Compounds useful for the treatment of disorders and methods related thereto

Abstract

Certain embodiments disclosed herein relate to benzyl- and phenyl-substituted compounds of general Formula (I), to processes for their preparation, to compositions including the compounds of general: Formula (I), and to their use for treating diseases, disorders, or conditions. The diseases, disorders, or conditions include, for example, mental illnesses and neurological disorders: R1 X1 R4 R5. Q R3 X2 R2 Formula (I).

Description

COMPOUNDS USEFUL FOR THE TREATMENT OF DISORDERS AND METHODS RELATED THERETOCROSS-REFERENCE TO RELATED APPLICATION(S) AND CLAIM OF PRIORITY

[0001] This application claims the benefit of priority of U.S. Provisional Application Nos. 63 / 677,119 and 63 / 677,123, each filed in the U.S. Patent & Trademark Office on July 30, 2024, the complete disclosures of which are incorporated herein by reference.FIELD

[0002] Embodiments disclosed herein relate to benzyl- and phenyl-substituted compounds of general Formula (I), and methods of using such compounds, including methods for the treatment of different diseases, disorders, and conditions, including, for example, mental illnesses and neurological diseases, disorders, and conditions in the fields of psychiatry, neurobiology, and pharmacotherapy, among others.BACKGROUND

[0003] Mental health disorders, or mental illnesses, refer to a wide range of disorders that include, but are not limited to, depressive disorders, anxiety and panic disorders, schizophrenia, eating disorders, substance misuse disorders, post-traumatic stress disorder, attention deficit / hyperactivity disorder, and obsessive-compulsive disorder. Many mental health disorders, as well as neurological disorders, are impacted by alterations, dysfunction, degeneration, and / or damage to the brain.

[0004] There is a need in the art for development of compounds for additional effective treatments for the above and other diseases, disorders, and conditions discussed herein.SUMMARY

[0005] This Summary is provided to introduce a selection of representative concepts in a simplified form, which representative concepts are further described below in the Detailed Description. This Summary is not necessarily intended to identify key features or essential features of the claimed subject matter, nor is it or the objects and benefits described herein intended to be used to limit the scope of the claimed subject matter.

[0006] The present application includes one or more compounds of Formula (I) or a stereoisomer thereof:R1X1R4R5QR3X2R2(I) or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl, or R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl, or R2is selected from CH and CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2, or R2is selected from CH and CH2 linked with R14and Y is CR14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from SH, CN, NO2, I, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyl, optionally substituted O C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-Csalkyl, optionally substituted SC1-C8alkyl, optionally substitutedC1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1- C6alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl, or R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo, or R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is absent to provide a direct bond with the Q group or is selected from C1-C2alkylene (including CH2, CH2CH2 and CH(CH3)), CH(halo), CH(OH), CH(SH), CH(OCH3), a carbonyl group having aeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R7is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R8is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;each R9is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R10is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R12is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R13is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl, or R14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, X2, and R14; m is selected from 0, 1 , and 2; n is selected from 0, 1 , and 2; o is selected from 0, 1 , and 2; p is selected from 0, 1 , and 2; q is selected from 0, 1 , and 2; r is selected from 0, 1 , and 2; s is selected from 0, 1 , and 2; t is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0007] In a further embodiment, the compounds of the disclosure are used as medicaments. Accordingly, the disclosure also includes a compound of the disclosure for use in the making or manufacture of a medicament.

[0008] In other embodiments, the compounds of the disclosure are used as ingredients in compositions and pharmaceutical compositions, including medicaments or other compositions and in the making or manufacture of compositions and pharmaceutical compositions.

[0009] The present disclosure also includes a method of treating a disease, disorder, and / or condition comprising administering a therapeutically effective amount of one or more compounds of the disclosure to a subject in need thereof. In some embodiments, the compounds of the disclosure are used to make medicaments for treatment of a disease, disorder, and / or condition. In some embodiments, the present disclosure relates to use of one or more compounds of this disclosure in the making or manufacture of a medicament or other composition for treating a disease, disorder, and / or condition.

[0010] The present disclosure also includes a method of treating depressive disorder, bipolar disorder, eating disorder, impulse control disorder, personality disorder, substance abuse disorder, behavioral addiction disorder, alcohol use disorder, post-traumatic stress disorder, anxiety disorder, stress disorder, neurodevelopmental disorder, pain disorder, headache disorder, inflammatory disorder, injury-related disorder, neurodegenerative disorder, functional disorder, psychotic disorder, hyperkinetic movement disorder, age-related macular degeneration, atherosclerosis, dissociative disorders, genetic brain disorders, hyperprolactinemia, hypersomnia, obesity, phobias, apathy disorders, and / or bu out. In some embodiments, the compounds of the disclosure are used to make medicaments for treatment of a depressive disorder, bipolar disorder, eating disorder, impulse control disorder, personality disorder, substance abuse disorder, alcohol use disorder, behavioral addiction disorder, post-traumatic stress disorder, anxiety disorder, stress disorder, neurodevelopmental disorder, pain disorder, headache disorder, inflammatory disorder, injury-related disorder, neurodegenerative disorder, functional disorder, psychotic disorder, hyperkinetic movement disorder, age-related macular degeneration, atherosclerosis, dissociative disorders, genetic brain disorders, hyperprolactinemia, hypersomnia, obesity, phobias, apathy disorders, and / or burnout. In some embodiments, the present disclosure relates to use of one or more compounds of this disclosure in the making or manufacture of a medicament for treating depressive disorder, bipolar disorder, eating disorder, impulse control disorder, personality disorder, substance abuse disorder, behavioral addiction disorder, alcohol use disorder, post-traumatic stress disorder, anxiety disorder, stress disorder, neurodevelopmental disorder, pain disorder, headache disorder, inflammatory disorder, injury-related disorder, neurodegenerative disorder, functional disorder, psychotic disorder, hyperkinetic movement disorder, age-related macular degeneration,atherosclerosis, ddiissssoocciiaattiivvee disorders, genetic brain disorders, hyperprolactinemia, hypersomnia, obesity, phobias, apathy disorders, and / or burnout.

