PLASMALOGEN DERIVATIVES AND USES THEREOF RELATED APPLICATIONS [0001] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application, U.S.S.N.63/212,034, filed June 17, 2021, which is incorporated herein by reference in its entirety. BACKGROUND [0002] Plasmalogens are ether phospholipids that comprise a vinyl ether moiety at the sn1 or sn2 position. In mammals, the vinyl ether moiety is typically incorporated at the sn1 position, while the sn2 substituent usually comprises an unsaturated fatty acid residue. Plasmalogens are found throughout various human tissues, including the nervous, immune, and cardiovascular systems. Changes to lipid metabolism are associated with the onset and pathology of various diseases, including, but not limited to, neurological diseases, cardiovascular diseases, metabolic diseases, liver diseases, and cancer. There is a particular need for compounds that cross the blood-brain barrier so that the compounds can exert their activity in the central nervous system (CNS). Despite efforts towards understanding transport across the blood-brain barrier and blood-retinal barriers, efficient delivery directly into the CNS has remained a major challenge in developing potential therapeutics. SUMMARY OF THE INVENTION [0003] Impairment to the biosynthetic pathway of ether lipids may have deleterious downstream effects in subjects with various diseases (e.g., liver diseases, neurological diseases, ophthalmic diseases, metabolic disorders, mitochondrial diseases, cardiovascular diseases, infectious diseases, pulmonary diseases, skin diseases, genetic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, hematological diseases, painful conditions, psychiatric disorders, immune disorders, and spleen diseases). Ether lipids and, in particular, plasmalogen ether species are negatively associated with neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, some genetic diseases, such as Zellweger syndrome, and pulmonary diseases, such as neonatal respiratory distress syndrome. Plasmalogen deficiency is also linked to defects in peroxisome functions and associated disorders. Accordingly, plasmalogen replacement therapy may be used to increase plasmalogen levels in deficient patients. This therapeutic approach may correct various issues, including issues associated with neurological function. Without

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wishing to be bound by a particular theory, the inventors posit that plasmalogen species disclosed herein may be effectively transported by Mfsd2a and achieve improved blood-brain barrier and/or blood-retinal barrier permeability. Additionally, compounds comprising a vinyl ether moiety do not require metabolic conversion and may therefore be effective at low doses. [0004] The present disclosure relates in part to new compounds that can be transported across the blood-brain barrier or blood-retinal barrier, such as by Mfsd2a, and compositions, kits, and methods of using and preparing such compounds. [0005] In one aspect, provided herein are compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and pharmaceutical compositions thereof. In certain embodiments, the compounds provided herein are transported by Mfsd2a and can therefore be used for the treatment and/or prevention of diseases (e.g., liver diseases, neurological diseases, ophthalmic diseases, metabolic disorders, mitochondrial diseases, cardiovascular diseases, infectious diseases, pulmonary diseases, skin diseases, genetic diseases, proliferative diseases, inflammatory diseases, autoimmune diseases, hematological diseases, painful conditions, psychiatric disorders, immune disorders, and spleen diseases). [0006] The present disclosure also provides methods of using the compounds and compositions provided herein, e.g., for treating and/or preventing a disease, disorder, or condition (e.g., a liver disease, a neurological disease, an ophthalmic disease, a metabolic disorder, a mitochondrial disease, a cardiovascular disease, an infectious disease, a pulmonary disease, a skin disease, a genetic disease, a proliferative disease, an inflammatory disease, an autoimmune disease, a hematological disease, a painful condition, a psychiatric disorder, an immune disorder, or a spleen disease) in a subject. In some embodiments, the disease is a neurological disease. In some embodiments, the disease is a pulmonary disease. In some embodiments, the disease is a genetic disease. In some embodiments, the disease is an ophthalmic disease. [0007] In another aspect, the present disclosure provides kits comprising a compound provided herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co- crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a pharmaceutical composition thereof.

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[0008] In one aspect, the disclosure provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, wherein R ¹ , R ² , L ¹ , and X are as defined herein. [0009] In certain embodiments, the compound is of Formula (I-A): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , L ¹ and L ² are as defined herein. [0010] In certain embodiments, the compound is of Formula (I-A-i): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and L ² are as defined herein. [0011] In certain embodiments, the compound is of Formula (I-A-ii): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ¹ , R ² , L ¹ , and L ² are as defined herein.

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[0012] In certain embodiments, the compound is of Formula (I-A-iii): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ¹ , R ² , L ¹ , and L ² are as defined herein. [0013] In certain embodiments, the compound is of Formula (I-B): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ¹ , R ² , R ³ , R ⁴ , L ¹ , and L ² are as defined herein. [0014] In certain embodiments, the compound is of Formula (I-C): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ¹ , R ² , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , and X are as defined herein. [0015] In another aspect, the disclosure provides compounds of Formula (II): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, or prodrug thereof, wherein R ^1' , R ^2' , R ^3' , R ^4' , X, Y, Z, *, and n are as defined herein.

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[0016] In certain embodiments, the compound is of Formula (II-A): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ^1' , R ^2" , R ^3' , R ^4' , X, Y, Z, *, and n are as defined herein. [0017] In certain embodiments the compound is of Formula (II-B): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ^1' , R ^2' , R ^3' , R ^4' , Y, Z, and n are as defined herein. [0018] In certain embodiments, the compound is of Formula (II-C): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ^1' , R ^2' , R ^3' , R ^4' , X, Z, and n are as defined herein.

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[0019] In certain embodiments, the compound is of Formula (II-D): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein R ^1' , R ^2' , R ^3' , R ^4' , X, Y, and n are as defined herein. [0020] In another aspect, the present disclosure provides compositions comprising a compound provided herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof; and a pharmaceutically acceptable carrier and/or excipient. In certain embodiments, the composition is a pharmaceutical composition. In some embodiments, the pharmaceutical composition further comprises an additional pharmaceutical agent. In certain embodiments, a pharmaceutical composition provided herein is formulated for oral administration. In some embodiments, the composition is a nutraceutical composition comprising a compound provided herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co- crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof; and a nutraceutically acceptable carrier and/or excipient. In certain embodiments, a nutraceutical composition provided herein is formulated for oral administration. [0021] In another aspect, the present disclosure provides methods for treating and/or preventing a disease, disorder, or condition in a subject comprising administering to the subject an effective amount of a compound provided herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a pharmaceutical composition thereof. In some embodiments, the disease is a neurological disease. In some embodiments, the disease is a liver disease, a neurological disease, an ophthalmic disease, a metabolic disorder, a mitochondrial disease, a cardiovascular disease, an infectious disease, a pulmonary disease, a skin disease, a genetic disease, a proliferative disease, an inflammatory disease, an autoimmune disease, a hematological disease, a painful condition, a psychiatric disorder, an immune disorder, or a spleen disease. In certain embodiments, the disease is a

6/200 neurodegenerative disease. In some embodiments, the disease is dementia, Alzheimer’s disease, Parkinson’s disease, a Parkinson’s disease-related disorder, Huntington’s disease, amyotrophic lateral sclerosis (ALS), a prion disease, corticobasal degeneration, frontotemporal dementia, HIV-related cognitive impairment, mild cognitive impairment, a motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Friedreich’s ataxia, Lewy body disease, Alpers’ disease, Batten disease, cerebro-oculo-facio-skeletal syndrome, corticobasal degeneration, Gerstmann-Straussler-Scheinker disease, Kuru, Leigh’s disease, monomelic amyotrophy, multiple system atrophy, multiple system atrophy with orthostatic hypotension (Shy-Drager syndrome), multiple sclerosis (MS), neurodegeneration with brain iron accumulation, opsoclonus myoclonus, posterior cortical atrophy, primary progressive aphasia, progressive supranuclear palsy, vascular dementia, progressive multifocal leukoencephalopathy, dementia with Lewy bodies, lacunar syndromes, hydrocephalus, Wernicke-Korsakoff's syndrome, post-encephalitic dementia, cancer and chemotherapy- associated cognitive impairment and dementia, or depression-induced dementia and pseudodementia. In certain embodiments, the disease is dementia, Alzheimer’s disease, other Parkinson’s disease, Huntington’s disease, a prion disease, amyotrophic lateral sclerosis, or multiple sclerosis. In some embodiments, the disease is dementia, or Alzheimer’s disease. In some embodiments, the disease is dementia. In certain embodiments, the disease is Alzheimer’s disease. In certain embodiments, the disease is Parkinson’s disease. [0022] In another aspect, provided herein is a method of transporting a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, across the blood-brain barrier or blood-retinal barrier. In some embodiments, the method comprises administering to a subject a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In certain embodiments, the method comprises contacting a cell, tissue, or biological sample with a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In some embodiments, the method is an in vitro method. In some embodiments, the method is an in vivo method. [0023] In yet another aspect, provided herein is a method of transporting a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co- crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a

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pharmaceutical composition thereof, via the Mfsd2a protein in a subject, biological sample, tissue, or cell. In some embodiments, the method comprises administering to a subject a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In certain embodiments, the method comprises contacting a cell, tissue, or biological sample with a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In some embodiments, the method is an in vitro method. In some embodiments, the method is an in vivo method. In some embodiments, the method is an ex vivo method. [0024] In another aspect, provided herein is a method of increasing plasmalogen levels in a subject, biological sample, tissue, or cell, comprising administering to the subject or contacting the biological sample, tissue, or cell with compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [0025] In another aspect, provided herein is a method of increasing plasmalogen levels in the brain or central nervous system of a subject, comprising administering to the subject a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [0026] In another aspect, the present disclosure provides a kit comprising a compound provided herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co- crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof; or a composition provided herein; and instructions for using the compound, pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or composition thereof. [0027] The details of certain embodiments of the present disclosure are set forth in the Detailed Description of Certain Embodiments, as described below. Other features, objects, and advantages of the present disclosure will be apparent from the Definitions, Examples, and Claims. It should be understood that the aspects described herein are not limited to specific embodiments, methods, or configurations, and as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and, unless specifically defined herein, is not intended to be limiting.

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DEFINITIONS Chemical Definitions [0028] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 ^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999;Michael B. Smith, March’s Advanced Organic Chemistry, 7 ^th Edition, John Wiley & Sons, Inc., New York, 2013; Richard C. Larock, Comprehensive Organic Transformations, John Wiley & Sons, Inc., New York, 2018; and Carruthers, Some Modern Methods of Organic Synthesis, 3 ^rd Edition, Cambridge University Press, Cambridge, 1987. [0029] Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); and Wilen, S.H., Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The present disclosure additionally encompasses compounds as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. [0030] Unless otherwise provided, formulae and structures depicted herein include compounds that do not include isotopically enriched atoms, and also include compounds that include isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, replacement of ¹⁹ F with ¹⁸ F, or the replacement of a carbon by a ¹³ C- or ¹⁴ C-enriched carbon are within the scope of the disclosure. Such compounds are useful, for example, as analytical tools or probes in biological assays.

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[0031] The term “isotopes” refers to variants of a particular chemical element such that, while all isotopes of a given element share the same number of protons in each atom of the element, those isotopes differ in the number of neutrons. [0032] When a range of values is listed, it is intended to encompass each value and sub-range within the range. A range is inclusive of the values at the two ends of the range unless otherwise provided. For example “C1-6 alkyl” encompasses, C1, C2, C3, C4, C5, C6, C1–6, C1–5, C _1–4 , C _1–3 , C _1–2 , C _2–6 , C _2–5 , C _2–4 , C _2–3 , C _3–6 , C _3–5 , C _3–4 , C _4–6 , C _4–5 , and C _5–6 alkyl. [0033] The term “aliphatic” refers to alkyl, alkenyl, alkynyl, and carbocyclic groups. Likewise, the term “heteroaliphatic” refers to heteroalkyl, heteroalkenyl, heteroalkynyl, and heterocyclic groups. [0034] The term “alkyl” refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“C1–20 alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C1–12 alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C _1–10 alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C1–9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C1–8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C1–7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C _1–6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1–5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C1–4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C _1–3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C _1–2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C ₁ alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C2-6 alkyl”). Examples of C1–6 alkyl groups include methyl (C1), ethyl (C2), propyl (C3) (e.g., n-propyl, isopropyl), butyl (C ₄ ) (e.g., n-butyl, tert-butyl, sec-butyl, isobutyl), pentyl (C ₅ ) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tert-amyl), and hexyl (C6) (e.g., n-hexyl). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), n-dodecyl (C12), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents (e.g., halogen, such as F). In certain embodiments, the alkyl group is an unsubstituted C _1–12 alkyl (such as unsubstituted C _1–6 alkyl, e.g., −CH ₃ (Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec-Bu or s-Bu), unsubstituted isobutyl (i-Bu)). In certain embodiments, the alkyl group is a substituted C _1–12 alkyl (such as

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substituted C _1–6 alkyl, e.g., –CH ₂ F, –CHF ₂ , –CF ₃ , –CH ₂ CH ₂ F, –CH ₂ CHF ₂ , –CH ₂ CF ₃ , or benzyl (Bn)). [0035] The term “haloalkyl” is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. “Perhaloalkyl” is a subset of haloalkyl, and refers to an alkyl group wherein all of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo. In some embodiments, the haloalkyl moiety has 1 to 20 carbon atoms (“C _1–20 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 10 carbon atoms (“C1–10 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 9 carbon atoms (“C1–9 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 8 carbon atoms (“C _1–8 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 7 carbon atoms (“C _1–7 haloalkyl”).In some embodiments, the haloalkyl moiety has 1 to 6 carbon atoms (“C1–6 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 5 carbon atoms (“C1–5 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 4 carbon atoms (“C _1–4 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 3 carbon atoms (“C1–3 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 2 carbon atoms (“C1–2 haloalkyl”). In some embodiments, all of the haloalkyl hydrogen atoms are independently replaced with fluoro to provide a “perfluoroalkyl” group. In some embodiments, all of the haloalkyl hydrogen atoms are independently replaced with chloro to provide a “perchloroalkyl” group. Examples of haloalkyl groups include –CHF ₂ , −CH ₂ F, −CF ₃ , −CH ₂ CF ₃ , −CF ₂ CF ₃ , −CF ₂ CF ₂ CF ₃ , −CCl ₃ , −CFCl ₂ , −CF ₂ Cl, and the like. [0036] The term “alkenyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 1 to 20 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 double bonds). In some embodiments, an alkenyl group has 1 to 20 carbon atoms (“C1-20 alkenyl”). In some embodiments, an alkenyl group has 1 to 12 carbon atoms (“C1–12 alkenyl”). In some embodiments, an alkenyl group has 1 to 11 carbon atoms (“C1–11 alkenyl”). In some embodiments, an alkenyl group has 1 to 10 carbon atoms (“C _1–10 alkenyl”). In some embodiments, an alkenyl group has 1 to 9 carbon atoms (“C1–9 alkenyl”). In some embodiments, an alkenyl group has 1 to 8 carbon atoms (“C1–8 alkenyl”). In some embodiments, an alkenyl group has 1 to 7 carbon atoms (“C _1–7 alkenyl”). In some embodiments, an alkenyl group has 1 to 6 carbon atoms (“C _1–6 alkenyl”). In some embodiments, an alkenyl group has 1 to 5 carbon atoms (“C1–5 alkenyl”). In some embodiments, an alkenyl group has 1 to 4 carbon atoms (“C1–4 alkenyl”). In some embodiments, an alkenyl group has 1 to 3 carbon atoms (“C _1–3 alkenyl”). In some

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embodiments, an alkenyl group has 1 to 2 carbon atoms (“C _1–2 alkenyl”). In some embodiments, an alkenyl group has 1 carbon atom (“C1 alkenyl”). The one or more carbon- carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C _1–4 alkenyl groups include methylidenyl (C ₁ ), ethenyl (C ₂ ), 1-propenyl (C ₃ ), 2- propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like. Examples of C1–6 alkenyl groups include the aforementioned C2-4 alkenyl groups as well as pentenyl (C5), pentadienyl (C ₅ ), hexenyl (C ₆ ), and the like. Additional examples of alkenyl include heptenyl (C7), octenyl (C8), octatrienyl (C8), and the like. Unless otherwise specified, each instance of an alkenyl group is independently unsubstituted (an “unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents. In certain embodiments, the alkenyl group is an unsubstituted C _1-20 alkenyl. In certain embodiments, the alkenyl group is a substituted C1-20 alkenyl. In an alkenyl group, a C=C double bond for which the stereochemistry is not specified (e.g., −CH=CHCH ₃ or ) may be in the (E)- or (Z)- configuration. [0037] The term “alkynyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 1 to 20 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C1-20 alkynyl”). In some embodiments, an alkynyl group has 1 to 10 carbon atoms (“C1-10 alkynyl”). In some embodiments, an alkynyl group has 1 to 9 carbon atoms (“C _1-9 alkynyl”). In some embodiments, an alkynyl group has 1 to 8 carbon atoms (“C _1- 8 alkynyl”). In some embodiments, an alkynyl group has 1 to 7 carbon atoms (“C1-7 alkynyl”). In some embodiments, an alkynyl group has 1 to 6 carbon atoms (“C1-6 alkynyl”). In some embodiments, an alkynyl group has 1 to 5 carbon atoms (“C _1-5 alkynyl”). In some embodiments, an alkynyl group has 1 to 4 carbon atoms (“C _1-4 alkynyl”). In some embodiments, an alkynyl group has 1 to 3 carbon atoms (“C1-3 alkynyl”). In some embodiments, an alkynyl group has 1 to 2 carbon atoms (“C _1-2 alkynyl”). In some embodiments, an alkynyl group has 1 carbon atom (“C ₁ alkynyl”). The one or more carbon- carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl). Examples of C1-4 alkynyl groups include, without limitation, methylidynyl (C1), ethynyl (C2), 1-propynyl (C ₃ ), 2-propynyl (C ₃ ), 1-butynyl (C ₄ ), 2-butynyl (C ₄ ), and the like. Examples of C1-6 alkenyl groups include the aforementioned C2-4 alkynyl groups as well as pentynyl (C5), hexynyl (C6), and the like. Additional examples of alkynyl include heptynyl (C7), octynyl (C ₈ ), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted

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alkynyl”) with one or more substituents. In certain embodiments, the alkynyl group is an unsubstituted C1-20 alkynyl. In certain embodiments, the alkynyl group is a substituted C1-20 alkynyl. [0038] The term “carbocyclyl” or “carbocyclic” refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms (“C3-14 carbocyclyl”) and zero heteroatoms in the non-aromatic ring system. In some embodiments, a carbocyclyl group has 3 to 14 ring carbon atoms (“C _3-14 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 13 ring carbon atoms (“C3-13 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 12 ring carbon atoms (“C3-12 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 11 ring carbon atoms (“C _3-11 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C _3-10 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C3-8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C3-7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C _3-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C4-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C5-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C _5-10 carbocyclyl”). Exemplary C3-6 carbocyclyl groups include cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C ₆ ), cyclohexadienyl (C ₆ ), and the like. Exemplary C _3-8 carbocyclyl groups include the aforementioned C _3-6 carbocyclyl groups as well as cycloheptyl (C ₇ ), cycloheptenyl (C ₇ ), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptanyl (C7), bicyclo[2.2.2]octanyl (C8), and the like. Exemplary C3-10 carbocyclyl groups include the aforementioned C _3-8 carbocyclyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro-1H-indenyl (C9), decahydronaphthalenyl (C10), spiro[4.5]decanyl (C10), and the like. Exemplary C3-8 carbocyclyl groups include the aforementioned C _3-10 carbocyclyl groups as well as cycloundecyl (C11), spiro[5.5]undecanyl (C11), cyclododecyl (C12), cyclododecenyl (C12), cyclotridecane (C13), cyclotetradecane (C14), and the like. As the foregoing examples illustrate, in certain embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon-carbon double or triple bonds. “Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one

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or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C3-14 carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted C _3-14 carbocyclyl. [0039] In some embodiments, “carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms (“C3-14 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms (“C _3-10 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C _3-8 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C3-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms (“C4-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms (“C _5-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C5-10 cycloalkyl”). Examples of C5-6 cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C5). Examples of C3-6 cycloalkyl groups include the aforementioned C _5-6 cycloalkyl groups as well as cyclopropyl (C ₃ ) and cyclobutyl (C4). Examples of C3-8 cycloalkyl groups include the aforementioned C3-6 cycloalkyl groups as well as cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an “unsubstituted cycloalkyl”) or substituted (a “substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is an unsubstituted C3-14 cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C3-14 cycloalkyl. In certain embodiments, the carbocyclyl includes 0, 1, or 2 C=C double bonds in the carbocyclic ring system, as valency permits. [0040] The term “heterocyclyl” or “heterocyclic” refers to a radical of a 3- to 14-membered non-aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“3–14 membered heterocyclyl”). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon- carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more

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heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl group is an unsubstituted 3–14 membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3–14 membered heterocyclyl. In certain embodiments, the heterocyclyl is substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl, wherein 1, 2, or 3 atoms in the heterocyclic ring system are independently oxygen, nitrogen, or sulfur, as valency permits. [0041] In some embodiments, a heterocyclyl group is a 5–10 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–8 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–6 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heterocyclyl”). In some embodiments, the 5–6 membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. [0042] Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include azirdinyl, oxiranyl, and thiiranyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5- dione. Exemplary 5-membered heterocyclyl groups containing 2 heteroatoms include dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups

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containing 3 heteroatoms include triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6- membered heterocyclyl groups containing 1 heteroatom include piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include triazinyl. Exemplary 7-membered heterocyclyl groups containing 1 heteroatom include azepanyl, oxepanyl and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetra- hydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8-naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydropyrano[3,4-b]pyrrolyl, 5,6- dihydro-4H-furo[3,2-b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-b]pyranyl, 5,7-dihydro-4H- thieno[2,3-c]pyranyl, 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydrofuro[2,3- b]pyridinyl, 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2- c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2-b]pyridinyl, 1,2,3,4-tetrahydro-1,6-naphthyridinyl, and the like. [0043] Affixing the suffix “-ene” to a group indicates the group is a divalent moiety, e.g., alkylene is the divalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, alkynylene is the divalent moiety of alkynyl, heteroalkylene is the divalent moiety of heteroalkyl, heteroalkenylene is the divalent moiety of heteroalkenyl, heteroalkynylene is the divalent moiety of heteroalkynyl, carbocyclylene is the divalent moiety of carbocyclyl, heterocyclylene is the divalent moiety of heterocyclyl, arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl. [0044] A group is optionally substituted unless expressly provided otherwise. The term “optionally substituted” refers to being substituted or unsubstituted. In certain embodiments, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted. “Optionally substituted” refers to a group which is substituted or unsubstituted (e.g., “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “substituted” or “unsubstituted” alkynyl, “substituted” or “unsubstituted” heteroalkyl, “substituted” or “unsubstituted” heteroalkenyl, “substituted” or “unsubstituted” heteroalkynyl, “substituted” or “unsubstituted” carbocyclyl,

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“substituted” or “unsubstituted” heterocyclyl, “substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group). In general, the term “substituted” means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds, and includes any of the substituents described herein that results in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. The present disclosure is not limited in any manner by the exemplary substituents described herein. C _1–20 alkenyl, C _1–20 alkynyl, heteroC _1–20 alkyl, heteroC _1–20 alkenyl, heteroC _1–20 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

17/200 or two geminal hydrogens on a carbon atom are replaced with the group wherein: each instance of R ^aa is independently selected from C _1–20 alkyl, C _1–20 perhaloalkyl, C1–20 alkenyl, C1–20 alkynyl, heteroC1–20 alkyl, heteroC1–20alkenyl, heteroC1–20alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5- 14 membered heteroaryl, or two R ^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^bb is independently selected from hydrogen, −OH, −OR ^aa , alkyl, C1–20 perhaloalkyl, C1–20 alkenyl, C1–20 alkynyl, heteroC1–20alkyl, heteroC1– 20alkenyl, heteroC1–20alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two R ^bb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^cc is independently selected from hydrogen, C _1–20 alkyl, C _1– 20 perhaloalkyl, C1–20 alkenyl, C1–20 alkynyl, heteroC1–20 alkyl, heteroC1–20 alkenyl, heteroC1–20 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5- 14 membered heteroaryl, or two R ^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups;

−C(=O)SR ^ee , −C(=S)SR ^ee , −SC(=S)SR ^ee , −P(=O)(OR ^ee ) ₂ , −P(=O)(R ^ee ) ₂ , −OP(=O)(R ^ee )2, −OP(=O)(OR ^ee )2, C1–10 alkyl, C1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10alkyl, heteroC1–10alkenyl, heteroC1–10alkynyl, C3-10 carbocyclyl, 3- 10 membered heterocyclyl, C _6-10 aryl, and 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups, or two geminal R ^dd substituents are joined to form =O or =S; each instance of R ^ee is independently selected from C1–10 alkyl, C1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10 alkyl, heteroC1–10 alkenyl, heteroC _1–10 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl, 3-10 membered heterocyclyl, and 3- 10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; each instance of R ^ff is independently selected from hydrogen, C _1–10 alkyl, C _1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10 alkyl, heteroC1–10 alkenyl, heteroC1–10 alkynyl, C3-10 carbocyclyl, 3-10 membered heterocyclyl, C6-10 aryl, and 5- 10 membered heteroaryl, or two R ^ff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; each instance of R ^gg is independently halogen, −CN, −NO ₂ , −N ₃ , −SO ₂ H, −SO3H, −OH, −OC1–6 alkyl, −ON(C1–6 alkyl)2, −N(C1–6 alkyl)2, −N(C1–6 alkyl)3 ⁺ X ⁻ , −NH(C1–6 alkyl)2 ⁺ X ⁻ , −NH2(C1–6 alkyl) ⁺ X ⁻ , −NH3 ⁺ X ⁻ , −N(OC1–6 alkyl)(C1–6 alkyl), −N(OH)(C _1–6 alkyl), −NH(OH), −SH, −SC _1–6 alkyl, −SS(C _1–6 alkyl), −C(=O)(C _1–6 alkyl), −CO2H, −CO2(C1–6 alkyl), −OC(=O)(C1–6 alkyl), −OCO2(C1–6 alkyl), −C(=O)NH2, −C(=O)N(C1–6 alkyl)2, −OC(=O)NH(C1–6 alkyl), −NHC(=O)( C1–6 alkyl), −N(C _1–6 alkyl)C(=O)( C _1–6 alkyl), −NHCO ₂ (C _1–6 alkyl), −NHC(=O)N(C _1–6 alkyl)2, −NHC(=O)NH(C1–6 alkyl), −NHC(=O)NH2, −C(=NH)O(C1–6 alkyl), −OC(=NH)(C1–6 alkyl), −OC(=NH)OC1–6 alkyl, −C(=NH)N(C1–6 alkyl)2, −C(=NH)NH(C _1–6 alkyl), −C(=NH)NH ₂ , −OC(=NH)N(C _1–6 alkyl) ₂ , −OC(NH)NH(C _{1– 6} alkyl), −OC(NH)NH ₂ , −NHC(NH)N(C _1–6 alkyl) ₂ , −NHC(=NH)NH ₂ , −NHSO ₂ (C _1–6 alkyl), −SO2N(C1–6 alkyl)2, −SO2NH(C1–6 alkyl), −SO2NH2, −SO2C1–6 alkyl, −SO2OC1–6 alkyl, −OSO2C1–6 alkyl, −SOC1–6 alkyl, −Si(C1–6 alkyl)3, −OSi(C1–6 alkyl) ₃ −C(=S)N(C _1–6 alkyl) ₂ , C(=S)NH(C _1–6 alkyl), C(=S)NH ₂ , −C(=O)S(C _1–6 alkyl),

