl, -(C=O)CHR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH₂, or - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂.

[0248] In embodiments, Re is absent. In embodiments, Re is hydrogen. In embodiments, Re is alkyl. In embodiments, Re is -CHR?-(P=O)-ORA(ORB). In embodiments, Re is -CHR7- O(C=O)-alkyl-(C=O)ORc. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3. In embodiments, Re is -CHR7-O(C=O)-alkyl-NH₂. In embodiments, Re is -CHR?-O(C=O) -alkyl-N(alkyl)₂. In embodiments, Re is -CHR₇-O(C=O)-aryl. In embodiments, Re is - (C=O)-alkyl. In embodiments, Re is -(C=O)CHR7-NH₂. In embodiments, Re is - (C=O)CH(NH₂)-alkyl-NH₂. In embodiments, Re is -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂. In embodiments, Reis -(C=O)-alkyl-(NH)(C=NH)-NH₂.

[0249] In embodiments, Rio is -CHR₇-O-aryl, -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid. In embodiments, Rio is heteroaryl, alkyl, alkoxy, or amino acid. In embodiments, Rio is alkyl, alkoxy, or amino acid. In embodiments, Rio is alkoxy or amino acid. In embodiments, Rio is -CHR₇-O-aryl, -CHR?-aryl-O(C=O)- CH₂-NH(alkyl), heteroaryl, alkyl, or alkoxy. In embodiments, Rio is -CHR₇-O-aryl, - CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is - CHR?-O-aryl, -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), or heteroaryl. In embodiments, Rio is -CHR?-O-aryl or -CHR7-aryl-O(C=O)-CH₂-NH(alkyl). In embodiments, Rio is - CHR7-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, alkyl, or alkoxy. In embodiments, Rio is -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is - CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is - CHR₇-aryl-O(C=O)-CH₂-NH(alkyl) or heteroaryl. In embodiments, Rio is -CHR7-O- (P=O)ORA(ORB), -CHR7-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, alkyl, or alkoxy. In embodiments, Rio is -CHR₇-O-(P=O)ORA(OR_B), -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is -CHR?-O-(P=O)ORA(ORB), -CHR?-aryl- O(C=O)-CH₂-NH(alkyl), or heteroaryl. In embodiments, Rio is -CHR7-O- (P=O)ORA(ORB), -CHR₇-O-aryl, heteroaryl, alkyl, or alkoxy. In embodiments, Rio is - CHR?-O-(P=O)ORA(ORB), -CHR₇-O-aryl, heteroaryl, or alkyl. In embodiments, Rio is -CHR?-O-(P=O)ORA(ORB), -CHR₇-O-aryl, or heteroaryl. In embodiments, Rio is - CHR₇-O-(P=O)OR_A(ORB), -CHR₇-O-aryl, -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), alkyl, or alkoxy. In embodiments, Rio is — CHR?-O-(P=O)ORA(ORB), -CHR₇-O-aryl, - CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), or alkyl. [0250] In embodiments, Rio is hydrogen. In embodiments, Rio is alkyl. In embodiments, Rio is -CHR₇-O-(P=O)ORA(OR_B), -CHR₇-O-aryl, or -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl). In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB) or -CHR₇-O-aryl. In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2- NH(alkyl). In embodiments, Rio is -CHR₇-O-aryl or -CHR₇-aryl-O(C=O)-CH2- NH(alkyl).

[0251] In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB). In embodiments, Rio is -CHR₇- O-aryl. In embodiments, Rio is -CHR₇-aryl-O(C=O)-CH2-NH(alkyl). In embodiments, Rio is heteroaryl. In embodiments, Rio is alkyl. In embodiments, Rio is alkoxy. In embodiments, Rio is amino acid.

[0252] In embodiments, R₇ is hydrogen. In embodiments, R₇ is alkyl. In embodiments, R₇ is a Ci-Ce alkyl. In embodiments, R₇ is a Ci alkyl. In embodiments, R₇ is a C₂ alkyl. In embodiments, R₇ is a C3 alkyl.

[0253] In embodiments, RA, RB, and R_c are each independently alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or ketal.

[0254] In embodiments, RA, RB, and Rc are each hydrogen. In embodiments, RA and R_c are each hydrogen. In embodiments, RA and RB are each hydrogen. In embodiments, RB and Rc are each hydrogen.

[0255] In embodiments, RA, RB, and R_c are each alkyl. In embodiments, RA and Rc are each alkyl. In embodiments, RA and RB are each alkyl. In embodiments, RB and R_c are each alkyl. [0256] In embodiments, RA is hydrogen. In embodiments, RB is hydrogen. In embodiments, Re is hydrogen.

[0257] In embodiments, RA is hydrogen and RB is alkyl. In embodiments, RA is alkyl and RB is hydrogen.

[0258] In embodiments, Rc is hydrogen. In embodiments Rc is alkyl.

[0259] In embodiments, Re is -CHR?-(P=O)-ORA(ORB), and RA and RB hydrogen.

[0260] In embodiments, Re is -CHR?-(P=O)-ORA(ORB), and RA, RB, and R? are hydrogen.

[0261] In embodiments, Re is -CHR7-O(C=O)-alkyl-(C=O)ORc, and Rc is hydrogen.

[0262] In embodiments, Re is -CHR7-O(C=O)-alkyl-(C=O)ORc, and Rc and R? are hydrogen.

[0263] In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a Ci-Ce alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a Ci alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C2 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C3 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C4 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a C5 alkyl. In embodiments, Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3, and the alkyl is a Ce alkyl.

[0264] In embodiments, Re is -CHR7-O(C=O)-aryl, and R7 is hydrogen. In embodiments, Re is -CHR7-O(C=O)-aryl, and R7 is alkyl.

[0265] In embodiments, Rs is hydrogen, alkyl, or -(C=O)ORc.

[0266] In embodiments, Rs is hydrogen. In embodiments, Rs is alkyl. In embodiments, Rs is Ci-Ce alkyl. In embodiments, Rs is Ci alkyl. In embodiments, Rs is C2 alkyl. In embodiments, Rs is C3 alkyl. In embodiments, Rs is a C4 alkyl. In embodiments, Rs is C5 alkyl. In embodiments, Rs is Ce alkyl.

[0267] In embodiments, Rs is -(C=O)OR_c. In embodiments, Rs is -(C=O)ORc and Rc is hydrogen. In embodiments, Rs is -(C=O)ORc and Rc is alkyl. In embodiments, Rs is - (C=O)OR_c and R_c is heteroalkyl. In embodiments, Rs is -(C=O)ORc and R_c is cycloalkyl. In embodiments, Rs is -(C=O)OR_c and Rc is alkoxy. In embodiments, Rs is -(C=O)ORc and Rc is hemiacetal. In embodiments, Rs is -(C=O)OR_c and Rc is ketal. In embodiments, Rs is -(C=O)OR_c and Rc is amino acid. [0268] In embodiments, R9 is hydrogen, alkyl, or halogen. In embodiments, R9 is hydrogen. In embodiments, R9 is alkyl. In embodiments, R9 is halogen.

[0269] In embodiments, m is an integer from 1-4. In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3. In embodiments, m is 4.

[0270] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)-CH2- NH(alkyl).

[0271] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is - CHR₇-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0272] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)-CH2- NH(alkyl).