[0011] The disclosure additionally provides a process for the preparation of compounds of the disclosure. The disclosure further provides use of compounds of the disclosure in the making or manufacture of medicines. General and specific processes are discussed in more detail below and set forth in the examples below.

[0012] This disclosure further provides intermediates for the compounds disclosed herein, methods of making the intermediates, and methods for making the compounds from the intermediates.

[0013] Other features of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the disclosure, are given by way of illustration only and the scope of the claims should not be limited by these embodiments but should be given the broadest interpretation consistent with the description as a whole.DETAILED DESCRIPTIONDefinitions

[0014] Unless otherwise indicated, the definitions and embodiments described in this section and other sections are intended to be applicable to all embodiments and aspects of the present disclosure herein described for which they are suitable as would be understood by a person skilled in the art.

[0015] The present description refers to a number of chemical terms and abbreviations used by those skilled in the art. Nevertheless, definitions of selected terms are provided for clarity and consistency.

[0016] As used in the present disclosure, the singular forms “a,” “an,” and “the” include plural references unless the content clearly dictates otherwise. For example, an embodiment including “a compound” should be understood to present certain aspects with one compound, or two or more additional compounds. It will be understood by those with skill in the art that if a specific number of an introduced claim element is intended, such intent will be explicitly recited in the claim, and in the absence of such recitation no such limitation is present. For a non-limiting example, as an aid to understanding, the appended claims contain usage of the introductory phrases “at least one” and “one or more” to introduce claim elements. However, the use of suchphrases should not be construed to imply that the introduction of a claim element by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim element to embodiments containing only one such element, even when the same claim includes the introductory phrase “one or more” or “at least one” and indefinite articles, such as “a” or “an”; the same holds true for the use in the claims of definite articles.

[0017] The terms “about,” “substantially,” and “approximately,” as used herein, mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies or unless the context suggests otherwise to a person skilled in the art.

[0018] In embodiments comprising an “additional” or “second” component, such as an additional or second compound, the second component, as used herein, is not the same component as the other components or first component. A “third” component is not the same component as the other, first and second components and further enumerated or “additional” components are similarly different components. It should be understood, for example, that although a first group and a second group refer to two groups, the first and second groups may be the same species, for example, both C1-C6alkyl, or methyl. “First,” “second,” “third,” etc. in this context is not meant to imply an order or sequence, other than the order in which the terms appear in the claims, unless the claims clearly indicate otherwise.

[0019] The term “administered,” as used herein, means administration of a therapeutically effective amount of one or more compounds or compositions of the disclosure to a cell, tissue, organ, or subject.

[0020] The term “alkenyl," as used herein, whether it is used alone or as part of another group, means substituted or unsubstituted, straight or branched chain, unsaturated hydrocarbon groups containing at least one double bond. The term C2-C6alkenyl (or C2-ealkenyl) means an alkenyl group having 2, 3, 4, 5, or 6 carbon atoms. An alkenyl may contain other unsaturated alkyl groups, such as at least one triple bond. Alkenyl groups may be substituted by alkyl or alkynyl groups.

[0021] The term “alkyl,” as used herein, whether it is used alone or as part of another group, means substituted or unsubstituted, straight or branched chain, saturated hydrocarbon groups, unless the context clearly indicates otherwise, e.g., an “unsubstituted alkyl” is not substituted . The number of carbon atoms that are possible in the referenced alkyl group are indicated by the prefix “Cn-Cm” and “Co,” where n, m, and o are integers. Thus, for example, the term “C1-C6alkyl” (or “C1-salkyl”) means an alkyl group having 1 , 2, 3, 4, 5, or 6 carbon atoms and includes, for example, any of the hexyl alkyl and pentyl alkyl isomers as well as n-, iso-, sec-, and tert-butyl, n- and isopropyl, ethyl, and methyl. As another example, “C1-C4alkyl” refers to n-, iso-, sec-, and tert-butyl, n- and iso-propyl, ethyl, and methyl. Unless otherwise stated, an “alkyl” group includes all isomers. As another example, “Cialkyl” refers to a methyl group; “C2alkyl” refers to an ethyl group; “Csalkyl” refers to a propyl group (e.g., n-propyl or iso-propyl)); “C4alkyl” refers to a butyl group (e.g., n- butyl, sec-butyl, isobutyl, or tert-butyl); “Csalkyl” refers to a pentyl group and any of its isomers; and “C6alkyl” refers to a hexyl group and any of its isomers. As another example, “propyl” includes n-propyl and iso-propyl; “butyl” includes n-butyl, sec-butyl, isobutyl, and tert-butyl; etc.