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−C(=S)SC _1–6 alkyl, −SC(=S)SC _1–6 alkyl, −P(=O)(OC _1–6 alkyl) ₂ , −P(=O)(C _1–6 alkyl) ₂ , −OP(=O)(C1–6 alkyl)2, −OP(=O)(OC1–6 alkyl)2, C1–10 alkyl, C1–10 perhaloalkyl, C1–10 alkenyl, C1–10 alkynyl, heteroC1–10 alkyl, heteroC1–10 alkenyl, heteroC1–10 alkynyl, C3- 1 ₀ carbocyclyl, C _6-10 aryl, 3-10 membered heterocyclyl, or 5-10 membered heteroaryl; or two geminal R ^gg substituents are joined to form =O or =S; and each X ⁻ is a counterion. [0046] In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −OR ^aa , −SR ^aa , −N(R ^bb )2, –CN, –SCN, –NO2, −C(=O)R ^aa , −CO2R ^aa , −C(=O)N(R ^bb )2, −OC(=O)R ^aa , −OCO ₂ R ^aa , −OC(=O)N(R ^bb ) ₂ , −NR ^bb C(=O)R ^aa , −NR ^bb CO ₂ R ^aa , or −NR ^bb C(=O)N(R ^bb ) ₂ . In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, −OR ^aa , −SR ^aa , −N(R ^bb )2, −OC(=O)N(R ^bb )2, −NR ^bb C(=O)R ^aa , −NR ^bb CO2R ^aa , or −NR ^bb C(=O)N(R ^bb )2, wherein R ^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine- sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each R ^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C _1–10 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −OR ^aa , −SR ^aa , −N(R ^bb )2, –CN, –SCN, or –NO2. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen moieties) or unsubstituted C _1–10 alkyl, −OR ^aa , −SR ^aa , −N(R ^bb )2, –CN, –SCN, or –NO2, wherein R ^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each R ^bb is independently hydrogen, substituted (e.g.,

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substituted with one or more halogen) or unsubstituted C _1–10 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). [0047] In certain embodiments, the molecular weight of a carbon atom substituent is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g/mol. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and/or silicon atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and/or nitrogen atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and/or iodine atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, and/or chlorine atoms. [0048] The term “halo” or “halogen” refers to fluorine (fluoro, −F), chlorine (chloro, −Cl), bromine (bromo, −Br), or iodine (iodo, −I). [0049] The term “amino” refers to the group −NH ₂ . The term “substituted amino,” by extension, refers to a monosubstituted amino, a disubstituted amino, or a trisubstituted amino. In certain embodiments, the “substituted amino” is a monosubstituted amino or a disubstituted amino group. [0050] The term “monosubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with one hydrogen and one group other than hydrogen, and includes groups selected from −NH(R ^bb ), −NHC(=O)R ^aa , −NHCO ₂ R ^aa , −NHC(=O)N(R ^bb ) ₂ , −NHC(=NR ^bb )N(R ^bb ) ₂ , −NHSO ₂ R ^aa , −NHP(=O)(OR ^cc ) ₂ , and −NHP(=O)(N(R ^bb )2)2, wherein R ^aa , R ^bb and R ^cc are as defined herein, and wherein R ^bb of the group −NH(R ^bb ) is not hydrogen. [0051] The term “disubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with two groups other than hydrogen, and includes groups selected from −N(R ^bb )2, −NR ^bb C(=O)R ^aa , −NR ^bb CO2R ^aa , −NR ^bb C(=O)N(R ^bb ) ₂ , −NR ^bb C(=NR ^bb )N(R ^bb ) ₂ , −NR ^bb SO ₂ R ^aa , −NR ^bb P(=O)(OR ^cc ) ₂ , and −NR ^bb P(=O)(N(R ^bb )2)2, wherein R ^aa , R ^bb , and R ^cc are as defined herein, with the proviso that the nitrogen atom directly attached to the parent molecule is not substituted with hydrogen. [0052] The term “acyl” refers to a group having the general formula −C(=O)R ^aa , −C(=O)OR ^aa , −C(=O)−O−C(=O)R ^aa , −C(=O)SR ^aa , −C(=O)N(R ^bb ) ₂ , −C(=S)R ^aa , −C(=S)N(R ^bb )2, and −C(=S)S(R ^aa ), −C(=NR ^bb )R ^aa , −C(=NR ^bb )OR ^aa , −C(=NR ^bb )SR ^aa , and −C(=NR ^bb )N(R ^bb )2, wherein R ^aa and R ^bb are as defined herein. Exemplary acyl groups include

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aldehydes (−CHO), carboxylic acids (−CO ₂ H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas. [0053] The term “carbonyl” refers to a group wherein the carbon directly attached to the parent molecule is sp ² hybridized, and is substituted with an oxygen, nitrogen or sulfur atom, e.g., a group selected from ketones (–C(=O)R ^aa ), carboxylic acids (–CO2H), aldehydes (– CHO), esters (–CO2R ^aa , –C(=O)SR ^aa , –C(=S)SR ^aa ), amides (–C(=O)N(R ^bb )2, – C(=O)NR ^bb SO ₂ R ^aa , −C(=S)N(R ^bb ) ₂ ), and imines (–C(=NR ^bb )R ^aa , –C(=NR ^bb )OR ^aa ), – C(=NR ^bb )N(R ^bb )2), wherein R ^aa and R ^bb are as defined herein. [0054] Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quaternary nitrogen atoms. Exemplary nitrogen atom substituents include hydrogen, −OH, −OR ^aa , −N(R ^cc ) ₂ , −CN, −C(=O)R ^aa , −C(=O)N(R ^cc ) ₂ , −SO2R ^cc , −SO2OR ^cc , −SOR ^aa , −C(=S)N(R ^cc )2, −C(=O)SR ^cc , −C(=S)SR ^cc , −P(=O)(OR ^cc )2, −P(=O)(R ^aa ) ₂ , −P(=O)(N(R ^cc ) ₂ ) ₂ , C _1–20 alkyl, C _1–20 perhaloalkyl, C _1–20 alkenyl, C _1–20 alkynyl, hetero C1–20 alkyl, hetero C1–20 alkenyl, hetero C1–20 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two R ^cc groups attached to an N atom are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups, and wherein R ^aa , R ^bb , R ^cc and R ^dd are as defined above. [0055] In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −C(=O)R ^aa , −CO2R ^aa , −C(=O)N(R ^bb )2, or a nitrogen protecting group. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)R ^aa , −CO2R ^aa , −C(=O)N(R ^bb )2, or a nitrogen protecting group, wherein R ^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C _1-10 alkyl, or an oxygen protecting group when attached to an oxygen atom; and each R ^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C _1-6 alkyl or a nitrogen protecting group. [0056] In certain embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also referred to herein as an “amino protecting group”). Nitrogen protecting groups include −OH, −OR ^aa , −N(R ^cc ) ₂ , −C(=O)R ^aa , −CO ₂ R ^aa , −C(=O)N(R ^cc ) ₂ ,

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−SO ₂ R ^aa , −C(=NR ^cc )R ^aa , −C(=NR ^cc )OR ^aa , −C(=NR ^cc )N(R ^cc ) ₂ , −SO ₂ N(R ^cc ) ₂ , −SO ₂ R ^cc , −SO2OR ^cc , −SOR ^aa , −C(=S)N(R ^cc )2, −C(=O)SR ^cc , −C(=S)SR ^cc , C1–10 alkyl (e.g., aralkyl, heteroaralkyl), C1–20 alkenyl, C1–20 alkynyl, hetero C1–20 alkyl, hetero C1–20 alkenyl, hetero C _1–20 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl groups, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups, and wherein R ^aa , R ^bb , R ^cc and R ^dd are as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 ^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. In certain embodiments, the nitrogen protecting group does not form a urea with the nitrogen to which it is attached. In certain embodiments, the nitrogen protecting group is not −C(=O)N(R ^cc )2. [0057] For example, in certain embodiments, at least one nitrogen protecting group is an amide group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)R ^aa ) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3- phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivatives, benzamide, p-phenylbenzamide, o-nitophenylacetamide, o- nitrophenoxyacetamide, acetoacetamide, (N’-dithiobenzyloxyacylamino)acetamide, 3-(p- hydroxyphenyl)propanamide, 3-(o-nitrophenyl)propanamide, 2-methyl-2-(o- nitrophenoxy)propanamide, 2-methyl-2-(o-phenylazophenoxy)propanamide, 4- chlorobutanamide, 3-methyl-3-nitrobutanamide, o-nitrocinnamide, N-acetylmethionine derivatives, o-nitrobenzamide, and o-(benzoyloxymethyl)benzamide. [0058] In certain embodiments, at least one nitrogen protecting group is a carbamate group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)OR ^aa ) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of methyl carbamate, ethyl carbamate, 9- fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7- dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10- tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-

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phenylethyl carbamate (hZ), 1–(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1- dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1- dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2′- and 4′-pyridyl)ethyl carbamate (Pyoc), 2-(N,N-dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4- nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p- nitobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4- dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3-dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4-dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2-triphenylphosphonioisopropyl carbamate (Ppoc), 1,1- dimethyl-2-cyanoethyl carbamate, m-chloro-p-acyloxybenzyl carbamate, p- (dihydroxyboryl)benzyl carbamate, 5-benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)- 6-chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl(o- nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2-dimethoxyacylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N- dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2- pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methylcyclohexyl carbamate, 1-methyl-1- cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl- 1-(p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4- pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t- butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate.

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[0059] In certain embodiments, at least one nitrogen protecting group is a sulfonamide group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −S(=O)2R ^aa ) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6- trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4- methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9- anthracenesulfonamide, 4-(4′,8′-dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide. [0060] In certain embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of phenothiazinyl-(10)-acyl derivatives, N’-p-toluenesulfonylaminoacyl derivatives, N’-phenylaminothioacyl derivatives, N-benzoylphenylalanyl derivatives, N- acetylmethionine derivatives, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N- dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4- tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5- triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5-triazacyclohexan-2-one, 1- substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2- (trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4- nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4- methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7- dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N’- oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2- pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N-p- nitrobenzylideneamine, N-salicylideneamine, N-5-chlorosalicylideneamine, N-(5-chloro-2- hydroxyphenyl)phenylmethyleneamine, N-cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1- cyclohexenyl)amine, N-borane derivatives, N-diphenylborinic acid derivatives, N-

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[phenyl(pentaacylchromium- or tungsten)acyl]amine, N-copper chelate, N-zinc chelate, N- nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys). In some embodiments, two instances of a nitrogen protecting group together with the nitrogen atoms to which the nitrogen protecting groups are attached are N,N’-isopropylidenediamine. [0061] In certain embodiments, at least one nitrogen protecting group is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts. [0062] In certain embodiments, each oxygen atom substituent is hydrogen or independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)R ^aa , −CO ₂ R ^aa , −C(=O)N(R ^bb ) ₂ , or an oxygen protecting group. In certain embodiments, each oxygen atom substituents is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −C(=O)R ^aa , −CO2R ^aa , −C(=O)N(R ^bb )2, or an oxygen protecting group, wherein R ^aa is hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or an oxygen protecting group when attached to an oxygen atom; and each R ^bb is independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C _1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each oxygen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl or an oxygen protecting group. [0063] In certain embodiments, the substituent present on an oxygen atom is an oxygen protecting group (also referred to herein as a “hydroxyl protecting group”). Oxygen protecting groups include −R ^aa , −N(R ^bb )2, −C(=O)SR ^aa , −C(=O)R ^aa , −CO2R ^aa , −C(=O)N(R ^bb ) ₂ , −C(=NR ^bb )R ^aa , −C(=NR ^bb )OR ^aa , −C(=NR ^bb )N(R ^bb ) ₂ , −S(=O)R ^aa , −SO ₂ R ^aa , −Si(R ^aa )3, −P(R ^cc )2, −P(R ^cc )3 ⁺ X ⁻ , −P(OR ^cc )2, −P(OR ^cc )3 ⁺ X ⁻ , −P(=O)(R ^aa )2, −P(=O)(OR ^cc )2, and −P(=O)(N(R ^bb ) 2)2, wherein X ⁻ , R ^aa , R ^bb , and R ^cc are as defined herein. Oxygen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 ^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. [0064] In certain embodiments, the oxygen protecting group, together with the oxygen atom to which the oxygen protecting group is attached, is selected from the group consisting of

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methoxy, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p- methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2- methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3- bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4- methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4- methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4- methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzo furan-2-yl, 1-ethoxyethyl, 1- (2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1- benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t- butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p- methoxybenzyl (PMB), 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N-oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α- naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p- methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4’- bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4″-tris(4,5- dichlorophthalimidophenyl)methyl, 4,4′,4″-tris(levulinoyloxyphenyl)methyl, 4,4′,4″- tris(benzoyloxyphenyl)methyl, 4,4'-Dimethoxy-3"'-[N-(imidazolylmethyl) ]trityl Ether (IDTr- OR), 4,4'-Dimethoxy-3"'-[N-(imidazolylethyl)carbamoyl]trityl Ether (IETr-OR), 1,1-bis(4- methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10- oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t- butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4- oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6- trimethylbenzoate (mesitoate), methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), ethyl

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carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), isobutyl carbonate, vinyl carbonate, allyl carbonate, t-butyl carbonate (BOC or Boc), p- nitrophenyl carbonate, benzyl carbonate, p-methoxybenzyl carbonate, 3,4-dimethoxybenzyl carbonate, o-nitrobenzyl carbonate, p-nitrobenzyl carbonate, S-benzyl thiocarbonate, 4- ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4- nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2- (methylthiomethoxy)ethyl carbonate (MTMEC-OR), 4-(methylthiomethoxy)butyrate, 2- (methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4- (1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2-butenoate, o- (methoxyacyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N’,N’- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). In certain embodiments, at least one oxygen protecting group is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl. [0065] In certain embodiments, the molecular weight of a substituent is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g/mol. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and/or silicon atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and/or nitrogen atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and/or iodine atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, and/or chlorine atoms. In certain embodiments, a substituent comprises 0, 1, 2, or 3 hydrogen bond donors. In certain embodiments, a substituent comprises 0, 1, 2, or 3 hydrogen bond acceptors. [0066] Use of the phrase “at least one instance” refers to 1, 2, 3, 4, or more instances, but also encompasses a range, e.g., for example, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 4, from 2 to 3, or from 3 to 4 instances, inclusive. [0067] The disclosure is not intended to be limited in any manner by the above exemplary listing of substituents. Additional terms may be defined in other sections of this disclosure.

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Other Definitions [0068] As used herein, the term “salt” refers to any and all salts, and encompasses pharmaceutically acceptable salts. Salts include ionic compounds that result from the neutralization reaction of an acid and a base. A salt is composed of one or more cations (positively charged ions) and one or more anions (negative ions) so that the salt is electrically neutral (without a net charge). Salts of the compounds of this disclosure include those derived from inorganic and organic acids and bases. Examples of acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2– naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, hippurate, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N ⁺ (C _1–4 alkyl) ₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further salts include ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. [0069] The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic

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acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N ⁺ (C _1-4 alkyl) ₄ ⁻ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. In some embodiments, the pharmaceutically acceptable salt is an alkali metal salt. In some embodiments, the pharmaceutically acceptable salt is a nontoxic ammonium, quaternary ammonium, or amine cation. [0070] The term “solvate” refers to forms of the compound, or a salt thereof, that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds described herein may be prepared, e.g., in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric solvates and non-stoichiometric solvates. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of a crystalline solid. “Solvate” encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates. [0071] The term “stoichiometric solvate” refers to a solvate, which comprises a compound (e.g., a compound disclosed herein) and a solvent, wherein the solvent molecules are an integral part of the crystal lattice, in which they interact strongly with the compound and each other. The removal of the solvent molecules will cause instability of the crystal network,

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which subsequently collapses into an amorphous phase or recrystallizes as a new crystalline form with reduced solvent content. [0072] The term “non-stoichiometric solvate” refers to a solvate, which comprises a compound (e.g., a compound disclosed herein) and a solvent, wherein the solvent content may vary without major changes in the crystal structure. The amount of solvent in the crystal lattice only depends on the partial pressure of solvent in the surrounding atmosphere. In the fully solvated state, non-stoichiometric solvates may, but not necessarily have to, show an integer molar ratio of solvent to the compound. During drying of a non-stoichiometric solvate, a portion of the solvent may be removed without significantly disturbing the crystal network, and the resulting solvate can subsequently be resolvated to give the initial crystalline form. Unlike stoichiometric solvates, the desolvation and resolvation of non- stoichiometric solvates is not accompanied by a phase transition, and all solvation states represent the same crystal form. [0073] The term “hydrate” refers to a compound that is associated with water. Typically, the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R⋅x H ₂ O, wherein R is the compound, and x is a number greater than 0. A given compound may form more than one type of hydrate, including, e.g., monohydrates (x is 1), lower hydrates (x is a number greater than 0 and smaller than 1, e.g., hemihydrates (R⋅0.5 H2O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R⋅2 H2O) and hexahydrates (R⋅6 H2O)). [0074] The term “tautomers” or “tautomeric” refers to two or more interconvertible compounds resulting from at least one formal migration of a hydrogen atom and at least one change in valency (e.g., a single bond to a double bond, a triple bond to a single bond, or vice versa). The exact ratio of the tautomers depends on several factors, including temperature, solvent, and pH. Tautomerizations (i.e., the reaction providing a tautomeric pair) may catalyzed by acid or base. Exemplary tautomerizations include keto-to-enol, amide-to-imide, lactam-to-lactim, enamine-to-imine, and enamine-to-(a different enamine) tautomerizations. [0075] It is also to be understood that compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”.

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[0076] Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (−)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. [0077] The term “co-crystal” refers to a crystalline structure comprising at least two different components (e.g., a compound disclosed herein and an acid), wherein each of the components is independently an atom, ion, or molecule. In certain embodiments, none of the components is a solvent. In certain embodiments, at least one of the components is a solvent. A co-crystal of a compound disclosed herein and an acid is different from a salt formed from a compound disclosed herein and the acid. In the salt, a compound disclosed herein is complexed with the acid in a way that proton transfer (e.g., a complete proton transfer) from the acid to a compound disclosed herein easily occurs at room temperature. In the co-crystal, however, a compound disclosed herein is complexed with the acid in a way that proton transfer from the acid to a compound disclosed herein does not easily occur at room temperature. In certain embodiments, in the co-crystal, there is no proton transfer from the acid to a compound disclosed herein. In certain embodiments, in the co-crystal, there is partial proton transfer from the acid to a compound disclosed herein. Co-crystals may be useful to improve the properties (e.g., solubility, stability, and ease of formulation) of a compound disclosed herein. [0078] The term “polymorph” refers to a crystalline form of a compound (or a salt, hydrate, or solvate thereof). All polymorphs have the same elemental composition. Different crystalline forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Various polymorphs of a compound can be prepared by crystallization under different conditions. [0079] The term “prodrugs” refers to compounds that have cleavable groups and become by solvolysis or under physiological conditions the compounds described herein, which are pharmaceutically active in vivo. Such examples include, but are not limited to, choline ester derivatives and the like, N-alkylmorpholine esters and the like. Other derivatives of the

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compounds described herein have activity in both their acid and acid derivative forms, but in the acid sensitive form often offer advantages of solubility, tissue compatibility, or delayed release in the mammalian organism (see, Bundgard, H., Design of Prodrugs, pp.7-9, 21-24, Elsevier, Amsterdam 1985). Prodrugs include acid derivatives well known to practitioners of the art, such as, for example, esters prepared by reaction of the parent acid with a suitable alcohol, or amides prepared by reaction of the parent acid compound with a substituted or unsubstituted amine, or acid anhydrides, or mixed anhydrides. Simple aliphatic or aromatic esters, amides, and anhydrides derived from acidic groups pendant on the compounds described herein are particular prodrugs. In some cases it is desirable to prepare double ester type prodrugs such as (acyloxy)alkyl esters or ((alkoxycarbonyl)oxy)alkylesters. C ₁ -C ₈ alkyl, C ₂ -C ₈ alkenyl, C ₂ -C ₈ alkynyl, aryl, C ₇ -C ₁₂ substituted aryl, and C ₇ -C ₁₂ arylalkyl esters of the compounds described herein may be preferred. [0080] Glycerol is prochiral with respect to reactions of the two primary alcohols. In substituted derivatives, such as plasmalogens, stereospecific numbering (sn) is used. Conventionally, the hydroxyl group of the second carbon of glycerol (sn2) is on the left on a Fischer projection, the sn1 carbon at the top, and the sn3 carbon at the bottom. The spatial configuration (D or L) of the glycero-molecule is identified by the residues on the positions sn1 and sn3. [0081] The term “plasmalogen” refers to vinyl ether phospholipids comprising a vinyl ether moiety at the 1-position, an ester moiety at the 2-position, and a head group (e.g., a phosphate head group) at the 3-position of a glycerol backbone. Plasmalogens include plasmenylcholines and plasmenylethalomines. The term “plasmalogen species” refers to both plasmalogens and plasmalogen derivatives. In some embodiments, the vinyl ether moiety is a saturated or unsaturated aliphatic group (e.g., C16:0, C18:0, or C18:1). In some embodiments, the acyl group is a saturated or unsaturated fatty acid (e.g., docosahexaenoic acid or arachidonic acid). In some embodiments, the vinyl ether moiety is at the sn1 position. In some embodiments, the phosphate head group is at the sn3 position. [0082] The terms “composition” and “formulation” are used interchangeably herein. [0083] A “subject” to which administration is contemplated refers to a human (i.e., male or female of any age group, e.g., pediatric subject (e.g., infant, child, or adolescent) or adult subject (e.g., young adult, middle-aged adult, or senior adult)) or non-human animal. In certain embodiments, the non-human animal is a mammal (e.g., primate (e.g., cynomolgus monkey or rhesus monkey), commercially relevant mammal (e.g., cattle, pig, horse, sheep, goat, cat, or dog), or bird (e.g., commercially relevant bird, such as chicken, duck, goose, or

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turkey)). In certain embodiments, the non-human animal is a fish, reptile, or amphibian. The non-human animal may be a male or female at any stage of development. The non-human animal may be a transgenic animal or genetically engineered animal. The term “patient” refers to a human subject in need of treatment of a disease. [0084] The term “biological sample” refers to any sample including tissue samples (such as tissue sections and needle biopsies of a tissue); cell samples (e.g., cytological smears (such as Pap or blood smears) or samples of cells obtained by microdissection); samples of whole organisms (such as samples of yeasts or bacteria); or cell fractions, fragments or organelles (such as obtained by lysing cells and separating the components thereof by centrifugation or otherwise). Other examples of biological samples include blood, serum, urine, semen, fecal matter, cerebrospinal fluid, interstitial fluid, mucous, tears, sweat, pus, biopsied tissue (e.g., obtained by a surgical biopsy or needle biopsy), nipple aspirates, milk, vaginal fluid, saliva, swabs (such as buccal swabs), or any material containing biomolecules that is derived from a first biological sample. [0085] The term “tissue” refers to any biological tissue of a subject (including a group of cells, a body part, or an organ) or a part thereof, including blood and/or lymph vessels. In some embodiments, the tissue is a biological tissue which is the object to which a compound, particle, and/or composition of the invention is delivered. A tissue may be an abnormal or unhealthy tissue, which may need to be treated. A tissue may also be a normal or healthy tissue that is under a higher than normal risk of becoming abnormal or unhealthy, which may need to be prevented. [0086] The term “administer,” “administering,” or “administration” refers to implanting, absorbing, ingesting, injecting, inhaling, or otherwise introducing a compound described herein, or a composition thereof, in or on a subject. [0087] The terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease described herein. In some embodiments, treatment may be administered after one or more signs or symptoms of the disease have developed or have been observed. In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease. For example, treatment may be administered to a susceptible subject prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of exposure to a pathogen). Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence. [0088] The terms “condition,” “disease,” and “disorder” are used interchangeably.

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[0089] An “effective amount” of a compound described herein refers to an amount sufficient to elicit the desired biological response. An effective amount of a compound described herein may vary depending on such factors as the desired biological endpoint, severity of side effects, disease, or disorder, the identity, pharmacokinetics, and pharmacodynamics of the particular compound, the condition being treated, the mode, route, and desired or required frequency of administration, the species, age and health or general condition of the subject. In certain embodiments, an effective amount is a therapeutically effective amount. In certain embodiments, an effective amount is a prophylactic treatment. In certain embodiments, an effective amount is the amount of a compound described herein in a single dose. In certain embodiments, an effective amount is the combined amounts of a compound described herein in multiple doses. In certain embodiments, the desired dosage is delivered three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage is delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). [0090] In certain embodiments, an effective amount of a compound for administration one or more times a day to a 70 kg adult human comprises about 0.0001 mg to about 3000 mg, about 0.0001 mg to about 2000 mg, about 0.0001 mg to about 1000 mg, about 0.001 mg to about 1000 mg, about 0.01 mg to about 1000 mg, about 0.1 mg to about 1000 mg, about 1 mg to about 1000 mg, about 1 mg to about 100 mg, about 10 mg to about 1000 mg, or about 100 mg to about 1000 mg, of a compound per unit dosage form. [0091] In certain embodiments, the compounds of the present disclosure may be administered orally or parenterally at dosage levels sufficient to deliver from about 0.001 mg/kg to about 100 mg/kg, from about 0.01 mg/kg to about 50 mg/kg, preferably from about 0.1 mg/kg to about 40 mg/kg, preferably from about 0.5 mg/kg to about 30 mg/kg, from about 0.01 mg/kg to about 10 mg/kg, from about 0.1 mg/kg to about 10 mg/kg, and more preferably from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic effect. [0092] It will be appreciated that dose ranges as described herein provide guidance for the administration of provided pharmaceutical compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult.