[0273] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is - CHR₇-O-(P=O)OR_A(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0274] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)-CH2- NH(alkyl).

[0275] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is - CHR₇-O-(P=O)OR_A(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0276] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)- CH₂-NH(alkyl).

[0277] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR₇-O-(P=O)OR_A(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0278] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)- CH₂-NH(alkyl). [0279] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR₇-O-(P=O)ORA(OR_B) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0280] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is hydrogen, R3 and R4 are absent, and Rio is -CHR₇-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)- CH₂-NH(alkyl).

[0281] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is hydrogen, R3 and R4 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR₇-O-(P=O)OR_A(ORB) or -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl).

[0282] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, and Rio is -CHR₇-O-(P=O)OR_A(OR_B) or -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl).

[0283] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, and R3, R4, and R5 are absent, W is NRe, Re is hydrogen, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR₇-O- (P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl).

[0284] In embodiments, the present disclosure provides a compound of Formula III or pharmaceutically acceptable salts thereof selected from Table 3.

Table 3, Compounds of Formula III of the Present Disclosure

Compounds of Formula IV:

[0285] In embodiments, provided herein is a compound of Formula IV:

Formula IV or a pharmaceutically acceptable salt thereof; wherein,

X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR7-, or -CH2-;

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

R₉ is hydrogen, alkyl, or halogen;

Rio is -CHR₇-O-(P=O)OR_A(ORB), -CHR₇-O-aryl, -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid,

A- is a pharmaceutically acceptable anion.

[0286] In embodiments of Formula IV:

Ri and R2 are each independently hydrogen, alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring; X, Y and Z are each independently hydrogen, halogen, -O-, -S-, -NR₇-, or -CH₂-;

R3, R4, and R5 are each independently absent, hydrogen, alkyl, or -CHR₇(P=O)- ORA(ORB);

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

Ro is hydrogen, alkyl, or halogen;

A- is a pharmaceutically acceptable anion.

[0287] In embodiments, the present disclosure provides for compounds of Formula (IVa):

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R₂ are each methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, C1-C3 alkyl, -CH₂-O- (P=O)ORA(ORB), or -(P=O)-ORA(ORB), wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is -O-;

RIO is -CHR₇-O-(P=O)OR_A(OR_B), -CHR₇-O-aryl, -CH₂-aryl-O(C=O)-CH₂- NH(alkyl), wherein RA and RB are each independently hydrogen or methyl; and A' is a pharmaceutically acceptable anion.

[0288] In embodiments, Ri and R2 are each independently alkyl, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, cycloalkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently hydrogen, alkyl, or cycloalkyl.

[0289] In embodiments, Ri and R2 are each independently hydrogen or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently cycloalkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, Ri and R2 are each independently alkyl or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or cycloalkyl. In embodiments, Ri and R2 are each independently hydrogen or alkyl.

[0290] In embodiments, Ri and R2 are each alkyl. In embodiments, Ri and R2 are each hydrogen. In embodiments, one of Ri and R2 is hydrogen and one of Ri and R2 is alkyl.

[0291] In embodiments, Ri and R2 together with the atoms to which they are attached form a heterocyclic ring. In embodiments, the heterocyclic ring is a monocyclic, bicyclic, tricyclic, or tetracyclic ring. In embodiments, the heterocyclic ring is a monocyclic ring. In embodiments, the heterocyclic ring is a bicyclic ring. In embodiments, the heterocyclic ring is a tricyclic ring. In embodiments, the heterocyclic ring is a tetracyclic ring.

[0292] In embodiments, X, Y and Z are each independently halogen, -O-, -S-, -NR?-,or - CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, - NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -S-, or -NR7-. [0293] In embodiments, X, Y and Z are each independently -O-, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently halogen, -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, -NR7-, or - CH2-. In embodiments, halogen, -O-, -S-, or -CH2-. In embodiments, halogen, -O-, - S-, or -NR7-.

[0294] In embodiments, X, Y and Z are each independently hydrogen, -S-, -NR7-, or -CH2- . In embodiments, X, Y and Z are each independently hydrogen, -O-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, -O-, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -CH2-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -S-, or -NR7-. In embodiments, X, Y and Z are each independently hydrogen, halogen, -O-, or -S-.

[0295] In embodiments, X, Y and Z are each independently -S-, -NR7-, or -CH2-. In embodiments, X, Y and Z are each independently -O-, -NR7-, or-CH2- In embodiments,

[0296] In embodiments, X, Y and Z are each independently hydrogen or halogen. In embodiments, X, Y, and Z are each independently hydrogen or -O-. In embodiments, X,

[0297] In embodiments, X, Y and Z are each independently halogen or -O-. In embodiments, X, Y and Z are each independently halogen or -S-. In embodiments, X, Y and Z are each independently halogen or -NR7-. In embodiments, X, Y and Z are each independently halogen or -CH2-. [0298] In embodiments, X, Y, and Z are each independently -O- or -S-. In embodiments, X, Y, and Z are each independently -O- or -NR7-. In embodiments, Z, Y, and Z are each independently -O- or -CH2-. In embodiments, X, Y, and Z are each independently -S- or -NR7-. In embodiments, Z, Y, and Z are each independently -S- or -CH2-.

[0299] In embodiments, X is hydrogen. In embodiments, X is halogen. In embodiments, X is -O-. In embodiments, X is -S-. In embodiments, X is -NR7-. In embodiments, X is - CH2-.

[0300] In embodiments, Y is hydrogen. In embodiments, Y is halogen. In embodiments, Y is -O-. In embodiments, Y is -S-. In embodiments, Y is -NR7-. In embodiments, Y is - CH2-.

[0301] In embodiments, Y is hydrogen. In embodiments, Z is halogen. In embodiments, Z is -O-. In embodiments, Z is -S-. In embodiments, Z is -NR7-. In embodiments, Z is - CH2-.

[0302] In embodiments, R3, R4, and R5 are each independently hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)- ORA(ORB). In embodiments, R3, R4, and Rs are each independently absent, alkyl, -(C=O)- alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl- (NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-OR_A(OR_B), or - (P=O)-ORA(OR_B). In embodiments, R3, R4, and Rs are each independently absent, hydrogen, -(C=O)-alkyl, -(C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CR?-NH2, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, CHR7(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CHR7-NH2, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)-ORA(OR_B). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇- NH₂, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, - CHR7(P=0)-0RA(0RB), or -(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, -(C=O)CR₇-NH2, -

[0303] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)- alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, or -CHR₇(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH2)-alkyl-NH2, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or -CHR₇(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl- (NH)(C=NH)-NH₂, or -CHR₇(P=O)-ORA(ORB). In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)CH(NH₂)-alkyl-NH₂, -(C=O)CH(NH2)- alkyl-(NH)(C=NH)-NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, or -CHR₇(P=O)- ORA(ORB).

[0304] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -(C=O)CR₇-NH₂. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)CH(NH2)-alkyl-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, or -(C=O)-alkyl-(NH)(C=NH)- NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)-alkyl, or -CHR₇(P=O)-OR_A(OR_B). [0305] In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, - (C=O)CH(NH₂)-alkyl-NH2, or -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2. In embodiments, R3, R4, and R5 are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or -(C=O)-alkyl-(NH)(C=NH)-NH₂. In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(OR_B).

