TLR RECEPTOR LIGANDS-BASED VACCINE ADJUVANTS

Abstract

Lipidized oxoadenines of formula (I) are TLR7 / 8 receptor ligands useful for modulating immune responses. These compounds may have therapeutic applications in the treatment of cancer, infectious diseases, allergies, or autoimmune disorders (SEE FORMULA).

Description

This application claims priority over U.S. provisional application no. s62 / 851,941, filed on May 23, 2019, and U.S. provisional application no. a62 / 975,054, filed on February 11, 2020, the full content of which is incorporated by reference. Declaration of government interest This invention was made with government support under contract number HHSN272200900036C awarded by the U.S. National Institutes of Health. The government has certain rights in the invention. Technical field This disclosure relates to lipidated TLR7 / 8 receptor ligand compounds (ToH-Like Receptors 7 and 8, Tol type receptors 7 and 8) and methods of use thereof, e.g., as vaccine adjuvants. Background The development of novel immunotherapies and vaccine adjuvants based on Toll-like receptor (TLR) ligands has been a rapidly expanding area of ​​research over the past 10 years, with clinical success in multiple indications and several approved products. Of the 10 known TLRs identified in humans, five are associated with the recognition of bacterial components (TLR 1, 2, 4, 5, 6), and four others (TLR 3, 7, 8, 9) appear to be restricted to cytoplasmic compartments, participating in the detection of viral RNA (TLR 3, 7, 8) and unmethylated DNA (TLR 9). One of the most promising classes of immunotherapeutic agents includes compounds targeting TLR7 / 8. Several different classes of small molecules mimic the natural viral mRNA ligands (rich in U and / or G) of TLR7 / 8. These include oxoguanosines, which primarily interact with TLR7, and adenine derivatives, which bind to TLR7 and / or TLR8. One class of TLR-active adenine derivatives are the oxoadenines, which were initially developed to overcome certain side effects associated with imidazoquinolines. Despite the fact that the oxoadenine class has better overall toxicity / bioactivity profiles than imidazoquinolines, administration can still lead to a systemic inflammatory reaction that limits its use in human clinical settings.In fact, most of the TLR7 / 8 agonists currently in development tend to exhibit toxic properties, are insoluble or unstable, and / or have relevant immunostimulatory effects. Therefore, there is a need for effective and safe TLR7 and / or TLR8 receptor ligand compounds for vaccines and immunotherapies. Summary In one aspect, compounds of formula (I) are disclosed: MA / (i) or a pharmaceutically acceptable salt thereof, wherein R1es alkyl Ci-Ce; R2 is H, C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R3 is C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R4, at each occurrence, is independently selected between Ce-C2 alkyl and C6-C20 alkenyl; n is 1, 2, 3, 4, 5 or 6; m is 2, 3, 4, 5 or 6; Z is (alkyl C2-CeO)q; and q is 1,2,3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In another aspect, the invention provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In another aspect, the invention provides a vaccine composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and an antigen. In another aspect, the invention provides a formulation comprising a microparticle or nanoparticle comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. In another aspect, the invention provides an adjuvant composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. In another aspect, the invention provides a method for modulating an immune reaction in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or of a pharmaceutically acceptable salt, or of a pharmaceutical composition thereof. Another aspect of the invention provides a method for treating, preventing, or reducing susceptibility to cancer in a subject comprising administering to a subject in need a therapeutically effective amount of the compound of formula (I) or of a pharmaceutically acceptable salt, or of a pharmaceutical composition thereof. ML / Another aspect of the invention provides a method for treating, preventing, or reducing susceptibility to an infectious disease in a subject comprising administering to a subject in need a therapeutically effective amount of the compound of formula (I) or of a pharmaceutically acceptable salt, or of a pharmaceutical composition thereof. Another aspect of the invention provides a method for treating, preventing, or reducing susceptibility to an allergy in a subject comprising administering to a subject in need a therapeutically effective amount of the compound of formula (I) or of a pharmaceutically acceptable salt, or of a pharmaceutical composition thereof. Another aspect of the invention provides a method for treating, preventing, or reducing susceptibility to an autoimmune condition in a subject comprising administering to a subject in need a therapeutically effective amount of the compound of formula (I) of or a pharmaceutically acceptable salt, or of a pharmaceutical composition thereof. In another aspect, the invention provides compounds of formula (I) or a pharmaceutically acceptable salt, or a pharmaceutical composition thereof, for use in a method of modulating an immune reaction. In another aspect, the invention provides compounds of formula (I) or a pharmaceutically acceptable salt, or a pharmaceutical composition thereof, for use in a method of treating, preventing, or reducing susceptibility to cancer, an infectious disease, an allergy, or an autoimmune condition. In another aspect, the invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt, or a pharmaceutical composition thereof, for the manufacture of a drug to modulate an immune reaction. In another aspect, the invention provides for the use of a compound of formula (I) or a pharmaceutically acceptable salt, or a pharmaceutical composition thereof, for the manufacture of a medicament to treat, prevent, or reduce susceptibility to cancer, an infectious disease, an allergy, or an autoimmune disease. Other aspects and achievements of the dissemination will become evident in light of the following description and the following drawings. Brief description of the drawings Figure 1 shows the structural formulas of compounds CRX-601, Compound A, Compound B, and Compound C. Figure 2A and Figure 2B are graphs of the reactions of INFα (Figure 2A) and IL-12p70 (Figure 2B) in the supernatants of human NPCs (Peripheral Blood Mononuclear Cells) stimulated with varying concentrations of selected TLR agonist compounds. Figure 3A, Figure 3B, Figure 3C, and Figure 3D are graphs of antigen-specific IgG (Figures 3A–3B) and IgG2A (Figures 3C–3D) titers observed in a murine influenza virus fractionation study using varying concentrations of liposomal formulations of CRX-601 and UM-1007, or of CRX-601 and UM-1007 co-encapsulated. Values ​​were recorded 14 days post-infection. MA / a single intramuscular vaccination in previously untreated mice (14Dd1, Figures 3A, 3C) and after administration of a second booster vaccination (14Dd2, Figures 3B, 3D). Figure 4A and Figure 4B are graphs of IgG1 (Figure 4A) and IgG2 (Figure 4B) titers observed in a study of fractionated influenza virus in minipigs from Yucatán using varying concentrations of liposomal formulations of CRX-601 and UM-1007, or of CRX-601 and UM-1007 encapsulated together. Values ​​were recorded 14 days after administration of a booster vaccine (14Dd2). Figure 5A, Figure 5B and Figure 50 are graphs of TNFα (Figure 5A), INFα (Figure 5B) and IL-12p70 (Figure 50) reactions in the supernatants of human NSCLC stimulated with varying concentrations of TLR agonists CRX-601, Compound A and Compound C. Figure 6A and Figure 6B are graphs showing the effects on mean tumor volume and median tumor volume in young female Balb / c mice after treatment with 10 mg or 50 mg of UM-1007. Detailed description This document describes a class of compounds that can act as TLR7 / 8 ligands, which may be useful for novel immunotherapies and vaccine adjuvants. The TLR7 / 8 ligands are novel PEGylated and lipidated oxoadenine compounds. The compounds of the invention have been shown to induce interferon-α and other immunostimulatory cytokines and may possess an improved activity-toxicity profile compared to other known oxoadenine-based TLR7 / 8 ligands. 1. Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as that commonly known to a person skilled in the art. In case of conflict, this document, including its definitions, shall prevail. The preferred methods and materials are described below, although in practice or testing, similar or equivalent methods and materials may be used. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are for illustrative purposes only and are not intended to be limiting. The terms and expressions comprise, include, have, may, contain, and variants thereof, as used herein, are intended as open-ended transitional expressions, terms, or words that do not preclude the possibility of additional actions or structures. The singular forms a, one, and the include plural references unless the context clearly indicates otherwise. This disclosure also contemplates other realizations that comprise, consist of, and essentially consist of the realizations or elements presented herein, whether or not explicitly stated. The modifier "approximately" used in relation to a quantity includes the stated value and has the meaning dictated by the context (for example, it includes at least the degree of error associated with measuring the particular quantity). It should also be considered that the modifier "approximately" discloses the interval defined by the absolute values ​​of the two endpoints. For example, the expression "from approximately 2 to approximately 4" also discloses the interval from 2 to 4. The term "approximately" can refer to plus or minus 10% of the stated number. For example, "approximately 10%" can indicate an interval from 9% to 11%, and "approximately 1" can mean from 0.9 to 1.1. Other meanings of "approximately" may become apparent from the context, such as rounding up; thus, for example, "approximately 1" can also mean from 0.5 to 1.4. The expression immune reaction includes any reaction associated with innate and adaptive immunity including, but not limited to, increases or decreases in the expression, production or secretion of cytokines (e.g., expression, production or secretion of IL-1, IL-6, IL-17, TNFα), cytotoxicity, migration of immune cells, antibody production and / or cellular immune reactions. The expression modulating an immune reaction or modulation of an immune reaction or modulating an immune reaction includes positively regulating, enhancing, stimulating, improving or increasing an immune reaction, as defined herein. The definitions of functional groups and specific chemical terms are described in more detail below. For the purposes of this disclosure, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th ed., inside cover, and specific functional groups are defined generally as defined therein. In addition, the general principles of organic chemistry, as well as specific functional groups and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March, March's Advanced Organic Chemistry, 5th ed., John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3.aedition, Cambridge University Press, Cambridge, 1987; the full contents of each of which are incorporated herein by reference. The term alkyl, as used herein, means a saturated hydrocarbon chain, linear or branched, containing from 1 to 10 carbon atoms. The expression lower alkyl or C1-C3 alkyl means a linear or branched hydrocarbon chain containing from 1 to 6 carbon atoms. The term C1-C3 alkyl means a linear or branched hydrocarbon chain containing from 1 to 3 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, β-butyl, tere-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, 4,4-dimethylpentan-2-yl, n-heptyl, n-octyl, n-nonyl, and ondecyl. The term alkenyl, as used herein, means a linear or branched hydrocarbon chain containing at least one carbon-carbon double bond and from 1 to 10 carbon atoms. ML / The term alkylene, as used herein, refers to a divalent group derived from a linear or branched hydrocarbon chain of 1 to 10 carbon atoms, for example, 2 to 5 carbon atoms. Representative examples of alkylene include, but are not limited to, -CH2CH2, -CH2CH2CH2-, -CH2CH(CH3)CH2-, -CH2CH2CH2CH2-, -CH2CH(CH3)CH2CH2-, and -CH2CH2CH2CH2CH2-. In some cases, the number of carbon atoms in a hydrocarbyl (e.g., alkyl or cycloalkyl) substituent is indicated by the prefix Cx-Cy-, where x is the minimum and y is the maximum number of carbon atoms in the substituent. Thus, for example, C1-C3 alkyl refers to an alkyl substituent containing 1 to 3 carbon atoms. The term substituents refers to a group substituted on an aryl, heteroaryl, phenyl, or pyridinyl group at any atom of that group. Any atom can be substituted. The term substituted refers to a group that may be further substituted with one or more substituent groups other than hydrogen. Substituent groups include, but are not limited to, halogen, =O(oxo), =S(thioxo), cyano, nitro, fluoroalkyl, alkoxyfluoroalkyl, fluoroalkoxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, heteroalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclo, cycloalkylalkyl, heteroarylalkyl, arylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylene, aryloxy, phenoxy, benzyloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, sulfonylamino, sulfinilamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, sulfinil, -COOH, ketone, amide, carbamate, and acyl.For example, if a group is described as optionally substituted (such as alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heteroalkyl, heterocycle, or another group, such as an R group), it may have 0, 1, 2, 3, 4, or 5 substituents independently selected from halogen, =0 (oxo), =S (thioxo), cyano, nitro, fluoroalkyl, alkoxyfluoroalkyl, fluoroalkoxy, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, heteroalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocycle, cycloalkylalkyl, heteroarylalkyl, arylalkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylene, aryloxy, phenoxy, benzyloxy, amino, alkylamino, acylamino, aminoalkyl, arylamino, sulfonylamino, sulfinamino, sulfonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, sulfinyl, -COOH, ketone, amide, carbamate and acyl. The expression — designates a single bond (— ) or a double bond (= ). For the compounds described herein, the groups and substituents thereof may be selected according to the permitted valency of the atoms and substituents, so that the selections and substitutions result in a stable compound, e.g., one that does not undergo spontaneous transformation, such as by rearrangement, cyclization, elimination, etc. When substituent groups are specified by their conventional chemical formulas, written from left to right, that formula also encompasses the same substituent that would result from writing the structure from right to left. For example, -CH2NH- is also intended to encompass -NHCH2-. For the enumeration of numerical intervals in this document, each intermediate number between them is explicitly considered with the same degree of precision. For example, for the interval 6-9, the numbers 7 and 8 are considered in addition to 6 and 9, and for the interval 6.0-7.0, the numbers 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly considered. MA / 2. Compounds In one aspect, a compound of formula (I) is disclosed: (I) or a pharmaceutically acceptable salt thereof, wherein R1es alkyl Ci-Cs; R2 is H, C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R3 is C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R4, at each occurrence, is independently selected between Ce-C2 alkyl and C6-C20 alkenyl; n is 1, 2, 3, 4, 5 or 6; m is 2, 3, 4, 5 or 6; Z is (alkyl C2-C6-O)q; yq is 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some embodiments, R2 is hydrogen or C(O)R4, wherein R4, when present, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3 at each occurrence. In some embodiments, R3 is C(O)R4, wherein R4, in each occurrence, is independently selected from (CH2)i0CH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, R4, in each occurrence, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, R4 is (CH2)i4CH3. In some embodiments, R2 and R3 are each C(O)R4, where R4, in each occurrence, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, R2 and R3 are each C(O)R4, where R4, in each occurrence, is (CH2)i4CH3. In some embodiments, R2 is hydrogen and R3 is C(O)R4, where R4 is selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (OH2)i6OH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, n is 1. In some embodiments, m is 2. In illustrative embodiments, n is 1 and m is 2. ML / In some embodiments, Z is (alkylene C2-O)q, where q is 3, 6, 9, 12 or 