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[0093] A “therapeutically effective amount” of a compound described herein is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to delay or minimize one or more symptoms associated with the condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms, signs, or causes of the condition, and/or enhances the therapeutic efficacy of another therapeutic agent. In certain embodiments, a therapeutically effective amount is an amount sufficient for transport via Mfsd2a in a subject. In certain embodiments, a therapeutically effective amount is an amount sufficient for treating a disease, disorder, or condition in a subject. In certain embodiments, a therapeutically effective amount is an amount sufficient for treating a neurological disease in a subject. In certain embodiments, a therapeutically effective amount is an amount sufficient for transport via Mfsd2a and treating a disease, disorder, or condition in a subject. In certain embodiments, a therapeutically effective amount is an amount sufficient for transport via Mfsd2a and treating a neurological disease in a subject. [0094] A “prophylactically effective amount” of a compound described herein is an amount sufficient to prevent a condition, or one or more symptoms associated with the condition or prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the condition. The term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent. In certain embodiments, a prophylactically effective amount is an amount sufficient for transport via Mfsd2a in a subject. In certain embodiments, a prophylactically effective amount is an amount sufficient for preventing a disease, disorder, or condition in a subject. In certain embodiments, a prophylactically effective amount is an amount sufficient for preventing a neurological disease in a subject. In certain embodiments, a prophylactically effective amount is an amount sufficient for transport via Mfsd2a and preventing a disease, disorder, or condition in a subject. In certain embodiments, a prophylactically effective amount is an amount sufficient for transport via Mfsd2a and preventing a neurological disease in a subject. [0095] The term “prevent,” “preventing,” or “prevention” refers to a prophylactic treatment of a subject who is not and was not with a disease but is at risk of developing the disease or who was with a disease, is not with the disease, but is at risk of regression of the disease. In

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certain embodiments, the subject is at a higher risk of developing the disease or at a higher risk of regression of the disease than an average healthy member of a population. [0096] The term “neurological disease” refers to any disease of the nervous system, including diseases that involve the central nervous system (brain, brainstem and cerebellum), the peripheral nervous system (including cranial nerves), and the autonomic nervous system (parts of which are located in both central and peripheral nervous system). Neurodegenerative diseases refer to a type of neurological disease marked by the loss of nerve cells, including, but not limited to, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, tauopathies (including frontotemporal dementia), and Huntington’s disease. Examples of neurological diseases include, but are not limited to, headache, stupor and coma, dementia, seizure, sleep disorders, trauma, infections, neoplasms, neuro-ophthalmology, movement disorders, demyelinating diseases, spinal cord disorders, and disorders of peripheral nerves, muscle and neuromuscular junctions. Neurological disorders also include synuclienopathies. Synuclienopathies include, but are not limited to Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Addiction and mental illness, include, but are not limited to, bipolar disorder and schizophrenia, are also included in the definition of neurological diseases. Further examples of neurological diseases include acquired epileptiform aphasia; acute disseminated encephalomyelitis; adrenoleukodystrophy; agenesis of the corpus callosum; agnosia; Aicardi syndrome; Alexander disease; Alpers’ disease; alternating hemiplegia; Alzheimer’s disease; amyotrophic lateral sclerosis; anencephaly; Angelman syndrome; angiomatosis; anoxia; aphasia; apraxia; arachnoid cysts; arachnoiditis; Arnold-Chiari malformation; arteriovenous malformation; Asperger syndrome; ataxia telangiectasia; attention deficit hyperactivity disorder; autism; autonomic dysfunction; back pain; Batten disease; Behcet’s disease; Bell’s palsy; benign essential blepharospasm; benign focal; amyotrophy; benign intracranial hypertension; Binswanger’s disease; blepharospasm; Bloch Sulzberger syndrome; brachial plexus injury; brain abscess; bbrain injury; brain tumors (including glioblastoma multiforme); spinal tumor; Brown-Sequard syndrome; Canavan disease; carpal tunnel syndrome (CTS); causalgia; central pain syndrome; central pontine myelinolysis; cephalic disorder; cerebral aneurysm; cerebral arteriosclerosis; cerebral atrophy; cerebral gigantism; cerebral palsy; Charcot-Marie-Tooth disease; chemotherapy- induced neuropathy and neuropathic pain; Chiari malformation; chorea; chronic inflammatory demyelinating polyneuropathy (CIDP); chronic pain; chronic regional pain syndrome; Coffin Lowry syndrome; coma, including persistent vegetative state; congenital facial diplegia; corticobasal degeneration; cranial arteritis; craniosynostosis; Creutzfeldt-

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Jakob disease; cumulative trauma disorders; Cushing’s syndrome; cytomegalic inclusion body disease (CIBD); cytomegalovirus infection; dancing eyes-dancing feet syndrome; Dandy-Walker syndrome; Dawson disease; De Morsier’s syndrome; Dejerine-Klumpke palsy; dementia; dermatomyositis; diabetic neuropathy; diffuse sclerosis; dysautonomia; dysgraphia; dyslexia; dystonias; early infantile epileptic encephalopathy; empty sella syndrome; encephalitis; encephaloceles; encephalotrigeminal angiomatosis; epilepsy; Erb’s palsy; essential tremor; Fabry’s disease; Fahr’s syndrome; fainting; familial spastic paralysis; febrile seizures; Fisher syndrome; Friedreich’s ataxia; frontotemporal dementia and other “tauopathies”; Gaucher’s disease; Gerstmann’s syndrome; giant cell arteritis; giant cell inclusion disease; globoid cell leukodystrophy; Guillain-Barre syndrome; HTLV-1 associated myelopathy; Hallervorden-Spatz disease; head injury; headache; hemifacial spasm; hereditary spastic paraplegia; heredopathia atactica polyneuritiformis; herpes zoster oticus; herpes zoster; Hirayama syndrome; HIV-associated dementia and neuropathy (see also neurological manifestations of AIDS); holoprosencephaly; Huntington’s disease and other polyglutamine repeat diseases; hydranencephaly; hydrocephalus; hypercortisolism; hypoxia; immune- mediated encephalomyelitis; inclusion body myositis; incontinentia pigmenti; infantile; phytanic acid storage disease; Infantile Refsum disease; infantile spasms; inflammatory myopathy; intracranial cyst; intracranial hypertension; Joubert syndrome; Kearns-Sayre syndrome; Kennedy disease; Kinsbourne syndrome; Klippel Feil syndrome; Krabbe disease; Kugelberg-Welander disease; kuru; Lafora disease; Lambert-Eaton myasthenic syndrome; Landau-Kleffner syndrome; lateral medullary (Wallenberg) syndrome; learning disabilities; Leigh’s disease; Lennox-Gastaut syndrome; Lesch-Nyhan syndrome; leukodystrophy; Lewy body dementia; lissencephaly; locked-in syndrome; Lou Gehrig’s disease (aka motor neuron disease or amyotrophic lateral sclerosis); lumbar disc disease; lyme disease-neurological sequelae; Machado-Joseph disease; macrencephaly; megalencephaly; Melkersson-Rosenthal syndrome; Menieres disease; meningitis; Menkes disease; metachromatic leukodystrophy; microcephaly; migraine; Miller Fisher syndrome; mini-strokes; mitochondrial myopathies; Mobius syndrome; monomelic amyotrophy; motor neurone disease; moyamoya disease; mucopolysaccharidoses; multi-infarct dementia; multifocal motor neuropathy; multiple sclerosis and other demyelinating disorders; multiple system atrophy with postural hypotension; muscular dystrophy; myasthenia gravis; myelinoclastic diffuse sclerosis; myoclonic encephalopathy of infants; myoclonus; myopathy; myotonia congenital; narcolepsy; neurofibromatosis; neuroleptic malignant syndrome; neurological manifestations of AIDS; neurological sequelae of lupus; neuromyotonia; neuronal ceroid lipofuscinosis;

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neuronal migration disorders; Niemann-Pick disease; O’Sullivan-McLeod syndrome; occipital neuralgia; occult spinal dysraphism sequence; Ohtahara syndrome; olivopontocerebellar atrophy; opsoclonus myoclonus; optic neuritis; orthostatic hypotension; overuse syndrome; paresthesia; Parkinson’s disease; paramyotonia congenita; paraneoplastic diseases; paroxysmal attacks; Parry Romberg syndrome; Pelizaeus-Merzbacher disease; periodic paralyses; peripheral neuropathy; painful neuropathy and neuropathic pain; persistent vegetative state; pervasive developmental disorders; photic sneeze reflex; phytanic acid storage disease; Pick’s disease; pinched nerve; pituitary tumors; polymyositis; porencephaly; Post-Polio syndrome; postherpetic neuralgia (PHN); postinfectious encephalomyelitis; postural hypotension; Prader-Willi syndrome; primary lateral sclerosis; prion diseases; progressive; hemifacial atrophy; progressive multifocal leukoencephalopathy; progressive sclerosing poliodystrophy; progressive supranuclear palsy; pseudotumor cerebri; Ramsay-Hunt syndrome (Type I and Type II); Rasmussen’s Encephalitis; reflex sympathetic dystrophy syndrome; Refsum disease; repetitive motion disorders; repetitive stress injuries; restless legs syndrome; retrovirus-associated myelopathy; Rett syndrome; Reye’s syndrome; Saint Vitus Dance; Sandhoff disease; Schilder’s disease; schizencephaly; septo-optic dysplasia; shaken baby syndrome; shingles; Shy-Drager syndrome; Sjogren’s syndrome; sleep apnea; Soto’s syndrome; spasticity; spina bifida; spinal cord injury; spinal cord tumors; spinal muscular atrophy; stiff-person syndrome; stroke; Sturge-Weber syndrome; subacute sclerosing panencephalitis; subarachnoid hemorrhage; subcortical arteriosclerotic encephalopathy; sydenham chorea; syncope; syringomyelia; tardive dyskinesia; Tay-Sachs disease; temporal arteritis; tethered spinal cord syndrome; Thomsen disease; thoracic outlet syndrome; tic douloureux; Todd’s paralysis; Tourette syndrome; transient ischemic attack; transmissible spongiform encephalopathies; transverse myelitis; traumatic brain injury; tremor; trigeminal neuralgia; tropical spastic paraparesis; tuberous sclerosis; vascular dementia (multi-infarct dementia); vasculitis including temporal arteritis; Von Hippel-Lindau Disease (VHL); Wallenberg’s syndrome; Werdnig-Hoffman disease; West syndrome; whiplash; Williams syndrome; Wilson’s disease; neonatal adrenoleukodystrophy (NALD), and Zellweger syndrome. [0097] The term “dementia” is used herein to indicate both cognitive impairment per se, as well as pathologies causing cognitive impairment. In some embodiments, dementia is caused by one or more neurological disorders. Dementia includes, but is not limited to, dementia associated with Alzheimer’s disease, dementia with Lewy bodies, frontotemporal lobe dementia, vascular induced dementia (e.g., multi-infarct dementia), anoxic event induced

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dementia (e.g., cardiac arrest), trauma to the brain induced dementia (e.g., dementia pugilistica), dementia resulting from exposure to an infectious agent (e.g., Creutzfeldt-Jakob Disease) or toxic agent (e.g., alcohol-induced dementia), autism, multiple sclerosis, Parkinson's disease, bipolar disorder, ischemia, Huntington's chorea, major depressive disorder, closed head injury, hydrocephalus, amnesia, anxiety disorder, traumatic brain injury, obsessive compulsive disorder, schizophrenia, mental retardation, and/or epilepsy. [0098] The term “metabolic disorder” refers to any disorder that involves an alteration in the normal metabolism of carbohydrates, lipids, proteins, nucleic acids, or a combination thereof. A metabolic disorder is associated with either a deficiency or excess in a metabolic pathway resulting in an imbalance in metabolism of nucleic acids, proteins, lipids, and/or carbohydrates. Factors affecting metabolism include, and are not limited to, the endocrine (hormonal) control system (e.g., the insulin pathway, the enteroendocrine hormones including GLP-1, PYY or the like), the neural control system (e.g., GLP-1 in the brain), or the like. Examples of metabolic disorders include, but are not limited to, diabetes (e.g., Type I diabetes, Type II diabetes, gestational diabetes), hyperglycemia, hyperinsulinemia, insulin resistance, and obesity. [0099] The terms “cardiovascular disease” or “cardiac diseases and disorders” refers to conditions affecting the heart of blood vessels. In some embodiments, cardiovascular disease is associated with build-up of fatty deposits inside the arteries. In some embodiments, cardiovascular disease is associated with damage to arteries (e.g., in the brain, heart, kidneys, ad eyes). Cardiovascular diseases include, but are not limited to, angina, arrhythmia, congenital heart disease, coronary artery disease, heart attack, heart failure, dilated cardiomyopathy, hypertrophic cardiomyopathy, mitral regurgitation, mitral valve prolapse, pulmonary stenosis, aortic stenosis, atrial fibrillation, rheumatic heart disease, radiation heart disease, peripheral artery disease, aneurysm, renal artery disease, Raynaud’s disease, peripheral venous disease, ischemic stroke, transient ischemic attack, venous blood clots, blood clotting disorders, or Buerger’s disease, cerebrovascular disease, deep vein thrombosis, pulmonary embolism, hypertension, circulatory shock, myocardial reperfusion injury, and atherosclerosis. [00100] A “proliferative disease” refers to a disease that occurs due to abnormal growth or extension by the multiplication of cells (Walker, Cambridge Dictionary of Biology; Cambridge University Press: Cambridge, UK, 1990). In some embodiments, a proliferative disease is associated with one or more of: 1) the pathological proliferation of normally quiescent cells; 2) the pathological migration of cells from their normal location (e.g.,

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metastasis of neoplastic cells); 3) the pathological expression of proteolytic enzymes such as the matrix metalloproteinases (e.g., collagenases, gelatinases, and elastases); or 4) the pathological angiogenesis as in proliferative retinopathy and tumor metastasis. Exemplary proliferative diseases include cancers (i.e., “malignant neoplasms”), benign neoplasms, angiogenesis, inflammatory diseases, and autoimmune diseases. [00101] The term “angiogenesis” refers to the physiological process through which new blood vessels form from pre-existing vessels. Angiogenesis is distinct from vasculogenesis, which is the de novo formation of endothelial cells from mesoderm cell precursors. The first vessels in a developing embryo form through vasculogenesis, after which angiogenesis is responsible for most blood vessel growth during normal or abnormal development. Angiogenesis is a vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, angiogenesis is also a fundamental step in the transition of tumors from a benign state to a malignant one, leading to the use of angiogenesis inhibitors in the treatment of cancer. In some embodiments, angiogenesis is chemically stimulated by angiogenic proteins, such as growth factors (e.g., VEGF). “Pathological angiogenesis” refers to abnormal (e.g., excessive or insufficient) angiogenesis that amounts to and/or is associated with a disease. [00102] The terms “neoplasm” and “tumor” are used herein interchangeably and refer to an abnormal mass of tissue wherein the growth of the mass surpasses and is not coordinated with the growth of a normal tissue. In certain embodiments, a neoplasm or tumor is “benign” or “malignant,” depending on the following characteristics: degree of cellular differentiation (including morphology and functionality), rate of growth, local invasion, and metastasis. A “benign neoplasm” is generally well differentiated, has characteristically slower growth than a malignant neoplasm, and remains localized to the site of origin. In addition, a benign neoplasm does not have the capacity to infiltrate, invade, or metastasize to distant sites. Exemplary benign neoplasms include, but are not limited to, lipoma, chondroma, adenomas, acrochordon, senile angiomas, seborrheic keratoses, lentigos, and sebaceous hyperplasias. In some cases, certain “benign” tumors may later give rise to malignant neoplasms, which may result from additional genetic changes in a subpopulation of the tumor’s neoplastic cells, and these tumors are referred to as “pre-malignant neoplasms.” An exemplary pre-malignant neoplasm is a teratoma. In contrast, a “malignant neoplasm” is generally poorly differentiated (anaplasia) and has characteristically rapid growth accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue. Furthermore, a malignant neoplasm generally has the capacity to metastasize to distant sites. The term “metastasis,” “metastatic,”

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or “metastasize” refers to the spread or migration of cancerous cells from a primary or original tumor to another organ or tissue and is typically identifiable by the presence of a “secondary tumor” or “secondary cell mass” of the tissue type of the primary or original tumor and not of that of the organ or tissue in which the secondary (metastatic) tumor is located. For example, a prostate cancer that has migrated to bone is said to be metastasized prostate cancer and includes cancerous prostate cancer cells growing in bone tissue. [00103] The term “cancer” refers to a class of diseases characterized by the development of abnormal cells that proliferate uncontrollably and have the ability to infiltrate and destroy normal body tissues. See, e.g., Stedman’s Medical Dictionary, 25th ed.; Hensyl ed.; Williams & Wilkins: Philadelphia, 1990. Exemplary cancers include, but are not limited to, acoustic neuroma; adenocarcinoma; adrenal gland cancer; anal cancer; angiosarcoma (e.g., lymphangiosarcoma, lymphangioendotheliosarcoma, hemangiosarcoma); appendix cancer; benign monoclonal gammopathy; biliary cancer (e.g., cholangiocarcinoma); bladder cancer; breast cancer (e.g., adenocarcinoma of the breast, papillary carcinoma of the breast, mammary cancer, medullary carcinoma of the breast); brain cancer (e.g., meningioma, glioblastomas, glioma (e.g., astrocytoma, oligodendroglioma), medulloblastoma); bronchus cancer; carcinoid tumor; cervical cancer (e.g., cervical adenocarcinoma); choriocarcinoma; chordoma; craniopharyngioma; colorectal cancer (e.g., colon cancer, rectal cancer, colorectal adenocarcinoma); connective tissue cancer; epithelial carcinoma; ependymoma; endotheliosarcoma (e.g., Kaposi’s sarcoma, multiple idiopathic hemorrhagic sarcoma); endometrial cancer (e.g., uterine cancer, uterine sarcoma); esophageal cancer (e.g., adenocarcinoma of the esophagus, Barrett’s adenocarcinoma); Ewing’s sarcoma; ocular cancer (e.g., intraocular melanoma, retinoblastoma); familiar hypereosinophilia; gall bladder cancer; gastric cancer (e.g., stomach adenocarcinoma); gastrointestinal stromal tumor (GIST); germ cell cancer; head and neck cancer (e.g., head and neck squamous cell carcinoma, oral cancer (e.g., oral squamous cell carcinoma), throat cancer (e.g., laryngeal cancer, pharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer)); hematopoietic cancers (e.g., leukemia such as acute lymphocytic leukemia (ALL) (e.g., B-cell ALL, T-cell ALL), acute myelocytic leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myelocytic leukemia (CML) (e.g., B-cell CML, T-cell CML), and chronic lymphocytic leukemia (CLL) (e.g., B- cell CLL, T-cell CLL)); lymphoma such as Hodgkin lymphoma (HL) (e.g., B-cell HL, T-cell HL) and non-Hodgkin lymphoma (NHL) (e.g., B-cell NHL such as diffuse large cell lymphoma (DLCL) (e.g., diffuse large B-cell lymphoma), follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma

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(MCL), marginal zone B-cell lymphomas (e.g., mucosa-associated lymphoid tissue (MALT) lymphomas, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma), primary mediastinal B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma (i.e., Waldenström’s macroglobulinemia), hairy cell leukemia (HCL), immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma and primary central nervous system (CNS) lymphoma; and T-cell NHL such as precursor T-lymphoblastic lymphoma/leukemia, peripheral T-cell lymphoma (PTCL) (e.g., cutaneous T-cell lymphoma (CTCL) (e.g., mycosis fungoides, Sezary syndrome), angioimmunoblastic T-cell lymphoma, extranodal natural killer T-cell lymphoma, enteropathy type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and anaplastic large cell lymphoma); a mixture of one or more leukemia/lymphoma as described above; and multiple myeloma (MM)), heavy chain disease (e.g., alpha chain disease, gamma chain disease, mu chain disease); hemangioblastoma; hypopharynx cancer; inflammatory myofibroblastic tumors; immunocytic amyloidosis; kidney cancer (e.g., nephroblastoma a.k.a. Wilms’ tumor, renal cell carcinoma); liver cancer (e.g., hepatocellular cancer (HCC), malignant hepatoma); lung cancer (e.g., bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung); leiomyosarcoma (LMS); mastocytosis (e.g., systemic mastocytosis); muscle cancer; myelodysplastic syndrome (MDS); mesothelioma; myeloproliferative disorder (MPD) (e.g., polycythemia vera (PV), essential thrombocytosis (ET), agnogenic myeloid metaplasia (AMM) a.k.a. myelofibrosis (MF), chronic idiopathic myelofibrosis, chronic myelocytic leukemia (CML), chronic neutrophilic leukemia (CNL), hypereosinophilic syndrome (HES)); neuroblastoma; neurofibroma (e.g., neurofibromatosis (NF) type 1 or type 2, schwannomatosis); neuroendocrine cancer (e.g., gastroenteropancreatic neuroendoctrine tumor (GEP-NET), carcinoid tumor); osteosarcoma (e.g.,bone cancer); ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma); papillary adenocarcinoma; pancreatic cancer (e.g., pancreatic andenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), Islet cell tumors); penile cancer (e.g., Paget’s disease of the penis and scrotum); pinealoma; primitive neuroectodermal tumor (PNT); plasma cell neoplasia; paraneoplastic syndromes; intraepithelial neoplasms; prostate cancer (e.g., prostate adenocarcinoma); rectal cancer; rhabdomyosarcoma; salivary gland cancer; skin cancer (e.g., squamous cell carcinoma (SCC), keratoacanthoma (KA), melanoma, basal cell carcinoma (BCC)); small bowel cancer (e.g., appendix cancer); soft tissue sarcoma (e.g., malignant fibrous histiocytoma (MFH), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma);

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sebaceous gland carcinoma; small intestine cancer; sweat gland carcinoma; synovioma; testicular cancer (e.g., seminoma, testicular embryonal carcinoma); thyroid cancer (e.g., papillary carcinoma of the thyroid, papillary thyroid carcinoma (PTC), medullary thyroid cancer); urethral cancer; vaginal cancer; and vulvar cancer (e.g., Paget’s disease of the vulva). [00104] The term “liver disease” or “hepatic disease” refers to damage to or a disease of the liver. Non-limiting examples of liver disease include intrahepatic cholestasis (e.g., alagille syndrome, biliary liver cirrhosis), fatty liver (e.g., alcoholic fatty liver, Reye’s syndrome), hepatic vein thrombosis, hepatolenticular degeneration (i.e., Wilson's disease), hepatomegaly, liver abscess (e.g., amebic liver abscess), liver cirrhosis (e.g., alcoholic, biliary, and experimental liver cirrhosis), alcoholic liver diseases (e.g., fatty liver, hepatitis, cirrhosis), parasitic liver disease (e.g., hepatic echinococcosis, fascioliasis, amebic liver abscess), jaundice (e.g., hemolytic, hepatocellular, cholestatic jaundice), cholestasis, portal hypertension, liver enlargement, ascites, hepatitis (e.g., alcoholic hepatitis, animal hepatitis, chronic hepatitis (e.g., autoimmune, hepatitis B, hepatitis C, hepatitis D, drug induced chronic hepatitis), toxic hepatitis, viral human hepatitis (e.g., hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E), granulomatous hepatitis, secondary biliary cirrhosis, hepatic encephalopathy, varices, primary biliary cirrhosis, primary sclerosing cholangitis, hepatocellular adenoma, hemangiomas, bile stones, liver failure (e.g., hepatic encephalopathy, acute liver failure), angiomyolipoma, calcified liver metastases, cystic liver metastases, fibrolamellar hepatocarcinoma, hepatic adenoma, hepatoma, hepatic cysts (e.g., Simple cysts, Polycystic liver disease, hepatobiliary cystadenoma, choledochal cyst), mesenchymal tumors (mesenchymal hamartoma, infantile hemangioendothelioma, hemangioma, peliosis hepatis, lipomas, inflammatory pseudotumor), epithelial tumors (e.g., bile duct hamartoma, bile duct adenoma), focal nodular hyperplasia, nodular regenerative hyperplasia, hepatoblastoma, hepatocellular carcinoma, cholangiocarcinoma, cystadenocarcinoma, tumors of blood vessels, angiosarcoma, Karposi's sarcoma, hemangioendothelioma, embryonal sarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, carcinosarcoma, teratoma, carcinoid, squamous carcinoma, primary lymphoma, peliosis hepatis, erythrohepatic porphyria, hepatic porphyria (e.g., acute intermittent porphyria, porphyria cutanea tarda), and Zellweger syndrome. [00105] The term “ophthalmic disease” includes diseases of the eye and ocular appendages. In some embodiments, an ophthalmic disease may affect the eyelids, tear organ, cornea, iris, pupil, lens, retina, or sclera. In certain embodiments, the ophthalmic disease or disorder is

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selected from dry eye, retinal disease, glaucoma, retinal degeneration, macular degeneration, diabetic retinopathy, retinitis pigmentosa, retinal vein occlusion, retinal vascular occlusion, traumatic optic neuropathy, neurotrophic keratopathy, Leber congenital amaurosis, diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), and optic nerve degeneration. [00106] The term “lung disease” or “pulmonary disease” refers to a disease of the lung. Examples of lung diseases include, but are not limited to, bronchiectasis, bronchitis, bronchopulmonary dysplasia, interstitial lung disease, occupational lung disease, emphysema, cystic fibrosis, acute respiratory distress syndrome (ARDS), severe acute respiratory syndrome (SARS), respiratory distress syndrome, neonatal respiratory distress syndrome (NRDS), infant respiratory distress syndrome (IRDS), hyaline membrane disease, surfactant deficiency, surfactant protein-B deficiency, bronchopulmonary dysplasia, asthma (e.g., intermittent asthma, mild persistent asthma, moderate persistent asthma, severe persistent asthma), chronic bronchitis, chronic obstructive pulmonary disease (COPD), emphysema, interstitial lung disease, sarcoidosis, asbestosis, aspergilloma, aspergillosis, pneumonia (e.g., lobar pneumonia, multilobar pneumonia, bronchial pneumonia, interstitial pneumonia), pulmonary fibrosis, pulmonary tuberculosis, rheumatoid lung disease, pulmonary embolism, and lung cancer (e.g., non-small-cell lung carcinoma (e.g., adenocarcinoma, squamous-cell lung carcinoma, large-cell lung carcinoma), small-cell lung carcinoma). [00107] The term “genetic disease” refers to a disease caused by one or more abnormalities in the genome of a subject, such as a disease that is present from birth of the subject. In some embodiments, a genetic disease is heritable and is passed down from the parents’ genes. In other embodiments, a genetic disease is caused by mutations or changes of the DNAs and/or RNAs of the subject. In such cases, the genetic disease will be heritable if it occurs in the germline. Exemplary genetic diseases include, but are not limited to, Aarskog-Scott syndrome, Aase syndrome, achondroplasia, acrodysostosis, addiction, adreno- leukodystrophy, albinism, ablepharon-macrostomia syndrome, alagille syndrome, alkaptonuria, alpha-1 antitrypsin deficiency, Alport’s syndrome, Alzheimer’s disease, asthma, autoimmune polyglandular syndrome, androgen insensitivity syndrome, Angelman syndrome, ataxia, ataxia telangiectasia, atherosclerosis, attention deficit hyperactivity disorder (ADHD), autism, baldness, Batten disease, Beckwith-Wiedemann syndrome, Best disease, bipolar disorder, brachydactyl), breast cancer, Burkitt lymphoma, chronic myeloid leukemia, Charcot-Marie-Tooth disease, Crohn’s disease, cleft lip, Cockayne syndrome, Coffin Lowry syndrome, colon cancer, congenital adrenal hyperplasia, Cornelia de Lange

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syndrome, Costello syndrome, Cowden syndrome, craniofrontonasal dysplasia, Crigler- Najjar syndrome, Creutzfeldt-Jakob disease, cystic fibrosis, deafness, depression, diabetes, diastrophic dysplasia, DiGeorge syndrome, Down’s syndrome, dyslexia, Duchenne muscular dystrophy, Dubowitz syndrome, ectodermal dysplasia Ellis-van Creveld syndrome, Ehlers- Danlos, epidermolysis bullosa, epilepsy, essential tremor, familial hypercholesterolemia, familial Mediterranean fever, fragile X syndrome, Friedreich’s ataxia, Gaucher disease, glaucoma, glucose galactose malabsorption, glutaricaciduria, gyrate atrophy, Goldberg Shprintzen syndrome (velocardiofacial syndrome), Gorlin syndrome, Hailey-Hailey disease, hemihypertrophy, hemochromatosis, hemophilia, hereditary motor and sensory neuropathy (HMSN), hereditary non polyposis colorectal cancer (HNPCC), Huntington’s disease, immunodeficiency with hyper-IgM, juvenile onset diabetes, Klinefelter’s syndrome, Kabuki syndrome, Leigh’s disease, long QT syndrome, lung cancer, malignant melanoma, manic depression, Marfan syndrome, Menkes syndrome, miscarriage, mucopolysaccharide disease, multiple endocrine neoplasia, multiple sclerosis, muscular dystrophy, myotrophic lateral sclerosis, myotonic dystrophy, neurofibromatosis, Niemann-Pick disease, Noonan syndrome, obesity, ovarian cancer, pancreatic cancer, Parkinson’s disease, paroxysmal nocturnal hemoglobinuria, Pendred syndrome, peroneal muscular atrophy, phenylketonuria (PKU), polycystic kidney disease, Prader-Willi syndrome, primary biliary cirrhosis, prostate cancer, REAR syndrome, Refsum disease, retinitis pigmentosa, retinoblastoma, Rett syndrome, Sanfilippo syndrome, schizophrenia, severe combined immunodeficiency, sickle cell anemia, spina bifida, spinal muscular atrophy, spinocerebellar atrophy, sudden adult death syndrome, Tangier disease, Tay-Sachs disease, thrombocytopenia absent radius syndrome, Townes- Brocks syndrome, tuberous sclerosis, Turner syndrome, Usher syndrome, von Hippel-Lindau syndrome, Waardenburg syndrome, Weaver syndrome, Werner syndrome, Williams syndrome, Wilson’s disease, xeroderma piginentosum, and Zellweger syndrome. [00108] The terms “inflammatory disease” and “inflammatory condition” are used interchangeably herein, and refer to a disease or condition caused by, resulting from, or resulting in inflammation. Inflammatory diseases and conditions include those diseases, disorders or conditions that are characterized by signs of pain (dolor, from the generation of noxious substances and the stimulation of nerves), heat (calor, from vasodilatation), redness (rubor, from vasodilatation and increased blood flow), swelling (tumor, from excessive inflow or restricted outflow of fluid), and/or loss of function (functio laesa, which can be partial or complete, temporary or permanent. Inflammation takes on many forms and includes, but is not limited to, acute, adhesive, atrophic, catarrhal, chronic, cirrhotic, diffuse,