[0306] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, - (C=O)-alkyl.

[0307] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)CR7-NH₂.

[0308] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)CH(NH₂)-alkyl-NH2.

[0309] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (C=O)-alkyl-(NH)(C=NH)-NH₂.

[0310] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - CHR₇(P=O)-ORA(ORB).

[0311] In embodiments, R3, R4, and Rs are each independently absent, hydrogen, alkyl, or - (P=O)-ORA(ORB).

[0312] In embodiments, R3 and R4 are hydrogen and Rs is -CHR₇(P=O)-ORA(ORB).

[0313] In embodiments, R3 and Rs are hydrogen and R4 is -CHR₇(P=O)-ORA(ORB).

[0314] In embodiments, R4 and Rs are hydrogen and R3 is -CHR₇(P=O)-ORA(ORB).

[0315] In embodiments, R3 and R4 are hydrogen and Rs is alkyl.

[0316] In embodiments, R3 and Rs are hydrogen and R4 is alkyl.

[0317] In embodiments, R4 and Rs are hydrogen and R3 is alkyl.

[0318] In embodiments, R3, R4, and Rs are each hydrogen.

[0319] In embodiments, R3 and R4 are hydrogen, Rs is hydrogen, X and Y are absent, and Z is

-O-. [0320] In embodiments, R3 and R4 are hydrogen, R5 is alkyl, X and Y are absent, and Z is -O-

[0321] In embodiments, R3 and R5 are hydrogen, R4 is hydrogen, X and Z are absent, and Y is -O-.

[0322] In embodiments, R3 and R5 are hydrogen, R4 is alkyl, X and Z are absent, and Y is -O-

[0323] In embodiments, R4 and R5 are hydrogen, R3 is hydrogen, Y and Z are absent, and X is -O-.

[0324] In embodiments, R4 and R5 are hydrogen, R3 is alkyl, Y and Z are absent, and X is -O-

[0325] In embodiments, W is oxygen or sulfur. In embodiments, W is oxygen or NRe. In embodiments, W is sulfur or NRe. In embodiments, W is oxygen. In embodiments, W is sulfur. In embodiments, W is NRe.

[0326] In embodiments, Rio is -CHRz-O-aryl, -CHR7-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid. In embodiments, Rio is heteroaryl, alkyl, alkoxy, or amino acid. In embodiments, Rio is alkyl, alkoxy, or amino acid. In embodiments, Rio is alkoxy or amino acid. In embodiments, Rio is -CHR?-O-aryl, -CHR?-aryl-O(C=O)- CH2-NH(alkyl), heteroaryl, alkyl, or alkoxy. In embodiments, Rio is -CHRz-O-aryl, - CHR7-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is - CHR?-O-aryl, -CHR7-aryl-O(C=O)-CH2-NH(alkyl), or heteroaryl. In embodiments, Rio is -CHR?-O-aryl or -CHR7-aryl-O(C=O)-CH2-NH(alkyl). In embodiments, Rio is - CHR7-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, alkyl, or alkoxy. In embodiments, Rio is -CHR7-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is - CHR7-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is - CHR7-aryl-O(C=O)-CH2-NH(alkyl) or heteroaryl. In embodiments, Rio is -CHR7-O- (P=O)ORA(ORB), -CHR7-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, alkyl, or alkoxy. In embodiments, Rio is -CHR₇-O-(P=O)ORA(OR_B), -CHR₇-aryl-O(C=O)-CH2-NH(alkyl), heteroaryl, or alkyl. In embodiments, Rio is -CHR7-O-(P=O)ORA(ORB), -CHR?-aryl- O(C=O)-CH2-NH(alkyl), or heteroaryl. In embodiments, Rio is -CHR7-O- (P=O)ORA(ORB), -CHR?-O-aryl, heteroaryl, alkyl, or alkoxy. In embodiments, Rio is - CHR7-O-(P=O)ORA(ORB), -CHR?-O-aryl, heteroaryl, or alkyl. In embodiments, Rio is -CHR7-O-(P=O)ORA(ORB), -CHR?-O-aryl, or heteroaryl. In embodiments, Rio is - CHR₇-O-(P=O)ORA(ORB), -CHR₇-O-aryl, -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl), alkyl, or alkoxy. In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB), -CHR₇-O-aryl, - CHR₇-aryl-O(C=O)-CH2-NH(alkyl), or alkyl.

[0327] In embodiments, Rio is hydrogen. In embodiments, Rio is alkyl. In embodiments, Rio is -CHR₇-O-(P=O)OR_A(ORB), -CHR₇-O-aryl, or -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl). In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB) or -CHR₇-O-aryl. In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl). In embodiments, Rio is -CHR₇-O-aryl or -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl).

[0328] In embodiments, Rio is -CHR₇-O-(P=O)ORA(ORB). In embodiments, Rio is -CHR₇- O-aryl. In embodiments, Rio is -CHR₇-aryl-O(C=O)-CH₂-NH(alkyl). In embodiments, Rio is heteroaryl. In embodiments, Rio is alkyl. In embodiments, Rio is alkoxy. In embodiments, Rio is amino acid.

[0329] In embodiments, R₇ is hydrogen. In embodiments, R₇ is alkyl. In embodiments, R₇ is a Ci-Ce alkyl. In embodiments, R₇ is a Ci alkyl. In embodiments, R₇ is a C₂ alkyl. In embodiments, R₇ is a C3 alkyl.

[0330] In embodiments, RA, RB, and R_c are each independently alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, alkoxy, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, hemiacetal, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, ketal, or an amino acid. In embodiments, RA, RB, and R_c are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or an amino acid. In embodiments, RA, RB, and Rc are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, or ketal.

[0331] In embodiments, RA, RB, and Rc are each hydrogen. In embodiments, RA and R_c are each hydrogen. In embodiments, RA and RB are each hydrogen. In embodiments, RB and Rc are each hydrogen. [0332] In embodiments, RA, RB, and R_c are each alkyl. In embodiments, RA and Re are each alkyl. In embodiments, RA and RB are each alkyl. In embodiments, RB and R_c are each alkyl.

[0333] In embodiments, RA is hydrogen. In embodiments, RB is hydrogen. In embodiments, Rc is hydrogen.

[0334] In embodiments, RA is hydrogen and RB is alkyl. In embodiments, RA is alkyl and RB is hydrogen.

[0335] In embodiments, Rc is hydrogen. In embodiments Rc is alkyl.

[0336] In embodiments, Rs is hydrogen, alkyl, or -(C=O)ORc.

[0337] In embodiments, Rs is hydrogen. In embodiments, Rs is alkyl. In embodiments, Rs is Ci-Ce alkyl. In embodiments, Rs is Ci alkyl. In embodiments, Rs is C2 alkyl. In embodiments, Rs is C3 alkyl. In embodiments, Rs is a C4 alkyl. In embodiments, Rs is C5 alkyl. In embodiments, Rs is Ce alkyl.