16. In illustrative embodiments, q is 3. q may be 3, 6, 9, 12 or 16 in any of the embodiments in this document. The alkylene of Z can be a linear-chain alkylene, i.e., an n-alkylene. For example, Z can be (n-alkylene C2-C6-O)q. Z can be (CH2CH2-O)q. Z can be (CH2CH2-O)3. Z can be (CH2CH2-O)6, Z can be (CH2CH2-O)g, Z can be (CH2CH2-O)i2, or it can be (CH2CH2-O)i6. In the compounds disclosed herein, Z is oriented with the terminal carbon of Z attached to the phosphate moiety and the oxygen of Z forming part of the glycerol moiety, as shown in formula (II). (the) or a pharmaceutically acceptable salt thereof, wherein R1es alkyl Ci-Cs; R2 is H, C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R3 is C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R4, at each occurrence, is independently selected between Ce-C2 alkyl and C6-C20 alkenyl; n is 1, 2, 3, 4, 5 or 6; m is 2, 3, 4, 5 or 6; MA / Z is (alkyl C2-Ce-O)q; yq is 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. In some embodiments, R2 is hydrogen or C(O)R4, wherein R4, when present, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3 at each occurrence. In some embodiments, R3 is C(O)R4, where R4, in each occurrence, is independently selected from (OH2)ιοOH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, R4, in each occurrence, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH-CH(CH2)7CH3. In some embodiments, R4 is (CH2)i4CH3. In some embodiments, R2 and R3 are each C(O)R4, where R4, in each occurrence, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)ieCH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, R2 and R3 are each C(O)R4, where R4, in each occurrence, is (CHkjuCHs). In some embodiments, R2 is hydrogen and R3 is C(O)R4, where R4 is selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3. In some embodiments, n is 1. In some embodiments, m is 2. In illustrative embodiments, n is 1 and m is 2. In some embodiments, Z is (alkylene C2-O)q, where q is 3, 6, 9, 12 or 16. In illustrative embodiments, q is 3. The compound, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of: ML / UZU^ / UUX^OU MA / The compound may exist as a stereoisomer in which asymmetric or chiral centers are present. The stereoisomer is either R or S depending on the configuration of the substituents around the chiral carbon atom. The terms R and S used herein are configurations as defined in the 1974 ILJPAC Recommendations for Section E, Fundamental Stereochemistry, in Puré Appl. Chem., 1976, 45: 13-30. The disclosure considers different MA / stereoisomers and mixtures thereof are specifically included within the scope of this disclosure. Stereoisomers include enantiomers and diastereomers, as well as mixtures of enantiomers or diastereomers. Individual stereoisomers of compounds can be prepared synthetically from commercially available starting materials containing asymmetric or chiral centers or by preparing racemic mixtures, followed by resolution methods well known to those skilled in the art. These resolution methods are illustrated by (1) attaching a mixture of enantiomers to a chiral auxiliary agent, separating the resulting diastereomer mixture by recrystallization or chromatography, and optionally releasing the optically pure product from the auxiliary agent as described in Furniss, Hannaford, Smith, and Tatchell, Vogel's Textbook of Practical Organic Chemistry 5.aedition (1989), Longman Scientific & Technical, Essex CM20 2JE, England (or more recent versions thereof); or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns or (3) fractional recrystallization methods. It must be understood that the compound may possess tautomeric forms, as well as geometric isomers, and that these also constitute realizations of disclosure. This disclosure also includes an isotopically labeled compound that is identical to those listed in formula (I), except that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number generally found in nature. Examples of isotopes suitable for inclusion in the compounds of this disclosure are hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as, but not limited to, 2H, 3H, 13C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, 18F, and 36Cl, respectively. Substitution with heavier isotopes such as deuterium, i.e., 2H, may provide certain therapeutic advantages due to greater metabolic stability, for example, an increased in vivo half-life or reduced dosage requirements, and therefore, in some circumstances, may be preferable.The compound may contain positron-emitting isotopes for medical imaging studies and Positron Emission Tomography (PET) to determine receptor distribution. Suitable positron-emitting isotopes that may be contained in compounds of formula (I) are 11C, 13N, 15O, and 18F. Generally, isotope-labeled compounds of formula (I) can be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying examples, using an appropriate isotope-labeled reagent instead of an unlabeled reagent. a. Pharmaceutically acceptable salts The disclosed compounds may exist in the form of pharmaceutically acceptable salts. The term "pharmaceutically acceptable salt" refers to salts or dipolar ions of the compounds that are soluble or dispersible in water or oil, suitable for the treatment of disorders without causing undue toxicity, irritation, or allergic reaction, proportionate to a reasonable risk-benefit ratio, and effective for their intended use. Salts may be prepared during the final isolation and purification of the compounds or separately by reacting an amino group of the compounds with a suitable acid. For example, a compound may be dissolved in a suitable solvent, such as, but not limited to, methanol and water, and treated with at least one equivalent of an acid, such as hydrochloric acid. The resulting salt may precipitate and be isolated by filtration and dried under reduced pressure.Alternatively, the solvent and excess acid can be removed under reduced pressure, yielding a salt. Representative salts include acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, formate, isethionate, fumarate, lactate, maleate, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, oxalate, maleate, pivalate, propionate, succinate, tartrate, trichloroacetate, trifluoroacetate, glutamate, para-toluenesulfonate, undecanoate, hydrochloric acid, hydrobromic acid, sulfuric acid, acid phosphoric and similar. The amino groups of the compounds can also be quaternized with alkyl chlorides, bromides, and iodides such as methyl, ethyl, propyl, isopropyl, butyl, lauryl, myristyl, stearyl, and the like. Base addition salts can be prepared during the final isolation and purification of disclosed compounds by reacting a carboxyl or phosphate group with a suitable base, such as the hydroxide, carbonate, or bicarbonate of a metal cation, such as lithium, sodium, potassium, calcium, magnesium, or aluminum, or a primary, secondary, or tertiary organic amine. Quaternary amine salts can be prepared, such as those derived from methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, tributylamine, pyridine, α-,α-dimethylaniline, β-methylpiperidine, N-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, α-,α-dibenzylphenethylamine, β-phenamine, and N,N'-dibenzylethylenediamine, ethylenediamine, ethanolamine, diethanolamine, piperidine, piperazine, and the like. In some embodiments, the pharmaceutically acceptable salt is a choline salt. Compounds and intermediates can be isolated and purified by methods well known to those skilled in organic synthesis. Examples of conventional methods for isolating and purifying compounds may include, but are not limited to, chromatography on solid supports such as silica gel, alumina, or silica derivatized with alkylsilane groups, recrystallization at high or low temperature with optional pretreatment with activated carbon, thin-layer chromatography, distillation at different pressures, vacuum sublimation, and trituration, as described, for example, in Vogel's Textbook of Practical Organic Chemistry, 5th edition (1989), by Furniss, Hannaford, Smith, and Tatchell, published by Longman Scientific & Technical, Essex CM20 2JE, England. The compounds described herein, or pharmaceutically acceptable salts thereof, may be included in a formulation. The formulation may comprise a microparticle or nanoparticle, including, but not limited to, a liposome, micelle, polymer, block copolymer, silica, emulsion, or a combination thereof. The formulation may comprise organic, inorganic, and / or lipid constituents and may contribute to the immunomodulatory effect of the compound and / or affect its biodistribution, bioavailability, and / or toxicity. b. Biological activity The compounds disclosed herein, including compounds of formula (I), may have biological activity that makes them useful as immunological adjuvants or MA / Immunomodulators. For example, the compounds can stimulate the immune system's response to a co-administered antigen. In some embodiments, the compounds of formula (I) are TLR7 antagonists. In some embodiments, the compounds of formula (I) are TLR8 antagonists. In some embodiments, the compounds have Th1-stimulating adjuvant activity. In some embodiments, the compounds can mimic cytokine production in a sample or when administered to a subject. The compounds can stimulate the production of Th1-type cytokines. Examples of cytokines include IFN-γ, IL-2, and IL-12. Such activity can be tested according to established methods. For example, the levels of such cytokines can be measured in peripheral blood mononuclear cell (PBC) samples following exposure to the compounds. Conditions that may be mediated by TLR7 and / or TLR8 activity include, but are not limited to, inflammation, including, but not limited to, inflammatory or allergic diseases such as asthma, allergic rhinitis, hypersensitivity lung diseases, eosinophilic pneumonitis, delayed-type hypersensitivity, atherosclerosis, pancreatitis, gastritis, osteoarthritis, psoriasis, sarcoidosis, pulmonary fibrosis, respiratory distress syndrome, bronchiolitis, chronic obstructive pulmonary disease, sinusitis, cystic fibrosis, and dermatitis; autoimmune diseases including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, Sjögren's disease, ankylosing spondylitis, scleroderma, diabetes, graft rejection, including graft-versus-host disease, and inflammatory bowel diseases including, but not limited to, Crohn's disease and ulcerative colitis;infectious diseases including, but not limited to, those caused by hepatitis viruses (e.g., hepatitis B virus, hepatitis C virus), human immunodeficiency virus, papillomavirus, herpesvirus, respiratory viruses (e.g., influenza virus, respiratory syncytial virus, rhinovirus, metapneumovirus, parainfluenza virus, SARS [Severe Acute Respiratory Syndrome]) and West Nile virus; microbial infections caused, for example, by bacteria, fungi or protozoa including, but not limited to, tuberculosis, bacterial pneumonia, aspergillosis, histoplasmosis, candidiasis, pneumocystosis, leprosy, chlamydia, cryptococcal disease, cryptosporidiosis, toxoplasmosis, leishmaniasis, malaria and trypanosomiasis;various cancers, in particular, the treatment of cancers known to be sensitive to immunotherapy and which include, but are not limited to, renal cell carcinoma, lung cancer, breast cancer, colorectal cancer, bladder cancer, melanoma, leukemia, lymphomas and ovarian cancer; basal cell carcinoma; actinic keratosis; genital papillomavirus infections; and liver regeneration; 3. Compositions The disclosed compounds may be incorporated into pharmaceutical compositions, adjuvant compositions, and vaccine compositions that may be suitable for administration to a subject (such as a patient, who may be human or non-human). a. Pharmaceutical compositions The disclosed compounds may be incorporated into pharmaceutical compositions. Pharmaceutical compositions may include a therapeutically effective amount or a prophylactically effective amount of the agent. A therapeutically effective amount refers to an effective quantity, at the doses and for the periods of time necessary to achieve the desired therapeutic result. A person skilled in the art may determine a therapeutically effective amount of the composition, and it may vary depending on factors such as the pathological condition, age, sex, and weight of the individual, and the composition's ability to produce a desired reaction in the individual. A therapeutically effective amount is also one in which the therapeutically beneficial effects outweigh any toxic or harmful effects of a compound of the invention (e.g., a compound of formula (I)).A prophylactically effective amount refers to the effective quantity, dosage, and time period necessary to achieve the desired prophylactic outcome. Typically, because a prophylactic dose is used in subjects before or at an earlier stage of the disease, the prophylactically effective amount will be less than the therapeutically effective amount. Pharmaceutical compositions and formulations may include additional therapeutic agents. In some embodiments, the additional therapeutic agent is an adjuvant, an immunostimulant, a chemotherapeutic agent, an immunomodulatory agent, or a combination thereof. Pharmaceutical compositions and formulations may include an adjuvant. Adjuvants are additives that enhance humoral and / or cell-mediated immune responses to a vaccine antigen. Any adjuvant may be useful in the pharmaceutical compositions and formulations described herein. The adjuvant may interact with a member of the TLR family. In some embodiments, the adjuvant is a TLR4 ligand. TLR4 ligands include CRX-601 (Figure 1), monophosphoryl lipid A (MPLA), glucopyranosyl lipid A (GLA), CRX-547, aminoalkylglucosamide 4-phosphate (AGP) class lipid A mimetics, and other TLR4 ligands described in Khalaf et al., Bioorg. Med. Chem. Lett. (2015) 25(3), 547-553 and U.S. Patents 7,960,522 and 7,063,967, which are incorporated herein by reference. Other TLR4 ligands include compounds described in WO2019 / 157509, which is incorporated herein by reference. For example, the ligand of ML / U^U^ / UU^OU ML / acceptable of the same. In some embodiments, the adjuvant is an aluminum salt. The aluminum salt may include phosphate, sulfate, hydroxide, or a combination thereof. In some embodiments, the aluminum salt is potassium aluminum sulfate, which may be in hydrated form. The aluminum salt may also be an aluminum hydroxide gel. The aluminum salt may also be a wet aluminum phosphate gel. MA / Aluminum salt adjuvants may be called alum. In some embodiments, a compound such as that disclosed herein is adsorbed onto the aluminum salt. The pharmaceutical composition may further comprise an antigen. In some embodiments, the antigen is adsorbed to the aluminum salt with a compound disclosed herein. Suitable antigens include microbial pathogens, bacteria, viruses, proteins, glycoproteins, lipoproteins, peptides, glycopeptides, lipopeptides, toxoids, carbohydrates, and tumor-specific antigens. Mixtures of two or more antigens may be used. In some embodiments, the antigen is obtained from a bacterium, virus, bacteriophage, fungus, prion, neoplasm, autoantigen, animal, plant, recombinant material, or synthetic material. In one embodiment, the antigen of a vaccine composition is in the form of a peptide, polypeptide, protein, or immunogenic portion thereof. In some embodiments, the antigen is a hapten, a hapten conjugated to a carrier protein, polypeptide, or other polymer, or derivatives thereof.In some embodiments, the antigen is an allergen. Pharmaceutical compositions and formulations may include an immunostimulant. Immunostimulants stimulate the immune system by inducing the activation or increasing the activity of any of its components. Any of the many known molecules or compounds with immunostimulatory activity may be used in disclosed pharmaceutical compositions and formulations. Pharmaceutical compositions and formulations may include a chemotherapeutic agent. The chemotherapeutic agent may include any drug used in the treatment of cancer or any radiation sensitizing agent. Chemotherapeutic agents may include alkylating agents (including, but not limited to, cyclophosphamide, mechlorethamine, chlorambucil, melphalan, dacarbazine, nitrosoureas, and temozolomide), anthracyclines (including, but not limited to, daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, and valrubicin), cytoskeletal disruptors or taxanes (including, but not limited to, paclitaxel, docetaxel, abraxane, and taxotere), epothilones, histone deacetylase inhibitors (including, but not limited to, vorinostat and romidepsin), topoisomerase inhibitors (including, but not limited to, irinotecan, topotecan, etoposide, tenoposide, and tafluposide), kinase inhibitors (including, but not limited to,bortezomib, erlotinib, gefitinib, imantinib, vemurafenib and vismodegib), nucleotide analogues and precursor analogues (including, but not limited