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disseminated, exudative, fibrinous, fibrosing, focal, granulomatous, hyperplastic, hypertrophic, interstitial, metastatic, necrotic, obliterative, parenchymatous, plastic, productive, proliferous, pseudomembranous, purulent, sclerosing, seroplastic, serous, simple, specific, subacute, suppurative, toxic, traumatic, and/or ulcerative inflammation. The term “inflammatory disease” may also refer to a dysregulated inflammatory reaction that causes an exaggerated response by macrophages, granulocytes, and/or T-lymphocytes leading to abnormal tissue damage and/or cell death. An inflammatory disease can be either an acute or chronic inflammatory condition and can result from infections or non-infectious causes. Inflammatory diseases include, without limitation, atherosclerosis, arteriosclerosis, autoimmune disorders, multiple sclerosis, systemic lupus erythematosus, polymyalgia rheumatica (PMR), gouty arthritis, degenerative arthritis, tendonitis, bursitis, psoriasis, cystic fibrosis, arthrosteitis, rheumatoid arthritis, inflammatory arthritis, Sjogren’s syndrome, giant cell arteritis, progressive systemic sclerosis (scleroderma), ankylosing spondylitis, polymyositis, dermatomyositis, pemphigus, pemphigoid, diabetes (e.g., Type I), myasthenia gravis, Hashimoto’s thyroiditis, Graves’ disease, Goodpasture’s disease, mixed connective tissue disease, sclerosing cholangitis, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, pernicious anemia, inflammatory dermatoses, usual interstitial pneumonitis (UIP), asbestosis, silicosis, bronchiectasis, berylliosis, talcosis, pneumoconiosis, sarcoidosis, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, giant cell interstitial pneumonia, cellular interstitial pneumonia, extrinsic allergic alveolitis, Wegener’s granulomatosis and related forms of angiitis (temporal arteritis and polyarteritis nodosa), inflammatory dermatoses, hepatitis, delayed-type hypersensitivity reactions (e.g., poison ivy dermatitis), pneumonia, respiratory tract inflammation, Adult Respiratory Distress Syndrome (ARDS), encephalitis, immediate hypersensitivity reactions, asthma, hayfever, allergies, acute anaphylaxis, rheumatic fever, glomerulonephritis, pyelonephritis, cellulitis, cystitis, chronic cholecystitis, ischemia (ischemic injury), reperfusion injury, allograft rejection, host- versus-graft rejection, appendicitis, arteritis, blepharitis, bronchiolitis, bronchitis, cervicitis, cholangitis, chorioamnionitis, conjunctivitis, dacryoadenitis, dermatomyositis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, gingivitis, ileitis, iritis, laryngitis, myelitis, myocarditis, nephritis, omphalitis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, pharyngitis, pleuritis, phlebitis, pneumonitis, proctitis, prostatitis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, testitis, tonsillitis, urethritis, urocystitis, uveitis, vaginitis, vasculitis, vulvitis, vulvovaginitis, angitis, chronic bronchitis, osteomyelitis, optic neuritis, temporal arteritis, transverse

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myelitis, necrotizing fasciitis, and necrotizing enterocolitis. An ocular inflammatory disease includes, but is not limited to, post-surgical inflammation. [00109] Additional exemplary inflammatory conditions include, but are not limited to, inflammation associated with acne, anemia (e.g., aplastic anemia, haemolytic autoimmune anaemia), asthma, arteritis (e.g., polyarteritis, temporal arteritis, periarteritis nodosa, Takayasu's arteritis), arthritis (e.g., crystalline arthritis, osteoarthritis, psoriatic arthritis, gouty arthritis, reactive arthritis, rheumatoid arthritis and Reiter's arthritis), ankylosing spondylitis, amylosis, amyotrophic lateral sclerosis, autoimmune diseases, allergies or allergic reactions, atherosclerosis, bronchitis, bursitis, chronic prostatitis, conjunctivitis, Chagas disease, chronic obstructive pulmonary disease, cermatomyositis, diverticulitis, diabetes (e.g., type I diabetes mellitus, Type II diabetes mellitus), a skin condition (e.g., psoriasis, eczema, burns, dermatitis, pruritus (itch)), endometriosis, Guillain-Barre syndrome, infection, ischaemic heart disease, Kawasaki disease, glomerulonephritis, gingivitis, hypersensitivity, headaches (e.g., migraine headaches, tension headaches), ileus (e.g., postoperative ileus and ileus during sepsis), idiopathic thrombocytopenic purpura, interstitial cystitis (painful bladder syndrome), gastrointestinal disorder (e.g., selected from peptic ulcers, regional enteritis, diverticulitis, gastrointestinal bleeding, eosinophilic gastrointestinal disorders (e.g., eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic colitis), gastritis, diarrhea, gastroesophageal reflux disease (GORD, or its synonym GERD), inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis, collagenous colitis, lymphocytic colitis, ischaemic colitis, diversion colitis, Behcet's syndrome, indeterminate colitis) and inflammatory bowel syndrome (IBS)), lupus, multiple sclerosis, morphea, myeasthenia gravis, myocardial ischemia, nephrotic syndrome, pemphigus vulgaris, pernicious aneaemia, peptic ulcers, polymyositis, primary biliary cirrhosis, neuroinflammation associated with brain disorders (e.g., Parkinson's disease, Huntington's disease, and Alzheimer's disease), prostatitis, chronic inflammation associated with cranial radiation injury, pelvic inflammatory disease, reperfusion injury, regional enteritis, rheumatic fever, systemic lupus erythematosus, schleroderma, scierodoma, sarcoidosis, spondyloarthopathies, Sjogren's syndrome, thyroiditis, transplantation rejection, tendonitis, trauma or injury (e.g., frostbite, chemical irritants, toxins, scarring, burns, physical injury), vasculitis, vitiligo and Wegener's granulomatosis. In certain embodiments, the inflammatory disorder is selected from arthritis (e.g., rheumatoid arthritis), inflammatory bowel disease, inflammatory bowel syndrome, asthma, psoriasis, endometriosis, interstitial cystitis and prostatistis. In certain embodiments, the inflammatory condition is an acute inflammatory condition (e.g., for example,

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inflammation resulting from infection). In certain embodiments, the inflammatory condition is a chronic inflammatory condition (e.g., conditions resulting from asthma, arthritis and inflammatory bowel disease). The compounds may also be useful in treating inflammation associated with trauma and non-inflammatory myalgia. The compounds disclosed herein may also be useful in treating inflammation associated with cancer. [00110] An “autoimmune disease” refers to a disease arising from an inappropriate immune response of the body of a subject against substances and tissues normally present in the body. In other words, the immune system mistakes some part of the body as a pathogen and attacks its own cells. In certain embodiments, this is restricted to certain organs (e.g., in autoimmune thyroiditis) or involve a particular tissue in different places (e.g., Goodpasture’s disease which may affect the basement membrane in both the lung and kidney). The treatment of autoimmune diseases is typically with immunosuppression, e.g., medications which decrease the immune response. Exemplary autoimmune diseases include, but are not limited to, glomerulonephritis, Goodpasture’s syndrome, necrotizing vasculitis, lymphadenitis, peri- arteritis nodosa, systemic lupus erythematosis, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosis, psoriasis, ulcerative colitis, systemic sclerosis, dermatomyositis/polymyositis, anti-phospholipid antibody syndrome, scleroderma, pemphigus vulgaris, ANCA-associated vasculitis (e.g., Wegener’s granulomatosis, microscopic polyangiitis), uveitis, Sjogren’s syndrome, Crohn’s disease, Reiter’s syndrome, ankylosing spondylitis, Lyme disease, Guillain-Barré syndrome, Hashimoto’s thyroiditis, and cardiomyopathy. [00111] A “hematological disease” includes a disease which affects a hematopoietic cell or tissue. Hematological diseases include diseases associated with aberrant hematological content and/or function. Examples of hematological diseases include diseases resulting from bone marrow irradiation or chemotherapy treatments for cancer, diseases such as pernicious anemia, hemorrhagic anemia, hemolytic anemia, aplastic anemia, sickle cell anemia, sideroblastic anemia, anemia associated with chronic infections such as malaria, trypanosomiasis, HTV, hepatitis virus or other viruses, myelophthisic anemias caused by marrow deficiencies, renal failure resulting from anemia, anemia, polycythemia, infectious mononucleosis (EVI), acute non-lymphocytic leukemia (ANLL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), acute myelomonocytic leukemia (AMMoL), polycythemia vera, lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia, Wilm’s tumor, Ewing’s sarcoma, retinoblastoma, hemophilia, disorders associated with an increased risk of thrombosis, herpes, thalassemia, antibody-mediated disorders such

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as transfusion reactions and erythroblastosis, mechanical trauma to red blood cells such as micro-angiopathic hemolytic anemias, thrombotic thrombocytopenic purpura and disseminated intravascular coagulation, infections by parasites such as Plasmodium, chemical injuries from, e.g., lead poisoning, and hypersplenism. [00112] A “painful condition” includes, but is not limited to, neuropathic pain (e.g., peripheral neuropathic pain), central pain, deafferentiation pain, chronic pain (e.g., chronic nociceptive pain, and other forms of chronic pain such as post–operative pain, e.g., pain arising after hip, knee, or other replacement surgery), pre–operative pain, stimulus of nociceptive receptors (nociceptive pain), acute pain (e.g., phantom and transient acute pain), noninflammatory pain, inflammatory pain, pain associated with cancer, wound pain, burn pain, postoperative pain, pain associated with medical procedures, pain resulting from pruritus, painful bladder syndrome, pain associated with premenstrual dysphoric disorder and/or premenstrual syndrome, pain associated with chronic fatigue syndrome, pain associated with pre–term labor, pain associated with withdrawl symptoms from drug addiction, joint pain, arthritic pain (e.g., pain associated with crystalline arthritis, osteoarthritis, psoriatic arthritis, gouty arthritis, reactive arthritis, rheumatoid arthritis or Reiter’s arthritis), lumbosacral pain, musculo–skeletal pain, headache, migraine, muscle ache, lower back pain, neck pain, toothache, dental/maxillofacial pain, visceral pain and the like. One or more of the painful conditions contemplated herein can comprise mixtures of various types of pain provided above and herein (e.g., nociceptive pain, inflammatory pain, neuropathic pain, etc.). In some embodiments, a particular pain can dominate. In other embodiments, the painful condition comprises two or more types of pains without one dominating. A skilled clinician can determine the dosage to achieve a therapeutically effective amount for a particular subject based on the painful condition. [00113] The term “psychiatric disorder” refers to a disease of the mind and includes diseases and disorders listed in the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV), published by the American Psychiatric Association, Washington D. C. (1994). Psychiatric disorders include, but are not limited to, anxiety disorders (e.g., acute stress disorder agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, separation anxiety disorder, social phobia, and specific phobia), childhood disorders, (e.g., attention-deficit/hyperactivity disorder, conduct disorder, and oppositional defiant disorder), eating disorders (e.g., anorexia nervosa and bulimia nervosa), mood disorders (e.g., depression, bipolar disorder, cyclothymic disorder, dysthymic disorder, and major depressive disorder), personality disorders (e.g., antisocial

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personality disorder, avoidant personality disorder, borderline personality disorder, dependent personality disorder, histrionic personality disorder, narcissistic personality disorder, obsessive-compulsive personality disorder, paranoid personality disorder, schizoid personality disorder, and schizotypal personality disorder), psychotic disorders (e.g., brief psychotic disorder, delusional disorder, schizoaffective disorder, schizophreniform disorder, schizophrenia, and shared psychotic disorder), substance-related disorders (e.g., alcohol dependence, amphetamine dependence, cannabis dependence, cocaine dependence, hallucinogen dependence, inhalant dependence, nicotine dependence, opioid dependence, phencyclidine dependence, and sedative dependence), adjustment disorder, autism, delirium, dementia, multi-infarct dementia, learning and memory disorders (e.g., amnesia and age- related memory loss), and Tourette’s disorder. [00114] Immune disorders, such as auto-immune disorders, include, but are not limited to, arthritis (including rheumatoid arthritis, spondyloarthopathies, gouty arthritis, degenerative joint diseases such as osteoarthritis, systemic lupus erythematosus, Sjogren’s syndrome, ankylosing spondylitis, undifferentiated spondylitis, Behcet’s disease, haemolytic autoimmune anaemias, multiple sclerosis, amyotrophic lateral sclerosis, amylosis, acute painful shoulder, psoriatic, and juvenile arthritis), asthma, atherosclerosis, osteoporosis, bronchitis, tendonitis, bursitis, skin condition (e.g., psoriasis, eczema, burns, dermatitis, pruritus (itch)), enuresis, eosinophilic disease, gastrointestinal disorder (e.g., selected from peptic ulcers, regional enteritis, diverticulitis, gastrointestinal bleeding, eosinophilic gastrointestinal disorders (e.g., eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic colitis), gastritis, diarrhea, gastroesophageal reflux disease (GORD, or its synonym GERD), inflammatory bowel disease (IBD) (e.g., Crohn’s disease, ulcerative colitis, collagenous colitis, lymphocytic colitis, ischaemic colitis, diversion colitis, Behcet’s syndrome, indeterminate colitis) and inflammatory bowel syndrome (IBS)), and disorders ameliorated by a gastroprokinetic agent (e.g., ileus, postoperative ileus and ileus during sepsis; gastroesophageal reflux disease (GORD, or its synonym GERD); eosinophilic esophagitis, gastroparesis such as diabetic gastroparesis; food intolerances and food allergies and other functional bowel disorders, such as non-ulcerative dyspepsia (NUD) and non- cardiac chest pain (NCCP, including costo-chondritis)). [00115] An “infection” or “infectious disease” refers to an infection with a microorganism, such as a protozoa, fungus, bacteria, or virus. Various infections include, but are not limited to, skin infections, GI infections, urinary tract infections, genito-urinary infections, sepsis, blood infections, and systemic infections.

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[00116] As used herein, “mitochondrial disorders” related to disorders that are due to abnormal mitochondria, such as, for example, a mitochondrial genetic mutation, enzyme pathways, etc. Examples of disorders include, but are not limited to: loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays, and susceptibility to infection. [00117] The term “skin condition” or “skin disease” refers to a condition related to the skin. Exemplary skin conditions or skin diseases include, but are not limited to, but are not limited to, acanthoma fissuratum, acanthosis nigricans, accessory tragus, acne, acne excoriée, acne keloidalis nuchae, acquired digital fibrokeratoma, acrochordons, acrodermatitis enteropathica, acropustulosis of infancy, actinic cheilitis, actinic keratosis, actinic purpura, dolorosa (Dercum’s disease), albinism, alkaptonuria, allergic contact dermatitis, alopecia areata, alopecia mucinosa, androgenetic alopecia, anetoderma, angioedema, angiofibroma, angiokeratoma, angiomas, angular cheilitis, aphthous ulcer, aplasia cutis congenita, ashy dermatosis, asteatotic eczema, atopic dermatitis, atrophie blanche, atrophoderma of pasini and pierini, atypical moles, balanitis, basal cell carcinoma, basal cell nevus syndrome, Becker’s nevus, bee and wasp stings, black hairy tongue, Blaschko’s lines, blue nevus, boils, Bowen’s disease, Bowenoid papulosis, brachioradial pruritus, bullous pemphigoid, Buruli ulcer, calcipotriene, canker sore, capsaicin, carbuncle, cellulitis, central centrifugal cicatricial alopecia, chancroid, cherry angioma, chicken pox, chondrodermatitis nodularis helicis, condyloma acuminata, confluent and reticulated papillomatosis, congenital adrenal hyperplasia, contact dermatitis, Cowden syndrome, cutaneous T cell lymphoma, cutis marmorata, cysts, dandruff, Darier disease, dermal fillers, dermatitis herpetiformis, dermatofibroma, dermatofibrosarcoma protuberans, dermatographism, dermatomyositis, dermatosis papulosa nigra, diaper dermatitis, digital mucous cyst, discoid lupus erythematosus, disseminated superficial actinic porokeratosis, DRESS syndrome, dry skin, dyshidrotic dermatitis, dysplastic moles, eczema, Ehlers-Danlos syndrome, elastosis perforans serpiginosa, epidermal cyst, epidermal nevus, epidermolysis bullosa, epidermolysis bullosa acquisita, erosive pustular dermatosis, erysipelas, erythema ab igne, erythema annulare centrifugum, erythema dyschromicum perstans, erythema infectiosum, erythema multiforme, erythema nodosum, erythema toxicum neonatorum, erythrasma, erythromelalgia, etanercept, exanthem subitum, Fabry disease, Favre-Racouchot syndrome, female pattern hair loss, fifth disease (also referred to as erythema infectiosum), fire ant bites, fish tank granuloma, flea bites, focal dermal hypoplasia, folliculitis, Fordyce spots, Fox-Fordyce

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disease, frostbite, fungal infections, furuncle, geographic tongue, Gianotti-Crosti syndrome, glomus tumor, Gorlin syndrome, granuloma annulare, granuloma inguinale, green nail syndrome, Grover’s disease, habit tic nail deformity, Hailey-Hailey disease, hair loss, hair removal, hair transplantation, halo moles, hand rashes, hand foot and mouth disease, head lice, hemangiomas, Henoch-Schonlein purpura, hereditary hemorrhagic telangiectasia, herpes, herpes zoster, hidradenitis suppurativa, hidrocystoma, hirsutism, hives, hot tub folliculitis, hyperhidrosis, hyperpigmentation, hypersensitivity vasculitis, hypomelanosis of ito, ichthyosis, idiopathic guttate hypomelanosis, impetigo, incontinentia pigmenti, ingenol mebutate, intertrigo, itching, Jessner lymphocytic infiltrate, jiggers, juvenile plantar dermatosis, juvenile xanthogranuloma, Kaposi’s sarcoma, Kawasaki’s disease, keloids and hypertrophic scars, keratoacanthoma, keratosis follicularis spinulosa decalvans, keratosis pilaris, Kyrle’s disease, leiomyoma, leishmaniasis, lentigines, lentigo maligna, leprosy, leukocytoclastic vasculitis, leukoplakia, lice, lichen amyloidosis, lichen nitidus, lichen planus, lichen sclerosus, lichen simplex chronicus, lichen spinulosus, lichen striatus, linear IgA bullous dermatosis, lipodermatosclerosis, lipoma, loose anagen syndrome, Lyme disease, lymphangioma circumscriptum, lymphogranuloma venereum, majocchi granuloma, mastocytoma, mastocytosis, measles, melanoma, acral lentiginous, melanoma in situ, melanonychia, melasma, Melkersson-Rosenthal syndrome, meralgia paresthetica, Merkel cell carcinoma, metastatic skin cancer, methotrexate, milia, miliaria, moles, molluscum contagiosum, Mongolian spot, monilethrix, morphea, mucocele, muir-torre syndrome, mycophenolate mofetil, mycosis fungoides, myiasis, nail fungus, necrobiosis lipoidica diabeticorum, neurofibromatosis, nevoid basal cell carcinoma syndrome, nevus achromicus, nevus anemicus, nevus flammeus, nevus sebaceus, nevus spilus, nevus of ota and ito, notalgia paresthetica, nummular eczema, ochronosis, onycholysis, onychomycosis, onychophagia, orange palpebral spots, paederus dermatitis, Paget’s disease, palmoplantar pustulosis, panniculitis, parapsoriasis, paronychia nail infection, pediculosis, pellagra, pemphigus, pemphigoid gestationis, perioral dermatitis, perleche, Peutz-Jeghers syndrome, phytophotodermatitis, pilar cyst, pilomatricoma, pimecrolimus, pitted keratolysis, pityriasis alba, pityriasis lichenoides, pityriasis rosea, pityriasis rubra pilaris, pityrosporum folliculitis, poikiloderma of civatte, poison ivy dermatitis, polymorphous light eruption, porokeratosis of mibelli, porphyria cutanea tarda, postherpetic neuralgia, pressure ulcers, progressive pigmentary purpura, prurigo nodularis, prurigo pigmentosa, pruritic urticarial papules and plaques of pregnancy, pseudofolliculitis barbae, pseudoxanthoma elasticum, psoriasis, punctate palmoplantar keratoderma, pyoderma gangrenosum, pyogenic granuloma, red

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scrotum syndrome, rheumatoid nodules, rocky mountain spotted fever, rosacea, roseola infantum, sarcoidosis, scabies, scarlet fever, Schamberg’s disease, scleroderma, sebaceous cyst, sebaceous hyperplasia, seborrheic dermatitis, seborrheic keratoses, shingles, skin tags, spider angioma, spider bites, spitz nevus, sporotrichosis, squamous cell carcinoma, staphylococcal scalded skin syndrome, stasis dermatitis, steatocystoma multiplex, Stevens Johnson syndrome, stretch marks, striae, Sturge-Weber syndrome, subacute cutaneous lupus erythematosus, subungual hematoma, sweet’s syndrome, swimmer’s itch, syphilis, syringoma, systemic lupus erythematosus, systemic sclerosis, elangiectasia macularis eruptiva perstans, telogen effluvium hair loss, tinea, tinea incognito, tinea versicolor, toxic epidermal necrolysis, transient neonatal pustular melanosis, tretinoin, trichilemmal cyst, trichotillomania, tuberous sclerosis, twenty nail dystrophy, urticaria, urticaria pigmentosum, varicella, vitiligo, warts, washboard nail, xanthelasma, xeroderma pigmentosum, xerosis, or xerotic eczema. [00118] The term “spleen disease” refers to a disease of the spleen. Example of spleen diseases include, but are not limited to, splenomegaly, spleen cancer, asplenia, spleen trauma, idiopathic purpura, Felty’s syndrome, Hodgkin’s disease, and immune-mediated destruction of the spleen. [00119] Other than in the examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” “About” and “approximately” mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, or more typically, within 5%, 4%, 3%, 2%, or 1% of a given value or range of values. [00120] Unless otherwise required by context, singular terms shall include pluralities, and plural terms shall include the singular. D ^ETAILED D ^{ESCRIPTION OF} C ^ERTAIN E ^MBODIMENTS [00121] Provided herein are compounds, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and pharmaceutical compositions and kits thereof. The compounds provided herein may cross the blood-brain barrier and/or blood-retinal barrier and can therefore be used to treat and/or prevent diseases and conditions in a subject, such as diseases or conditions associated with plasmalogen deficiency of one or more plasmalogens, including, but not limited to, neurodegenerative diseases, genetic diseases, and pulmonary

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diseases. Without wishing to be bound by any particular theory, the plasmalogen deficiency may be caused by reduced synthesis (e.g., due to peroxisomal dysfunction) or transport, or by increased degradation (e.g., due to cytochrome C activity, oxidative stress, inflammation, or homeostatic conversion). [00122] Also provided herein are methods of treating and/or preventing a disease, disorder, or condition in a subject comprising administering an effective amount of a compound or composition provided herein to the subject. The compound or composition may be administered as a monotherapy or in combination with another therapy, as described herein. Other uses of the compounds and pharmaceutical compositions provided herein include methods of transporting a compound or composition provided herein via Mfsd2a, including but not limited to transport via Mfsd2a across the blood-brain barrier or blood-retinal barrier, and methods of increasing plasmalogen levels in the brain or central nervous system of a subject. Compounds Compounds of Formula (I) [00123] In one aspect, provided herein are compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ; L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; X is selected from R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C _1-6 alkyl, or R ⁵ is absent when

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L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. [00124] In certain embodiments, the compound of Formula (I) is not: , or a pharmaceutically acceptable salt thereof. [00125] In another aspect, the present disclosure provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ;

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L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; X is selected from R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C _1-6 alkyl, or R ⁵ is absent when L ² is optionally substituted C1-10 alkylene or optionally substituted carbocyclylene. [00126] In certain embodiments, the compound is of Formula (I-A): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ¹ is optionally substituted C _7-25 alkyl; R ² is optionally substituted ; L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C1-6 alkyl; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. [00127] In certain embodiments, the compound is of Formula (I-A): or a pharmaceutically acceptable salt thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ;

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L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C1-6 alkyl; and L ² is optionally substituted C1-10 alkylene or optionally substituted carbocyclylene. [00128] In certain embodiments, the compound is of Formula (I-A-i): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ¹ is optionally substituted C _7-25 alkyl; R ² is optionally substituted R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C _1-6 alkyl; R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or C1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene; provided that at least one of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ is not hydrogen. [00129] In certain embodiments, the compound is of Formula (I-A-i): or a pharmaceutically acceptable salt thereof, wherein: R ¹ is optionally substituted C _7-25 alkyl; R ² is optionally substituted ; R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C _1-6 alkyl;

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R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or C _1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene; provided that at least one of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ is not hydrogen. [00130] In certain embodiments, the compound is of Formula (I-A-ii): -ii), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ¹ is optionally substituted C _7-25 alkyl; R ² is optionally substituted L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; and L ² is optionally substituted C1-10 alkylene or optionally substituted carbocyclylene. [00131] In certain embodiments, the compound is of Formula (I-A-ii): -ii), or a pharmaceutically acceptable salt thereof, wherein: R ¹ is optionally substituted C _7-25 alkyl; R ² is optionally substituted ; L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; and L ² is optionally substituted C1-10 alkylene or optionally substituted carbocyclylene.