[0338] In embodiments, Rs is -(C=O)OR_c. In embodiments, Rs is -(C=O)ORc and Rc is hydrogen. In embodiments, Rs is -(C=O)ORc and Rc is alkyl. In embodiments, Rs is - (C=O)OR_c and R_c is heteroalkyl. In embodiments, Rs is -(C=O)ORc and R_c is cycloalkyl. In embodiments, Rs is -(C=O)OR_c and Rc is alkoxy. In embodiments, Rs is -(C=O)ORc and Rc is hemiacetal. In embodiments, Rs is -(C=O)OR_c and Rc is ketal. In embodiments, Rs is -(C=O)OR_c and Rc is amino acid.

[0339] In embodiments, R9 is hydrogen, alkyl, or halogen. In embodiments, R9 is hydrogen. In embodiments, R9 is alkyl. In embodiments, R9 is halogen.

[0340] In embodiments, m is an integer from 1-4. In embodiments, m is 1. In embodiments, m is 2. In embodiments, m is 3. In embodiments, m is 4.

[0341] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and Rs are absent, and Rio is -CHR?-O-(P=O)ORA(ORB) or -CHR?-aryl-O(C=O)-CH2- NH(alkyl).

[0342] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is alkyl, R3 and R5 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR?-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl). [0343] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)-CH2- NH(alkyl).

[0344] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is alkyl, R4 and R5 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0345] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)-CH2- NH(alkyl).

[0346] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is alkyl, R3 and R4 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0347] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)- CH₂-NH(alkyl).

[0348] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, Y is -O-, R4 is hydrogen, R3 and R5 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR7-O- (P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0349] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and R5 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)- CH₂-NH(alkyl).

[0350] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, X is -O-, R3 is hydrogen, R4 and R5 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR7-O- (P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0351] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is hydrogen, R3 and R4 are absent, and Rio is -CHR7-O-(P=O)ORA(ORB) or -CHR7-aryl-O(C=O)- CH₂-NH(alkyl).

[0352] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, Z is -O-, R5 is hydrogen, R3 and R4 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR7-O- (P=O)ORA(ORB) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl). [0353] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, R3, R4, and R5 are absent, and Rio -CHR₇-O-(P=O)ORA(OR_B) or -CHR₇-aryl-O(C=O)-CH2-NH(alkyl).

[0354] In embodiments, Ri and R2 are alkyl, X, Y, and Z are hydrogen, and R3, R4, and R5 are absent, Rs is hydrogen, R9 is hydrogen, and Rio is -CHR₇-O-(P=O)ORA(ORB) or -CHR₇- aryl-O(C=O)-CH₂-NH(alkyl).

[0355] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, R3 and R5 are absent, Y is -O-, R4 is -CHR₇-O-(P=O)ORA(ORB), and Rio is hydrogen.

[0356] In embodiments, Ri and R2 are alkyl, X and Z are hydrogen, R3 and R5 are absent, Y is -O-, R4 is -CHR₇-O-(P=O)ORA(ORB), RS is hydrogen, R9 is hydrogen, and Rio is hydrogen.

[0357] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, R3 and R4 are absent, Z is -O-, R5 is -CHR₇-O-(P=O)ORA(ORB) and Rio is hydrogen.

[0358] In embodiments, Ri and R2 are alkyl, X and Y are hydrogen, R3 and R4 are absent, Z is -O-, R5 is -CHR₇-O-(P=O)ORA(ORB), RS is hydrogen, R9 is hydrogen, and Rio is hydrogen.

[0359] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, R4 and R5 are absent, X is -O-, R3 is -CHR₇-O-(P=O)ORA(ORB) and Rio is hydrogen.

[0360] In embodiments, Ri and R2 are alkyl, Y and Z are hydrogen, R4 and R5 are absent, X is -O-, R3 is -CHR₇-O-(P=O)ORA(ORB), RS is hydrogen, R9 is hydrogen, and Rio is hydrogen.

[0361] In embodiments, the present disclosure provides a compound of Formula IV or pharmaceutically acceptable salts thereof selected from Table 4.

Table 4, Compounds of Formula IV of the Present Disclosure

Compositions

[0362] In embodiments of the present disclosure, a pharmaceutical composition comprises a therapeutically effective amounts of one or more compounds of the present disclosure (e.g., a compound of Formula I, II, III, IV or Table 1-4) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. [0363] The pharmaceutically acceptable excipients and adjuvants are added to the composition or formulation for a variety of purposes. In embodiments, a pharmaceutical composition comprising one or more compounds disclosed herein, or a pharmaceutically acceptable salt thereof, further comprise a pharmaceutically acceptable carrier. In embodiments, a pharmaceutically acceptable carrier includes a pharmaceutically acceptable excipient, binder, and/or diluent. In embodiments, suitable pharmaceutically acceptable carriers include, but are not limited to, inert solid fillers or diluents and sterile aqueous or organic solutions. In embodiments, suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylase, magnesium stearate, talc, silicic acid, viscous paraffin, and the like.

[0364] For the purposes of this disclosure, the compounds of the present disclosure can be formulated for administration by a variety of means including orally, parenterally, by inhalation spray, topically, or rectally in formulations containing pharmaceutically acceptable carriers, adjuvants and vehicles. The term parenteral as used here includes subcutaneous, intravenous, intramuscular, and intraarterial injections with a variety of infusion techniques. Intraarterial and intravenous injection as used herein includes administration through catheters.

Methods

[0365] In one aspect, the present disclosure provides methods of treating or preventing neurological disorders in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject.

[0366] In embodiments, the neurological disorder is a mood disorder. In embodiments, the mood disorder is clinical depression, postnatal depression or postpartum depression, perinatal depression, atypical depression, melancholic depression, psychotic major depression, cationic depression, seasonal affective disorder, dysthymia, double depression, depressive personality disorder, recurrent brief depression, major depressive disorder, minor depressive disorder, bipolar disorder or manic depressive disorder, depression caused by chronic medical conditions, treatment-resistant depression, refractory depression, suicidality, suicidal ideation, or suicidal behavior. In embodiments, the method described herein provides therapeutic effect to a subject suffering from depression (e.g., moderate or severe depression). In embodiments, the mood disorder is associated with neuroendocrine diseases and disorders, neurodegenerative diseases and disorders (e.g., epilepsy), movement disorders, tremor (e.g., Parkinson's Disease), or women's health disorders or conditions. In embodiments, the mood disorder is depression. In embodiments, the mood disorder is treatment-resistant depression or major depressive disorder. In embodiments, the mood disorder is major depressive disorder. In embodiments, the mood disorder is treatment-resistant depression.

[0367] In embodiments, the present disclosure provides methods of treating or preventing PTSD, mood disorders, general anxiety disorder, addictive disorders, and/or drug dependence in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject.

[0368] In embodiments, the present disclosure provides methods of treating or preventing PTSD in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject.

[0369] In embodiments, the methods include treating PTSD through induction and maintenance therapy by administering a compound disclosed herein, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In embodiments, the compounds of the present disclosure are used for induction and maintenance therapy to treat PTSD with an improved safety profile when compared to treatment with the entactogenic, oneirophrenic or psychedelic compound (e.g., dimethyltryptamine or related compound, psilocybin, or MDMA) alone.