to, azacitidine, azathioprine, capecitabine, cytarabine, doxyfluridine, fluorouracil, gemcitabine, hydroxyurea, mercaptopurine, methotrexate and thioguanine), peptide antibiotics (including, but not limited to, bleomycin and actinomycin), platinum-based agents (including, but not limited to, carboplatin, cisplatin and oxaliplatin), retinoids (including, but not limited to, tretinoin, alitretinoin and bexarotene), vinca alkaloids and derivatives (including, but not limited to, vinblastine, vincristine, vindesine and vinorelbine) or combinations thereof. Pharmaceutical compositions and formulations may include an immunomodulatory agent. Immunomodulatory agents include interferons, antigens, tumor phagocytosis inducers, and other immune-enhancing agents (e.g., immune checkpoint inhibitors). MA / immunomodulatory agent may be an immune checkpoint inhibitor, a tumor phagocytosis inducer, or a combination of both. Interferons include interferon a, interferon a-2a, interferon a-2b, interferon β, interferon y-la, ACTIMMUNE® (interferon γ-lb) or interferon y-nl, combinations thereof and similar. In some embodiments, the immunomodulatory agent is an immune checkpoint inhibitor. Immune checkpoints regulate the function of T lymphocytes in the immune system. T lymphocytes play a central role in cell-mediated immunity. Checkpoint proteins interact with specific ligands that signal the T lymphocyte and essentially turn off or inhibit its function. Checkpoint inhibitor therapies can unblock an existing immune response or prevent the initiation of an immune response. Because many immune checkpoints are regulated by interactions between receptors and specific ligand pairs, monoclonal antibodies or other agents can be used to block this interaction and prevent immunosuppression.A checkpoint inhibitor can be a biologic therapeutic agent, a small molecule, a monoclonal antibody, a humanized antibody, a fully human antibody, a fusion protein, or a combination thereof. The checkpoint inhibitor can inhibit a checkpoint protein, including, for example, CTLA-4, PD-L1, PD-L2, PD-1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK1, CHK2, A2aR, and the B-7 family ligands. The checkpoint inhibitor can interact with a checkpoint protein ligand, which includes, for example, CTLA-4, PDL1, PDL2, PD1, B7-H3, B7-H4, BTLA, HVEM, TIM3, GAL9, LAG3, VISTA, KIR, 2B4, CD160, CGEN-15049, CHK 1, CHK2, A2aR and the B-7 family ligands. Immune checkpoint inhibitors include PD-1 inhibitors (e.g., nivolumab, pidilizumab, sintilimab), PD-L1 inhibitors (e.g., atezolizumab, avelumab, durvalumab, BMS-936559), CTLA4 inhibitors (e.g., ipilimumab, tremelimumab), or IDO inhibitors (e.g., indoximod, epacadostat). In some embodiments, the immunomodulatory agent is a tumor phagocytosis inducer. Cell surface immunostimulatory polypeptides and their receptors are important for the elimination and destruction of foreign materials, including mammalian cells or bacteria. Cell surface immunostimulatory polypeptides and their receptors activate phagocytosis. A phagocytosis inducer can induce cell surface polypeptides and their receptors to activate phagocytosis. Tumor phagocytosis inducers include anti-CD47 monoclonal antibodies (e.g., Hu5F9-G4, CC-90002, ZF1, AMMS4-G4, IBI188, SRF231), anti-SIRPa fusion proteins (e.g., TTI-621, TTI-622), and anti-SIRPa monoclonal antibodies (e.g.,OSE-172), bispecific antibodies against antitumor antigens / anti-CD47 and inhibitors of the leukocyte immunoglobulin-like receptor B1 (LILRB1), which binds to β2 microglobulin, and the major histocompatibility complex class 1 (MHC class β2M). Bispecific antibodies against antitumor antigens / anti-CD47 include bispecific anti-CD47 / CD19 antibodies (e.g., TG-1801), bispecific anti-CD20 antibodies. CD47 / mesothelin (e.g., NI-1801), bispecific anti-CD47 / 4-1 BB antibodies (e.g., DSP107), bispecific anti-CD47 / CD20 antibodies, bispecific anti-CD47 / CD33 antibodies (e.g., HMBD004). Other immunomodulatory agents include ALFAFERONE®, BAM-002, BEROMUN® (tasonermin), BEXXAR® (tositumomab), CamPath® (alemtuzumab), CTLA4 (cytotoxic lymphocyte antigen 4), decarbazine, denileucine, epratuzumab, GRANOCYTE® (lenograstim), lentinan, leukocyte interferon alpha, imiquimod, MDX-010, melanoma vaccine, mitumomab, molgramostim, MYLOTARGTM® (gemtuzumab ozogamicin). NEUPOGEN® (filgrastlm), OncoVAC-CL, OvaRex® (oregovomab), pemtumomab(Y-muHMFGI), PROVENGE®, sargaramostim, sizofilan, teceleucine, TheraCys®, ubenimex, VIRULIZIN®, Z-IOO, WF-IO, PROLEUKIN® (aldesleucine), ZADAXIN® (timalfasine), ZENAPAX® (daclizumab), ZEVALIN® (90Y-Ibritumomab tiuxetan) and similar drugs, including, but not limited to, STING (STimulator of INterferon Genes) and NOD (Nucleotide-binding Oligomerization Domain). In the methods and uses described herein, the pharmaceutical combination of the compound of formula (I) or a pharmaceutically acceptable salt, or the composition thereof, and an adjuvant and / or immunomodulatory agent may be administered / used simultaneously, separately, or sequentially and in any order, and the components may be administered separately or as a fixed combination. For example, the therapeutic treatment according to the invention may comprise the administration of a first active ingredient in the form of a free or pharmaceutically acceptable salt and the administration of a second active ingredient in the form of a free or pharmaceutically acceptable salt, simultaneously or sequentially in any order, in therapeutically effective amounts or in amounts effective together, e.g., at daily doses corresponding to the amounts described herein.The individual active ingredients of the combination can be administered separately at different times during therapy or simultaneously in single or split dosage forms. Therefore, the present invention is understood to encompass all such simultaneous or alternating treatment regimens, and the term "administer" should be interpreted accordingly. Thus, a pharmaceutical combination, as used herein, defines a fixed combination in a single dosage form or separate dosage forms for combined administration, where the combined administration can be independent, occurring simultaneously or at different times. As a further example, adjuvants or immunomodulatory agents can be administered / used simultaneously (e.g., by co-injection), separately, or sequentially, followed by the administration of the compound of formula (I), or vice versa. Pharmaceutical compositions and formulations may include pharmaceutically acceptable carriers. The term pharmaceutically acceptable carrier, as used herein, means a non-toxic, inert, solid, semi-solid, or liquid filler, diluent, encapsulating material, or formulation aid of any kind. Examples of materials that may serve as pharmaceutically acceptable carriers include, but are not limited to, sugars such as: MA / lactose, glucose and sucrose; starches such as, but not limited to, corn starch and potato starch; cellulose and its derivatives such as, but not limited to, sodium carboxymethylcellulose, ethylcellulose and cellulose acetate; tragacanth powder; malt; gelatin; talc; excipients such as, but not limited to, cocoa butter and suppository waxes; oils such as, but not limited to, peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols such as propylene glycol; esters such as, but not limited to, ethyl oleate and ethyl laurate; agar; buffering agents such as, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline solution; Ringer's solution;ethyl alcohol and phosphate buffer solutions, as well as other compatible non-toxic lubricants such as, but not limited to, sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening agents, flavorings and perfumes, preservatives and antioxidants, which may also be present in the composition at the formulator's discretion. Therefore, physiologically acceptable compounds and their salts can be formulated for administration, for example, by solid dosage form, eye drops, in an oil-based topical formulation, by injection, inhalation (either by mouth or nose), implants, or by oral, buccal, sublingual, parenteral, or rectal administration. Techniques and formulations can generally be found at Remington's Pharmaceutical Sciences (Meade Publishing Co., Easton, PA). Therapeutic compositions should normally be sterile and stable under the conditions of manufacture and storage. The route of administration of the disclosed compounds and the form of the composition will determine the type of carrier used. The composition may be in a variety of forms suitable, for example, for systemic administration (e.g., oral, rectal, nasal, sublingual, buccal, implants, or parenteral) or topical administration (e.g., dermal, pulmonary, nasal, auditory, ocular, liposome delivery systems, or iontophoresis). Carriers for systemic administration typically include at least one of the following: diluents, lubricants, binders, disintegrants, colorants, flavorings, sweeteners, antioxidants, preservatives, glidants, solvents, suspending agents, wetting agents, surfactants, combinations thereof, and others. All carriers are optional in the compositions. Suitable diluents include sugars such as glucose, lactose, dextrose, and sucrose; diols such as propylene glycol; calcium carbonate; sodium carbonate; sugar alcohols such as glycerin; mannitol; and sorbitol. Typically, the amount of diluent(s) in a systemic or topical formulation is approximately 50 to 90%. Suitable lubricants include silica, talc, stearic acid and its magnesium and calcium salts, calcium sulfate; and liquid lubricants such as polyethylene glycol and vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil, and theobroma oil. Typically, the amount of lubricant(s) in a systemic or topical formulation is approximately 5 to 10%. MA / Suitable binders include polyvinylpyrrolidone; magnesium aluminum silicate; starches such as corn starch and potato starch; gelatin; tragacanth; and cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, methylcellulose, microcrystalline cellulose, and sodium carboxymethylcellulose. Typically, the amount of binder(s) in a systemic formulation is approximately 5 to approximately 50%. Suitable disintegrants include agar, alginic acid and its sodium salt, effervescent mixtures, croscarmellose, crospovidone, sodium starch glycolate, sodium starch glycolate, clays, and ion-exchange resins. Typically, the amount of disintegrant(s) in a systemic or topical formulation is approximately 0.1% to approximately 10%. Suitable colorants include a dye such as an FD&C dye. When used, the amount of dye in a systemic or topical formulation is typically approximately 0.005 to approximately 0.1%. Suitable flavorings include menthol, mint, and fruit flavorings. Typically, the amount of flavoring(s), when used, in a systemic or topical formulation is approximately 0.1 to approximately 1.0%. 1. Suitable sweeteners include aspartame and saccharin. Typically, the amount of sweetener(s) in a systemic or topical formulation is approximately 0.001 to approximately 1%. 1.2Suitable antioxidants include butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and vitamin E. Typically, the amount of antioxidant(s) in a systemic or topical formulation is approximately 0.1 to approximately 5%. 1. Suitable preservatives include benzalkonium chloride, methylparaben, and sodium benzoate. Typically, the amount of preservative(s) in a systemic or topical formulation is approximately 0.01 to approximately 5%. 1. Suitable gliders include silicon dioxide. Typically, the amount of glide(s) in a systemic or topical composition is approximately 1 to approximately 5%. 1. Suitable solvents include water, isotonic saline solution, ethyl oleate, glycerin, hydroxylated castor oils, alcohols such as ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and phosphate buffer solutions. Typically, the amount of solvent(s) in a systemic or topical composition is from approximately 0 to approximately 100%. In one embodiment, the compounds of the invention are formulated in 2% glycerol in sterile water. In a further embodiment, compound UM-1007 is formulated in 2% glycerol in sterile water. The 2% glycerol-in-sterile-water formulations may be for parenteral administration. 1. Suitable suspending agents include AVICEL RC-591 (from FMC Corporation of Philadelphia, PA) and sodium alginate. Typically, the amount of suspending agent(s) in a systemic or topical formulation is approximately 1 to approximately 8%. MA / 1. Suitable surfactants include lecithin, polysorbate 80, and sodium lauryl sulfate, and TWEENS from Atlas Powder Company of Wilmington, Delaware. Suitable surfactants include those described in CTFA Cosmetic Ingredient Handbook, 1992, pp. 587-592; Remington's Pharmaceutical Sciences, 15th ed., 1975, pp. 335-337; and Volume 1 of McCutcheon, Emulsifiers & Detergents, 1994, North American Edition, pp. 236-239. Typically, the amount of surfactant(s) in the systemic or topical formulation is approximately 0.1% to approximately 5%. 1. Although the amounts of components in systemic compositions may vary depending on the type of systemic composition prepared, in general, systemic compositions include 0.01% to 50% of an active compound (e.g., a compound of formula (I)) and 50% to 99.99% of one or more carriers. Typically, compositions for parenteral administration include 0.1% to 10% of active ingredients and 90% to 99.9% of a carrier that includes a diluent and a solvent. 1.2 Oral dosage forms can have different dosage forms. For example, solid forms include tablets, capsules, granules, and bulk powders. These oral dosage forms contain a safe and effective amount, usually at least approximately 5% and more particularly approximately 25% to approximately 50%, of active ingredients. Oral dosage compositions contain approximately 50% to approximately 95% of carriers and, more particularly, approximately 50% to approximately 75%. 1. Tablets may be compressed, crushed, enteric-coated, sugar-coated, film-coated, or multi-compression-compressed. Typically, tablets include an active ingredient and a carrier comprising ingredients selected from diluents, lubricants, binders, disintegrants, colorants, flavorings, sweeteners, glidants, and combinations thereof. Specific diluents include calcium carbonate, sodium carbonate, mannitol, lactose, and cellulose. Specific binders include starch, gelatin, and sucrose. Specific disintegrants include alginic acid and croscarmellose. Specific lubricants include magnesium stearate, stearic acid, and talc. Specific colorants are FD&C dyes, which may be added for aesthetic reasons.Preferably, chewable tablets contain sweeteners such as aspartame and saccharin, or flavorings such as menthol, mint, fruit flavorings or a combination thereof. 1.2 Typically, capsules (including implants, extended-release formulations, and sustained-release formulations) comprise an active compound (e.g., a compound of formula (I)) and a carrier comprising one or more diluents disclosed above in a capsule comprising gelatin. Typically, granules comprise a disclosed compound and preferably flow agents such as silicon dioxide to improve flow characteristics. Implants may be biodegradable or non-biodegradable. 1. The selection of carrier ingredients for oral compositions depends on secondary considerations such as taste, cost, and storage stability, which are not fundamental to the purposes of this invention. Solid compositions can be coated using conventional methods, typically with pH- or time-dependent coatings, so that a disclosed compound is released in the gastrointestinal tract in close proximity to the desired application site, or at different application sites and times to prolong the desired action. Coatings typically include one or more components selected from the group consisting of cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose phthalate, ethylcellulose, EUDRAGIT® coatings (available from Evonik Industries of Essen, Germany), waxes, and shellac. 1.2 Oral compositions may be in liquid form. Suitable liquid forms include aqueous solutions, emulsions, suspensions, solutions reconstituted from non-effervescent granules, suspensions reconstituted from non-effervescent granules, effervescent preparations reconstituted from effervescent granules, elixirs, tinctures, syrups, and the like. Typically, liquid compositions for oral administration include a disclosed compound and a carrier, specifically a carrier selected from diluents, colorants, flavorings, sweeteners, preservatives, solvents, suspending agents, and surfactants. Oral liquid compositions preferably include one or more ingredients selected from colorants, flavorings, and sweeteners. 1. Other compositions useful for achieving systemic administration of the present compounds include sublingual, buccal, and nasal dosage forms. Typically, such compositions include one or more soluble bulking agents such as diluents including sucrose, sorbitol, and mannitol; and binders such as gum arabic, microcrystalline cellulose, carboxymethylcellulose, and hydroxypropyl methylcellulose. Such compositions may also include lubricants, colorants, flavorings, sweeteners, antioxidants, and glides. 