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[00132] In certain embodiments, the compound is of Formula (I-A-iii): -iii), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ; L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. [00133] In certain embodiments, the compound is of Formula (I-A-iii): -iii), or a pharmaceutically acceptable salt thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ; L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. [00134] In certain embodiments, the compound is of Formula (I-B): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted

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L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; R ³ and R ⁴ are each independently hydrogen or optionally substituted C1-6 alkyl; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. [00135] In certain embodiments, the compound is of Formula (I-B): or a pharmaceutically acceptable salt thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ; L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene; R ³ and R ⁴ are each independently hydrogen or optionally substituted C _1-6 alkyl; and L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. [00136] In certain embodiments, the compound is of Formula (I-C): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ¹ is optionally substituted C7-25 alkyl; R ² is optionally substituted ; X is selected from R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C1-6 alkyl, or R ⁵ is absent when

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L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene; and R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or C1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl. [00137] In some embodiments, R ¹ is optionally substituted C7-25 alkyl. In certain embodiments, R ¹ is unsubstituted C _7-25 alkyl. In some embodiments, R ¹ is C _7-25 haloalkyl. In certain embodiments, R ¹ is C _7-25 fluoroalkyl. In some embodiments, R ¹ is C _7-25 alkyl substituted with at least one deuterium. In certain embodiments, R ¹ is C7-25 alkyl substituted with at least two deuterium atoms. In some embodiments, R ¹ is optionally substituted C12-20 alkyl. In certain embodiments, R ¹ is unsubstituted C _12-20 alkyl. In some embodiments, R ¹ is C12-20 haloalkyl. In certain embodiments, R ¹ is C12-20 fluoroalkyl. In some embodiments, R ¹ is C12-20 alkyl substituted with at least one deuterium. In certain embodiments, R ¹ is C12-20 alkyl substituted with at least two deuterium atoms. In some embodiments, R ¹ is optionally substituted C14-18 alkyl. In certain embodiments, R ¹ is unsubstituted C14-18 alkyl. In some embodiments, R ¹ is C14-18 haloalkyl. In certain embodiments, R ¹ is C14-18 fluoroalkyl. In some embodiments, R ¹ is C _14-18 alkyl substituted with at least one deuterium. In certain embodiments, R ¹ is C _14-18 alkyl substituted with at least two deuterium atoms. In some embodiments, R ¹ is optionally substituted C14 alkyl. In certain embodiments, R ¹ is unsubstituted C14 alkyl. In some embodiments, R ¹ is C14 haloalkyl. In certain embodiments, R ¹ is C ₁₄ fluoroalkyl. In some embodiments, R ¹ is C ₁₄ alkyl substituted with at least one deuterium. In certain embodiments, R ¹ is C14 alkyl substituted with at least two deuterium atoms. In some embodiments, R ¹ is optionally substituted C16 alkyl. In certain embodiments, R ¹ is unsubstituted C ₁₆ alkyl. In some embodiments, R ¹ is C ₁₆ haloalkyl. In certain embodiments, R ¹ is C16 fluoroalkyl. In some embodiments, R ¹ is C16 alkyl substituted with at least one deuterium. In certain embodiments, R ¹ is C16 alkyl substituted with at least two deuterium atoms. [00138] In certain embodiments, R ¹ is selected from the group consisting of ,

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. embodiments, R ¹ is selected from . [00139] In certain embodiments, R ¹ is selected from the group consisting of: . [00140] In some embodiments, R ¹ is selected from the group consisting of: some embodiments, R ¹ is selected from the group consisting of: . [00141] In certain embodiments, R ¹ is selected from the group consisting of: ,

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. certain embodiments, R ¹ is selected from . [00142] In certain embodiments, R ¹ is selected from the group consisting of: . In certain embodiments, R ¹ is selected from the group . [00143] In some embodiments, R ² is optionally substituted . certain embodiments, R ² is unsubstituted . some embodiments, R ² is substituted with a non-aliphatic substituent. In some embodiments, R ² is not substituted with an aliphatic substituent. In some embodiments, R ² is not substituted with an alkyl, alkenyl, alkynyl group.

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In some embodiments, R ² is not substituted with an alkyl, alkenyl, alkynyl group at the terminal position. In some embodiments, R ² is substituted at a vinylic or allylic position. [00144] In some embodiments, R ² is substituted with deuterium, halogen, −OC(=O)R ^aa , −OCO2R ^aa , −OC(=O)N(R ^bb )2, −NR ^bb C(=O)R ^aa , −NR ^bb CO2R ^aa , or −NR ^bb C(=O)N(R ^bb ) ₂ . In some embodiments, R ² is substituted C1-10 alkyl, deuterium, halogen, −OR ^aa , −SR ^aa , −N(R ^bb )2, –CN, –SCN, –NO2, −C(=O)R ^aa , −CO2R ^aa , −C(=O)N(R ^bb )2, −OC(=O)R ^aa , −OCO2R ^aa , −OC(=O)N(R ^bb )2, −NR ^bb C(=O)R ^aa , −NR ^bb CO ₂ R ^aa , or −NR ^bb C(=O)N(R ^bb ) ₂ , provided that the optionally substituted C1-10 alkyl is not at the terminal position. [00145] In some embodiments, R ² is some embodiments, R ² is substituted with at least one fluorine. In certain embodiments, R ² is substituted with at least one deuterium. [00146] In certain embodiments, R ² is selected from the group consisting of . [00147] In certain embodiments, R ¹ is unsubstituted C _7-25 alkyl, and R ² is unsubstituted . some embodiments, R ¹ is C7-25 haloalkyl, and R ² is unsubstituted . In certain embodiments, R ¹ is C _7-25 fluoroalkyl, and R ² is unsubstituted . some embodiments, R ¹ is unsubstituted C12-20 alkyl, and R ² is unsubstituted . certain embodiments, R ¹ is C12- ₂₀ haloalkyl, and R ² is unsubstituted

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. some embodiments, R ¹ is C _12- 20 fluoroalkyl, and R ² is unsubstituted . [00148] In certain embodiments, R ¹ is unsubstituted C _7-25 alkyl, and R ² is substituted with at least one fluorine. In some embodiments, R ¹ is C7-25 haloalkyl, and R ² is substituted with at least one fluorine. In certain embodiments, R ¹ is C _7-25 fluoroalkyl, and R ² is substituted with at least one fluorine. In some embodiments, R ¹ is unsubstituted C12-20 alkyl, and R ² is substituted with at least one fluorine. In certain embodiments, R ¹ is C _12-20 haloalkyl, and R ² is substituted with at least one fluorine. In some embodiments, R ¹ is C12-20 fluoroalkyl, and R ² is substituted with at least one fluorine. [00149] In certain embodiments, R ¹ is unsubstituted C7-25 alkyl, and R ² is substituted with at least one deuterium. In some embodiments, R ¹ is C _7-25 haloalkyl, and R ² is substituted with at least one deuterium. In certain embodiments, R ¹ is C7-25 fluoroalkyl, and R ² is substituted with at least one deuterium. In some embodiments, R ¹ is unsubstituted C _12-20 alkyl, and R ² is substituted with at least one deuterium. In certain embodiments, R ¹ is C12-20 haloalkyl, and R ² is substituted with at least one deuterium. In some embodiments, R ¹ is C _12-20 fluoroalkyl, and R ² is substituted with at least one deuterium.

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[00150] In some embodiments, X is selected from . [00151] In some embodiments, R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C _1-6 alkyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C1-4 alkyl. In some embodiments, R ³ , R ⁴ , and R ⁵ are each independently hydrogen or optionally substituted C1-2 alkyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each independently hydrogen or unsubstituted C _1-6 alkyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each independently hydrogen or unsubstituted C1-4 alkyl. In some embodiments, R ³ , R ⁴ , and R ⁵ are each independently hydrogen or unsubstituted C1-2 alkyl. [00152] In certain embodiments, at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. In some embodiments, at least two of R ³ , R ⁴ , and R ⁵ are hydrogen. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each hydrogen. In some embodiments, R ³ and R ⁴ are each hydrogen. In certain embodiments, R ³ and R ⁵ are each hydrogen. In some embodiments, R ⁴ and R ⁵ are each hydrogen. [00153] In certain embodiments, at least one of R ³ , R ⁴ , and R ⁵ is unsubstituted C1-6 alkyl. In some embodiments, at least one of R ³ and R ⁴ is optionally substituted C1-6 alkyl. In certain embodiments, at least one of R ³ and R ⁵ is optionally substituted C _1-6 alkyl. In some embodiments, at least one of R ⁴ and R ⁵ is optionally substituted C1-6 alkyl. In certain embodiments, R ³ and R ⁴ are each independently optionally substituted C1-6 alkyl. In some embodiments, R ³ and R ⁵ are each independently optionally substituted C _1-6 alkyl. In certain embodiments, R ⁴ and R ⁵ are each independently optionally substituted C _1-6 alkyl. In some embodiments, R ³ and R ⁴ are each methyl. In some embodiments, R ³ and R ⁵ are each methyl. In some embodiments, R ⁴ and R ⁵ are each methyl. In certain embodiments, R ⁵ is optionally substituted C _1-6 alkyl. In some embodiments, R ⁵ is methyl. [00154] In certain embodiments, R ³ and R ⁴ are hydrogen, and R ⁵ is unsubstituted C1-6 alkyl. In some embodiments, at least two of R ³ , R ⁴ , and R ⁵ are unsubstituted C1-6 alkyl. In some embodiments, R ³ is hydrogen, and at least one of R ⁴ and R ⁵ is unsubstituted C _1-6 alkyl. In

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certain embodiments, R ³ , R ⁴ , and R ⁵ are each unsubstituted C _1-6 alkyl. In some embodiments, are each independently methyl, ethyl, propyl, or butyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each methyl. In some embodiments, R ³ , R ⁴ , and R ⁵ are each ethyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each propyl. In some embodiments, R ³ , R ⁴ , and R ⁵ are each butyl. [00155] In certain embodiments, at least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C1-6 alkyl. In certain embodiments, R ³ and R ⁴ are hydrogen, and R ⁵ is optionally substituted C _1-6 alkyl. In some embodiments, at least two of R ³ , R ⁴ , and R ⁵ are optionally substituted C1-6 alkyl. In some embodiments, R ³ is hydrogen, and at least one of R ⁴ and R ⁵ is optionally substituted C _1-6 alkyl. In certain embodiments, R ³ is hydrogen, and R ⁴ is optionally substituted C _1-6 alkyl. In some embodiments, R ³ is hydrogen, and R ⁵ is optionally substituted C1-6 alkyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each optionally substituted C1-6 alkyl. [00156] In certain embodiments, at least one of R ³ , R ⁴ , and R ⁵ is C1-6 fluoroalkyl. In some embodiments, at least one of R ³ and R ⁴ is C _1-6 fluoroalkyl. In certain embodiments, at least one of R ³ and R ⁵ is C1-6 fluoroalkyl. In some embodiments, at least one of R ⁴ and R ⁵ is C1-6 fluoroalkyl. In certain embodiments, R ⁵ is C1-6 fluoroalkyl. In some embodiments, R ⁵ is - CH ₂ F, -CHF2, or -CF3. [00157] In certain embodiments, R ³ and R ⁴ are hydrogen, and R ⁵ is C1-6 fluoroalkyl. In some embodiments, at least two of R ³ , R ⁴ , and R ⁵ are C _1-6 fluoroalkyl. In some embodiments, R ³ is hydrogen, and at least one of R ⁴ and R ⁵ is C _1-6 fluoroalkyl. In certain embodiments, R ³ , R ⁴ , and R ⁵ are each C1-6 fluoroalkyl. In some embodiments, at least one of R ³ , R ⁴ , and R ⁵ is - CH2F, -CHF ₂ , or -CF ₃ . In certain embodiments, at least one of R ³ and R ⁴ is -CH ₂ F, -CHF ₂ , or -CF ₃ . In some embodiments, at least one of R ³ and R ⁵ is -CH2F, -CHF2, or -CF3. In certain embodiments, at least one of R ⁴ and R ⁵ is -CH2F, -CHF2, or -CF3. In certain embodiments, at least one of R ³ , R ⁴ , and R ⁵ is -CH ₂ F. In some embodiments, at least one of R ³ , R ⁴ , and R ⁵ is - CHF2. In certain embodiments, at least one of R ³ , R ⁴ , and R ⁵ is -CF3. [00158] In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form optionally substituted heterocyclyl. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form substituted heterocyclyl. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form unsubstituted heterocyclyl. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form 3- to 7-membered optionally substituted heterocyclyl. In certain embodiments, R ³ and R ⁴ are

68/200 joined together with the intervening atoms to form 5- to 6-membered optionally substituted heterocyclyl. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form optionally substituted an aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, or azepanyl ring. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form an unsubstituted aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, or azepanyl ring. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form optionally substituted pyrrolidinyl or piperidinyl. In certain embodiments, R ³ and R ⁴ are joined together with the intervening atoms to form unsubstituted pyrrolidinyl or piperidinyl. [00160] In certain embodiments, R ¹ is unsubstituted C7-25 alkyl, and at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. In some embodiments, R ¹ is C _7-25 haloalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. In certain embodiments, R ¹ is C7-25 fluoroalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. In some embodiments, R ¹ is unsubstituted C12-20 alkyl, and at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. In certain embodiments, R ¹ is C _12-20 haloalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. In some embodiments, R ¹ is C _12-20 fluoroalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is hydrogen. [00161] In certain embodiments, R ¹ is unsubstituted C7-25 alkyl, and at least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C _1-6 alkyl. In some embodiments, R ¹ is C _7-25 haloalkyl, and at

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least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C _1-6 alkyl. In certain embodiments, R ¹ is C7-25 fluoroalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C1-6 alkyl. In some embodiments, R ¹ is unsubstituted C12-20 alkyl, and at least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C _1-6 alkyl. In certain embodiments, R ¹ is C _12-20 haloalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C1-6 alkyl. In some embodiments, R ¹ is C12-20 fluoroalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is optionally substituted C1-6 alkyl ^. [00162] In certain embodiments, R ¹ is unsubstituted C _7-25 alkyl, and at least one of R ³ , R ⁴ , and R ⁵ is C1-6 fluoroalkyl. In some embodiments, R ¹ is C7-25 haloalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is C1-6 fluoroalkyl. In certain embodiments, R ¹ is C7-25 fluoroalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is C _1-6 fluoroalkyl. In some embodiments, R ¹ is unsubstituted C _12-20 alkyl, and at least one of R ³ , R ⁴ , and R ⁵ is C _1-6 fluoroalkyl. In certain embodiments, R ¹ is C _12-20 haloalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is C1-6 fluoroalkyl. In some embodiments, R ¹ is C12-20 fluoroalkyl, and at least one of R ³ , R ⁴ , and R ⁵ is C1-6 fluoroalkyl ^. [00163] In some embodiments, L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene. In certain embodiments, L ¹ is optionally substituted or optionally substituted carbocyclylene. In some embodiments, L ¹ is optionally substituted or optionally substituted heterocyclylene. In certain embodiments, L ¹ is optionally substituted carbocyclylene, or optionally substituted heterocyclylene. [00164] In some embodiments, L ¹ is optionally substituted , optionally substituted carbocyclylene, or optionally substituted heterocyclylene, wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is optionally substituted or optionally substituted carbocyclylene, wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, L ¹ is optionally substituted or optionally substituted heterocyclylene, wherein ** designates the point of attachment to -

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OC(O)R ² . In certain embodiments, L ¹ is optionally substituted carbocyclylene, or optionally substituted heterocyclylene, wherein ** designates the point of attachment to -OC(O)R ² . [00165] In some embodiments, L ¹ is optionally substituted . In certain embodiments, L ¹ is optionally substituted . In some embodiments, L ¹ is unsubstituted . In certain embodiments, L ¹ is substituted . In some embodiments, L ¹ is substituted with one or more fluorine atoms. In certain embodiments, L ¹ is substituted with one or more deuterium atoms. In some embodiments, L ¹ is substituted with one or more instances of optionally substituted C _1-6 alkyl. In certain embodiments, L ¹ is substituted with one or more instances of unsubstituted C1-6 alkyl. In some embodiments, L ¹ is substituted with one or more instances of substituted C1-6 alkyl. In some embodiments, L ¹ is substituted with optionally substituted carbocyclyl. In certain embodiments, L ¹ is substituted with unsubstituted carbocyclyl. In some embodiments, L ¹ is substituted with substituted carbocyclyl. In some embodiments, L ¹ is substituted with optionally substituted C3-6 carbocyclyl. In certain embodiments, L ¹ is substituted with unsubstituted C _3-6 carbocyclyl. In some embodiments, L ¹ is substituted with substituted C _3-6 carbocyclyl. In some embodiments, L ¹ is substituted with optionally substituted C3-4 carbocyclyl. In certain embodiments, L ¹ is substituted with unsubstituted C3-4 carbocyclyl. In some embodiments, L ¹ is substituted with substituted C3-4 carbocyclyl.

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¹ [00166] In some embodiments, L is optionally substituted , wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is optionally substituted , wherein ** designates the point of attachment to -OC(O)R ² . In 1 some embodiments, L is unsubstituted , wherein ** designates the point of 2 ¹ attachment to -OC(O)R . In certain embodiments, L is substituted , wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, L ¹ is substituted with one or more fluorine atoms, wherein ** designates the point of attachment to 2 ¹ -OC(O)R . In certain embodiments, L is substituted with one or more deuterium atoms, wherein ** designates the point of attachment to -OC(O)R ² . In some 1 embodiments, L is substituted with one or more instances of optionally substituted C1-6 alkyl, wherein ** designates the point of attachment to -OC(O)R ² . In certain 1 embodiments, L is substituted with one or more instances of unsubstituted C _1- 6 alkyl, wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, 1 L is substituted with one or more instances of substituted C _1-6 alkyl, wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, L ¹ is substituted with optionally substituted carbocyclyl, wherein ** designates the

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^{2 1} point of attachment to -OC(O)R . In certain embodiments, L is substituted with unsubstituted carbocyclyl, wherein ** designates the point of attachment to -OC(O)R ² . 1 In some embodiments, L is substituted with substituted carbocyclyl, wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, L ¹ is substituted with optionally substituted C3-6 carbocyclyl, wherein ** designates 2 ¹ the point of attachment to -OC(O)R . In certain embodiments, L is substituted with unsubstituted C _3-6 carbocyclyl, wherein ** designates the point of attachment to - 2 ¹ OC(O)R . In some embodiments, L is substituted with substituted C3-6 carbocyclyl, wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, L ¹ is substituted with optionally substituted C3-4 carbocyclyl, wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is substituted with unsubstituted C3-4 carbocyclyl, wherein ** designates the 2 ¹ point of attachment to -OC(O)R . In some embodiments, L is substituted with substituted C _3-4 carbocyclyl, wherein ** designates the point of attachment to -OC(O)R ² . [00167] In certain embodiments, L ¹ is optionally substituted carbocyclylene. In some embodiments, L ¹ is unsubstituted carbocyclylene. In certain embodiments, L ¹ is substituted carbocyclylene. In certain embodiments, L ¹ is optionally substituted C3-14 carbocyclylene. In certain embodiments, L ¹ is optionally substituted C ₃ - ₈ carbocyclylene. In certain embodiments, L ¹ is C ₃ - ₆ carbocyclylene. In certain embodiments, L ¹ is optionally substituted monocyclic carbocyclylene. In some embodiments, L ¹ is unsubstituted monocyclic carbocyclylene. In certain embodiments, L ¹ is substituted monocyclic carbocyclylene. In

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certain embodiments, L ¹ is optionally substituted C ₃ - ₁₄ monocyclic carbocyclylene. In certain embodiments, L ¹ is optionally substituted C3-8 monocyclic carbocyclylene. In certain embodiments, L ¹ is C3-6 monocyclic carbocyclylene. In certain embodiments, L ¹ is optionally substituted cyclopropylene, optionally substituted cyclobutylene, optionally substituted cyclopentylene, or optionally substituted cyclohexylene. In some embodiments, L ¹ is optionally substituted bicyclic carbocyclylene. In certain embodiments, L ¹ is unsubstituted bicyclic carbocyclylene. In some embodiments, L ¹ is substituted bicyclic carbocyclylene. In certain embodiments, L ¹ is optionally substituted C3-14 bicyclic carbocyclylene. In certain embodiments, L ¹ is optionally substituted C5-14 bicyclic carbocyclylene. In certain embodiments, L ¹ is optionally substituted C ₅ - ₁₀ bicyclic carbocyclylene. [00168] In some embodiments, L ¹ is optionally substituted heterocyclylene. In certain embodiments, L ¹ is unsubstituted heterocyclylene. In some embodiments, L ¹ is substituted heterocyclylene. In certain embodiments, L ¹ is optionally substituted 3-14 membered heterocyclylene. In certain embodiments, L ¹ is optionally substituted 3-8 membered heterocyclylene. In certain embodiments, L ¹ is optionally substituted monocyclic heterocyclylene. In some embodiments, L ¹ is unsubstituted monocyclic heterocyclylene. In certain embodiments, L ¹ is substituted monocyclic heterocyclylene. In certain embodiments, L ¹ is optionally substituted 3-14 membered monocyclic heterocyclylene. In certain embodiments, L ¹ is optionally substituted 3-8 membered monocyclic heterocyclylene. In some embodiments, L ¹ is optionally substituted bicyclic heterocyclylene. In certain embodiments, L ¹ is unsubstituted bicyclic heterocyclylene. In some embodiments, L ¹ is substituted bicyclic heterocyclylene. In certain embodiments, L ¹ is optionally substituted 5-14 membered bicyclic heterocyclylene. In certain embodiments, L ¹ is optionally substituted 5-10 membered bicyclic heterocyclylene. In certain embodiments, L ¹ is heterocyclylene comprising at least one oxygen atom. In some embodiments, L ¹ is heterocyclylene comprising at least one sulfur atom. In certain embodiments, L ¹ is heterocyclylene comprising at least one optionally substituted nitrogen atom. In some embodiments, L ¹ is heterocyclylene comprising at least one nitrogen atom substituted with hydrogen, optionally substituted C1-6 alkyl, or a nitrogen protecting group. In certain embodiments, L ¹ is heterocyclylene comprising at least one nitrogen atom substituted with hydrogen, unsubstituted C _1-6 alkyl, or a nitrogen protecting group. In certain embodiments, L ¹ is optionally substituted piperidinylene, optionally substituted tetrahydro-2H-pyranylene, or optionally substituted tetrahydro-2H-thiopyranylene.

74/200 [00169] In certain embodiments, L ¹ is selected from the group consisting of: , embodiments, L ¹ is selected from the group consisting of: , and certain embodiments, L ¹ is selected from the group consisting of:

75/200 [00170] In certain embodiments, L ¹ is selected from the group consisting of: , wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is selected from the group consisting of: ,

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, wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is selected from the group consisting of: , , , , , , , wherein ** designates the point of attachment to -OC(O)R ² . In some embodiments, L ¹ is selected from the group consisting of: , wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is selected from the group consisting of: wherein ** designates the point of attachment to -OC(O)R ² . In certain embodiments, L ¹ is selected from the group consisting of: , wherein ** designates the point of attachment to -OC(O)R ² . [00171] In some embodiments, L ² is optionally substituted C _1-10 alkylene or optionally substituted carbocyclylene. In certain embodiments, L ² is optionally substituted C1-6 alkylene or optionally substituted carbocyclylene. In some embodiments, L ² is optionally substituted

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C _1-4 alkylene or optionally substituted carbocyclylene. In some embodiments, L ² is substituted with fluorine. In some embodiments, L ² is optionally substituted C1-10 alkylene or optionally substituted C3-14 carbocyclylene. In certain embodiments, L ² is optionally substituted C _1-6 alkylene or optionally substituted C _3-8 carbocyclylene. In some embodiments, L ² is optionally substituted C1-4 alkylene or optionally substituted C3-8 carbocyclylene. In some embodiments, L ² is substituted with fluorine. [00172] In some embodiments, L ² is –(optionally substituted C _1-10 alkylene)-(optionally substituted carbocyclylene)-. In some embodiments, L ² is –(optionally substituted C1-10 alkylene)-(optionally substituted C3-14 carbocyclylene)-. In some embodiments, L ² is – (optionally substituted C _1-6 alkylene)-(optionally substituted C _3-8 carbocyclylene)-. In some embodiments, L ² is -(optionally substituted C _1-4 alkylene)-(optionally substituted C _3-14 carbocyclylene). In some embodiments, L ² is –(optionally substituted C1-4 alkylene)- (optionally substituted C3-8 carbocyclylene)-. In some embodiments, L ² is -(optionally substituted C ₁ alkylene)-(optionally substituted C _3-8 carbocyclylene)-. In some embodiments, L ² is -(optionally substituted C2 alkylene)-(optionally substituted C3-8 carbocyclylene)-. In some embodiments, L ² is -(optionally substituted C1-6 alkylene)-(optionally substituted C3-8 carbocyclylene)-(optionally substituted C _0-4 alkylene)-. In some embodiments, L ² is - (optionally substituted C1-4 alkylene)-(optionally substituted C3-8 carbocyclylene)-(optionally substituted C0-4 alkylene)-. [00173] In certain embodiments, L ² is optionally substituted C _1-10 alkylene. In some embodiments, L ² is unsubstituted C _1-10 alkylene. In certain embodiments, L ² is substituted C _1- 10 alkylene. In certain embodiments, L ² is optionally substituted C1-6 alkylene. In some embodiments, L ² is unsubstituted C1-6 alkylene. In certain embodiments, L ² is substituted C1-6 alkylene. In certain embodiments, L ² is optionally substituted C _1-4 alkylene. In some embodiments, L ² is unsubstituted C1-4 alkylene. In certain embodiments, L ² is substituted C1-4 alkylene. In some embodiments, L ² is optionally substituted ethylene, propylene, or butylene. In certain embodiments, L ² is optionally substituted ethylene or propylene. In some embodiments, L ² is optionally substituted ethylene. In some embodiments L ² is optionally substituted propylene. In some embodiments, L ² is C1-10 alkylene substituted with fluorine. In some embodiments, L ² is C _1-6 alkylene substituted with fluorine. In some embodiments, L ² is C _1-4 alkylene substituted with fluorine. [00174] In certain embodiments, L ² is optionally substituted carbocyclylene. In some embodiments, L ² is unsubstituted carbocyclylene. In certain embodiments, L ² is substituted carbocyclylene. In certain embodiments, L ² is carbocyclylene substituted with fluorine. In

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some embodiments, L ² is optionally substituted C _3-14 carbocyclylene. In some embodiments, L ² is optionally substituted C3-8 carbocyclylene. In certain embodiments, L ² is C3-6 carbocyclylene. In certain embodiments, L ² is optionally substituted monocyclic carbocyclylene. In some embodiments, L ² is unsubstituted monocyclic carbocyclylene. In certain embodiments, L ² is substituted monocyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C3-14 monocyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C ₃ - ₈ monocyclic carbocyclylene. In certain embodiments, L ² is C ₃ - ₆ monocyclic carbocyclylene. In certain embodiments, L ² is optionally substituted cyclopropylene, optionally substituted cyclobutylene, optionally substituted cyclopentylene, or optionally substituted cyclohexylene. In some embodiments, L ² is optionally substituted bicyclic carbocyclylene. In certain embodiments, L ² is unsubstituted bicyclic carbocyclylene. In some embodiments, L ² is substituted bicyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C3-14 bicyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C ₅ - ₁₄ bicyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C5-10 bicyclic carbocyclylene. In some embodiments, L ² is optionally substituted tricyclic carbocyclylene. In certain embodiments, L ² is unsubstituted tricyclic carbocyclylene. In some embodiments, L ² is substituted tricyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C3-14 tricyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C5-14 tricyclic carbocyclylene. In certain embodiments, L ² is optionally substituted C ₅ - ₁₀ tricyclic carbocyclylene. , certain embodiments, L ² is selected from the group consisting of: , some embodiments, L ² is selected from the group consisting of:

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group consisting of: . In certain embodiments, L ² is selected from the group consisting of: [00176] In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or optionally substituted C _1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or an optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or C1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or an optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or optionally substituted C _1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or an optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl; provided that at least one of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ is not hydrogen. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or C _1-6 alkyl, or R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl, or R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or an optionally substituted heterocyclyl, or R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl; provided that at least one of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ is not hydrogen.