[0370] In embodiments, the present disclosure provides methods of treating or preventing behavioral or mood disorders in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject. In embodiments, the behavioral or mood disorder includes anxiety, such as social anxiety in autistic subjects (e.g., autistic adults) and anxiety related to life-threatening illnesses. In embodiments, the behavioral or mood disorder includes stress (where moderation thereof is measured, e.g., by effects on amygdala responses). In embodiments, the anxiety disorder is panic disorder, obsessive-compulsive disorder, and/or general anxiety disorder. In embodiments, the subject suffers from a lack of motivation, attention, lack of accuracy in memory recall, speed of response, perseveration, and/or cognitive engagement. Further examples include depression (e.g., MDD or TRD), attention disorders, disorders of executive function and/or cognitive engagement, obsessive compulsive disorder, bipolar disorder, panic disorder, phobia, schizophrenia, psychopathy, antisocial personality disorder and/or neurocognitive disorders.

[0371] In embodiments, the present disclosure provides methods for treating an addictive disorder in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject. In embodiments, the addictive disorder is alcohol abuse, substance abuse, smoking, obesity, or mixtures thereof. In embodiments, the disorder is an eating disorder (e.g., anorexia nervosa, bulimia, nervosa, binge eating disorder, etc.) or an auditory disorder.

[0372] In embodiments, the present disclosure provides methods for treating an impulsive disorder in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject. In embodiments, the impulsive disorder is attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), Tourette’s syndrome, autism, or combinations thereof.

[0373] In embodiments, the present disclosure provides methods for treating a compulsive disorder in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to the subject. In embodiments, the compulsive disorder is obsessive compulsive disorder (OCD), gambling, aberrant sexual behavior, or combinations thereof.

[0374] In embodiments, the present disclosure provides methods for treating a personality disorder in a subject in need thereof, the methods comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula I, Formula II, Formula III, Formula IV, or Compounds of Tables 1-4), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In embodiments, the personality disorder is conduct disorder, antisocial personality, aggressive behavior, or combinations thereof to the subject.

[0375] The present disclosure also provides for the following embodiments:

Embodiment 1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof; wherein,

R3, R4, and R5 are each independently absent, hydrogen, alkyl, -(C=O)-alkyl, - (C=O)CR₇-NH₂, -(C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)- NH₂, -(C=O)-alkyl-(NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(OR_B), or -(P=O)- ORA(ORB);

W is oxygen, sulfur or NRe;

Re is absent, hydrogen, alkyl, -CHR₇-(P=O)-ORA(ORB), -CHR₇-O(C=O)-alkyl- (C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇- O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH₂- heterocyclic ring, -(C=O)-alkyl, -(C=O)CR7-NH2-(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)-alkyl-(NH)(C=NH)-NH₂;

R7 is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

R₉ is hydrogen, alkyl, or halogen;

RA, RB, and Re are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or an amino acid; and m is an integer from 1-4, and wherein, when Rs is hydrogen or alkyl: at least one of R3, R4, and R5 is -(C=O)-alkyl, -(C=O)CR?-NH2, - (C=O)CH(NH₂)-alkyl-NH2, -(C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, -(C=O)-alkyl- (NH)(C=NH)-NH₂, -CHR₇(P=O)-ORA(ORB), or -(P=O)-OR_A(OR_B); or

W is NR₆ and Re is -CHR₇-(P=O)-ORA(OR_B), -CHR₇-O(C=O)-alkyl- (C=O)OR_c, -CHR₇-O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇- O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, -CHR₇-O(C=O)-aryl-CH₂- heterocyclic ring, -(C=O)-alkyl, -(C=O)CR?-NH2 ,-(C=O)CH(NH2)-alkyl-NH2, - (C=O)CH(NH₂)-alkyl-(NH)(C=NH)-NH2, or -(C=O)-alkyl-(NH)(C=NH)-NH₂.

Embodiment 2. A compound of Formula (la):

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are each both are methyl;

X, Y, and Z are each either absent or -O-; R3, R4, and Rs are each independently absent, hydrogen, C1-C3 alkyl, or - CH2-(P=O)-(OH)2, wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when Rs is present Z is -O-;

Re is hydrogen, -CHR₇-(P=O)-ORA(OR_B), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl- N(alkyl)₂, -CHR₇-O(C=O)-aryl, or -CH2-O(C=O)-aryl-CH2-heterocyclic ring, wherein R₇ is hydrogen or methyl, and RA, R_B, and Re are each independently hydrogen or methyl; and wherein at least one of R3, R4, Rs, and Re are present and non-hydrogen, and wherein Re is H, at least one of R4 and Rs are -CHR7-(P=0)-0RA(0RB), and R3 is not -CH₂-(P=O)-OH(OH).

Embodiment 3. The compound of embodiment 1 or embodiment 2, wherein X is hydrogen and R3 is absent.

Embodiment 4. The compound of embodiment 1 or embodiment 2, wherein Y is hydrogen and R4 is absent.

Embodiment 5. The compound of embodiment 1 or embodiment 2, wherein Z is hydrogen and Rs is absent.

Embodiment 6. The compound of embodiment 1 or embodiment 2, wherein X is -O- and R3 is alkyl.

Embodiment 7. The compound of embodiment 1 or embodiment 2, wherein Y is -O- and R4 is alkyl.

Embodiment 8. The compound of embodiment 1 or embodiment 2, wherein Z is -O- and Rs is alkyl.

Embodiment 9. The compound of embodiment 1 or embodiment 2, wherein X is -O- and R3 is hydrogen.

Embodiment 10. The compound of embodiment 1 or embodiment 2, wherein Y is -O- and R4 is hydrogen.

Embodiment 11. The compound of embodiment 1 or embodiment 2, wherein Z is -O- and Rs is hydrogen.

Embodiment 12. The compound of embodiment 1 or embodiment 2, wherein X is -O- and R₃ is -CHR₇(P=O)-OR_A(OR_B). Embodiment 13. The compound of embodiment 1 or embodiment 2, wherein Y is -Gland R₄ is -CHR₇(P=O)-OR_A(ORB).

Embodiment 14. The compound of embodiment 1 or embodiment 2, wherein Z is -Gland R₅ is -CHR₇(P=O)-OR_A(ORB).

Embodiment 15. The compound of any one of embodiments 12 to 14, wherein RA and

RB are hydrogen.

Embodiment 16. The compound of any one of embodiments 12 to 15, wherein R? is hydrogen.

Embodiment 17. The compound of any of embodiments 1-16, wherein W is NRe.

Embodiment 18. The compound of embodiment 17, wherein Re is -CHR7-(P=0)-

ORA(ORB).

Embodiment 19. The compound of embodiment 18, wherein RA and RB hydrogen.

Embodiment 20. The compound of embodiment 17, wherein Re is -CHR7-0(C=0)- alkyl-(C=O)OR<

Embodiment 21. The compound of embodiment 20, wherein Rc is hydrogen.

Embodiment 22. The compound of embodiment 17, wherein Re is -CHR7-O(C=O)- alkyl-N⁺(alkyl)3.

Embodiment 23. The compound of embodiment 22, wherein the alkyl is a Ci-Ce alkyl.

Embodiment 24. The compound of embodiment 23, wherein the alkyl is a methyl.

Embodiment 25. The compound of embodiment 17, wherein Re is -CHR7-O(C=O)- alkyl-N(alkyl)2.

Embodiment 26. The compound of embodiment 25, wherein the alkyl is a Ci-Ce alkyl.

Embodiment 27. The compound of embodiment 26, wherein the alkyl is a methyl.