1.2The disclosed compounds may be administered topically. Topical compositions that can be applied locally to the skin may be in any form, including solids, solutions, oils, creams, ointments, gels, lotions, shampoos, rinse-in and leave-in hair conditioners, milks, cleansers, moisturizers, sprays, skin patches, and the like. Topical compositions include a disclosed compound (e.g., a compound of formula (I)) and a carrier. The carrier of the topical composition preferentially aids the penetration of the compounds through the skin. The carrier may further include one or more optional components. 1. The amount of carrier used in conjunction with a disclosed compound is sufficient to provide a practical quantity of composition for unit-dose administration of the compound. Techniques and compositions for preparing dosage forms useful in the methods of this invention are described in the following references: Modern Pharmaceutics, Chapters 9 and 10, Banker & Rhodes, eds. (1979); Lieberman et al., Pharmaceutical Dosage Forms: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms, 2nd ed., (1976). 1.2 A carrier may include a single ingredient or a combination of two or more ingredients. In topical compositions, the carrier includes a topical carrier. Suitable topical carriers include one or more ingredients selected from phosphate-buffered saline solution, water MA / Isotonic water, deionized water, monofunctional alcohols, symmetrical alcohols, aloe vera gel, allantoin, glycerin, vitamin A and E oils, mineral oil, propylene glycol, PPG-2 myristyl propionate, dimethyl isosorbide, castor oil, combinations thereof and similar. More particularly, carriers for cutaneous applications include propylene glycol, dimethyl isosorbide and water, and even more particularly, phosphate-buffered saline solution, isotonic water, deionized water, monofunctional alcohols and symmetrical alcohols. 1. The carrier of a topical composition may also include one or more ingredients selected from emollients, propellants, solvents, humectants, thickeners, powders, perfumes, pigments and preservatives, all of which are optional. 1. Suitable emollients include stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, propane-1,2-diol, butane-1,3-diol, mink oil, cetyl alcohol, isopropyl isostearate, stearic acid, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, sesame oil, coconut oil, peanut oil, castor oil, and lanolin alcohols. acetylated compounds, petroleum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate and combinations thereof.Skin-specific emollients include stearyl alcohol and polydimethylsiloxane. Typically, the amount of emollient(s) in a topical skin-based composition ranges from approximately 5% to approximately 95%. 1. Suitable propellants include propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide, and combinations thereof. Typically, the amount of propellant(s) in a topical composition is approximately 0% to approximately 95%. 1. Suitable solvents include water, ethyl alcohol, methylene chloride, isopropanol, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulfoxide, dimethylformamide, tetrahydrofuran, and combinations thereof. Specific solvents include ethyl alcohol and homotopic alcohols. Typically, the amount of solvent(s) in a topical composition is approximately 0% to approximately 95%. 1. Suitable humectants include glycerin, sorbitol, sodium 2-pyrrolidone-5-carboxylate, soluble collagen, dibutyl phthalate, gelatin, and combinations thereof. Specific humectants include glycerin. Typically, the amount of humectant(s) in a topical composition is from 0% to 95%. 1.2Typically, the amount of thickener(s) in a topical composition is approximately 0% to approximately 95%. 1. Suitable powders include β-cyclodextrins, hydroxypropyl cyclodextrins, chalk, talc, fuller's earth, kaolin, starch, gums, colloidal silicon dioxide, sodium polyacrylate, tetraalkylammonium smectites, trialkylarylammonium smectites, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, pyrolysis silica, carboxyvinyl polymer, sodium carboxymethylcellulose, ethylene glycol monostearate, and combinations thereof. Typically, the amount of powder(s) in a topical composition is from 0% to 95%. 1.2Normally, the amount of perfume in a topical composition is from approximately 0% to approximately 0.5%, in particular, from approximately 0.001% to approximately 0.1%. 1. Suitable pH-adjusting additives include HCl or NaOH in sufficient quantities to adjust the pH of a topical pharmaceutical composition. b. Adjuvant and vaccine compositions 1. The compounds can also be incorporated into adjuvant and vaccine compositions. The adjuvant composition can induce an immune response. In some embodiments, the adjuvant composition induces a Th1-type immune response. 1.2 Vaccine compositions may also include an antigen. Suitable antigens include microbial pathogens, bacteria, viruses, proteins, glycoproteins, lipoproteins, peptides, glycopeptides, lipopeptides, toxoids, carbohydrates, and tumor-specific antigens. Mixtures of two or more antigens may be used. In some embodiments, the antigen is derived from a bacterium, virus, bacteriophage, fungus, prion, neoplasm, autoantigen, animal, plant, recombinant material, or synthetic material. Antigens include bacterial, viral, fungal, plant, and cancer / tumor antigens described in WO2019 / 157509, which is incorporated herein by reference. 1.2 Adjuvant and vaccine compositions may include an effective amount of the disclosed compound. In the context of an adjuvant or vaccine composition, an effective amount refers to the quantity, dosage, and time periods necessary to achieve the desired outcome (e.g., to enhance an immune response to one or more antigens). The immune response can be measured, for example, by measuring antibody titers against an antigen, assessing the ability of a vaccine containing the compound to immunize a host in response to a disease or exposure to an antigen, etc.For example, administering an effective amount of a compound or composition to a subject increases one or more antibody titers by 10% or more compared to a non-immune control, by 20% or more compared to a non-immune control, by 30% or more compared to a non-immune control, by 40% or more compared to a non-immune control, by 50% or more compared to a non-immune control, by 50% or more compared to a non-immune control, by 70% or more compared to a non-immune control, by 80% or more compared to a non-immune control, by 90% or more compared to a non-immune control, or by 100% or more compared to a non-immune control. 1.2Vaccine preparation is a highly developed technique, and general guidance on vaccine preparation and formulation can be readily obtained from a variety of sources. One such example is New Trends and Developments in Vaccines, edited by Voller et al., University Park Press, Baltimore, Maryland, USA, 1978. The vaccine compositions of this disclosure may also contain other compounds, which may be biologically active or inactive. One or more immunogenic parts of other tumor antigens may be present, either incorporated into a fusion polypeptide or as a separate compound, within the vaccine composition. The polypeptides may be conjugated, but are not required to be, with other macromolecules as described, for example, in U.S. Patent Nos. 4,372,945 and 4,474,757. The vaccine compositions may generally be used for prophylactic and therapeutic purposes. 1. In one embodiment, the antigen of a vaccine composition is in the form of a peptide, polypeptide, protein, or immunogenic part thereof. An immunogenic part, as used herein, is a portion of a protein that is recognized (i.e., specifically bound) by a surface antigen receptor of B lymphocytes and / or T lymphocytes. Generally, such immunogenic parts comprise at least 5 amino acid residues, more preferably at least 10, and even more preferably at least 20 amino acid residues of an antigenic protein or a variant thereof. 1.2Generally, the immunogenic portions of antigenic polypeptides can be identified using well-established techniques, such as those summarized in Paul, Fundamental Immunology, 3rd ed., 243-247 (Raven Press, 1993) and the references cited therein. Such techniques include screening polypeptides based on their ability to react with antigen-specific antibodies, antisera, and / or T-cell clones or strains. As used herein, antisera and antibodies are antigen-specific if they bind specifically to an antigen (i.e., they react with the protein in an ELISA (Enzyme-Linked Immunosorbent Assay) or other immunoassay and do not react detectably with unrelated proteins). Such antisera and antibodies can be prepared as described herein using well-established techniques.An immunogenic portion of a protein is a part that reacts with antisera and / or T lymphocytes at a level not substantially lower than the reactivity of the whole polypeptide (e.g., in an ELISA and / or T-cell reactivity assay). Such immunogenic portions may react within such assays at a level similar to or greater than the reactivity of the whole polypeptide. Such screenings can generally be performed using methods well known to those skilled in the art, such as those described in Harlow and Lañe, Antibodies: A Laboratory Manual, Coid Spring Harbor Laboratory, 1988. For example, a polypeptide can be immobilized on a solid support and brought into contact with patient sera to allow antibodies from the sera to bind to the immobilized polypeptide. Unbound sera can then be removed, and bound antibodies can be detected using, for example, 125L-labeled protein A. 1. In some embodiments, the antigen is a hapten, a hapten conjugated to a carrier protein, polypeptide, or other polymer, or derivatives thereof. Haptens include small molecules that can generate an immune response, predominantly only when bound to a large carrier such as a protein. The hapten may be bound to a carrier protein and an additional moiety. Examples of haptens include aniline, o-, m-, and p-aminobenzoic acid, quinone, histamine, succinylglycine (HSG), hydralazine, halothane, indium-DTPA, fluorescein, biotin, digoxigenin, theophylline, and dinitrophenol. 1.2Common carrier proteins include serum globulin, albumin, ovalbumin, and many others, as well as synthetic polypeptides such as poly-L-glutamic acid. Polysaccharides and liposomes could also be used. 1. In some embodiments, the antigen is an allergen. An allergen includes naturally occurring proteins and other small molecules that have been shown to induce allergic reactions, i.e., IgE-mediated reactions, upon repeated exposure of an individual. Examples of naturally occurring allergens include pollen allergens (tree, weed, grass, and herb pollen), mite allergens (e.g., house dust mites and storage mites), insect allergens (inhalant allergens, saliva, and venom), animal allergens (e.g., saliva, hair, and dander from dogs, cats, horses, rats, mice, etc.), fungal allergens, and food allergens. Allergens also include drugs and latex. 1. In another embodiment, a compound or adjuvant composition described herein may be used in the preparation of DNA-based vaccine compositions. Illustrative vaccines of this type contain DNA encoding one or more polypeptide antigens, such that the antigen is generated in situ. The DNA may be present in any of a variety of delivery systems known to those skilled in the art, including nucleic acid expression systems, bacterial, and viral expression systems. Numerous gene delivery techniques are known in the art, such as those described by Rolland, Crit. Revdo. Therap. Drug Carrier Systems 15:143-198, 1998, and the references cited therein. Appropriate nucleic acid expression systems contain the DNA sequences necessary for expression in the patient (such as a suitable promoter and termination signal).Bacterial delivery systems involve the administration of a bacterium (such as Bacillus Calmette-Guérin) that expresses an immunogenic portion of the polypeptide on its cell surface or secretes such an epitope. In a preferred embodiment, the DNA is introduced using a viral expression system (e.g., variolavaccine virus or another smallpox virus, retrovirus, or adenovirus), which typically involves the use of a non-pathogenic (defective) replication-competent virus. Illustrative systems are disclosed, for example, in Fisher-Hoch et al., Proc. Nati. Acad. Sel. 86:317-321, 1989; Flexner et al., Ann. NY Acad. Sci. 569:86-103, 1989; Flexner et al., Vaccine 8:17-21, 1990. US Patent Nos. 4,603,112, 4,769,330 and 5,017,487; document WO 89 / 01973; US Patent Nos. 4,777,127; documents GB 2 200 651; EP 0,345,242; WO 91 / 02805; and Berkner, Biotechniques 6:616-627, 1988; Rosenfeld et al., Science 252:431-434, 1991; Kolls etal., Proc. Nati. AcademicSci. uses 91:215-219, 1994; Kass-Eisler et al., Proc. Nati. Acad. Sci. uses 90:11498-11502, 1993; Guzman et al., Circulation 88:2838-2848, 1993; and Guzman et al., Cir. Res. 73:1202-1207, 1993. Techniques for incorporating DNA into such expression systems are well known to experts in the field. 1. Alternatively, DNA can be naked, as described, for example, in Ulmer et al., Science 259:1745-1749, 1993 and reviewed in Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA can be increased by using the DNA to coat biodegradable beads that are efficiently transported into cells. 1.2Furthermore, it will become evident that a vaccine can contain pharmaceutically acceptable salts of the desired antigens. For example, such salts can be prepared from pharmaceutically acceptable, non-toxic bases, including organic bases (e.g., salts of primary, secondary, and tertiary amines and basic amino acids) and inorganic bases (e.g., salts of sodium, potassium, lithium, ammonium, calcium, and magnesium). 1. The adjuvant system can exhibit potent adjuvant effects when administered over a wide range of doses and ratios. The amount of antigen in each vaccine dose is generally selected to induce an immunoprotective response without producing the significant adverse side effects typical of vaccines. This amount will vary depending on the specific immunogen used and how it is presented. Of course, the administered dose may depend on age, weight, the type of concurrent treatment, if any, and the nature of the antigen administered. 1.2The immunogenic activity of a given quantity of a vaccine composition can be readily determined, for example, by monitoring the increase in antibody titer against the antigen used in the vaccine composition (Dalsgaard, K. Acta Veterinia Scandinavica 69:1-40 (1978)). Another common method involves intradermally injecting CD-1 mice with varying quantities of a vaccine composition, subsequently extracting serum from the mice, and analyzing the anti-immunogenic antibody, e.g., by ELISA. These and similar approaches will be obvious to anyone skilled in the art. 1. The antigen can be obtained and / or isolated from essentially any desired source, depending on the infectious disease, autoimmune disease, condition, cancer, pathogen, or illness to be treated with a given vaccine composition. For example, antigens can be obtained from viral sources, such as influenza virus, feline leukemia virus, feline immunodeficiency virus, human HIV-1, HIV-2, herpes simplex virus type 2, human cytomegalovirus, hepatitis A, B, C, or E, respiratory syncytial virus, human papillomavirus, rabies virus, measles virus, or foot-and-mouth disease virus. Illustrative antigens can also be obtained from bacterial sources such as anthrax, diphtheria, Lyme disease, malaria, tuberculosis, leishmaniasis, T. cruzi, Ehrlichia, Candida, etc., or from protozoa such as Babesia bovis or Plasmodium. Typically, the antigen(s) will comprise natural or synthetic amino acids, e.g., in the form of peptides, polypeptides, or proteins, and may include polysaccharides or mixtures thereof. Illustrative antigens may be isolated from natural sources, synthesized by solid-phase synthesis, or obtained using recombinant DNA techniques. 1. In another embodiment, tumor antigens can be used in vaccine compositions for cancer prophylaxis and / or therapy. Tumor antigens are surface molecules that are differentially expressed on tumor cells compared to non-tumor tissues. Tumor antigens make tumor cells immunologically distinct from normal cells and provide diagnostic and therapeutic targets for human cancers. Tumor antigens (MA) have been characterized as membrane proteins or as altered carbohydrate molecules of glycoproteins or glycolipids on the cell surface. Cancer cells often have distinctive tumor antigens on their surfaces, such as truncated epidermal growth factor, folate-binding protein, epithelial mucins, melanoferrin, carcinoembryonic antigen, prostate-specific membrane antigen, and HER2-neu, which are candidates for use in therapeutic cancer vaccines. Because tumor antigens are normal components or related to normal components of the body, the immune system often fails to mount an effective immune response against these antigens to destroy tumor cells. To achieve such a response, the adjuvant systems described herein can be used.As a result, exogenous proteins can enter the pathway to process endogenous antigens, leading to the production of cytotoxic T lymphocytes (CTLs). This adjuvant effect facilitates the production of antigen-specific CTLs, which seek out and destroy tumor cells that carry the tumor antigen(s) used for immunization on their surface. Illustrative cancers for which this approach can be used include prostate, colon, breast, ovarian, pancreatic, brain, head and neck cancers, melanoma, leukemia, lymphoma, and others. 