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[00177] In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or optionally substituted C1-6 alkyl. In certain embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, fluorine, or optionally substituted C1-6 alkyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or unsubstituted C1-6 alkyl. In certain embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen, halogen, or substituted C1-6 alkyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen or halogen. In certain embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen or fluorine. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen or optionally substituted C1-6 alkyl. In certain embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently hydrogen or unsubstituted C _1-6 alkyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently halogen or optionally substituted C1-6 alkyl. In certain embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently halogen or optionally substituted C1-6 alkyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently fluorine or optionally substituted C _1-6 alkyl. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are each independently fluorine or unsubstituted C1-6 alkyl. In some embodiments, R ⁶ and R ⁷ are each methyl. In some embodiments, R ⁹ and R ¹⁰ are each methyl. [00178] In certain embodiments, at least two of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are not hydrogen. In some embodiments, R ⁸ , R ⁹ , and R ¹⁰ are each hydrogen. In certain embodiments, R ⁶ , R ⁷ , and R ⁸ are each hydrogen. In some embodiments, R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are hydrogen. [00179] In certain embodiments, at least one of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ is halogen. In some embodiments, one of R ⁶ , R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ is fluorine; and the others are hydrogen. In certain embodiments, R ⁶ is fluorine, and R ⁷ , R ⁸ , R ⁹ , and R ¹⁰ are hydrogen. In some embodiments, R ⁸ is fluorine, and R ⁶ , R ⁷ , R ⁹ , and R ¹⁰ are hydrogen. In certain embodiments, R ¹⁰ is fluorine, and R ⁶ , R ⁷ , R ⁸ , and R ⁹ are hydrogen. [00180] In some embodiments, R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl. In certain embodiments, R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an unsubstituted carbocyclyl. In some embodiments, R ⁶ and R ⁷ are joined together with the intervening carbon atom to form a substituted carbocyclyl. In certain embodiments, R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an unsubstituted cyclohexyl, an unsubstituted cyclopentyl, an unsubstituted cyclobutyl, or an unsubstituted cyclopropyl. In some embodiments, R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an unsubstituted cyclobutyl or an unsubstituted cyclopropyl. In certain embodiments, R ⁶ and R ⁷ are joined together with

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the intervening carbon atom to form an unsubstituted cyclobutyl. In some embodiments, R ⁶ and R ⁷ are joined together with the intervening carbon atom to form an unsubstituted cyclopropyl. [00181] In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted carbocyclyl. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atom to form an unsubstituted carbocyclyl. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atom to form a substituted carbocyclyl. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atom to form an unsubstituted cyclohexyl, unsubstituted cyclopentyl, unsubstituted cyclobutyl, or unsubstituted cyclopropyl. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atom to form an unsubstituted cyclohexyl or unsubstituted cyclopentyl. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atom to form an unsubstituted cyclohexyl. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atom to form an unsubstituted cyclopentyl. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted heterocyclyl. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an unsubstituted heterocyclyl. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form a substituted heterocyclyl. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted heterocyclyl comprising at least one oxygen atom. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted heterocyclyl comprising at least one sulfur atom. In some embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted heterocyclyl comprising at least one optionally substituted nitrogen atom. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted heterocyclyl comprising at least one nitrogen atom substituted with hydrogen, optionally substituted C1-6 alkyl, or a nitrogen protecting group. In certain embodiments, R ⁶ and R ⁹ are joined together with the intervening carbon atoms to form an optionally substituted heterocyclyl, comprising at least one nitrogen atom substituted with hydrogen, unsubstituted C1-6 alkyl, or a nitrogen protecting group. [00182] In some embodiments, R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an optionally substituted carbocyclyl. In certain embodiments, R ⁹ and R ¹⁰ are

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joined together with the intervening carbon atom to form an unsubstituted carbocyclyl. In some embodiments, R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form a substituted carbocyclyl. In certain embodiments, R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an unsubstituted cyclohexyl, unsubstituted cyclopentyl, unsubstituted cyclobutyl, or unsubstituted cyclopropyl. In some embodiments, R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an unsubstituted cyclobutyl or unsubstituted cyclopropyl. In certain embodiments, R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an unsubstituted cyclobutyl. In some embodiments, R ⁹ and R ¹⁰ are joined together with the intervening carbon atom to form an unsubstituted cyclopropyl. [00183] In certain embodiments, the compound is: , , , ,

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, , , , , , , ,

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, , , , , ,

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, , ,

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, ,

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, , , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. [00184] In certain embodiments, the compound is: , , , ,

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, , , , , , , ,

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, , , , , ,

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, , ,

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, ,

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, , , or a pharmaceutically acceptable salt thereof. [00185] In certain embodiments, the compound is: , , , ,

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,

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, ,

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, , , , , , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. [00186] In certain embodiments, the compound is: , ,

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, , , , , , ,

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, ,

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, , or a pharmaceutically acceptable salt thereof.

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[00187] In certain embodiments, the compound is: , , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. [00188] In certain embodiments, the compound is: , , or a pharmaceutically acceptable salt thereof. [00189] In certain embodiments, the compound is: , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. [00190] In certain embodiments, the compound is: ,

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, or a pharmaceutically acceptable salt thereof. Compounds of Formula (II) [00191] In another aspect, provided herein are compounds of Formula (II): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, wherein: R ^1’ is optionally substituted C7-25 alkyl; R ^2’ is optionally substituted C _7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C _1-6 alkyl; n is 0, 1, 2, or 3; * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently hydrogen, halogen, or C1-6 alkyl. [00192] In another aspect, the compound is of Formula (II): or a pharmaceutically acceptable salt thereof, wherein: R ^1’ is optionally substituted C _7-25 alkyl; R ^2’ is optionally substituted C7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-6 alkyl;

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n is 0, 1, 2, or 3; * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently hydrogen, halogen, or C _1-6 alkyl. [00193] In certain embodiments, the compound is of Formula (II-A): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ^1’ is optionally substituted C _7-25 alkyl; R ^2” is optionally substituted ^; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C _1-6 alkyl; n is 0, 1, 2, or 3; * designates a point of attachment at one of positions X, Y, or Z; and the other two of positions X, Y, or Z are each independently hydrogen, halogen, or C _{1- 6} alkyl. [00194] In some embodiments, the compound is of Formula (II-A): or a pharmaceutically acceptable salt thereof, wherein: R ^1’ is optionally substituted C _7-25 alkyl; R ^2” is optionally substituted R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-6 alkyl; n is 0, 1, 2, or 3;

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* designates a point of attachment at one of positions X, Y, or Z; and the other two of positions X, Y, or Z are each independently hydrogen, halogen, or C1- 6 alkyl. [00195] In certain embodiments, the compound is of Formula (II-B): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ^1’ is optionally substituted C7-25 alkyl; R ^2’ is optionally substituted C _7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C _1-6 alkyl; n is 0, 1, 2, or 3; and Y and Z are each independently hydrogen, halogen, or C _1-6 alkyl. [00196] In some embodiments, the compound is of Formula (II-B): or a pharmaceutically acceptable salt thereof, wherein: R ^1’ is optionally substituted C7-25 alkyl; R ^2’ is optionally substituted C7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C _1-6 alkyl; n is 0, 1, 2, or 3; and Y and Z are each independently hydrogen, halogen, or C1-6 alkyl.

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[00197] In certain embodiments, the compound is of Formula (II-C): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ^1’ is optionally substituted C _7-25 alkyl; R ^2’ is optionally substituted C _7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-6 alkyl; n is 0, 1, 2, or 3; and X and Z are each independently hydrogen, halogen, or C _1-6 alkyl. [00198] In some embodiments, the compound is of Formula (II-C): or a pharmaceutically acceptable salt thereof, wherein: R ^1’ is optionally substituted C7-25 alkyl; R ^2’ is optionally substituted C _7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C _1-6 alkyl; n is 0, 1, 2, or 3; and X and Z are each independently hydrogen, halogen, or C1-6 alkyl.

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[00199] In certain embodiments, the compound is of Formula (II-D): or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, wherein: R ^1’ is optionally substituted C _7-25 alkyl; R ^2’ is optionally substituted C _7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-6 alkyl; n is 0, 1, 2, or 3; and X and Y are each independently hydrogen, halogen, or C _1-6 alkyl. [00200] In some embodiments, the compound is of Formula (II-D): or a pharmaceutically acceptable salt thereof, wherein: R ^1’ is optionally substituted C7-25 alkyl; R ^2’ is optionally substituted C _7-25 alkenyl; R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C _1-6 alkyl; n is 0, 1, 2, or 3; and X and Y are each independently hydrogen, halogen, or C1-6 alkyl. [00201] In some embodiments, R ^1’ is optionally substituted C _7-25 alkyl. In certain embodiments, R ^1’ is unsubstituted C7-25 alkyl. In some embodiments, R ^1’ is C7-25 haloalkyl. In certain embodiments, R ^1’ is C7-25 fluoroalkyl. In some embodiments, R ^1’ is C7-25 alkyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C _7-25 alkyl substituted with at least two deuterium atoms. In some embodiments, R ^1’ is optionally substituted C12-20 alkyl. In certain embodiments, R ^1’ is unsubstituted C12-20 alkyl. In some embodiments, R ^1’ is

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C _12-20 haloalkyl. In certain embodiments, R ^1’ is C _12-20 fluoroalkyl. In some embodiments, R ^1’ is C12-20 alkyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C12-20 alkyl substituted with at least two deuterium atoms. In some embodiments, R ^1’ is optionally substituted C _14-18 alkyl. In certain embodiments, R ^1’ is unsubstituted C _14-18 alkyl. In some embodiments, R ^1’ is C14-18 haloalkyl. In certain embodiments, R ^1’ is C14-18 fluoroalkyl. In some embodiments, R ^1’ is C14-18 alkyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C _14-18 alkyl substituted with at least two deuterium atoms. In some embodiments, R ^1’ is optionally substituted C14 alkyl. In certain embodiments, R ^1’ is unsubstituted C14 alkyl. In some embodiments, R ^1’ is C14 haloalkyl. In certain embodiments, R ^1’ is C ₁₄ fluoroalkyl. In some embodiments, R ^1’ is C ₁₄ alkyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C ₁₄ alkyl substituted with at least two deuterium atoms. In some embodiments, R ^1’ is optionally substituted C16 alkyl. In certain embodiments, R ^1’ is unsubstituted C16 alkyl. In some embodiments, R ^1’ is C16 haloalkyl. In certain embodiments, R ^1’ is C ₁₆ fluoroalkyl. In some embodiments, R ^1’ is C ₁₆ alkyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C16 alkyl substituted with at least two deuterium atoms. [00202] In some embodiments, R ^1’ is selected from the group consisting of: . some embodiments, R ^1’ is selected from ,

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. [00203] In certain embodiments, R ^1’ is selected from the group consisting of: . [00204] In some embodiments, R ^1’ is selected from the group consisting of: some embodiments, R ^1’ is selected from the group consisting of: . [00205] In certain embodiments, R ^1’ is selected from the group consisting of: . [00206] In some embodiments, R ^1’ is selected from the group consisting of:

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. In some embodiments, R ^1’ is selected from the group . [00207] In some embodiments, R ^2’ is optionally substituted C7-25 alkenyl. In certain embodiments, R ^2’ is unsubstituted C7-25 alkenyl. In some embodiments, R ^2’ is C7-25 haloalkenyl. In certain embodiments, R ^2’ is C _7-25 fluoroalkenyl. In some embodiments, R ^2’ is C _7-25 alkenyl substituted with at least one deuterium. In certain embodiments, R ^2’ is C _7-25 alkenyl substituted with at least two deuterium atoms. In some embodiments, R ^2’ is optionally substituted C _12-20 alkenyl. In certain embodiments, R ^2’ is unsubstituted C _12-20 alkenyl. In some embodiments, R ^2’ is C _12-20 haloalkenyl. In certain embodiments, R ^2’ is C _12-20 fluoroalkenyl. In some embodiments, R ^2’ is C12-20 alkenyl substituted with at least one deuterium. In certain embodiments, R ^2’ is C _12-20 alkenyl substituted with at least two deuterium atoms. In some embodiments, R ^2’ is optionally substituted C _14-18 alkenyl. In certain embodiments, R ^2’ is unsubstituted C14-18 alkenyl. In some embodiments, R ^2’ is C14-18 haloalkenyl. In certain embodiments, R ^2’ is C14-18 fluoroalkenyl. In some embodiments, R ^2’ is C14-18 alkenyl substituted with at least one deuterium. In certain embodiments, R ^2’ is C _14-18 alkenyl substituted with at least two deuterium atoms. In some embodiments, R ^2’ is optionally substituted C14 alkenyl. In certain embodiments, R ^2’ is unsubstituted C14 alkenyl. In some embodiments, R ^2’ is C ₁₄ haloalkenyl. In certain embodiments, R ^2’ is C ₁₄ fluoroalkenyl. In some embodiments, R ^2’ is C ₁₄ alkenyl substituted with at least one deuterium. In certain embodiments, R ^2’ is C14 alkenyl substituted with at least two deuterium atoms. In some embodiments, R ^2’ is optionally substituted C ₁₆ alkenyl. In certain embodiments, R ^2’ is unsubstituted C ₁₆ alkenyl. In some embodiments, R ^2’ is C ₁₆ haloalkenyl. In certain embodiments, R ^2’ is C16 fluoroalkenyl. In some embodiments, R ^2’ is C16 alkenyl substituted with at least one deuterium. In certain embodiments, R ^2’ is C16 alkenyl substituted with at least two deuterium atoms.

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[00208] In some embodiments, R ^2’ is linear optionally substituted C _7-25 alkenyl. In certain embodiments, R ^2’ is linear unsubstituted C7-25 alkenyl. In some embodiments, R ^2’ is linear optionally substituted C12-20 alkenyl. In certain embodiments, R ^2’ is linear unsubstituted C12-20 alkenyl. In some embodiments, R ^2’ is linear optionally substituted C _14-18 alkenyl. In certain embodiments, R ^2’ is linear unsubstituted C14-18 alkenyl. [00209] In some embodiments, R ^2’ comprises cis and trans double bonds. In certain embodiments, R ^2’ comprises only cis double bonds. In some embodiments, R ^2’ comprises only trans double bonds. [00210] In some embodiments, R ^2’ comprises at least two double bonds. In certain embodiments, R ^2’ comprises at least three double bonds. In some embodiments, R ^2’ comprises at least four double bonds. In certain embodiments, R ^2’ comprises at least five double bonds. In some embodiments, R ^2’ comprises at least six double bonds. In certain embodiments, R ^2’ comprises 1-8 double bonds. In some embodiments, R ^2’ comprises 1-6 double bonds. In certain embodiments, R ^2’ comprises 2-8 double bonds. In some embodiments, R ^2’ comprises 2-6 double bonds. In certain embodiments, R ^2’ comprises 1, 2, 3, 4, 5, or 6 double bonds. In some embodiments, R ^2’ comprises 2, 3, 4, 5, or 6 double bonds. In some embodiments, R ^2’ comprises 3, 4, 5, or 6 double bonds. In certain embodiments, R ^2’ comprises 3, 4, or 5 double bonds. [00211] In certain embodiments, R ^2’ comprises unconjugated double bonds. In some embodiments, R ^2’ comprises conjugated double bonds. In certain embodiments, R ^2’ comprises both conjugated and unconjugated double bonds. [00212] In some embodiments, R ^2’ is optionally substituted n embodiments, R ^2’ is u nsubstituted . In certain embodiments, R ^2’ is substituted . In some embodiments, substituted with a non-aliphatic substituent. In some embodiments, R ^2’ is not substituted with an aliphatic substituent. In some embodiments, R ^2’ is not substituted with an alkyl, alkenyl, alkynyl group. In some embodiments, R ^2’ is not substituted with an alkyl, alkenyl, alkynyl group at the terminal position. In some embodiments, R ^2’ is substituted at a vinylic or allylic position. [00213] In some embodiments, R ^2’ is substituted with deuterium,

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halogen, −OR ^aa , −SR ^aa , −N(R ^bb ) ₂ , –CN, –SCN, –NO ₂ , −C(=O)R ^aa , −CO ₂ R ^aa , −C(=O)N(R ^bb ) ₂ , −OC(=O)R ^aa , −OCO2R ^aa , −OC(=O)N(R ^bb )2, −NR ^bb C(=O)R ^aa , −NR ^bb CO2R ^aa , or −NR ^bb C(=O)N(R ^bb )2. In some embodiments, R ^2’ is substituted with optionally substituted C1-10 alkyl, deuterium, halogen, −OR ^aa , −SR ^aa , −N(R ^bb )2, –CN, –SCN, –NO2, −NR ^bb C(=O)R ^aa , −NR ^bb CO ₂ R ^aa , or −NR ^bb C(=O)N(R ^bb ) ₂ , provided that C _1-10 alkyl is not at the terminal position. [00214] In some embodiments, R ^2’ is substituted with halogen or deuterium. In some embodiments, R ^2’ is substituted with halogen. In some embodiments, R ^2’ is substituted with at least one fluorine. In certain embodiments, R ^2’ is substituted with at least one deuterium. [00215] In certain embodiments, R ^2’ is selected from the group consisting of . [00216] In certain embodiments, R ^2’ is . [00217] In some embodiments, R ^2” is optionally substituted n embodiments, R ^2” is u nsubstituted . In certain embodiments, R ^2” is substituted . In some embodiments, substituted with at least one fluorine. In certain embodiments, R ^2” is

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substituted with at least one deuterium. [00218] In certain embodiments, R ^2” is selected from the group consisting of . [00219] In certain embodiments, R ^2” is . [00220] In certain embodiments, R ^1’ is unsubstituted C7-25 alkyl, and R ^2’ is unsubstituted C7-25 alkenyl. In some embodiments, R ^1’ is C7-25 haloalkyl, and R ^2’ is unsubstituted C7-25 alkenyl. In certain embodiments, R ^1’ is C _7-25 fluoroalkyl, and R ^2’ is unsubstituted C _7-25 alkenyl. In some embodiments, R ^1’ is unsubstituted C _12-20 alkyl, and R ^2’ is unsubstituted C _12-20 alkenyl. In certain embodiments, R ^1’ is C12-20 haloalkyl, and R ^2’ is unsubstituted C12-20 alkenyl. In some embodiments, R ^1’ is C12-20 fluoroalkyl, and R ^2’ is unsubstituted C12-20 alkenyl. [00221] In certain embodiments, R ^1’ is unsubstituted C _7-25 alkyl, and R ^2’ is C _7-25 haloalkenyl. In some embodiments, R ^1’ is C7-25 haloalkyl, and R ^2’ is C7-25 haloalkenyl. In certain embodiments, R ^1’ is C7-25 fluoroalkyl, and R ^2’ is C7-25 haloalkenyl ^. In some embodiments, R ^1’ is unsubstituted C _12-20 alkyl, and R ^2’ is C _12-20 haloalkenyl. In certain embodiments, R ^1’ is C _12- 20 haloalkyl, and R ^2’ is C12-20 haloalkenyl. In some embodiments, R ^1’ is C12-20 fluoroalkyl, and R ^2’ is C12-20 haloalkenyl. [00222] In certain embodiments, R ^1’ is unsubstituted C _7-25 alkyl, and R ^2’ is C _7-25 fluoroalkenyl. In some embodiments, R ^1’ is C _7-25 haloalkyl, and R ^2’ is C _7-25 fluoroalkenyl. In certain embodiments, R ^1’ is C7-25 fluoroalkyl, and R ^2’ is C7-25 fluoroalkenyl. In some embodiments, R ^1’ is unsubstituted C12-20 alkyl, and R ^2’ is C12-20 fluoroalkenyl ^. In certain embodiments, R ^1’ is C _12-20 haloalkyl, and R ^2’ is C _12-20 fluoroalkenyl. In some embodiments, R ^1’ is C12-20 fluoroalkyl, and R ^2’ is C12-20 fluoroalkenyl. [00223] In certain embodiments, R ^1’ is unsubstituted C7-25 alkyl, and R ^2’ is C7-25 alkenyl substituted with at least one deuterium. In some embodiments, R ^1’ is C _7-25 haloalkyl, and R ^2’ is C7-25 alkenyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C7-25 fluoroalkyl, and R ^2’ is C7-25 alkenyl substituted with at least one deuterium. In some

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embodiments, R ^1’ is unsubstituted C _12-20 alkyl, and R ^2’ is C _7-25 alkenyl substituted with at least one deuterium. In certain embodiments, R ^1’ is C12-20 haloalkyl, and R ^2’ is C7-25 alkenyl substituted with at least one deuterium ^. In some embodiments, R ^1’ is C12-20 fluoroalkyl, and R ^2’ is C _7-25 alkenyl substituted with at least one deuterium. [00224] In some embodiments, R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-6 alkyl. [00225] In certain embodiments, R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-4 alkyl. In some embodiments, R ^3’ and R ^4’ are each independently hydrogen or optionally substituted C1-2 alkyl. In certain embodiments, R ^3’ and R ^4’ are each independently hydrogen or unsubstituted C _1-6 alkyl. In certain embodiments, R ^3’ and R ^4’ are each independently hydrogen or unsubstituted C _1-4 alkyl. In some embodiments, R ^3’ and R ^4’ are each independently hydrogen or unsubstituted C1-2 alkyl. [00226] In some embodiments, one of R ^3’ and R ^4’ is hydrogen. In certain embodiments, at least one of R ^3’ and R ^4’ is hydrogen. In some embodiments, R ^3’ and R ^4’ are each hydrogen. In certain embodiments, R ^3’ is hydrogen, and R ^4’ is unsubstituted C1-6 alkyl. In some embodiments, R ^3’ is hydrogen, and R ^4’ is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In some embodiments, R ^3’ is hydrogen, and R ^4’ is methyl, ethyl, propyl, or butyl. In some embodiments, R ^3’ is hydrogen, and R ^4’ is methyl. In some embodiments, R ^3’ is hydrogen, and R ^4’ is ethyl. [00227] In some embodiments, one of R ^3’ and R ^4’ is unsubstituted C _1-6 alkyl. In certain embodiments, at least one of R ^3’ and R ^4’ is unsubstituted C _1-6 alkyl. In some embodiments, R ^3’ and R ^4’ are each unsubstituted C1-6 alkyl. In some embodiments, R ^3’ and R ^4’ are each independently methyl, ethyl, propyl, butyl, pentyl, or hexyl. In some embodiments, R ^3’ and R ^4’ are each independently methyl, ethyl, propyl, or butyl. In some embodiments, R ^3’ is methyl, and R ^4’ is methyl, ethyl, propyl, butyl, pentyl, or hexyl. In certain embodiments, R ^3’ is methyl, and R ^4’ is methyl, ethyl, propyl, or butyl. In certain embodiments, R ^3’ and R ^4’ are each methyl. In some embodiments, R ^3’ and R ^4’ are each ethyl. In certain embodiments, R ^3’ and R ^4’ are each propyl. In some embodiments, R ^3’ and R ^4’ are each butyl. [00228] In some embodiments, one of R ^3’ and R ^4’ is optionally substituted C1-6 alkyl. In certain embodiments, at least one of R ^3’ and R ^4’ is optionally substituted C _1-6 alkyl. In some embodiments, R ^3’ and R ^4’ are each independently optionally substituted C _1-6 alkyl. [00229] In certain embodiments, one of R ^3’ and R ^4’ is C1-6 fluoroalkyl. In certain embodiments, at least one of R ^3’ and R ^4’ is C1-6 fluoroalkyl. In some embodiments, R ^3’ and R ^4’ are each C _1-6 fluoroalkyl. In some embodiments, at least one of R ^3’ and R ^4’ is -CH ₂ F, -

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CHF ₂ , or -CF ₃ . In certain embodiments, at least one of R ^3’ and R ^4’ is -CH ₂ F. In some embodiments, at least one of R ^3’ and R ^4’ is -CHF2. In certain embodiments, at least one of R ^3’ and R ^4’ is -CF3. [00230] In some embodiments, R ^3’ is hydrogen, and R ^4’ is C _1-6 fluoroalkyl. In certain embodiments, R ^3’ is hydrogen, and R ^4’ is -CH2F, CHF2, or -CF3. In some embodiments, R ^3’ is hydrogen, and R ^4’ is -CH2F. In certain embodiments, R ^3’ is hydrogen, and R ^4’ is -CHF2. In some embodiments, R ^3’ is hydrogen, and R ^4’ is -CF ₃ . [00231] In some embodiments, R ^3’ is unsubstituted C1-6 alkyl, and R ^4’ is C1-6 fluoroalkyl. In certain embodiments, R ^3’ is unsubstituted C1-6 alkyl, and R ^4’ is -CH2F, CHF2, or -CF ₃ . In some embodiments, R ^3’ is unsubstituted C _1-6 alkyl, and R ^4’ is -CH ₂ F. In certain embodiments, R ^3’ is unsubstituted C _1-6 alkyl, and R ^4’ is -CHF ₂ . In some embodiments, R ^3’ is unsubstituted C1-6 alkyl, and R ^4’ is -CF3. In some embodiments, R ^3’ is methyl, and R ^4’ is C1-6 fluoroalkyl. In certain embodiments, R ^3’ is methyl, and R ^4’ is -CH2F, CHF2, or -CF3. In some embodiments, R ^3’ is methyl, and R ^4’ is -CH ₂ F. In certain embodiments, R ^3’ is methyl, and R ^4’ is -CHF2. In some embodiments, R ^3’ is methyl, and R ^4’ is -CF3. [00232] In some embodiments, n is 0, 1, 2, or 3. In certain embodiments, n is 0, 1, or 2. In some embodiments, n is 0 or 1. In certain embodiments, n is 1 or 2. In some embodiments, n is 2 or 3. In certain embodiments, n is 0. In some embodiments, n is 1. In certain embodiments, n is 2. In some embodiments, n is 3. [00233] In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently hydrogen, halogen, or C1-6 alkyl. [00234] In certain embodiments, * designates a point of attachment at position X. In some embodiments, * designates a point of attachment at position Y. In certain embodiments, * designates a point of attachment at position Z. [00235] In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently hydrogen or halogen. In certain embodiments, * designates a point of attachment at position X; and Y and Z are each independently hydrogen or halogen. In some embodiments, * designates a point of attachment at position Y; and X and Z are each independently hydrogen or halogen. In certain embodiments, * designates a point of attachment at position Z; and X and Y are each independently hydrogen or halogen. [00236] In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently hydrogen or

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fluorine. In certain embodiments, * designates a point of attachment at position X; and Y and Z are each independently hydrogen or fluorine. In some embodiments, * designates a point of attachment at position Y; and X and Z are each independently hydrogen or fluorine. In certain embodiments, * designates a point of attachment at position Z; and X and Y are each independently hydrogen or fluorine. [00237] In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently hydrogen or C _1-6 alkyl. In certain embodiments, * designates a point of attachment at position X; and Y and Z are each independently hydrogen or C1-6 alkyl. In some embodiments, * designates a point of attachment at position Y; and X and Z are each independently hydrogen or C _1-6 alkyl. In certain embodiments, * designates a point of attachment at position Z; and X and Y are each independently hydrogen or C1-6 alkyl. [00238] In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each hydrogen. In certain embodiments, * designates a point of attachment at position X; and Y and Z are each hydrogen. In some embodiments, * designates a point of attachment at position Y; and X and Z are each hydrogen. In certain embodiments, * designates a point of attachment at position Z; and X and Y are each hydrogen. [00239] In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently halogen. In some embodiments, * designates a point of attachment at one of positions X, Y, and Z; and the other two of positions X, Y, and Z are each independently C1-6 alkyl. [00240] In certain embodiments, the compound is: ,

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, , , , , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof.