Embodiment 28. The compound of embodiment 17, wherein Re is -CHR7-O(C=O)- aryl.

Embodiment 29. The compound of any one of embodiments 18 to 28, wherein R? is hydrogen.

Embodiment 30. The compound of any one of embodiments 1 to 29, wherein m is 1.

Embodiment 31. The compounds of any one of embodiments 1 to 30, wherein Ri and R2 are each independently hydrogen or alkyl.

Embodiment 32. The compounds of any one of embodiments 1 to 31, wherein Ri and R2 are alkyl. Embodiment 33. The compound of embodiment 1, wherein the compound is:

Embodiment 34. The compound of embodiment 1, having the structure of Formula III:

Formula III, or a pharmaceutically acceptable salt thereof; wherein,

Rio is hydrogen, alkyl, -CHR7-0-(P=0)0RA(0RB), -CHRz-O-aryl, -CHR?-aryl- O(C=O)-CH2-NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid;

RA and RB are each independently hydrogen, alkyl, heteroalkyl, cycloalkyl, alkoxy, hemiacetal, ketal, or am amino acid; and

A' is a pharmaceutically acceptable anion.

Embodiment 35. A compound of embodiment 1, having the structure of Formula Illa:

(Illa), or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, or C1-C3 alkyl, wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is - O-; Rio is -CHR₇-O-(P=O)ORA(ORB), -CH₂-O-aryl, -CH₂-aryl-O(C=O)-CH₂-

NH(alkyl), wherein RA and RB are each independently hydrogen or methyl;

R? is hydrogen or alkyl; and

Embodiment 36. The compound of embodiment 34 or 35, wherein Rw is -CHR7-O- (P=O)ORA(OR_B).

Embodiment 37. The compound of embodiment 36, wherein RA and RB are hydrogen.

Embodiment 38. The compound of embodiment 36 or 37, wherein R7 is hydrogen.

Embodiment 39. The compound of embodiment 34 or 35, wherein Rw is -CHR7-O- aryl.

Embodiment 40. The compound of embodiment 39, wherein R7 is hydrogen.

Embodiment 41. The compound of any of embodiments 34 to 40, wherein the pharmaceutically acceptable salt is a sodium (Na⁺) or an ammonium (NH ) salt.

Embodiment 42. The compound of any of embodiments 34 to 41, wherein X is hydrogen and R3 is absent.

Embodiment 43. The compound of any of embodiments 34 to 42, wherein Y is hydrogen and R4 is absent.

Embodiment 44. The compound of any of embodiments 34 to 43, wherein Z is hydrogen and Rs is absent.

Embodiment 45. The compound of any of embodiments 34 to 44, wherein X is -O- and

R3 is alkyl.

Embodiment 46. The compound of any of embodiments 34 to 45, wherein Y is -O- and

R4 is alkyl.

Embodiment 47. The compound of any of embodiments 34 to 46, wherein Z is -O- and

Rs is alkyl.

Embodiment 48. The compound of any of embodiments 34 to 47, wherein X is -O- and

R3 is hydrogen.

Embodiment 49. The compound of any of embodiments 34 to 48, wherein Y is -O- and

R4 is hydrogen. Embodiment 50. The compound of any of embodiments 34 to 49, wherein Z is -O- and Rs is hydrogen.

Embodiment 51. The compound of any of embodiments 34 to 50, wherein Ri and R2 are each independently hydrogen or alkyl.

Embodiment 52. The compounds of any one of embodiments 34 to 51, wherein Ri and R2 are alkyl (such as methyl).

Embodiment 53. The compound embodiment 34, wherein the compound is:

Embodiment 54. A compound of Formula IV:

or a pharmaceutically acceptable salt thereof; wherein, Ri and R2 are each independently hydrogen, alkyl, cycloalkyl, -or Ri and R2 together with the atoms to which they are attached form a heterocyclic ring;

R₇ is hydrogen or alkyl;

Rs is hydrogen, alkyl, or -(C=O)ORc;

R₉ is hydrogen, alkyl, or halogen;

Rio is -CHR₇-O-(P=O)OR_A(ORB), -CHR₇-O-aryl, -CHR₇-aryl-O(C=O)-CH₂- NH(alkyl), heteroaryl, alkyl, alkoxy, or amino acid;

A' is a pharmaceutically acceptable anion.

Embodiment 55. A compound of Formula (IVa):

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are each methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, C1-C3 alkyl, -CH2-O- (P=O)ORA(ORB), or -(P=O)-ORA(ORB), wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is -O-; RIO is -CHR₇-O-(P=O)OR_A(OR_B), -CHR₇-O-aryl, -CH2-aryl-O(C=O)-CH₂-

NH(alkyl), wherein RA and RB are each independently hydrogen or methyl; and

A' is a pharmaceutically acceptable anion.

Embodiment 56. The compound of embodiment 54 or 55, wherein X is hydrogen and R3 is absent.

Embodiment 57. The compound of any of embodiments 54 to 56, wherein Y is hydrogen and R4 is absent.

Embodiment 58. The compound of any of embodiments 54 to 57, wherein Z is hydrogen and Rs is absent.

Embodiment 59. The compound of any of embodiments 54 to 58, wherein X is -O- and

R3 is alkyl.

Embodiment 60. The compound of any of embodiments 54 to 59, wherein Y is -O- and

R₄ is alkyl.

Embodiment 61. The compound of any of embodiments 54 to 60, wherein Z is -O- and

Rs is alkyl.

Embodiment 62. The compound of any of embodiments 54 to 61, wherein X is -O- and R3 is hydrogen.

Embodiment 63. The compound of any of embodiments 54 to 62, wherein Y is -O- and R₄ is hydrogen.

Embodiment 64. The compound of any of embodiments 54 to 63, wherein Z is -O- and Rs is hydrogen.

Embodiment 65. The compound of any of embodiments 54 to 64, wherein X is -O- and R₃ is -CHR₇(P=O)-OR_A(ORB).

Embodiment 66. The compound of any of embodiments 54 to 65, wherein Y is -O- and R₄ is -CHR₇(P=O)-ORA(OR_B).

Embodiment 67. The compound of any of embodiments 54 to 66, wherein Z is -O- and R₅ is -CHR₇(P=O)-ORA(ORB).

Embodiment 68. The compound of any of embodiments 54 to 67, wherein X is -O- and R₃ is -(P=O)-OR_A(ORB).

Embodiment 69. The compound of any of embodiments 54 to 68, wherein Y is -O- and R₄ is -(P=O)-OR_A(ORB).

Embodiment 70. The compound of any of embodiments 54 to 69, wherein Z is -O- and R₅ is -(P=O)-OR_A(ORB). Embodiment 71. The compound of any one of embodiments 54 to 70, wherein RA and RB are hydrogen.

Embodiment 72. The compound of any one of embodiments 54 to 71, wherein R7 is hydrogen.

Embodiment 73. The compound of any of embodiments 54 to 72, wherein Ri and R2 are each independently hydrogen or alkyl.

Embodiment 74. The compounds of any one of embodiments 54 to 73, wherein Ri and R2 are alkyl, such as methyl.

Embodiment 75. The compound of any of embodiments 54 to 74, wherein Rio is -CHR7- O-(P=O)ORA(ORB).