1. In one embodiment, the antigen present in the vaccine composition is not a foreign antigen, but an autoantigen; that is, the vaccine composition is directed against an autoimmune disease. Examples of autoimmune diseases include type 1 diabetes, organ-specific conventional autoimmunity, neurological disease, rheumatic / connective tissue diseases, autoimmune cytopenias, and related autoimmune diseases. Such organ-specific conventional autoimmunity may include thyroiditis (Graves' and Hashimoto's), gastritis, adrenalitis (Addison's), oophoritis, primary biliary cirrhosis, myasthenia gravis, gonadal insufficiency, hypoparathyroidism, alopecia, malabsorption syndrome, pernicious anemia, hepatitis, anti-receptor antibody diseases, and vitiligo.Such neurological diseases may include schizophrenia, Alzheimer's disease, depression, hypopituitarism, diabetes insipidus, dry synovitis, and multiple sclerosis. Such rheumatic / connective tissue diseases may include rheumatoid arthritis, systemic lupus erythematosus (SLE) or lupus, scleroderma, polymyositis, inflammatory bowel disease, dermatomyositis, ulcerative colitis, Crohn's disease, vasculitis, psoriatic arthritis, exfoliative psoriatic dermatitis, pemphigus vulgaris, and Sjögren's syndrome. Other autoimmune-related diseases may include autoimmune uvoretinitis, glomerulonephritis, post-myocardial infarction cardiotomy syndrome, pulmonary hemosiderosis, amyloidosis, sarcoidosis, aphthous stomatitis, and other immune-related diseases such as those presented herein and known in related techniques. 1. In one embodiment, the antigen can be covalently linked to an adjuvant such as the compound of formula I to produce a differentiated molecule that can exhibit an enhanced adjuvant effect on the antigen, which can be superior to the adjuvant effect that can be achieved in the absence of such a covalent link, as in a mixture of components (i.e., the antigen and a compound of formula (I)). The covalent link can be achieved by reaction through groups MA / functionals; for example, in the case of compound I, through a carboxylic acid group, a hydroxyl group, or an aldehyde functionality. An additional potentiated adjuvant effect for such a covalently bound antigen can be achieved by incorporating a mineral salt adjuvant with such compounds. Preferably, the mineral salt adjuvant comprises aluminum hydroxide or aluminum phosphate, although other known mineral salt adjuvants, such as calcium phosphate, zinc hydroxide, or calcium hydroxide, may be used. 1.2 Vaccine compositions may be formulated for any appropriate route of administration and thus administered by any means, including, for example, topical, oral, nasal, intravenous, intravaginal, epicutaneous, sublingual, intracranial, intradermal, intraperitoneal, subcutaneous, intramuscular, or inhalation administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline solution, alcohol, a fat, a wax, or a buffer. For oral administration, any of the above carriers or a solid carrier such as mannitol, lactose, starch, magnesium stearate, sodium saccharin, talc, cellulose, glucose, sucrose, or magnesium carbonate may be used. 1.2 In an illustrative embodiment, vaccine formulations are administered to mucous membranes, particularly the oral cavity, and preferably to a sublingual site, to generate an immune response. In many cases, oral administration may be preferred over traditional parenteral administration due to the ease and convenience offered by non-invasive delivery techniques. Moreover, this approach also provides a means of generating mucosal immunity, which can often be difficult to achieve with traditional parenteral administration, and which may provide protection against airborne pathogens and / or allergens.An additional advantage of oral administration is that sublingual administration of the vaccine can improve patient compliance, especially for pediatric applications, or for applications that traditionally require numerous injections over a prolonged period of time, such as allergy desensitization therapies. 1. Vaccine compositions may also include buffers (e.g., neutral buffered saline or phosphate-buffered saline), carbohydrates (e.g., glucose, mannose, sucrose, or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, bacteriostatic agents, chelating agents such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide), solutes that make the formulation isotonic, hypotonic, or weakly hypertonic with a recipient's blood, suspending agents, thickening agents, and / or preservatives. Alternatively, vaccine compositions may be formulated as a lyophilized product. The compounds may also be encapsulated within liposomes using well-established technology. 1.2Vaccine compositions may also include other adjuvants or immunoeffectors. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difeo Laboratories, Detroit, Mich.); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKine Beecham); mineral salts (e.g., aluminum, silica, kaolin, and carbon); and aluminum salts such as aluminum hydroxide gel (alum). AIK(SO4)2, ANa(SO4)2, AINH4(SO4) and Al(OH)3; calcium salts (e.g., Ca3(PO4)2), iron or zinc; an insoluble suspension of acylated tyrosine; adiated sugars; cationicly or anionically derivatized polysaccharides; polynucleotides (e.g., poly IC and polyAU acids); polyphosphazenes; cyanoacrylates; polymerase-(DL-lactide-co-glucoside); biodegradable microspheres; liposomes; lipid A and its derivatives; monophosphoryl lipid A; Mycobacterium tuberculosis wax D, as well as substances found in Corynebacterium parvum, Bordetella pertussis and members of the genus Brucella); bovine serum albumin; diphtheria toxoid; tetanus toxoid; edestin; keyhole limpet hemocyanin; pseudomonic toxin A; cholergenoid; cholera toxin; pertussis toxin; viral proteins; and Quil A. Aminoalkylglucosamine phosphate compounds may also be used (see, for example, WO 98 / 50399, U.S. patent no. e6,113,918 (which was issued under no.US serial number 08 / 853 826) and US serial number 09 / 074,720). In addition, adjuvants such as cytokines (e.g., GM-CSF or interleukin 2, 7, or 12), interferons, or tumor necrosis factor may also be used. Protein and polypeptide adjuvants may be obtained from natural or recombinant sources according to methods well known to those skilled in the art. When obtained from recombinant sources, the adjuvant may comprise a protein fragment containing at least the immunostimulatory portion of the molecule. Other known immunostimulatory macromolecules that can be used include, but are not limited to, polysaccharides, tRNA, non-metabolizable synthetic polymers such as polyvinylamine, polymethacrylic acid, polyvinylpyrrolidone, mixed polycondensates (with relatively high molecular weight) of 4',4-diaminodiphenylmethane-3,3'-dicarboxylic acid and 4-nitro-2-aminobenzoic acid (see, Sela, M., Science 166: 1365-1374 (1969)) or glycolipids, lipids or carbohydrates. 1. Within the vaccines provided herein, the adjuvant composition is preferably designed to induce a predominantly Th1-type immune response. High levels of Th1-type cytokines (e.g., IFN-γ, IL-2, and IL-12) tend to favor the induction of cell-mediated immune responses to an administered antigen. Conversely, high levels of Th2-type cytokines (e.g., IL-4, IL-5, IL-6, IL-10, and TNF-β) tend to favor the induction of humoral immune responses. Following administration of a vaccine as provided herein, a patient will maintain an immune response that includes both Th1 and Th2-type responses. In a preferred embodiment, where the response is predominantly Th1-type, the level of Th1-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines can be easily assessed using conventional assays.For a review of cytokine families, see Mosmann and Coffman, 1989, Ann. Rev. Immunol. 7:145-173. 1.2The compositions described herein can be administered as part of a sustained-release formulation (i.e., a formulation such as a capsule, sponge, or gel (comprising polysaccharides, for example) that effects a slow release of the compound after administration). Generally, such formulations can be prepared using well-established technology (see, e.g., Coombes et al., Vaccine 14:1429-1438, 1996) and administered, for example, by oral, rectal, or subcutaneous implantation, or by implantation at the desired target site. MA / sustained-release formulations may contain a polypeptide, polynucleotide, or antibody dispersed in a carrier matrix and / or contained within a reservoir surrounded by a rate-controlling membrane. The carriers used in such formulations are biocompatible and may also be biodegradable; preferably, the formulation provides a relatively constant level of release of the active component. Such carriers include microparticles of poly(lactide-co-glycolide), polyacrylate, latex, starch, cellulose, dextran, and similar materials. Other delayed-release carriers include supramolecular biovectors comprising a non-liquid hydrophilic core (e.g., a crosslinked polysaccharide or oligosaccharide) and, optionally, an outer layer comprising an amphiphilic compound, such as a phospholipid (see, e.g., U.S. Patent No. 85,151,254 and PCT applications WO 94 / 20078, WO / 94 / 23701 and WO 96 / 06638).The amount of active compound contained within a sustained-release formulation will vary depending on the implantation site, the expected rate and duration of release, as well as the nature of the condition to be treated or prevented. 1.2A variety of known delivery vehicles can be employed within pharmaceutical compositions and vaccines to facilitate the production of a cell-directed, antigen-specific immune response. Delivery vehicles include Antigen-Presenting Cells (APCs), such as dendritic cells, macrophages, B lymphocytes, monocytes, and other cells that can be engineered to be efficient APCs. Such cells may, but do not necessarily, be genetically modified to enhance antigen-presenting capacity, improve T-cell activation and / or maintenance of the response, have anti-target effects themselves, and / or be immunologically compatible with the recipient (i.e., HLA haplotype matched). APCs can generally be isolated from a variety of biological fluids and organs, including tumor and peritumoral tissues, and may be autologous, allogeneic, syngeneic, or xenogeneic cells. 1.2The compositions may comprise a liposome vesicle comprising the compound of formula I. Liposomes are generally produced from phospholipids or other lipid substances. Those skilled in the art are well acquainted with the procedures for preparing liposomes. Any vesicle-forming lipid comprising the compound of formula I may be employed. For clinical application, it is desirable that the lipid be non-toxic, physiologically acceptable, and metabolizable. Common bilayer-forming lipids with clinical potential include phospholipids, fatty acids, sphingolipids, glycosphingolipids, and steroids. Glycerol-containing phospholipids are the most commonly used component of liposome formulations with clinical utility. A commonly used example is phosphatidylcholine or lecithin. Steroid cholesterol and its derivatives are often included as components of liposomal membranes.The tendency of liposomes to aggregate and fuse can be controlled by including small amounts of acidic or basic lipids in the formulation. The properties of phospholipid-containing liposomes are determined by the phospholipid chemistry. Important considerations include hydrocarbon chain length, degree of unsaturation, degree of branching, and system temperature. MA / 1. Multilayer liposomes can be created by depositing a lipid mixture as a thin film by evaporation under reduced pressure, followed by dispersion with an excess volume of aqueous buffer containing the antigen, with or without organic solvents. Another method is to mix the aqueous phase containing the antigen with small unilamellar liposomes, followed by lyophilization. Multilayer liposomes are formed when the lyophilized product is rehydrated, typically with a small amount of distilled water. The small unilamellar liposomes used in this process are produced by dispersing the lipids in an aqueous medium, followed by a mechanical dispersion method such as ultrasonic homogenization, the use of a high-pressure device, or a solvent injection method.Large and intermediate-sized unilamellar liposomes can also be produced using conventional techniques, including detergent dialysis, extrusion through small-pore membranes at high pressure, freeze-thaw followed by slow swelling, dehydration followed by rehydration and dilution, or lipid dialysis in the presence of chaotropic ions. The size of the liposomes can be made more uniform by fractionation procedures such as centrifugation or size-exclusion chromatography, homogenization, or extrusion through capillary-pore membranes. 4. Methods of Use 1. The disclosed compounds and compositions can be used in various methods, including methods to modulate an immune reaction in a subject, methods to induce or enhance the immunogenicity of an antigen in a subject, and methods to treat, prevent, or reduce susceptibility to an allergy, an autoimmune condition, cancer, or a bacterial, viral, or prion infection. a. Immunomodulatory reaction 1. The disclosed compounds and compositions can be used in methods to modulate the immune reaction in a subject, comprising administering to the subject an effective amount of a compound described herein, an adjuvant composition described herein, a vaccine composition described herein, or a pharmaceutical composition described herein. 1. In some embodiments, the immune response in the subject is increased. In some embodiments, the subject suffers from cancer, an autoimmune disorder, an allergy, or an infectious disease. The infectious disease may be caused by a virus, a bacterium, or a prion or prion-like protein. 1. The disclosed compounds and compositions can be used in a method to induce an enhanced immune reaction in a subject. 1.2 An enhanced immune response can be induced by administering the compound or composition together with an antigen. Suitable antigens include microbial pathogens, bacteria, viruses, proteins, glycoproteins, lipoproteins, peptides, glycopeptides, lipopeptides, toxoids, carbohydrates, and tumor-specific antigens. Mixtures of two or more antigens may be used. MA / b. Induction or enhancement of the immunogenicity of an antigen 1. The disclosed compounds and compositions may be used in methods for inducing or enhancing the immunogenicity of an antigen in a subject comprising administering to the subject a vaccine composition comprising the antigen and an adjuvant composition comprising an effective amount of a compound or composition disclosed herein. 1. Suitable antigens include microbial pathogens, bacteria, viruses, proteins, glycoproteins, lipoproteins, peptides, glycopeptides, lipopeptides, toxoids, carbohydrates, and tumor-specific antigens. Mixtures of two or more antigens may be used. In some embodiments, the antigen is obtained from a bacterium, virus, bacteriophage, fungus, prion, neoplasm, autoantigen, animal, plant, recombinant material, or synthetic material. c. Methods for treating, preventing or reducing susceptibility to a disease and a disorder 1. The disclosed compounds and compositions may be used in methods for treating, preventing or reducing susceptibility to a disease or a disorder, comprising methods of administering to a subject in need a therapeutically effective amount of a compound or composition described herein. i. Allergy 1. In some realizations, the disease or disorder is an allergy or an allergic disease / condition. An allergy refers to acquired hypersensitivity to a substance (allergen). Allergic conditions include, for example, eczema, allergic rhinitis or coryza, hay fever, bronchial asthma, urticaria (hives), and food allergies and other atopic conditions. 