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[00241] In certain embodiments, the compound is: ,

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, or a pharmaceutically acceptable salt thereof. [00242] In certain embodiments, the compound is: , , , ,

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, , or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof. [00243] In certain embodiments, the compound is: , , ,

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, , , or a pharmaceutically acceptable salt thereof. [00244] In some instances, compounds and generic formulae provided herein are drawn in zwitterionic form. Any compound or generic formula drawn as a zwitterion herein is understood to also encompass the corresponding non-zwitterionic form. [00245] For example, compounds of Formula (I) wherein R ³ , R ⁴ , and R ⁵ (if present) are hydrogen (drawn in zwitterionic form herein) also encompass compounds wherein X is selected from (non-zwitterionic form). [00246] Similarly, for example, compounds of Formula (I-A), wherein R ³ , R ⁴ , and R ⁵ are hydrogen (drawn in zwitterionic form herein), also encompass compounds of the following formula (non-zwitterionic form): .

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[00247] Similarly, for example, compounds of Formula (I-A-i), wherein R ³ , R ⁴ , and R ⁵ are hydrogen (drawn in zwitterionic form herein), also encompass compounds of the following formula (non-zwitterionic form): [00248] Similarly, for example, compounds of Formula (I-A-iii) (drawn in zwitterionic form herein) also encompass compounds of the following formula (non-zwitterionic form): -iii). [00249] Similarly, for example, compounds of Formula (I-B), wherein R ³ and R ⁴ are hydrogen (drawn in zwitterionic form herein), also encompasses compounds of the following formula (non-zwitterionic form): . [00250] Additionally, compounds of Formula (II) wherein R ^3’ and R ^4’ are hydrogen (drawn in zwitterionic form herein) also encompass compounds of the following formula (non- zwitterionic form): .

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[00251] Similarly, for example, compounds of Formula (II-A) wherein R ^3’ and R ^4’ are hydrogen (drawn in zwitterionic form herein) also encompass compounds of the following formula (non-zwitterionic form): . [00252] Similarly, for example, compounds of Formula (II-B) wherein R ^3’ and R ^4’ are hydrogen (drawn in zwitterionic form herein) also encompass compounds of the following formula (non-zwitterionic form): . [00253] Similarly, for example, compounds of Formula (II-C) wherein R ^3’ and R ^4’ are hydrogen (drawn in zwitterionic form herein) also encompass compounds of the following formula (non-zwitterionic form): .

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[00254] Similarly, for example, compounds of Formula (II-D) wherein R ^3’ and R ^4’ are hydrogen (drawn in zwitterionic form herein) also encompass compounds of the following formula (non-zwitterionic form): . [00255] Compounds excluded by proviso in their zwitterionic form are also understood to be excluded in their non-zwitterionic form. Similarly, compounds excluded by proviso in their non-zwitterionic form are also understood to be excluded in their zwitterionic form. Compositions, Kits, and Administration [00256] The present disclosure provides compositions comprising a compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, and optionally a carrier and/or excipient. In some embodiments, the composition is a pharmaceutical composition. In certain embodiments, the pharmaceutical composition described herein comprises a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, and a pharmaceutically acceptable carrier and/or excipient. In some embodiments, the composition is a nutraceutical composition. In certain embodiments, the nutraceutical composition described herein comprises a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, and a carrier and/or excipient. [00257] In certain embodiments, the compound described herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, is provided in an effective amount in the composition. In certain embodiments, the effective amount is a therapeutically or prophylactically effective amount. [00258] In certain embodiments, the effective amount is an amount effective for treating a disease, disorder, or condition in a subject in need thereof. In some embodiments, the

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effective amount is an amount effective for treating a liver disease, neurological disease, ophthalmic disease, metabolic disorder, mitochondrial disease, cardiovascular disease, infectious disease, pulmonary disease, skin disease, genetic disease, proliferative disease, inflammatory disease, autoimmune disease, hematological disease, painful condition, psychiatric disorder, immune disorder, or spleen disease. In some embodiments, the effective amount is an amount effective for treating a neurological disease in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for treating Alzheimer’s disease in a subject in need thereof. In some embodiments, the effective amount is an amount effective for treating a genetic disease. In some embodiments, the effective amount is an amount effective for treating Zellweger syndrome. In some embodiments, the effective amount is an amount effective for treating a pulmonary disease. In some embodiments, the effective amount is an amount effective for treating NRDS. [00259] In some embodiments, the effective amount is an amount effective for preventing a disease, disorder, or condition in a subject in need thereof. In some embodiments, the effective amount is an amount effective for preventing a liver disease, neurological disease, ophthalmic disease, metabolic disorder, mitochondrial disease, cardiovascular disease, infectious disease, pulmonary disease, skin disease, genetic disease, proliferative disease, inflammatory disease, autoimmune disease, hematological disease, painful condition, psychiatric disorder, immune disorder, or spleen disease. In certain embodiments, the effective amount is an amount effective for preventing a neurological disease in a subject in need thereof. In some embodiments, the effective amount is an amount effective for preventing Alzheimer’s disease in a subject in need thereof. In some embodiments, the effective amount is an amount effective for preventing a genetic disease. In some embodiments, the effective amount is an amount effective for preventing Zellweger syndrome. In some embodiments, the effective amount is an amount effective for preventing a pulmonary disease. In some embodiments, the effective amount is an amount effective for preventing NRDS. [00260] Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include bringing the compound described herein (i.e., the “active ingredient”) into association with a carrier or excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired single- or multi-dose unit. [00261] Pharmaceutical compositions can be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. A “unit dose” is a discrete amount

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of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage, such as one-half or one-third of such a dosage. [00262] Relative amounts of the compound of the disclosure, pharmaceutically acceptable excipient, agent, and/or any additional ingredients in a composition described herein will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. The composition may comprise between 0.1% and 100% (w/w) agent. [00263] Pharmaceutically acceptable excipients used in manufacture of provided pharmaceutical compositions include inert diluents, dispersing and/or granulating agents, surface active agents and/or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and/or oils. Excipients and accessory ingredients, such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and perfuming agents, may also be present in the composition. [00264] Exemplary diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, and mixtures thereof. [00265] Exemplary granulating and/or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose, and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross- linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, quaternary ammonium compounds, and mixtures thereof. [00266] Exemplary surface active agents and/or emulsifiers include natural emulsifiers (e.g., acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g., bentonite (aluminum silicate) and Veegum (magnesium aluminum silicate)), long chain amino acid derivatives, high molecular weight alcohols (e.g., stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and

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propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g., carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g., carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monolaurate (Tween ^® 20), polyoxyethylene sorbitan (Tween ^® 60), polyoxyethylene sorbitan monooleate (Tween ^® 80), sorbitan monopalmitate (Span ^® 40), sorbitan monostearate (Span ^® 60), sorbitan tristearate (Span ^® 65), glyceryl monooleate, sorbitan monooleate (Span ^® 80), polyoxyethylene esters (e.g., polyoxyethylene monostearate (Myrj ^® 45), polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol ^® ), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g., Cremophor ^® ), polyoxyethylene ethers, (e.g., polyoxyethylene lauryl ether (Brij ^® 30)), poly(vinyl-pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic ^® F-68, poloxamer P-188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, and/or mixtures thereof. [00267] Exemplary binding agents include starch (e.g., cornstarch and starch paste), gelatin, sugars (e.g., sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol, etc.), natural and synthetic gums (e.g., acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (Veegum ^® ), and larch arabogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts, silicic acid, polymethacrylates, waxes, water, alcohol, and/or mixtures thereof. [00268] Exemplary preservatives include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, antiprotozoan preservatives, alcohol preservatives, acidic preservatives, and other preservatives. In certain embodiments, the preservative is an antioxidant. In other embodiments, the preservative is a chelating agent. [00269] Exemplary antioxidants include alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite. [00270] Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (e.g., sodium edetate, disodium edetate, trisodium edetate, calcium

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disodium edetate, dipotassium edetate, and the like), citric acid and salts and hydrates thereof (e.g., citric acid monohydrate), fumaric acid and salts and hydrates thereof, malic acid and salts and hydrates thereof, phosphoric acid and salts and hydrates thereof, and tartaric acid and salts and hydrates thereof. Exemplary antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal. [00271] Exemplary antifungal preservatives include butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid. [00272] Exemplary alcohol preservatives include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and phenylethyl alcohol. [00273] Exemplary acidic preservatives include vitamin A, vitamin C, vitamin E, beta- carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid. [00274] Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, Glydant ^® Plus, Phenonip ^® , methylparaben, Germall ^® 115, Germaben ^® II, Neolone ^® , Kathon ^® , and Euxyl ^® . [00275] Exemplary buffering agents include citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D-gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen- free water, isotonic saline, Ringer’s solution, ethyl alcohol, and mixtures thereof. [00276] Exemplary lubricating agents include magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol,

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sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, and mixtures thereof. [00277] Exemplary natural oils include almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary synthetic oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, and mixtures thereof. [00278] Liquid dosage forms for oral and parenteral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredients, the liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (e.g., cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. In certain embodiments for parenteral administration, the compounds described herein are mixed with solubilizing agents such as Cremophor®, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and mixtures thereof. [00279] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions can be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can be a sterile injectable solution, suspension, or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer’s solution, U.S.P., and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or

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suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or di-glycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. [00280] The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. [00281] In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution, which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form may be accomplished by dissolving or suspending the drug in an oil vehicle. [00282] Compositions for rectal or vaginal administration are typically suppositories which can be prepared by mixing the compounds described herein with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol, or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient. [00283] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or (a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrating agents such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solution retarding agents such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may include a buffering agent. [00284] Solid compositions of a similar type can be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular

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weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the art of pharmacology. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of encapsulating compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type can be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polethylene glycols and the like. [00285] The active ingredient can be in a micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings, and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active ingredient can be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may comprise buffering agents. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of encapsulating agents which can be used include polymeric substances and waxes. [00286] Dosage forms for topical and/or transdermal administration of a compound described herein may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, and/or patches. Generally, the active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier or excipient and/or any needed preservatives and/or buffers as can be required. Additionally, the present disclosure contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of an active ingredient to the body. Such dosage forms can be prepared, for example, by dissolving and/or dispensing the active ingredient in the proper medium. Alternatively or additionally, the rate can be controlled by either providing a rate controlling membrane and/or by dispersing the active ingredient in a polymer matrix and/or gel. [00287] Formulations suitable for topical administration include, but are not limited to, liquid and/or semi-liquid preparations such as liniments, lotions, oil-in-water and/or water-in-oil

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emulsions such as creams, ointments, and/or pastes, and/or solutions and/or suspensions. Topically administrable formulations may, for example, comprise from about 1% to about 10% (w/w) active ingredient, although the concentration of the active ingredient can be as high as the solubility limit of the active ingredient in the solvent. Formulations for topical administration may further comprise one or more of the additional ingredients described herein. [00288] Suitable devices for use in delivering injectable pharmaceutical compositions described herein include short needle devices. Injectable compositions can be administered by devices which limit the effective penetration length of a needle into the skin. Alternatively or additionally, conventional syringes can be used in the classical mantoux method of administration. Jet injection devices which deliver liquid formulations via a liquid jet injector and/or via a needle. Ballistic powder/particle delivery devices which use compressed gas to accelerate the compound in powder form are suitable. [00289] A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 to about 7 nanometers, or from about 1 to about 6 nanometers. Such compositions are conveniently in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant can be directed to disperse the powder and/or using a self-propelling solvent/powder dispensing container such as a device comprising the active ingredient dissolved and/or suspended in a low-boiling propellant in a sealed container. Such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nanometers and at least 95% of the particles by number have a diameter less than 7 nanometers. Alternatively, at least 95% of the particles by weight have a diameter greater than 1 nanometer and at least 90% of the particles by number have a diameter less than 6 nanometers. Dry powder compositions may include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form. [00290] Low boiling propellants generally include liquid propellants having a boiling point of below 65 °F at atmospheric pressure. Generally, the propellant may constitute 50 to 99.9% (w/w) of the composition, and the active ingredient may constitute 0.1 to 20% (w/w) of the composition. The propellant may further comprise additional ingredients such as a liquid non-ionic and/or solid anionic surfactant and/or a solid diluent (which may have a particle size of the same order as particles comprising the active ingredient).

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[00291] Pharmaceutical compositions described herein formulated for pulmonary delivery may provide the active ingredient in the form of droplets of a solution and/or suspension. Such formulations can be prepared, packaged, and/or sold as aqueous and/or dilute alcoholic solutions and/or suspensions, optionally sterile, comprising the active ingredient, and may conveniently be administered using any nebulization and/or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and/or a preservative, such as methylhydroxybenzoate. The droplets provided by this route of administration may have an average diameter in the range from about 0.1 to about 200 nanometers. [00292] Formulations described herein as being useful for pulmonary delivery are useful for intranasal delivery of a pharmaceutical composition described herein. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 to 500 micrometers. Such a formulation is administered by rapid inhalation through the nasal passage from a container of the powder held close to the nares. [00293] Formulations for nasal administration may, for example, comprise from about as little as 0.1% (w/w) to as much as 100% (w/w) of the active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation for buccal administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods, and may contain, for example, 0.1 to 20% (w/w) active ingredient, the balance comprising an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations for buccal administration may comprise a powder and/or an aerosolized and/or atomized solution and/or suspension comprising the active ingredient. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle and/or droplet size in the range from about 0.1 to about 200 nanometers, and may further comprise one or more of the additional ingredients described herein. [00294] A pharmaceutical composition described herein can be prepared, packaged, and/or sold in a formulation for ophthalmic administration. Such formulations may, for example, be in the form of eye drops including, for example, a 0.1-1.0% (w/w) solution and/or suspension of the active ingredient in an aqueous or oily liquid carrier or excipient. Such drops may further comprise buffering agents, salts, and/or one or more other of the additional

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ingredients described herein. Other opthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form and/or in a liposomal preparation. Ear drops and/or eye drops are also contemplated as being within the scope of this disclosure. [00295] Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with ordinary experimentation. [00296] Compounds provided herein are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions described herein will be decided by a physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject or organism will depend upon a variety of factors including the disease being treated and the severity of the disorder; the activity of the specific active ingredient employed; the specific composition employed; the age, body weight, general health, sex, and diet of the subject; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient employed; and like factors well known in the medical arts. [00297] The compounds and compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intraarticular, intra- arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and/or drops), mucosal, nasal, bucal, sublingual; by intratracheal instillation, bronchial instillation, and/or inhalation; and/or as an oral spray, nasal spray, and/or aerosol. Specifically, contemplated routes are intraarticular administration, oral administration, intravenous administration (e.g., systemic intravenous injection), regional administration via blood and/or lymph supply, and/or direct administration to an affected site. In general, the most appropriate route of administration will depend upon a variety of factors including the nature of the agent (e.g., its

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stability in the environment of the gastrointestinal tract), and/or the condition of the subject (e.g., whether the subject is able to tolerate oral administration). [00298] In certain embodiments, the compound or pharmaceutical composition described herein is suitable for intraarticular administration. In some embodiments the compound or pharmaceutical composition described herein is suitable for intraarticular injection. In certain embodiments, the intraarticular injection comprises direct injection into the closed cavity of a joint. In some embodiments, the joint is a knee joint, wrist joint, ankle joint, hip joint, shoulder joint, elbow joint, neck joint, spine joint, vertebral disc joints, finger joints, and toe joints. [00299] The exact amount of a compound of the disclosure required to achieve an effective amount will vary from subject to subject, depending, for example, on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular compound of the disclosure, mode of administration, and the like. An effective amount may be included in a single dose (e.g., single oral dose) or multiple doses (e.g., multiple oral doses). In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample, tissue, or cell, any two doses of the multiple doses include different or substantially the same amounts of an agent described herein. [00300] In certain embodiments, when multiple doses are administered to a subject or applied to a tissue or cell, the frequency of administering the multiple doses to the subject or applying the multiple doses to the tissue or cell may be, in non-limiting examples, three doses a day, two doses a day, one dose a day, one dose every other day, one dose every third day, one dose every week, one dose every two weeks, one dose every three weeks, or one dose every four weeks, or even slow dose controlled delivery over a selected period of time using a drug delivery device. In certain embodiments, when multiple doses are administered to a subject or applied to a biological sample, tissue, or cell, the duration between the first dose and last dose of the multiple doses is one day, two days, four days, one week, two weeks, three weeks, one month, two months, three months, four months, six months, nine months, one year, two years, three years, four years, five years, seven years, ten years, fifteen years, twenty years, or the lifetime of the subject, tissue, or cell. In certain embodiments, the duration between the first dose and last dose of the multiple doses is three months, six months, or one year. In certain embodiments, the duration between the first dose and last dose of the multiple doses is the lifetime of the subject, tissue, or cell. In certain embodiments, a dose (e.g., a single dose, or any dose of multiple doses) described herein includes independently between 0.1 µg and 1 µg, between 0.001 mg and 0.01 mg, between 0.01 mg and 0.1 mg, between 0.1 mg and 1 mg,

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between 1 mg and 3 mg, between 3 mg and 10 mg, between 10 mg and 30 mg, between 30 mg and 100 mg, between 100 mg and 300 mg, between 300 mg and 1,000 mg, or between 1 g and 10 g, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 1 mg and 3 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 3 mg and 10 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 10 mg and 30 mg, inclusive, of a compound described herein. In certain embodiments, a dose described herein includes independently between 30 mg and 100 mg, inclusive, of a compound described herein. [00301] Dose ranges as described herein provide guidance for the administration of provided compounds or compositions to an adult. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult. In certain embodiments, a dose described herein is a dose to an adult human whose body weight is 70 kg. [00302] A compound or composition, as described herein, can be administered in combination with one or more additional pharmaceutical agents (e.g., therapeutically and/or prophylactically active agents). The compounds or compositions can be administered in combination with additional pharmaceutical agents that improve their activity (e.g., potency and/or efficacy), improve bioavailability, improve safety, reduce drug resistance, reduce and/or modify metabolism, inhibit excretion, and/or modify distribution in a subject or cell. It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder, and/or it may achieve different effects. In certain embodiments, a pharmaceutical composition described herein including a compound described herein and an additional pharmaceutical agent shows a synergistic effect that is absent in a pharmaceutical composition including one of the compound and the additional pharmaceutical agent, but not both. In some embodiments, the additional pharmaceutical agent achieves a desired effect for the same disorder. In some embodiments, the additional pharmaceutical agent achieves different effects. [00303] The compound or composition can be administered concurrently with, prior to, or subsequent to one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved for

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human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. In certain embodiments, the additional pharmaceutical agent is a pharmaceutical agent useful for treating and/or preventing a disease, disorder, or condition . [00304] Each additional pharmaceutical agent may be administered at a dose and/or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be administered together with each other and/or with the compound or composition described herein in a single dose or composition or administered separately in different doses or compositions. The particular combination to employ in a regimen will take into account compatibility of the compound described herein with the additional pharmaceutical agent(s) and/or the desired therapeutic and/or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agent(s) in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. [00305] The additional pharmaceutical agents include, but are not limited to, anti- proliferative agents, anti-cancer agents, anti-angiogenesis agents, steroidal or non-steroidal anti-inflammatory agents, immunosuppressants, anti-bacterial agents, anti-viral agents, cardiovascular agents, cholesterol-lowering agents, anti-diabetic agents, anti-allergic agents, contraceptive agents, pain-relieving agents, anesthetics, anti–coagulants, inhibitors of an enzyme, steroidal agents, steroidal or antihistamine, antigens, vaccines, antibodies, decongestant, sedatives, opioids, analgesics, anti-pyretics, hormones, and prostaglandins. [00306] In certain embodiments, the composition is a food product. In certain embodiments, the food product is any item that is to be processed, partially processed, or unprocessed for consumption by an animal. In some embodiments, the food product is for consumption by a mammal. In some embodiments, the food product is for consumption by a human. In some embodiments, the food product is a food supplement, medical food, or infant formula. In certain embodiments, the food product is a food supplement. In some embodiments, the food product is a medical food. In certain embodiments, the food product is infant formula. In another aspect, the food product is a food additive. In another aspect, the food product is a dietary supplement.

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[00307] In certain embodiments, the composition further comprises a sweetener. Sweeteners can be used to improve palatability and are usually classified as natural or artificial. In some embodiments, a sweetener is a natural sweetener or artificial sweetener. Exemplary natural sweeteners include, but are not limited to, dextrose, fructose, glucose, liquid glucose, maltose, rebiana, glycyrrhizin, thaumatin, sorbitol, mannitol, isomalt, glycerol, maltitol, xylitol, and erythritol. Exemplary artificial sweeteners include, but are not limited to, saccharin, cyclamate, aspartame, acesulfame-K, sucralose, alitame, and neotame. In certain embodiments, sucralose is used as a sweetener. In certain embodiments, one or combination of neohespiridin dihydrochalcone, glycerol, and/or sucralose are used as sweeteners. In some embodiments, the concentration of the sweetener in the composition is between 0.01% and 5%, inclusive, by weight. In some embodiments, the concentration of the sweetener in the composition is between 0.01% and 1%, inclusive, by weight. In some embodiments, the concentration of the sweetener in the composition is between 0.5% and 1%, inclusive, by weight. In certain embodiments, the composition further comprises sucralose. In certain embodiments, the composition further comprises sucralose as about 0.01-0.25% based on the dry weight of all the components of the composition. [00308] In certain embodiments, a composition further comprises a colorant. A colorant can be added to enhance the aesthetic appeal of the composition, especially when formulation ingredients or drugs are presented in a non-solution form. Generally, any colorant could be added, such as for example FD&C pigments (for example, blue nº1, blue nº2, red nº3, red nº40, yellow nº5, or yellow nº 6). Exemplary colorants include, but are not limited to annatto extract, dehydrated beets (beet powder), canthaxanthin, caramel, β-apo-8'-carotenal, β- carotene, cochineal extract, carmine, sodium copper chlorophyllin, toasted partially defatted cooked cottonseed flour, ferrous gluconate, ferrous lactate, grape color extract, grape skin extract (enocianina), synthetic iron oxide, fruit juice, vegetable juice, carrot oil, paprika, paprika oleoresin, mica-based pearlescent pigments, riboflavin, saffron, spirulina extract, titanium dioxide, tomato lycopene extract; tomato lycopene concentrate, turmeric, turmeric oleoresin, alumina (dried aluminum hydroxide), calcium carbonate, potassium sodium copper chlorophyllin (chlorophyllin-copper complex), dihydroxyacetone, bismuth oxychloride, synthetic iron oxide, ferric ammonium ferrocyanide, ferric ferrocyanide, chromium hydroxide green, chromium oxide greens, guanine, pyrophyllite, mica, talc, aluminum powder, bronze powder, copper powder, zinc oxide, bismuth citrate, disodium EDTA-copper, guaiazulene, henna, lead acetate, pyrophyllite, silver, ultramarines, manganese violet, luminescent zinc sulfide, FD&C Blue No.1, FD&C Blue No.2, FD&C Green No.3, Orange B, Citrus Red

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No.2, FD&C Red No.3, FD&C Red No.40, FD&C Yellow No.5, FD&C Yellow No.6, D&C Blue No.4, D&C Green No.5, D&C Green No.6, D&C Green No.8, D&C Orange No.4, D&C Orange No.5, D&C Orange No.10, D&C Orange No.11, FD&C Red No.4, D&C Red No.6, D&C Red No.7, D&C Red No.17, D&C Red No.21, D&C Red No.22, D&C Red No.27, D&C Red No.28, D&C Red No.30, D&C Red No.31, D&C Red No.33, D&C Red No.34, D&C Red No.36, D&C Red No.39, D&C Violet No.2, D&C Yellow No. 7, Ext. D&C Yellow No.7, D&C Yellow No.8, D&C Yellow No.10, D&C Yellow No.11, D&C Black No.2, D&C Black No.3, D&C Brown No.1, and Ext. D&C Violet No.2. In certain embodiments, a colorant represents 0.001% to about 0.5% based on the weight of all the components of the composition. In some embodiments, the concentration of the colorant in the composition is between 0.001% and 5%, inclusive, by weight. In some embodiments, the concentration of the colorant in the composition is between 0.001% and 1%, inclusive, by weight. [00309] In certain embodiments, a provided composition further comprises a flavoring agent. In certain embodiments, the selection of a suitable flavoring agent to be added depends on the original taste sensation of the composition, including metallic, acidic, alkaline, salty, sweet, bitter and sour taste sensation. Certain flavoring agents, alone or in combination, mask specific taste sensations. For example, metallic taste could be masked with, but not limited to, flavoring agents based on berry fruits, grape, and/or peppermint. For example, acidic taste could be masked with, but not limited to, flavoring agents based on lemon, lime, grapefruit, orange, cherry, and/or strawberry. For example, alkaline taste could be masked with, but not limited to, flavoring agents based on aniseed, caramel, passion fruit, peach and/or banana. For example, salty taste could be masked with, but not limited to, flavoring agents based on butterscotch, caramel, hazelnut, spicy, maple, apricot, apple, peach, vanilla, and/or wintergreen mint. For example, bitter taste could be masked with, but not limited to, flavoring agents based on licorice, passion fruit, coffee, chocolate, peppermint, grapefruit, cherry, peach, raspberry, wild cherry, walnut, mint, and/or anise. For example, sweet taste could be masked with, but not limited to, flavoring agents based on grape, cream, caramel, banana, vanilla and/or fruit berry. For example, sour taste could be masked with, but not limited to, flavoring agents based on citrus flavors, licorice, root, bear and/or raspberry. Flavoring agents can be used alone or in combination and its selection will be dependent also upon the target population and any other substance (e.g., a pharmaceutical or nutraceutical agent) incorporated in the composition. The perception of the flavoring agent changes from individual to individual and also with age: typically a geriatric population will prefer mint or

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orange flavors whereas younger populations tend to prefer flavors like fruit punch, raspberry, etc. Generally, the amount of flavoring agent needed to mask an unpleasant taste or improve taste overall will depend not only on the composition of the formulation but also on the flavor type and its strength. [00310] In certain embodiments, a flavoring agent is a palatable flavor that has a long shelf life and which does not crystallize or precipitate out of the composition upon storage. In certain embodiments, flavoring agents are natural flavors, derived from various parts of the plants like leaves, fruits and flowers, or synthetic flavor oils or powders. Exemplary flavor oils for use in or as flavoring agents include, but are not limited to, peppermint oil, cinnamon oil, spearmint oil, and oil of nutmeg. Exemplary fruity flavors that for use in or as flavoring agents include, but are not limited to, vanilla, cocoa, coffee, chocolate and citrus. Exemplary fruit essence flavors for use in or as flavoring agents include, but are not limited to, apple, raspberry, cherry, and pineapple. The amount of flavoring agent added can vary with the flavor employed. In some embodiments, the concentration of the flavoring agent in the composition is between about 0% and 5%, by weight. In some embodiments, the concentration of the flavoring agent in the composition is between 0.001% and 5%, inclusive, by weight. In some embodiments, the concentration of the flavoring agent in the composition is between 0.1% and 1%, inclusive, by weight. In some embodiments, the concentration of the flavoring agent in the composition is between 0.5% and 1%, inclusive, by weight. [00311] In certain embodiments, a provided composition further comprises taste-masking. Taste-masking agents can be added to ameliorate the general organoleptic characteristics of the compositions. In certain embodiments, taste-masking agents are used to mask unpleasant taste of some components. The main taste sensations include metallic, acidic, alkaline, salty, sweet, bitter and sour. Exemplary of taste-masking agents include, but are not limited to, menthol, peppermint oil, L-menthol, cyclodextrins, glycerol, maltodextrins, ion-exchange resins, amino acids, gelatin, gelatinized starch, liposomes, lecithin, or lecithin-like substances and salts. The amount of taste-masking added can vary with the taste-masking employed. In certain embodiments, the taste-masking agent comprises about 0% to about 50% based on the dry weight of all the components of the composition. In certain embodiments, the taste- masking agent represents 0% to about 5% based on the dry weight of all the components of the composition. [00312] In another aspect, a provided composition further comprises a cooling agent. Cooling agents may also be added in order to improve the after-taste of the composition. Exemplary cooling agents include, but are not limited to, neohesperidine dihydrochalcone, menthol

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flavor, L-Menthol and some polyol sugars which are widely used for this purpose. Other components can also be added that should compete with sensory stimuli, such as Cremophor (which is used to coat the surface protein receptors), or saline solutions (e.g., sodium chloride, which competes within channel receptors with the bitter stimuli to reduce the overall perception of bitterness). In certain embodiments, the cooling agents in the composition is one or a combination of neohesperidine dihydrochalcone, menthol, and/or polyol sugar. In certain embodiments, the mucoadhesive composition further comprises cooling agents of about 0% to about 5% based on the weight of all the components of the composition. In certain embodiments, the mucoadhesive composition further comprises cooling agents as about 0.001% to about 2.5% based on the weight of all the components of the composition. [00313] In certain embodiments, a provided composition further comprises one or more preservatives. The preservative employed in the present disclosure can be any preservative, as long as does not negate other desirable properties of the composition. Example of a preservative is an antimicrobial preservative that is used to prevent or inhibit the growth of micro-organisms in the composition. Exemplary preservative agents include, but are not limited to, C ₃ -C ₈ alcohols, phenylethyl alcohol, chlorbutanol, p-hydroxybenzoic, acid esters, benzathonium chloride and benzalkonium chloride, benzoic acid, propyl galate, methylparaben, propylparaben, sorbic acid, sodium benzoate and/or potassium sorbate. The amount of preservative agent added can vary with the preservative agent employed. In certain embodiments, a preservative agent represents about 0% to about 45% based on the weight of all the components of the composition. In certain embodiments, a preservative agent represents about 0% to about 1% (e.g., 0.025% to 0.2%) based on the weight of all the components of the composition. [00314] Also encompassed by the disclosure are kits (e.g., pharmaceutical packs). The kits provided may comprise a pharmaceutical composition or compound provided herein and a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of a pharmaceutical composition or compound provided herein. In some embodiments, the pharmaceutical composition or compound provided in the first container and the second container are combined to form one unit dosage form. A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition.