Embodiment 76. The compound of any of embodiments 54 to 74, wherein Rio is -CHR7- O-aryl.

Embodiment 77. The compound of embodiment 54, wherein the compound is:

Embodiment 78. The compound of embodiment 1, having the structure of Formula II:

Formula II.

Embodiment 79. A compound of embodiment 1, having the structure of Formula Ila:

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and Rs are each independently absent, hydrogen, or C1-C3 alkyl, wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when Rs is present Z is - O-;

Re is hydrogen or C1-C3 alkyl, wherein at least one of R3, R4, and Rs are present and non-hydrogen, and wherein when Re is H, at least one of XR3 and ZRs are -O-(Ci-C3 alkyl).

Embodiment 80. The compound of embodiment 79, wherein at least two of R3, R4, Rs, and R_c are present and non-hydrogen. Embodiment 81. The compound of embodiment 79, wherein at least two of R3, R4, Rs are present and non-hydrogen.

Embodiment 82. The compound of embodiment 78, wherein m is 1.

Embodiment 83. The compound of any of embodiments 78-82, wherein Re is H.

Embodiment 84. The compound of any of embodiments 78-82, wherein Re is alkyl.

Embodiment 85. The compound of any of embodiments 78-84, wherein X is hydrogen and R3 is absent.

Embodiment 86. The compound of any of embodiments 78-85, wherein Y is hydrogen and R4 is absent.

Embodiment 87. The compound of any of embodiments 78-86, wherein Z is hydrogen and Rs is absent.

Embodiment 88. The compound of any of embodiments 78-87, wherein X is -O- and

R3 is alkyl.

Embodiment 89. The compound of any of embodiments 78-88, wherein Y is -O- and

R4 is alkyl.

Embodiment 90. The compound of any of embodiments 78-89, wherein Z is -O- and Rs is alkyl.

Embodiment 91. The compound of any of embodiments 78-90, wherein X is -O- and

R3 is hydrogen.

Embodiment 92. The compound of any of embodiments 78-91, wherein Y is -O- and

R4 is hydrogen.

Embodiment 93. The compound of any of embodiments 78-92, wherein Z is -O- and Rs is hydrogen.

Embodiment 94. The compounds of any one of embodiments 78 to 93, wherein Ri and R2 are each independently hydrogen or alkyl.

Embodiment 95. The compounds of any one of embodiments 78 to 94, wherein Ri and

R2 are alkyl.

Embodiment 96. The compound of embodiment 34, wherein the compound is:

Embodiment 97. A composition comprising a therapeutically effective amount of at least one compound of any of embodiments 1 to 96.

Embodiment 98. The composition of embodiment 97, further comprising a pharmaceutically acceptable excipient.

Embodiment 99. An oral dosage form comprising the composition of embodiments 96 and 97.

Embodiment 100. A method of treating post-traumatic stress disorder (PTSD) in a subject in need thereof, comprising administering a compound of any of embodiments 1 to 96 or a composition of any of embodiments 97 to 99 to the subject.

Embodiment 101. A method of treating depression in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of any of embodiments 1 to 96 or a composition of any of embodiments 97 to 99 to the subject.

Embodiment 102. The method of embodiment 101, wherein the depression is a major depressive disorder (MDD) or treatment-resistant depression (TRD).

Embodiment 103. A method of treating an anxiety disorder in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of any of embodiments 1 to 96 or a composition of any of embodiments 97 to 99 to the subject.

Claims

CLAIMS What is claimed:

1. A compound of Formula (la):

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are each both are methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, C1-C3 alkyl, or -CH2-(P=O)-(OH)2, wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is -O-;

Re is hydrogen, -CHR₇-(P=O)-ORA(OR_B), -CHR₇-O(C=O)-alkyl-(C=O)ORc, -CHR₇- O(C=O)-alkyl-N⁺(alkyl)₃, -CHR₇-O(C=O)-alkyl-NH₂, -CHR₇-O(C=O) -alkyl-N(alkyl)₂, -CHR₇-O(C=O)-aryl, or -CH2-O(C=O)-aryl-CH2-heterocyclic ring, wherein R₇ is hydrogen or methyl, and RA, RB, and R_c are each independently hydrogen or methyl; and wherein at least one of R3, R4, Rs, and Re are present and non-hydrogen, and wherein Re is H, at least one of R4 and Rs are -CHR₇-(P=O)-ORA(ORB), and R3 is not -CH2- (P=O)-OH(OH).

2. The compound of claim 1, wherein X is hydrogen and R3 is absent.

3. The compound of claim 1, wherein Y is hydrogen and R4 is absent.

4. The compound of claim 1, wherein Z is hydrogen and Rs is absent.

5. The compound of claim 1, wherein X is -O- and R3 is alkyl.

6. The compound of claim 1, wherein Y is -O- and R4 is alkyl.

7. The compound of claim 1, wherein Z is -O- and Rs is alkyl.

8. The compound of claim 1, wherein X is -O- and R3 is hydrogen.

9. The compound of claim 1, wherein Y is -O- and R4 is hydrogen.

10. The compound of claim 1, wherein Z is -O- and Rs is hydrogen.

11. The compound of claim 1, wherein X is -O- and R3 is -CHR7(P=O)-ORA(ORB).

12. The compound of claim 1, wherein Y is -O- and R4 is -CHR7(P=O)-ORA(ORB).

13. The compound of claim 1, wherein Z is -O- and Rs is -CHR7(P=O)-ORA(ORB).

14. The compound of any one of claims 11 to 13, wherein RA and RB are hydrogen.

15. The compound of any one of claims 11 to 14, wherein R7 is hydrogen.

16. The compound of any of claims 1-15, wherein W is NRe.

17. The compound of claim 16, wherein Re is -CHR7-(P=O)-ORA(ORB).

18. The compound of claim 17, wherein RA and RB hydrogen.

19. The compound of claim 16, wherein Re is -CHR7-O(C=O)-alkyl-(C=O)ORc.

20. The compound of claim 19, wherein Rc is hydrogen.

21. The compound of claim 16, wherein Re is -CHR7-O(C=O)-alkyl-N⁺(alkyl)3.

22. The compound of claim 21, wherein the alkyl is a Ci-Ce alkyl.

23. The compound of claim 22, wherein the alkyl is a methyl.

24. The compound of claim 16, wherein Re is -CHR7-O(C=O)-alkyl-N(alkyl)2.

25. The compound of claim 24, wherein the alkyl is a Ci-Ce alkyl.

26. The compound of claim 25, wherein the alkyl is a methyl.

27. The compound of claim 16, wherein Re is -CHR7-O(C=O)-aryl.

28. The compound of any one of claims 17 to 27, wherein R7 is hydrogen.

29. The compound of any one of claims 1 to 28, wherein m is 1.

30. The compounds of any one of claims 1 to 29, wherein Ri and R2 are each independently hydrogen or alkyl.

31. The compounds of any one of claims 1 to 30, wherein Ri and R2 are alkyl.

32. The compound of claim 1, wherein the compound is:

33. A compound of claim 1, having the structure of Formula Illa:

(Illa), or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, or C1-C3 alkyl, wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is -O-;

Rio is -CHR₇-O-(P=O)ORA(OR_B), -CH₂-O-aryl, -CH₂-aryl-O(C=O)-CH₂-NH(alkyl), wherein RA and RB are each independently hydrogen or methyl;

R7 is hydrogen or alkyl; and

A' is a pharmaceutically acceptable anion, wherein when Rio is -CHR7-0-(P=0)0H(0H), at least one of R3, R4, and R5 are present, and XR3 and ZR5 are not -OH, and YR4 is not -OCH3.