1. The method can reduce, inhibit or stop / prevent an allergic reaction or an inflammatory reaction (e.g., slow down or stop the production of antibodies or the amount of antibodies against a specific antigen). ii. Autoimmune Condition 1. In some realizations, the disease or disorder is an autoimmune condition. Autoimmune conditions occur when an individual's immune system attacks their own organs or tissues, producing a clinical condition associated with the destruction of that tissue. Autoimmune conditions include, for example, rheumatoid arthritis, insulin-dependent diabetes mellitus, acquired immunodeficiency syndrome (AIDS), hemolytic anemias, rheumatic fever, Crohn's disease, Guillain-Barré syndrome, psoriasis, thyroiditis, Graves' disease, myasthenia gravis, glomerulonephritis, autoimmune hepatitis, multiple sclerosis, and systemic lupus erythematosus. The method may reduce, inhibit, or stop an autoimmune reaction. ii. Infection or infectious disease 1. In some realizations, the disease or disorder is an infection or infectious disease. Infectious diseases are caused by infectious agents that include, but are not limited to, viruses, bacteria, fungi, protozoa, parasites, and prions or prion-like proteins. In MA / In some realizations, the infectious disease or infection may be caused by a bacterium, a virus, or a prion or prion-like protein. 1.2Viral diseases that can be treated by the methods of the present invention include, but are not limited to, those caused by hepatitis A virus, hepatitis B virus, hepatitis C virus, influenza virus, varicella virus, adenovirus, herpes simplex virus type I (HSV-I), herpes simplex virus type II (HSV-II), dengue virus, Ebola virus, Zika virus, rinderpest virus, rhinovirus, ECHO virus (Enteric Cytopathic Human Orphan Virus), rotavirus, respiratory syncytial virus, papillomavirus, papovavirus, cytomegalovirus, equinovirus, arbovirus, hunttavirus, Coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, and human immunodeficiency virus type I (HIV-l) and human immunodeficiency virus type II (HIV-lI). 1.2Bacterial diseases that can be treated by the methods of the present invention include, but are not limited to, diseases caused by mycobacteria, rickettsia, mycoplasma and Neisseria, and cholera, gonorrhea, Lyme disease, whooping cough, plague, syphilis, tuberculosis, Rocky Mountain spotted fever and legionellosis. iv. Cancer 1. In some embodiments, the disease or disorder is cancer. The method can reduce or inhibit the proliferation of cancer cells. The methods can be used with any cancer cell or in a subject who has any type of cancer, for example, those described by the U.S. National Cancer Institute. Illustrative cancers may include the following: 1. Digestive / gastrointestinal cancers such as anal cancer; bile duct cancer; extrahepatic bile duct cancer; appendix cancer; carcinoid tumor; gastrointestinal cancer; colon cancer; colorectal cancer including childhood colorectal cancer; esophageal cancer including childhood esophageal cancer; gallbladder cancer; gastric (stomach) cancer, including childhood gastric (stomach) cancer; hepatocellular (liver) cancer, including adult (primary) hepatocellular (liver) cancer and childhood (primary) hepatocellular (liver) cancer; pancreatic cancer, including childhood pancreatic cancer; sarcoma; rhabdomyosarcoma; islet cell cancer of the pancreas; rectal cancer; and small bowel cancer; 1. Endocrine cancers such as islet cell carcinoma (endocrine pancreas); carcinoma of the adrenal cortex, including infantile adrenal cortex carcinoma; gastrointestinal carcinoid tumor; parathyroid cancer; pheochromocytoma; pituitary tumor; thyroid cancer, including infantile thyroid cancer; infantile multiple endocrine neoplasia syndrome; and infantile carcinoid tumor; 1. Eye cancers such as intraocular melanoma and retinoblastoma; 1. Musculoskeletal cancers such as the Ewing family of tumors; malignant fibrous osteosarcoma / histiocytoma of bone; infantile rhabdomyosarcoma; soft tissue sarcoma, including adult and infantile soft tissue sarcoma; clear cell sarcoma of tendon sheaths; and uterine sarcoma; MA / \1 .\2breast cancer such as breast cancer including childhood and male breast cancer, and breast cancer during pregnancy; 1. Neurological cancers such as infantile brainstem glioma; brain tumor; infantile cerebellar astrocytoma; infantile cerebral astrocytoma / malignant glioma; infantile ependymoma; infantile medulloblastoma; infantile supratentorial and pineal primitive neuroectodermal tumors; infantile visual pathway and hypothalamic glioma; other infantile brain cancers; carcinoma of the adrenal cortex; primary central nervous system lymphoma; infantile cerebellar astrocytoma; neuroblastoma; craniopharyngioma; spinal cord tumors; atypical teratoid / rhabdoid tumor of the central nervous system; embryonal tumors of the central nervous system; and infantile supratentorial primitive neuroectodermal tumors and pituitary tumor; 1. Genitourinary cancers such as bladder cancer, including childhood bladder cancer; renal cell (kidney) cancer; ovarian cancer, including childhood ovarian cancer; epithelial ovarian cancer; ovarian tumor of low malignant potential; penile cancer; prostate cancer; renal cell cancer, including childhood renal cell cancer; renal pelvis and ureter, transitional cell cancer; testicular cancer; urethral cancer; vaginal cancer; vulvar cancer; cervical cancer; Wilms tumor and other childhood renal tumors; endometrial cancer; and gestational trophoblastic tumor; germ cell cancers such as childhood extracranial germ cell tumor; extragonadal germ cell tumor; ovarian germ cell tumor; 1. Head and neck cancers such as lip and oral cavity cancer; oral cancer, including childhood oral cancer; hypopharyngeal cancer; laryngeal cancer, including childhood laryngeal cancer; metastatic squamous cell carcinoma of the neck with occult primary tumor; mouth cancer; nasal cavity and paranasal sinus cancer; nasopharyngeal cancer, including childhood nasopharyngeal cancer; oropharyngeal cancer; parathyroid cancer; pharyngeal cancer; salivary gland cancer, including childhood salivary gland cancer; throat cancer; and thyroid cancer; 1. 2Hematologic / blood cell cancers such as leukemia (e.g., acute lymphoblastic leukemia including childhood and adult acute lymphoblastic leukemia; acute myeloid leukemia including childhood and adult acute myeloid leukemia; chronic lymphocytic leukemia; chronic myelogenous leukemia; and hairy cell leukemia); a lymphoma (e.g., AIDS-related lymphoma; cutaneous T-cell lymphoma; Hodgkin lymphoma including childhood and adult Hodgkin lymphoma, and Hodgkin lymphoma during pregnancy; non-Hodgkin lymphoma including childhood and adult non-Hodgkin lymphoma, and non-Hodgkin lymphoma during pregnancy; mycosis fungoides, Sezary syndrome, Waldenstrom macroglobulinemia, and primary lymphoma of the central nervous system); and other hematologic cancers (e.g., chronic myeloproliferative disorders; multiple myeloma / plasma cell neoplasia; myelodysplastic syndromes; and myelodysplastic or myeloproliferative disorders);. 1. Lung cancer, such as non-small cell lung cancer; and small cell lung cancer; 1. Respiratory cancers such as adult malignant mesothelioma; childhood malignant mesothelioma; malignant thymoma; childhood thymoma; thymic carcinoma; bronchial adenomas / carcinoids including ML / infantile bronchial adenomas / carcinoids; pleuropulmonary blastema; non-small cell lung cancer; and small cell lung cancer; 1. Skin cancers such as Kaposi's sarcoma; Merkel cell carcinoma; melanoma; and childhood skin cancer; 1. 2 Malignant neoplasms related to AIDS; M.\2other childhood cancers, unusual childhood cancers and cancers of unknown primary site; and \1.\2metastases of the cancers mentioned above. 5. Kits \1.\2In one aspect, the disclosure provides kits comprising at least one disclosed compound or a pharmaceutically acceptable salt thereof, or a composition comprising the compound or a pharmaceutically acceptable salt thereof, and one or more of: (a) at least one antigen; (b) at least one additional therapeutic agent; and (c) instructions for administering the compound or composition. 1. In some embodiments, the at least one disclosed compound and the at least one additional antigen or at least one additional therapeutic agent are formulated together. In some embodiments, the at least one disclosed compound and the at least one additional antigen or at least one additional therapeutic agent are packaged together. Kits may also comprise compounds and / or products packaged, formulated, and / or administered together with other components. For example, a drug manufacturer, drug distributor, physician, compounding pharmacist, or pharmacist may provide a kit comprising a disclosed compound and / or product and another component for administration to a patient. 1. The disclosed kits may be used in connection with the disclosed methods of use. 1.2The kits may also include information, instructions, or both, stating that the use of the kit will provide enhanced immunity against certain pathogens in mammals (particularly humans). The information and instructions may be in the form of words, images, or both, and similar media. In addition, or alternatively, the kit may include the compound, a composition, or both; and information, instructions, or both, relating to methods of administering the compound or composition, preferably for the benefit of treating or preventing medical conditions in mammals (e.g., humans). 1. The compounds and processes of disclosure can be better understood with reference to the following examples, which are intended as an illustration and not a limitation of the scope of disclosure. 6. Examples It will be readily apparent to those skilled in the art that other appropriate modifications and adaptations to the disclosure described herein can be readily applied and appreciated, and can be made using suitable equivalents without departing from the scope of this disclosure or the aspects and realizations disclosed herein. Having described MA / Now, this disclosure in detail will be more clearly understood by reference to the following examples, which are merely intended to illustrate some aspects and realizations of the disclosure and should not be seen as limiting its scope. The disclosures of all journal, U.S. patent, and publication references herein are incorporated herein by reference in their entirety. 1.2The abbreviations used in the schemes and the descriptions that follow include the following: DCC is Λ / ,Λ / '-dicyclohexylcarbodiimide; DMAP is A / ,A / -dimethylpyridin-4-amine; DMF is dimethylformamide; eq are equivalents; IFNα is interferon α; IgG is immunoglobulin G; IL-12p70 is interleukin 12p70; Im-OTf is imidazolium trifluoromethanesulfonate; Pal is C(O)(CH2)i4CH3; CMNP is a peripheral blood mononuclear cell; PEG is polyethylene glycol; PMB is para-methoxybenzyl; ta is room temperature; TBAI is tetrabutylammonium iodide; TEA is trimethylamine; THF is tetrahydrofuran; TLR is a Toll-like receptor; TNFα is tumor necrosis factor α; 14Dd1 is 14 days after primary immunization; and 14Dd2 is 14 days after secondary immunization. Example 1. Illustrative synthesis for Compound UM-1007 A. Synthesis of PEGylated glycerol \1.\2The required dipalmitoyl PEGylated glycerol 5 was prepared in 5 steps from commercially available triethylene glycol monochloride (1). 1. DCC palmitic acid, DMAP 2. AgSbF6, (CH3O)3Ph, HCl 4 N, MeOH CH2CI2, 50 °C -------------► ' ' 3 i -------------------► 5 % OH 89 % \1 .\2p-Methoxybenzyl chloride (3 eq) and tetra-n-butylammonium iodide (0.02 eq) were added to a solution of 1 in anhydrous DMF (2.0 M), and the solution was cooled to 0 °C. Sodium hydride (1.25 eq) was slowly added to the cold solution. After stirring at 0 °C for 30 min, the reaction mixture was heated to a boiling point. After 4 h, the reaction mixture was slowly inactivated with a saturated sodium bicarbonate solution and extracted with chloroform. The organic layer was dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by silica gel chromatography (10 to 40% ethyl acetate in heptane), giving 2 in the form of a colorless oil with a 90% yield. Sodium hydride (1.5 eq) was slowly added to a solution of 2 (1.5 eq), 1,2-sn-isopropylidene-glycerol (1.0 eq) and tetra-n-butylammonium iodide (0.05 eq) in anhydrous THF (0.69 M).After 15 h at 75 °C, more 2 (0.5 eq) and sodium hydride (1.5 eq) were added, and the reaction mixture was stirred at 75 °C. After 6 hours, the reaction mixture was cooled to room temperature, inactivated by the addition of brine, and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by silica gel chromatography (20–80% ethyl acetate in heptane), yielding 3 as a colorless oil in a 74% yield. 0.4 N HCl was added to a solution of 3 in methanol (0.32 M; CH3OH:HCl 29 / 1 v / v), and the reaction mixture was stirred to room temperature. After 1 h, the reaction mixture was inactivated with a saturated sodium bicarbonate solution and extracted with chloroform. The organic layer was dried over sodium sulfate, filtered, and concentrated under vacuum.The crude product was purified by silica gel chromatography (0–12% methanol in chloroform), yielding a colorless oil in 79% yield. DCC (2.1 eq) and DMAP (0.05 eq) were added to a cold (0 °C) solution of 4 and palmitic acid (2.1 eq) in CH₂Cl₂ (0.29 M), and the reaction mixture was stirred at 0 °C. After 30 min, the reaction mixture was heated to a boiling point. After 15 h, more palmitic acid (0.5 eq) and DCC (0.5 eq) were added, and stirring continued for 24 h. The reaction mixture was filtered, and the crude product was partially purified by silica gel chromatography (0–50% ethyl acetate in heptane). A solution of the partially purified crude product and trimethoxybenzene (0.5 eq) in anhydrous CH2CI2 (0.17 M) prepared under nitrogen was added with a cannula to a solution of silver hexafluoroantimonate (V) (0.05 eq) in anhydrous CH2CI2 (0.09 M) under nitrogen.After 2 days at room temperature, more silver hexafluoroantimonate (V) (0.05 eq) and trimethoxybenzene (0.5 eq) were added, and the reaction mixture was stirred at 50 °C. 24 h later, the reaction mixture was concentrated under vacuum and purified by silica gel chromatography (10 to 70% ethyl acetate in heptane), giving 5 in the form of a white solid with a yield of 89%. 1H NMR (CDCI3, 400 MHz), δ 5.23 (m, 1H), 4.34 (dd, 1H), 4.16 (dd, 1H), 3.50-3.74 (m, 14 H), 2.49 (t, 1H), 2.30 (dd, 4H), 1.60 (m, 4 H), 1.25 (m, 48H), 0.88 (t, 6H). B. Synthesis of Compound UM-1007 \1 .\2The oxoadenine UM-1007 was prepared by phospholipidation of the oxadenine core 8 with a phosphoramidite solution 7 generated in situ from 5 as shown below, using the previously developed tandem method Tetrahedron Lett., 2016, 57, 2063-2066). MA / UM-1007 OH 2. f-BuOOH 3. ASD 4. HCI 0.5 N Overall performance of 33% 1. Commercially available phosphorodiamidita 6 (1.3 eq) was added to a solution of PEGylated dipalmitoyl glycerol 5 (1.3 eq) in anhydrous methylene chloride (0.12 M) under nitrogen, followed by the slow addition of tetrazole (1.5 eq). After stirring at room temperature for 1 h, the reaction mixture was cooled to 0 °C, and oxoadenine 8 (1.0 eq) and imidazolium triflate (2.0 eq) were added. The reaction mixture was stirred at 0 °C for 10 min and then heated to room temperature. After 1 h, the reaction mixture was inactivated by the addition of a saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate and concentrated, yielding a crude phosphite. tert-Butyl hydroperoxide (5.5 M in nonane, 2.0 eq) was added to a crude phosphite solution in anhydrous methylene chloride (0.12 M). After 30 min at room temperature, the reaction mixture was concentrated under vacuum and dissolved in acetonitrile / triethylamine (2.8:1 v / v, 0.05 M), and the reaction mixture was stirred at room temperature overnight.After vacuum concentration, the reaction mixture was purified by silica gel chromatography (from 20-100% methanol / acetonitrile (50 / 50) in chloroform), giving UM-1007 with an overall yield of 36%. 1H NMR (400 MHz, CDCI3 / CD3OD) δ 5.20 (m, 1H), 5.12 (m, 1H), 4.35 (dd, 1H), 4.12-4.17 (m, 3H), 4.05 (c, 2H), 3.79 (sa, 2H), 3.59-3.70 (m, 12H), 3.26 (sa, 2H), 2.80 (sa, 1H), 2.32 (c, 4H), 1.95 (m, 2H), 1.77 (m, 2H), 1.58 (m, 4H), 1.42 (m, 2H), 1.26 (m, 51H), 0.88 (m, 9H). 13C NMR (100 MHz, CDCI3 / CD3OD) δ 174.2, 173.9, 160.7, 153.9, 149.9, 148.5, 106.4, 98.8, 77.8, 73.2, 71.1, 70.9, 70.8, 70.7, 70.5, 70.3, 69.7, 65.4, 65.3, 63.1, 58.8, 53.3, 47.0, 38.6, 34.6, 34.4, 32.2, 29.9, 29.8, 29.6, 29.4, 29.3, 27.4, 25.2, 25.1,22.9, 20.0, 19.0, 18.9, 14.2, 14.1, 8.8. HRMS (High-Resolution Mass Spectrometry) [M+H]+calculated: 1141.7868, found: 1141.7906. Example 2. Biological activity A. In vitro activity of Compound UM-1007 1. The reactions of IFNo and IL-12p70 were measured in primary human peripheral blood mononuclear cells (PBCs) after exposure to different concentrations of oxoadenine compounds. 