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[00315] In one aspect, the present disclosure provides a kit comprising a compound provided herein, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof; or a composition provided herein; and instructions for using the compound, pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, prodrug, or composition thereof. In some embodiments, provided are kits including a first container comprising a compound or pharmaceutical composition described herein. In certain embodiments, the kits are useful for treating a disease, disorder, or condition in a subject in need thereof. In certain embodiments, the kits are useful for preventing a disease, disorder, or condition in a subject in need thereof. In certain embodiments, the kits are useful for reducing the risk of developing a disease in a subject in need thereof. In certain embodiments, the kits are useful for treating a neurological disease in a subject in need thereof. In certain embodiments, the kits are useful for preventing a neurological disease in a subject in need thereof. In certain embodiments, the kits are useful for reducing the risk of developing a neurological disease in a subject in need thereof. In certain embodiments, the kits are useful for treating Alzheimer’s disease in a subject in need thereof. In certain embodiments, the kits are useful for preventing Alzheimer’s disease in a subject in need thereof. In certain embodiments, the kits are useful for reducing the risk of developing Alzheimer’s disease in a subject in need thereof. [00316] In certain embodiments, a kit described herein further includes instructions for using the kit. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, the kits and instructions provide for treating a disease, disorder, or condition in a subject in need thereof. In certain embodiments, the kits and instructions provide for preventing a disease, disorder, or condition in a subject in need thereof. In certain embodiments, the kits and instructions provide for reducing the risk of developing a disease in a subject in need thereof. A kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition. Methods of Use [00317] Provided herein are methods and uses of the compounds provided herein, and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers,

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stereoisomers, isotopically labeled derivatives, and prodrugs thereof, and pharmaceutical compositions thereof. [00318] In one aspect, provided herein is a method of treating a disease, disorder, or condition in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof. [00319] In another aspect, provided herein is a method of preventing a disease, disorder, or condition in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof. [00320] In another aspect, provided herein is a method of treating a disease, disorder, or condition in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof. [00321] In another aspect, provided herein is a method of preventing a disease, disorder, or condition in a subject in need thereof comprising administering to the subject an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof. [00322] In another aspect, the present disclosure provides the use of a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, in the manufacture of a medicament for treating a disease, disorder, or condition in a subject. [00323] In another aspect, the present disclosure provides the use of a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, in the manufacture of a medicament for preventing a disease, disorder, or condition in a subject. [00324] In another aspect, the present disclosure provides the use of a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, in the manufacture of a medicament for treating a disease, disorder, or condition in a subject.

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[00325] In another aspect, the present disclosure provides the use of a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, in the manufacture of a medicament for preventing a disease, disorder, or condition in a subject. [00326] In another aspect, the present disclosure provides a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in treating a disease, disorder, or condition in a subject. [00327] In another aspect, the present disclosure provides a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in preventing a disease, disorder, or condition in a subject. [00328] In another aspect, the present disclosure provides a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in treating a disease, disorder, or condition in a subject. [00329] In another aspect, the present disclosure provides a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in preventing a disease, disorder, or condition in a subject. [00330] In certain embodiments, the disease, disorder, or condition is a liver disease, a neurological disease, an ophthalmic disease, a metabolic disorder, a mitochondrial disease, a cardiovascular disease, an infectious disease, a pulmonary disease, a skin disease, a genetic disease, a proliferative disease, an inflammatory disease, an autoimmune disease, a hematological disease, a painful condition, a psychiatric disorder, an immune disorder, or a spleen disease. In some embodiments, the disease is a neurological disease, ophthalmic disease, liver disease, metabolic disease, cardiovascular disease, cancer, pulmonary disease, or genetic disease. In some embodiments, the disease is a neurological disease, ophthalmic disease, liver disease, metabolic disease, cardiovascular disease, or cancer. In certain embodiments, the disease, disorder, or condition is a liver disease, a neurological disease, an ophthalmic disease, metabolic disorder, pulmonary disease, or genetic disease. In certain embodiments, the disease, disorder, or condition is a liver disease, a neurological disease, an ophthalmic disease, or a metabolic disorder. In some embodiments, the disease, disorder, or condition is a neurological disease, an ophthalmic disease, a pulmonary disease, or a genetic

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disease. In some embodiments, the disease, disorder, or condition is a neurological disease or an ophthalmic disease. In certain embodiments, the disease, disorder, or condition is an ophthalmic disease. In some embodiments, the disease is a peroxisomal disorder. [00331] In some embodiments, the disease is a genetic disease. In some embodiments, the disease is a congenital disorder. In some embodiments, the disease is a leukodystrophy. In some embodiments, the disease is Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), or infantile Refsum disease. In some embodiments, the disease is Zellweger syndrome. In some embodiments, the disease is neonatal adrenoleukodystrophy (NALD). In some embodiments, the disease is infantile Refsum disease. [00332] In certain embodiments, the disease, disorder, or condition is a pulmonary disease. In some embodiments, the pulmonary disease is bronchiectasis, bronchitis, bronchopulmonary dysplasia, interstitial lung disease, occupational lung disease, emphysema, cystic fibrosis, acute respiratory distress syndrome (ARDS), severe acute respiratory syndrome (SARS), respiratory distress syndrome, neonatal respiratory distress syndrome (NRDS), infant respiratory distress syndrome (IRDS), hyaline membrane disease, surfactant deficiency, surfactant protein-B deficiency, bronchopulmonary dysplasia, asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD), emphysema, interstitial lung disease, sarcoidosis, asbestosis, aspergilloma, aspergillosis, pneumonia, pulmonary fibrosis, pulmonary tuberculosis, rheumatoid lung disease, pulmonary embolism, or lung cancer. In certain embodiments, the pulmonary disease is acute respiratory distress syndrome (ARDS), severe acute respiratory syndrome (SARS), respiratory distress syndrome, neonatal respiratory distress syndrome (NRDS), infant respiratory distress syndrome (IRDS), hyaline membrane disease, surfactant deficiency, surfactant protein-B deficiency, or bronchopulmonary dysplasia. In some embodiments, the pulmonary disease is respiratory distress syndrome, neonatal respiratory distress syndrome (NRDS), infant respiratory distress syndrome (IRDS), hyaline membrane disease, surfactant deficiency, surfactant protein-B deficiency, or bronchopulmonary dysplasia. In certain embodiments, the pulmonary disease is acute respiratory distress syndrome (ARDS). In certain embodiments, the pulmonary disease is severe acute respiratory syndrome (SARS). In certain embodiments, the pulmonary disease is respiratory distress syndrome. In certain embodiments, the pulmonary disease is neonatal respiratory distress syndrome (NRDS). In certain embodiments, the pulmonary disease is infant respiratory distress syndrome (IRDS). In certain embodiments, the pulmonary disease is hyaline membrane disease. In certain embodiments, the pulmonary disease is surfactant deficiency. In certain embodiments, the pulmonary disease is surfactant

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protein-B deficiency. In certain embodiments, the pulmonary disease is bronchopulmonary dysplasia. [00333] In some embodiments, the disease, disorder, or condition is a neurological disease. In certain embodiments, the neurological disease is a neurodegenerative disease. In some embodiments, the disease is dementia, Alzheimer’s disease, Parkinson’s disease, a Parkinson’s disease-related disorder, Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), a prion disease, corticobasal degeneration, frontotemporal dementia, HIV-related cognitive impairment, mild cognitive impairment, a motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Friedreich’s ataxia, Lewy body disease, Alpers’ disease, Batten disease, cerebro-oculo-facio-skeletal syndrome, corticobasal degeneration, Gerstmann-Straussler-Scheinker disease, Kuru, Leigh’s disease, monomelic amyotrophy, multiple system atrophy, multiple system atrophy with orthostatic hypotension (Shy-Drager syndrome), multiple sclerosis (MS), neurodegeneration with brain iron accumulation, opsoclonus myoclonus, posterior cortical atrophy, primary progressive aphasia, progressive supranuclear palsy, vascular dementia, progressive multifocal leukoencephalopathy, dementia with Lewy bodies, lacunar syndromes, hydrocephalus, Wernicke-Korsakoff’s syndrome, post-encephalitic dementia, cancer and chemotherapy-associated cognitive impairment and dementia, or depression-induced dementia and pseudodementia. In some embodiments, the disease is a synuclienopathy. In some embodiments, the disease is Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy. In certain embodiments, the disease is dementia, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, a prion disease, amyotrophic lateral sclerosis, or multiple sclerosis. In some embodiments, the disease is dementia, or Alzheimer’s disease. In certain embodiments, the disease is Alzheimer’s disease. In some embodiments, the disease is an advanced neurological disease. In certain embodiments, the disease is an advanced neurodegenerative disease. In some embodiments, the disease is advanced Alzheimer’s disease. In some embodiments, the disease is a neurological disease in the early stages. In certain embodiments, the disease is a neurodegenerative disease in the early stages. In some embodiments, the disease is Alzheimer’s disease in the early stages. In certain embodiments, treating and/or preventing the early-stage disease leads to reversal. [00334] In certain embodiments, the disease is a neurological disease, and treating and/or preventing the disease improves cognitive function. In some embodiments, the disease is a neurological disease, and treating and/or preventing the disease delays disease progression. In certain embodiments, the disease is a neurological disease, and treating and/or preventing the

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disease corrects issues with neurological function. In certain embodiments, the disease is a neurodegenerative disease, and treating and/or preventing the disease improves cognitive function. In some embodiments, the disease is a neurodegenerative disease, and treating and/or preventing the disease delays disease progression. In certain embodiments, the disease is a neurodegenerative disease, and treating and/or preventing the disease corrects issues with neurological function. [00335] In some embodiments, the disease is dementia, Alzheimer’s disease, Parkinson’s disease, a Parkinson’s disease-related disorder, Huntington’s disease, Amyotrophic Lateral Sclerosis (ALS), a prion disease, corticobasal degeneration, frontotemporal dementia, HIV- related cognitive impairment, mild cognitive impairment, a motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Friedreich’s ataxia, Lewy body disease, Alpers’ disease, Batten disease, cerebro-oculo-facio-skeletal syndrome, corticobasal degeneration, Gerstmann-Straussler-Scheinker disease, Kuru, Leigh’s disease, monomelic amyotrophy, multiple system atrophy, multiple system atrophy with orthostatic hypotension (Shy-Drager syndrome), multiple sclerosis (MS), neurodegeneration with brain iron accumulation, opsoclonus myoclonus, posterior cortical atrophy, primary progressive aphasia, progressive supranuclear palsy, vascular dementia, progressive multifocal leukoencephalopathy, dementia with Lewy bodies, lacunar syndromes, hydrocephalus, Wernicke-Korsakoff’s syndrome, post-encephalitic dementia, cancer and chemotherapy- associated cognitive impairment and dementia, or depression-induced dementia and pseudodementia, and treating and/or preventing the disease improves cognitive function. In certain embodiments, the disease is dementia, Alzheimer’s disease, Parkinson’s disease, a Parkinson’s disease-related disorder, Huntington’s disease, Amyotrophic Lateral Sclerosis (ALS), a prion disease, corticobasal degeneration, frontotemporal dementia, HIV-related cognitive impairment, mild cognitive impairment, a motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Friedreich’s ataxia, Lewy body disease, Alpers’ disease, Batten disease, cerebro-oculo-facio-skeletal syndrome, corticobasal degeneration, Gerstmann-Straussler-Scheinker disease, Kuru, Leigh’s disease, monomelic amyotrophy, multiple system atrophy, multiple system atrophy with orthostatic hypotension (Shy-Drager syndrome), multiple sclerosis (MS), neurodegeneration with brain iron accumulation, opsoclonus myoclonus, posterior cortical atrophy, primary progressive aphasia, progressive supranuclear palsy, vascular dementia, progressive multifocal leukoencephalopathy, dementia with Lewy bodies, lacunar syndromes, hydrocephalus, Wernicke-Korsakoff’s syndrome, post-encephalitic dementia, cancer and chemotherapy-associated cognitive impairment and

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dementia, or depression-induced dementia and pseudodementia, and treating and/or preventing the disease delays disease progression. In some embodiments, the disease is dementia, Alzheimer’s disease, Parkinson’s disease, a Parkinson’s disease-related disorder, Huntington’s disease, Amyotrophic Lateral Sclerosis (ALS), a prion disease, corticobasal degeneration, frontotemporal dementia, HIV-related cognitive impairment, mild cognitive impairment, a motor neuron disease, spinocerebellar ataxia, spinal muscular atrophy, Friedreich’s ataxia, Lewy body disease, Alpers’ disease, Batten disease, cerebro-oculo-facio- skeletal syndrome, corticobasal degeneration, Gerstmann-Straussler-Scheinker disease, Kuru, Leigh’s disease, monomelic amyotrophy, multiple system atrophy, multiple system atrophy with orthostatic hypotension (Shy-Drager syndrome), multiple sclerosis (MS), neurodegeneration with brain iron accumulation, opsoclonus myoclonus, posterior cortical atrophy, primary progressive aphasia, progressive supranuclear palsy, vascular dementia, progressive multifocal leukoencephalopathy, dementia with Lewy bodies, lacunar syndromes, hydrocephalus, Wernicke-Korsakoff's syndrome, post-encephalitic dementia, cancer and chemotherapy-associated cognitive impairment and dementia, or depression-induced dementia and pseudodementia, and treating and/or preventing the disease corrects issues with neurological function. [00336] In certain embodiments, the neurodegenerative disease is dementia. In some embodiments, the neurodegenerative disease is mild cognitive impairment, Creutzfeldt-Jakob disease, dementia with Lewy bodies, vascular dementia, mixed dementia, young-onset dementia, alcohol-related dementia, HIV-associated neurocognitive disorder, frontotemporal lobar dementia, or Alzheimer’s disease. In some embodiments, the neurodegenerative disease is mild cognitive impairment. In some embodiments, the neurodegenerative disease is Creutzfeldt-Jakob disease. In some embodiments, the neurodegenerative disease is dementia with Lewy bodies. In some embodiments, the neurodegenerative disease is vascular dementia. In some embodiments, the neurodegenerative disease is mixed dementia. In some embodiments, the neurodegenerative disease is young-onset dementia. In some embodiments, the neurodegenerative disease is alcohol-related dementia. In some embodiments, the neurodegenerative disease is HIV-associated neurocognitive disorder. In some embodiments, the neurodegenerative disease is frontotemporal lobar dementia. In some embodiments, the neurodegenerative disease is neuronal ceroid lipofuscinosis. In some embodiments, the neurodegenerative disease is associated with cerebral ischemia reperfusion injury. In some embodiments, the disease is Alzheimer’s disease or Parkinson’s disease.

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[00337] In some embodiments, the disease is Alzheimer’s disease. In certain embodiments, the disease is Alzheimer’s disease, and treating and/or preventing the disease improves cognitive function. In some embodiments, the disease is Alzheimer’s disease, and treating and/or preventing the disease delays disease progression. In certain embodiments, the disease is Alzheimer’s disease, and treating and/or preventing the disease corrects issues with neurological function. In certain embodiments, the Alzheimer’s disease is early stage. In some embodiments, the Alzheimer’s disease is late stage. In certain embodiments, the Alzheimer’s disease is familial Alzheimer’s disease. In certain embodiments, the Alzheimer’s disease is early-onset Alzheimer’s disease. In certain embodiments, the Alzheimer’s disease is inflammatory, non-inflammatory, or cortical Alzheimer’s disease. In some embodiments, the Alzheimer’s disease is inflammatory Alzheimer’s disease. In certain embodiments, the Alzheimer’s disease is non-inflammatory Alzheimer’s disease. In some embodiments, the Alzheimer’s disease is cortical Alzheimer’s disease. In some embodiments, the Alzheimer’s disease is mild, moderate, or severe. In certain embodiments, the Alzheimer’s disease is mild. In some embodiments, the Alzheimer’s disease is moderate. In certain embodiments, the Alzheimer’s disease is severe. [00338] In some embodiments, the disease is Parkinson’s disease. In certain embodiments, the disease is Parkinson’s disease, and treating and/or preventing the disease improves cognitive function. In some embodiments, the disease is Parkinson’s disease, and treating and/or preventing the disease delays disease progression. In certain embodiments, the disease is Parkinson’s disease, and treating and/or preventing the disease corrects issues with neurological function. [00339] In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a pharmaceutical composition thereof, is administered orally. In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a pharmaceutical composition thereof, is administered once daily. In certain embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a pharmaceutical composition thereof, is administered orally once daily. [00340] In another aspect, provided herein is a method of transporting a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, across the blood-

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brain barrier or blood-retinal barrier comprising administering to a subject the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00341] In another aspect, provided herein is a method of transporting a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, across the blood- brain barrier or blood-retinal barrier comprising administering to a subject the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00342] In another aspect, provided herein is a compound of Formula (I) or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport across the blood-brain barrier or blood-retinal barrier comprising administering to a subject the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00343] In another aspect, provided herein is a compound of Formula (II) or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport across the blood-brain barrier or blood-retinal barrier comprising administering to a subject the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00344] In certain embodiments, transport is across the blood-brain barrier. In some embodiments, transport is across the blood-retinal barrier. In some embodiments, the compound accumulates in the blood-brain barrier. In certain embodiments, the compound accumulates in the brain. In some embodiments, the compound accumulates in the blood retinal barrier. In certain embodiments, the compound accumulates in the eye. In some embodiments, transport across the blood-brain barrier or blood-retinal barrier occurs via the Mfsd2a protein. [00345] In another aspect, provided herein is a method of transporting a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal,

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tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, via the Mfsd2a protein in a subject, biological sample, tissue, or cell comprising administering to the subject or contacting the biological sample, tissue, or cell with the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In some embodiments, the method comprises administering to a subject the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, and Mfsd2a transports the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. In some embodiments, the method comprises contacting a cell, tissue, or biological sample with the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In some embodiments, the method comprises contacting a cell or biological sample with the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00346] In another aspect, provided herein is a method of transporting a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, via the Mfsd2a protein in a subject, biological sample, tissue, or cell comprising administering to the subject or contacting the biological sample, tissue, or cell with the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In some embodiments, the method comprises administering to a subject the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, and Mfsd2a transports the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. In some embodiments, the method comprises contacting a cell, tissue, or biological sample with the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In some embodiments, the method comprises contacting a cell or biological sample with the compound of Formula (II), or a

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pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00347] In another aspect, provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport via the Mfsd2a protein in a subject, biological sample, tissue, or cell. In another aspect, provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport via the Mfsd2a protein comprising administering to a subject the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In another aspect, provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport via the Mfsd2a protein comprising contacting a biological sample, tissue, or cell with the compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00348] In another aspect, provided herein is a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport via the Mfsd2a protein in a subject, biological sample, tissue, or cell. In another aspect, provided herein is a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport via the Mfsd2a protein comprising administering to a subject the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In another aspect, provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, for transport via the Mfsd2a protein comprising contacting a biological sample, tissue, or cell with the compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof.

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[00349] In another aspect, provided herein is a method of increasing plasmalogen levels in a subject, biological sample, tissue, or cell, comprising administering to the subject or contacting the biological sample, tissue, or cell with a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In another aspect, provided herein is a method of increasing plasmalogen levels in the brain or central nervous system of a subject, comprising administering to the subject a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00350] In another aspect, provided herein is a method of increasing plasmalogen levels in a subject, biological sample, tissue, or cell, comprising administering to the subject or contacting the biological sample, tissue, or cell with a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. In another aspect, provided herein is a method of increasing plasmalogen levels in the brain or central nervous system of a subject, comprising administering to the subject a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof. [00351] In another aspect, the present disclosure provides a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in increasing plasmalogen levels in a subject, biological sample, tissue, or cell. In another aspect, the present disclosure provides a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in increasing plasmalogen levels in the brain or central nervous system of a subject. [00352] In another aspect, the present disclosure provides a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in increasing plasmalogen levels in a subject, biological sample, tissue, or cell. In another aspect, the present disclosure provides a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer,

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stereoisomer, isotopically labelled compound, or prodrug thereof, or a composition thereof, for use in increasing plasmalogen levels in the brain or central nervous system of a subject. [00353] In another aspect, provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, for increasing plasmalogen levels in a subject, biological sample, tissue, or cell. In another aspect, provided herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, for increasing plasmalogen levels in the brain or central nervous system of a subject. [00354] In another aspect, provided herein is a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, for increasing plasmalogen levels in a subject, biological sample, tissue, or cell. In another aspect, provided herein is a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof, for increasing plasmalogen levels in the brain or central nervous system of a subject. [00355] In some embodiments, plasmalogen levels are increased in a subject. In some embodiments, the method comprises administering a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof to a subject. In some embodiments, the method comprises administering a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof to a subject. [00356] In some embodiments, plasmalogen levels are increased in a biological sample, tissue, or cell. In some embodiments, the method comprises contacting a biological sample, tissue, or cell with a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof to a subject. In some embodiments, the method comprises contacting a biological sample, tissue, or cell with a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer,

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stereoisomer, isotopically labeled derivative, or prodrug thereof, or a composition thereof to a subject. [00357] In some embodiments, the compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labelled compound, or prodrug thereof, or the composition is transported by the Mfsd2a protein. [00358] In some embodiments, plasmalogen levels are increased in the blood, brain, central nervous system, heart, kidney, muscle, and/or liver. In some embodiments, plasmalogen levels increase in the blood, brain, central nervous system, muscle, and/or heart. In some embodiments, plasmalogen levels increase in the brain and/or central nervous system. In some embodiments, plasmalogen levels in the brain increase. In some embodiments, plasmalogen levels in the CNS increase. In some embodiments, plasmalogen levels increase in the blood. In some embodiments, plasmalogen levels increase in plasma. In some embodiments, plasmalogen levels increase in serum. In some embodiments, plasmalogen levels increase in the heart. In some embodiments, plasmalogen levels increase in the kidney. In some embodiments, plasmalogen levels increase in the muscle. In some embodiments, plasmalogen levels increase in the liver. In some embodiments, levels of one or more docosahexaenoic acid (DHA)-containing plasmalogens increase. [00359] In some embodiments, plasmalogen levels increase by at least 5%, 10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%,90%, 100%, 125%, 150%, 200%, 300%, 400%, or 500%. In some embodiments, plasmalogen levels increase by at least 5%, 10%, 15%, or 20%. In some embodiments, plasmalogen levels increase by at least 20%, 25%, 30%, 35%, 40%, 45%, or 50%. In some embodiments, plasmalogen levels increase by at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%. In some embodiments, plasmalogen levels increase by at least 100%, 125%, 150%, or 200%. In some embodiments, plasmalogen levels increase by at least 200%, 300%, 400%, or 500%. In some embodiments, plasmalogen levels increase by about 5-25%, about 10-40%, about 25-50%, about 40-60%, about 50-75%, about 60-80%, about 75-100%, or greater than about 100%. [00360] In some embodiments, transport via the Mfsd2a protein occurs across the blood- brain barrier or blood-retinal barrier. In certain embodiments, transport via the Mfsd2a protein occurs across the blood-brain barrier. In some embodiments, transport via the Mfsd2a protein occurs across the blood-retinal barrier. In some embodiments, the compound accumulates in the blood-brain barrier. In certain embodiments, the compound accumulates in the brain. In some embodiments, the compound accumulates in the blood retinal barrier. In certain embodiments, the compound accumulates in the eye.

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[00361] In certain embodiments, the method is in vivo. In some embodiments, in vivo methods provided herein comprise administering to a subject an effective amount of a compound provided herein, or a composition thereof. In certain embodiments, the subject is a mammal. In some embodiments, the subject is a human. In certain embodiments, the subject is mouse. In some embodiments, the subject is a wild type mouse. In certain embodiments, the subject is a genetically modified mouse. In some embodiments, the genetically modified mouse comprises in its genome a homozygous disruption of the Mfsd2a gene. [00362] In certain embodiments, the method is in vitro. In some embodiments, in vitro methods provided herein can be carried out, e.g., in an assay, cell culture, or biological sample. In certain embodiments, the cell comprises a human wild type Mfsd2a cDNA or mutant human Mfsd2a cDNA. In some embodiments, the cell comprises a human wild type Mfsd2a cDNA. In certain embodiments, the cell comprises a mutant human Mfsd2a cDNA. In some embodiments, the cell is HEK 293. In some embodiments, the mutant human Mfsd2a cDNA comprises a mutation at a position corresponding to D93 or D97 in the human Mfsd2a protein sequence. E ^XAMPLES [00363] In order that the present disclosure may be more fully understood, the following examples are set forth. The synthetic and biological examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting in their scope. Synthesis [00364] Compounds of Formula (I) may be synthesized according to the following synthetic scheme.

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EQUIVALENTS AND SCOPE [00365] In the claims, articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The present disclosure includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The present disclosure includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process. [00366] Furthermore, the present disclosure encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the present disclosure, or aspects of the present disclosure, is/are referred to as comprising particular elements and/or features, certain embodiments of the present disclosure or aspects of the present disclosure consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub–range within the stated ranges in different embodiments of the present disclosure, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. [00367] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made

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without departing from the spirit or scope of the present disclosure, as defined in the following claims.

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