34. The compound of claim 33, wherein Rio is -CHR7-0-(P=0)0RA(0RB).

35. The compound of claim 34, wherein RA and RB are hydrogen.

36. The compound of claim 34 or 35, wherein R7 is hydrogen.

37. The compound of claim 33, wherein Rio is -CHR₇-O-aryl.

38. The compound of claim 37, wherein R7 is hydrogen.

39. The compound of any of claims 33 to 38, wherein the pharmaceutically acceptable salt is a sodium (Na⁺) or an ammonium (NH4⁺) salt.

40. The compound of any of claims 33 to 39, wherein X is hydrogen and R3 is absent.

41. The compound of any of claims 33 to 40, wherein Y is hydrogen and R4 is absent.

42. The compound of any of claims 33 to 41, wherein Z is hydrogen and R5 is absent.

43. The compound of any of claims 33 to 42, wherein X is -O- and R3 is alkyl.

44. The compound of any of claims 33 to 43, wherein Y is -O- and R4 is alkyl.

45. The compound of any of claims 33 to 44, wherein Z is -O- and R5 is alkyl.

46. The compound of any of claims 33 to 45, wherein X is -O- and R3 is hydrogen.

47. The compound of any of claims 33 to 46, wherein Y is -O- and R4 is hydrogen.

48. The compound of any of claims 33 to 47, wherein Z is -O- and R5 is hydrogen.

49. The compound of any of claims 33 to 48, wherein Ri and R₂ are each independently hydrogen or alkyl.

50. The compounds of any one of claims 33 to 49, wherein Ri and R2 are alkyl (such as methyl).

51. The compound claim 33, wherein the compound is:

52. A compound of Formula (IVa):

or a pharmaceutically acceptable salt thereof, wherein:

Ri and R2 are each methyl;

X, Y, and Z are each either absent or -O-;

R3, R4, and R5 are each independently absent, hydrogen, C1-C3 alkyl, -CH2-O- (P=O)ORA(ORB), or -(P=O)-ORA(ORB), wherein when R3 is present X is -O-, when R4 is present Y is -O-, and when R5 is present Z is -O-; Rio is -CHR₇-O-(P=O)ORA(ORB), -CHR₇-O-aryl, -CH2-aryl-O(C=O)-CH₂-NH(alkyl), wherein RA and RB are each independently hydrogen or methyl; and

A' is a pharmaceutically acceptable anion.

53. The compound of claim 52, wherein X is hydrogen and R3 is absent.

54. The compound of any of claims 52 or 53, wherein Y is hydrogen and R4 is absent.

55. The compound of any of claims 52 to 54, wherein Z is hydrogen and R5 is absent.

56. The compound of any of claims 52 to 55, wherein X is -O- and R3 is alkyl.

57. The compound of any of claims 52 to 56, wherein Y is -O- and R4 is alkyl.

58. The compound of any of claims 52 to 57, wherein Z is -O- and R5 is alkyl.

59. The compound of any of claims 52 to 58, wherein X is -O- and R3 is hydrogen.

60. The compound of any of claims 52 to 59, wherein Y is -O- and R4 is hydrogen.

61. The compound of any of claims 52 to 60, wherein Z is -O- and R5 is hydrogen.

62. The compound of any of claims 52 to 61, wherein X is -O- and R3 is -CHR₇(P=O)-

ORA(ORB).

63. The compound of any of claims 52 to 62, wherein Y is -O- and R4 is -CHR₇(P=O)- ORA(ORB).

64. The compound of any of claims 52 to 63, wherein Z is -O- and R5 is -CHR₇(P=O)- ORA(ORB).

65. The compound of any of claims 52 to 64, wherein X is -O- and R3 is -(P=O)- ORA(ORB).

66. The compound of any of claims 52 to 65, wherein Y is -O- and R4 is -(P=O)- ORA(ORB).

67. The compound of any of claims 52 to 66, wherein Z is -O- and R5 is -(P=O)- ORA(ORB).

68. The compound of any one of claims 52 to 67, wherein RA and RB are hydrogen.

69. The compound of any one of claims 52 to 68, wherein R₇ is hydrogen.

70. The compound of any of claims 52 to 69, wherein Ri and R2 are each independently hydrogen or alkyl.

71. The compounds of any one of claims 52 to 70, wherein Ri and R2 are alkyl, such as methyl.

72. The compound of any of claims 52 to 71, wherein Rw is -CHR₇-O-(P=O)ORA(ORB).

73. The compound of any of claims 52 to 71, wherein Rw is -CHRy-O-aryl.

74. The compound of claim 52, wherein the compound is:

75. A compound of claim 1, having the structure of Formula Ila:

or a pharmaceutically acceptable salt thereof, wherein: Ri and R2 are methyl;

X, Y, and Z are each either absent or -O-;

76. The compound of claim 75, wherein at least two of R3, R4, Rs, and Re are present and non-hydrogen.

77. The compound of claim 75, wherein at least two of R3, R4, Rs are present and nonhydrogen.

78. The compound of any of claims 75-77, wherein Re is H.

79. The compound of any of claims 75-78, wherein Re is alkyl.

80. The compound of any of claims 75-79, wherein X is hydrogen and R3 is absent.

81. The compound of any of claims 75-80, wherein Y is hydrogen and R4 is absent.

82. The compound of any of claims 75-81, wherein Z is hydrogen and Rs is absent.

83. The compound of any of claims 75-82, wherein X is -O- and R3 is alkyl.

84. The compound of any of claims 75-83, wherein Y is -O- and R4 is alkyl.

85. The compound of any of claims 75-84, wherein Z is -O- and Rs is alkyl.

86. The compound of any of claims 75-85, wherein X is -O- and R3 is hydrogen.

87. The compound of any of claims 75-86, wherein Y is -O- and R4 is hydrogen.

88. The compound of any of claims 75-87, wherein Z is -O- and Rs is hydrogen.

89. The compounds of any one of claims 75 to 88, wherein Ri and R2 are each independently hydrogen or alkyl.

90. The compounds of any one of claims 75 to 89, wherein Ri and R2 are alkyl.

91. The compound of claim 75, wherein the compound is:

92. A composition comprising a therapeutically effective amount of at least one compound of any of claims 1 to 91.

93. The composition of claim 92, further comprising a pharmaceutically acceptable excipient.

94. An oral dosage form comprising the composition of claims 92 or 93.

95. A method of treating post-traumatic stress disorder (PTSD) in a subject in need thereof, comprising administering a compound of any of claims 1 to 91 or a composition of any of claims 92 to 94 to the subject.

96. A method of treating depression in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of any of claims 1 to 91 or a composition of any of claims 92 to 94 to the subject.

97. The method of claim 96, wherein the depression is a major depressive disorder (MDD) or treatment-resistant depression (TRD).

98. A method of treating an anxiety disorder in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of any of claims 1 to 91 or a composition of any of claims 92 to 94 to the subject.