1.2Liposomes were prepared using the thin-film method: phospholipids (DOPC and cholesterol at 40 and 10 mg / ml, respectively) and agonist(s) (TLR7 / 8 agonist fixed at 2 mg / ml) were dissolved in chloroform to the desired concentration in a round-bottom flask. The solvent was removed under vacuum by rotary evaporation at 45 °C, and the resulting dry film was placed in a vacuum chamber overnight to remove any residual solvent. Rehydration buffer was added to the dry film, and the suspension was homogenized by ultrasound to resuspend the phospholipids and form unilamellar vesicles. Ultrasonic homogenization was continued until the particle size was <200 nm, at which point the formulations were sterilized by filtration through a 0.22 µm PVDF filter.Agonist concentrations in the formulations were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) using a five-point standard curve. Whole human blood was drawn from healthy donors at the University of Montana (Missoula, MT) using a US Institutional Review Board approved protocol. Peripheral blood mononuclear cells (PBCs) were isolated by Ficoll Hypaque 1.077 gradient separation and cultured at 0.5 x 10⁶ cells / well in 96-well tissue culture plates containing RPMI-1640 medium (HyCone™, Logan, UT), Pen / Strep / Glutamine (HyCone™, Logan, UT), and 10% heat-inactivated FBS (Corning, Manassas, VA). Human CMNPs were stimulated for 24 h with increasing concentrations of the indicated compounds.The culture supernatants were analyzed to determine IL-12p70 and IFNa levels using the DuoSet® ELISA kit for human IL-12p70 (R&D Systems, Minneapolis, MN) and the VeriKine ELISA kit for human IFNa (Pestka Biomedical Laboratories, Inc., Piscataway, NJ). 1. 2PEGylated oxoadenine UM-1007 was a more potent IFNa inducer in human CMNPs than the corresponding non-PEGylated oxoadenine (Compound B) (see Figure 1 for its structure), when tested alone or in conjunction with the TLR4 agonist CRX-601, indicating that the introduction of a PEGylated connector increased IFNa induction (Figure 2A). 1.2While non-PEGylated oxoadenine (Compound B) induced IL-12p70 on its own at high doses (>10mM), PEGylated oxoadenine UM-1007 was a much more potent (125x) IL-12p70 inducer in human CMNPs than the corresponding non-PEGylated oxoadenine (Compound B) when combined with TLR4 agonist CRX-601, indicating that the introduction of a PEGylated connector increased synergy with TLR4 agonists for IL-12p70 induction (Figure 2B). B. Activity in v / Vodel Compound UM-1007 \1.\2Murine studies were carried out in a nursery accredited by the OLAW (Office of Laboratory Animal Welfare, Institute for the Welfare of Laboratory Animals of the USA) and the ma / t / zuzz / uutmou μλ / AAALAC (Association for Assessment and Accreditation of Laboratory Animal Care) in accordance with the guidelines of the IACUC (Institutional Animal Care and Use Committee) of the University of Montana for the care and use of laboratory animals. Balb / c mice (10 / group) received two intramuscular immunizations with increasing doses of adjuvant (3 different doses) and monovalent fractionated influenza virus (A / Victoria, H3N2) antigen (0.15 pg) on ​​Day 0 and Day 14. Serum was collected 14 days after the primary immunization (14Dd1) and 14 days after the secondary immunization (14Dd2) for antibody analysis by ELISA. ELISA plates were coated with 100 μI of fractionated influenza A / Victoria virus vaccine in detergent at 1 pg / ml.After washing (PBS [Phosphate-Buffered Saline] plus Tween 20) and blocking (SuperBiock, Scytek Laboratories), the plates were incubated with diluted serum for 1 h followed by mouse anti-IgG, IgG1, or IgG2a-HRP secondary antibody (Betil Laboratories) and TMB substrate (BD). The plates were read at 450 nm. Antibody titers were determined by calculating the titer of each sample at an OD of 0.3. 1.2The porcine studies were conducted by PAIRimmune (Laval, Canada), a contracted laboratory. Serum was collected from Yucatán minipigs (5 groups) on Day -21 and Day -1 for the evaluation of pre-existing influenza antibody titers. These pigs exhibited some low-level pre-existing influenza antibody titers. The pigs received two intramuscular immunizations (500 pl / dose) with adjuvants (2 different doses) and fractionated influenza virus antigen (1 / 10 of the human dose) on Day 0 and Day 21. Serum was collected 14 days after the primary immunization (14Dd1) and 14 days after the secondary immunization (14Dd2) for antibody analysis. ELISA plates were coated with 100 μI of fractionated influenza A / Victoria virus vaccine in detergent at 1 pg / ml.After washing (PBS plus Tween 20) and blocking (SuperBiock, Scytek Laboratories), the plates were incubated with diluted serum for 1 h followed by secondary antibodies conjugated with HRP anti-pig IgX and TMB substrate. The plates were read at 450 nm. Antibody titers were determined by calculating the titer of each sample at an OD of 0.3. 1. In a study of murine influenza virus fractions, UM-1007 was formulated in liposomes, either alone or encapsulated with the TLR4 agonist CRX-601 in a fixed TLR7 / 8:TLR4 ratio of 10:1. Potent influenza IgG titers were detected 14 days after a single intramuscular vaccination in previously untreated mice (14Dd1, Figure 3A). Titers were further enhanced by administration of a second booster vaccination (14Dd2, Figure 3B). UM-1007 potentiated titers in a dose-dependent manner with 10 pg, showing titers 17-fold higher than those in animals vaccinated with antigen alone. When encapsulated with CRX-601, this reaction was further enhanced >25-fold compared to the antigen-only group. 1. The UM-1007 was also evaluated as an adjuvant for the influenza vaccine in minipigs from Yucatán. UM-1007 was formulated in liposomes, either alone or encapsulated with the TLR4 agonist CRX-601. Liposomes containing only UM-1007 and mixed CRX-601 liposomes were also evaluated. The pigs used in this experiment exhibited some serum antibody titers. MA / pre-existing influenza vaccines. Regardless, all groups adjuvanted with TLR7 / 8-TLR4 agonists demonstrated higher mean antibody titers than the antigen-only group after single (not shown) or booster vaccination (14Dd2, Figure 4). Clear increases in influenza-specific IgG1 (Figure 4A) and IgG2 (Figure 4B) were demonstrated for co-encapsulated UM1007 and CRX-601 compared to CRX-601 or UM-1007 alone. Effect of acyl side chains on the in vitro activity of selected TLR agonists 1. Compound B has oleoyl-acyl chains while UM-1007 has palmitoylacyl chains (Figure 1). The previously observed increase in in vitro activity for UM-1007 versus Compound B was not due to the different acyl chains, as shown by comparing the activity of palmitoyl-oxoadenine Compound C with that of oleoyl-oxoadenine Compound A (Figure 5).Both oxoadenines induced similar levels of TNFa (Figure 5A), IFNa (Figure 5B) (a slight increase in activity was observed for palmitoyl-oxoadenine) and IL-12p70 (Figure 5C). Example 3. Biological activity A. Intravenous Activity of Compound UM-1007 1. 1 x 10⁶ CT26 cells (a murine colon cancer cell line, syngeneic in Balb / c mice) were implanted subcutaneously in the right flank of young female Balb / c mice (approximately 8 weeks old). When tumors reached a mean size of 75 mm³ (11 days after CT26 cell implantation), mice were randomly assigned to treatment groups. Starting on Day 12, 10 pg or 50 pg of UM-1007 in an aqueous formulation (2% glycerol in sterile water) was injected intravenously once weekly for two weeks. As shown in Figure 6A and Figure 6B, this resulted in slower tumor growth compared to untreated controls. Example 4. Adsorption of UM 1007 on alum Materials: 1. Alhydrogel® (10 mg / ml aluminum) is a wet gel suspension of aluminum hydroxide marketed by InvivoGen. Alhydrogel® particles have a net positive electrical charge at pH 5-7 and are suitable for the adsorption of negatively charged antigens (e.g., antigens with isoelectric points below the pH of the formulation). 1. Adju-Phos® (0.5% aluminum) is a wet gel suspension of aluminum phosphate marketed by InvivoGen. The Adju-Phos® particles have a negative electrical charge at pH 5-7 and are suitable for the adsorption of positively charged antigens (e.g., antigens with isoelectric points above the pH of the formulation). Methods: Preparation of aqueous formulation of UM 1007: 1.2 The UM 1007 is salted by a dry platform salting procedure using choline bicarbonate. In summary, UM 1007 was placed in a glass vial and an appropriate amount of tetrahydrofuran and 0.8 equivalents of choline bicarbonate were added, resulting in a solution MA / transparent. The mixture was thoroughly vortexed and the solvent evaporated under reduced pressure using a rotary evaporator. The thin film formed on the walls of the glass vial was rehydrated with 2% glycerol and homogenized ultrasonically using an ultrasonic bath homogenizer for 210 minutes at <35 °C to reduce particle size. The concentration of UM 1007 was estimated using an RP-HPLC method. Adsorption of UM 1007 on Alhydrogel and Adju-Phos: 1.2 The adsorption experiments of UM 1007 on Alhydrogel and Adju-Phos were performed using two different weight ratios of UM 1007 to aluminum (1:1 and 1:2 w / w) and three different solutions (2% glycerol, irrigation water (WIFI), and TRIS buffer (pH 8.1). A series of UM 1007-alum formulations were prepared at room temperature by mixing different amounts of aqueous UM 1007 formulation, the respective buffer buffer (2% glycerol, irrigation water, and TRIS buffer, pH 8.1), and the aluminum buffer solution (1 mg / ml of Alhydrogel or Adju-Phos). Alhydrogel and Adju-Phos were diluted to 1 mg / ml before the experiment. Different volumes of UM 1007 (0.7215 mg / ml) and alum (1 mg / ml) by rotating from one end to the other at room temperature for approximately 1 hour.The samples were centrifuged for 5 minutes at 4,000 rpm, and the supernatants were analyzed using an RP-HPLC method to determine the amount of unadsorbed UM 1007. The percentage of UM 1007 adsorbed onto alum was estimated relative to the amount of UM 1007 in the control sample. The results of the study are presented in Table 1. Table 1: Results of UM1007 adsorbed on alum under different conditions NA Formulation Description Percentage of UM1007 adsorbed 1 UM1007 control in 2% glycerol 0 2 UM1007: Alyhydrogel (1:2) in 2% (w / w) glycerol 99.8 ± 0.01 3 UM1007: Alyhydrogel (1:1) in 2% (w / w) glycerol 82.37 ± 0.64 4 UM1007: Alyhydrogel (1:2) in WIFI (w / w) 99.91 ± 1.4 5 UM1007: Alyhydrogel (1:2) in TRIS buffer at pH 8-1 (w / w) 98.28 ± 0.38 6 UM1007: Adju-Phos (1:2) in 2% glycerol (w / w) 9.20 ± 1.41 7 UM1007: Adju-Phos (1:1) in 2% glycerol (w / w) 6.50 ± 0.3 1. For the sake of completeness, different aspects of the invention are set out in the following numbered clauses: \1 ,\2Clause 1. A compound of formula (I), MA / (i) or a pharmaceutically acceptable salt thereof, wherein R1es alkyl Ci-Ce; R2 is H, C6-C20 alkyl, C6-C20 alkenyl or C(O)R4; R3 is C6-C20 alkyl, Cs-Czo alkenyl or C(O)R4; R4, at each occurrence, is independently selected between C6-C2 alkyl and C6-C20 alkenyl; n is 1, 2, 3, 4, 5 or 6; m is 2, 3, 4, 5 or 6; Z is (alkyl C2-C6-O)q; yq is 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20. \1 .\2Clause 2. The compound of clause 1 or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen or C(O)R4. \1.\2Clause 3. The compound of clause 1 or clause 2, or a pharmaceutically acceptable salt thereof, wherein R3 is C(O)R4. \1 .\2Clause 4. The compound of any one of clauses 1-3 or a pharmaceutically acceptable salt thereof, wherein R4, in each occurrence, is independently selected from (CH2)ioCH3, (CH2)i2CH3, (CH2)i4CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3. \1 .\2Clause 5. The compound of any one of clauses 1-4 or a pharmaceutically acceptable salt thereof, wherein R4 is (CH2)i4CH3. \1 .\2Clause 6. The compound of any one of clauses 1-5 or a pharmaceutically acceptable salt thereof, wherein n is 1. \1 A2Clause 7. The compound of any one of clauses 1-6 or a pharmaceutically acceptable salt thereof, wherein m is 2. \1 .\2Clause 8. The compound of any one of clauses 1-7 or a pharmaceutically acceptable salt thereof, wherein Z is (alkylene C2-O)q. \1 .\2Clause 9. The compound of any one of clauses 1-8 or a pharmaceutically acceptable salt thereof, wherein q is 3, 6, 9, 12 or 16. \1.\2Clause 10. The compound of any one of clauses 1-9 or a pharmaceutically acceptable salt thereof, wherein q is 3. \1 .\2Clause 11. The compound of clause 1, where the compound is a compound MA / of formula (the): (the) or a pharmaceutically acceptable salt thereof. 1. Clause 12. The compound of clause 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: ML / £ / ¿U¿¿ / UUiMOU MA / ,\1.\2Clause 13. The compound of any one of clauses 1-12, wherein the pharmaceutically acceptable salt is choline salt. \1A2Clause 14. The compound of any one of clauses 1-13 or a pharmaceutically acceptable salt thereof, wherein the compound is a TLR7 antagonist. \1.\2Clause 15. The compound of any one of clauses 1-13 or a pharmaceutically acceptable salt thereof, wherein the compound is a TLR8 antagonist. 1. Clause 16. A formulation comprising a microparticle or nanoparticle comprising the compound of any one of clauses 1-15 or a pharmaceutically acceptable salt thereof. \1.\2Clause 17. The formulation of clause 16, wherein the microparticle or nanoparticle comprises a liposome, a micelle, a polymer particle, a block copolymer, a silica particle, an emulsion or a combination thereof. \1.\2Clause 18. An adjuvant composition comprising an effective amount of a compound of any one of clauses 1-15 or a pharmaceutically acceptable salt thereof. MA / \1 .\2Clause 19. The adjuvant composition of clause 18, wherein the adjuvant composition induces a Th1-type immune reaction. 1. Clause 20. A method for inducing an enhanced immune reaction in a subject comprising administering to said subject an immunogenic composition comprising a compound of any one of clauses 1-15, a pharmaceutically acceptable salt thereof, or the adjuvant composition of clause 18 or clause 19. \1 .\2Clause 21. A vaccine composition comprising an antigen and a compound of any one of clauses 1-15, a pharmaceutically acceptable salt thereof or the adjuvant composition of clause 18 or clause 19. \1 .\2Clause 22. The vaccine composition of clause 21, wherein the antigen is obtained from a bacterium, a virus, a bacteriophage, a fungus, a prion, a neoplasm, an autoantigen, an animal, a plant, recombinant material or synthetic material. \1 .\2Clause 23. The vaccine composition of clause 21 or 22, wherein the antigen is in the form of a peptide or polypeptide. \1 .\2Clause 24. The vaccine composition of clause 21 or 22, wherein the antigen is in the form of a hapten or hapten conjugated to a carrier protein. 1. Clause 25. The vaccine composition of clause 21 or 22, where the antigen is an allergen. \1 .\2Clause 26. A method for inducing or enhancing the immunogenicity of an antigen in a subject, comprising administering to the subject a vaccine composition of any one of clauses 21-25 or a pharmaceutically acceptable salt thereof, or the adjuvant composition of clauses 18-19. \1 .\2Clause 27. A pharmaceutical composition comprising an effective amount of a compound of any one of clauses 1-15 or a pharmaceutically acceptable salt thereof. 1. Clause 28. The pharmaceutical composition of clause 27, which further comprises an additional therapeutic agent. 1. Clause 29. The pharmaceutical composition of clause 28, wherein the additional therapeutic agent is an adjuvant, an immunostimulant, a chemotherapeutic agent, an immunomodulatory agent or a combination thereof. \1 .\2Clause 30. a TLR4 ligand. \1 .\2Clause 31. an aluminum salt. \1 .\2Clause 32. The pharmaceutical composition of clause 29, where the adjuvant is The pharmaceutical composition of clause 29, where the adjuvant is The pharmaceutical composition of clause 31, wherein the compound of any one of claims 1-15 is adsorbed onto the aluminum salt. \1.\2Clause 33. The pharmaceutical composition of clause 32, further comprising an antigen adsorbed onto the aluminum salt of the compound. MA / \1.\2Clause 34. The pharmaceutical composition of clause 29, wherein the immunomodulatory agent is an immune checkpoint inhibitor, a tumor phagocytosis inducer, or a combination thereof. 1. Clause 35. A method for modulating an immune reaction in a subject, comprising administering to the subject the pharmaceutical composition of any one of clauses 27-34. \1 .\2Clause 36. The method of clause 35, whereby the immune reaction in the subject is increased. \1 .\2Clause 37. The method of clause 35 or 36, where the subject suffers from cancer, an autoimmune disorder, an allergy or an infectious disease. 1. Clause 38. The method of clause 37, wherein the infectious disease is a viral, bacterial or prion infection. 1. Clause 39. A method for treating, preventing, or reducing susceptibility to a disease or disorder in a subject comprising administering to a subject in need a therapeutically effective amount of the compound of any one of clauses 1-15, a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of any one of clauses 27-34. \1 .\2Clause 40. The method of clause 39, wherein the disease or disorder is an allergy, an autoimmune disease or disorder, an infection or infectious disease, or cancer. 1. Clause 41. The method of clause 40, wherein the infection or infectious disease is caused by a viral, bacterial or prion infection.

Claims

or a pharmaceutically acceptable salt thereof, wherein R1 is -CH(CH3)(CH2)2CH3; R2 is C(O)R4, Ce-C2o alkyl or Ce-C2o alkenyl; R3 is C(O)R4, Ce-C2o alkyl or Ce-C2o alkenyl; R4, in each occurrence, is independently selected from cis-Ce alkyl, C17-C16 alkyl and Cv-Ce alkenyl; n is 1; m is 2; Z is (C2-O)q alkyl; and q is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R2 is C(O)R4.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein R3 is C(O)R4.

4. The compound of any one of claims 1-3 or a pharmaceutically acceptable salt thereof, wherein R4, in each occurrence, is independently selected from (CH2)i4CH3, (CH2)ioCH3, (CH2)i2CH3, (CH2)i6CH3 and (CH2)7CH=CH(CH2)7CH3.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein R4 is (CH2)i4CH3.

6. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein q is 3, 6, 9, 12 or 16.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein q is 3.

8. The compound of claim 1, wherein the compound is a compound of formula MA / (la): (la) or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: μ λ / αζυζζ / υυα^ου MA / 10. The compound of claim 4, wherein the pharmaceutically acceptable salt is choline salt.

11. A formulation comprising a microparticle or nanoparticle comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

12. The formulation of claim 11, wherein the microparticle or nanoparticle comprises a liposome, a micelle, a polymer particle, a block copolymer, a silica particle, an emulsion, or a combination thereof.

13. A vaccine composition comprising an antigen and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14, further comprising a TLR4 ligand.

16. The pharmaceutical composition of claim 14, further comprising an aluminum MA / 56 salt.

17. The pharmaceutical composition of claim 16, wherein the compound or a pharmaceutically acceptable salt thereof is adsorbed onto the aluminum salt.

18. The pharmaceutical composition of claim 17, further comprising an antigen adsorbed onto the aluminum salt with the compound or pharmaceutically acceptable salt thereof.

19. A method for modulating an immune reaction in a subject, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

20. The method of claim 19, wherein the immune reaction in the subject is increased.

21. The method of claim 19, wherein the subject suffers from cancer, an autoimmune disorder, an allergy, or an infectious disease.

22. The method of claim 20, further comprising administering an antigen to the subject.

23. The method of claim 19, further comprising administering a therapeutically effective amount of a TLR4 ligand.

24. The method of claim 19, further comprising administering a therapeutically effective amount of an aluminum salt adjuvant.

25. The method of claim 24, wherein the compound or pharmaceutically acceptable salt thereof is adsorbed onto the aluminum salt adjuvant.