[0022] The term “alkynyl,” as used herein, whether it is used alone or as part of another group, means substituted or unsubstituted, straight or branched chain, unsaturated hydrocarbon groups containing at least one triple bond. The term C2-C6alkynyl (or C2-ealkynyl) means an alkynyl group having 2, 3, 4, 5, or 6 carbon atoms. Alkynyl groups may be substituted by alkyl or alkenyl groups.

[0023] The term “and / or,” as used herein, means that one or more of the listed items are present, or used, individually or in combination. In effect, this term means that “at least one of’ or “one or more” of the listed items is used or present. The term “and / or” with respect to pharmaceutically acceptable salts and / or solvates thereof means that the compounds of the disclosure exist as individual salts or solvates, as well as a combination of, for example, a salt of a solvate of a compound of the disclosure. As used herein, the term “and / or” means either or both (or any combination or all of the terms or expressions referred to), e.g., “A, B, and / or C” encompasses A alone; B alone; C alone; A and B; A and C; B and C; and A, B, and C.

[0024] The term “any member, combination, or subset thereof,” as used herein, when used to refer to a preceding list of possible members, means that any individual listed member, possible combination of listed members, or subset of listed members may be included. For example, if Z is selected from A, B, C, and D, including any member, combination, or subset thereof, then Z may be A, B, C, and D; A, B, and C; A, B, and D; A, C, and D; B, C, and D; A and B; A and C; A and D; B and C; B and D; C and D; A alone; B alone; C alone; or D alone. As another example, if A is C1-C4alkyl, then subsets of A (in the context of a subset of A, B, C, and D) include Cialkyl alone, Czalkyl alone, Csalkyl alone, C4alkyl alone, C1-C2alkyl, C1-Csalkyl, C1-C4alkyl, C2-C3alkyl, C2-C4alkyl, and C3-C4alkyl.

[0025] The term “aryl,” as used herein, whether it is used alone or as part of another group, refers to a substituted or unsubstituted aromatic carbocyclic ring or multi-ring structures (e.g., bi-cyclic). For example, for an aryl group that contains the prefix C6-C10, the corresponding carbocyclic group(s) contains 6, 7, 8, 9, or 10 carbon ring atoms.

[0026] The term “available,” as in “available hydrogen atoms” or “available hydrogen atoms” refers to atoms that would be known to a person skilled in the art to be capable of replacement by a substituent.

[0027] The term “benzofused,” as used herein, refers to a polycyclic group in which a benzene ring is fused with another ring.

[0028] The term “carbocyclic group," as used herein, refers to substituted or unsubstituted cyclic groups where all ring members are carbon atoms.

[0029] A first ring being “bridged” with a second ring means the first ring and the second ring share two non-adjacent atoms there between.

[0030] The term “composition(s) of the disclosure” or “composition(s) of the present disclosure” and the like, as used herein, refers to a composition, such a pharmaceutical composition, comprising one or more compounds of the disclosure.

[0031] The term “compound(s) of the disclosure" or “compound(s) of the present disclosure” and the like, as used herein, refers to a compound Formula (I) and includes, in some embodiments, pharmaceutically acceptable salts, solvates, and / or prodrugs thereof, unless the context clearly dictates otherwise.

[0032] As used in this disclosure and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “include” and “includes”) or “containing” (and any form of containing, such as “contain” and “contains”), are inclusive or open- ended and do not exclude additional, unrecited elements or process steps.

[0033] The term “consisting” and its derivatives, as used herein, are intended to be closed terms that specify the presence of the stated features, elements, components, groups, integers and / or steps and also exclude the presence of other unstated features, elements, components, groups, integers, and / or steps.

[0034] The term “consisting essentially of,” as used herein, is intended to specify the presence of the stated features, elements, components, groups, integers, and / or steps as well as those that do not materially affect the basic and novel characteristic(s) of those features, elements, components, groups, integers, and / or steps.

[0035] All “cyclic” groups, including aryl, heteroaryl, heterocycloalkyl, and cycloalkyl groups, contain one ring or more than one ring (i.e., are optionally polycyclic), unless otherwise indicated. When a cyclic group contains more than one ring, the rings may be fused, bridged, spirofused, or linked by a bond.

[0036] The term “cycloalkyl,” as used herein, whether it is used alone or as part of another group, means a substituted or unsubstituted, saturated or unsaturated, non-aromatic, carbocyclic ring or multi-ring structures (e.g., bi-cyclic), unless otherwise specified. For example, the term C3- Cycycloalkyl (or Cs-ycycloalkyl) means a cycloalkyl group having 3, 4, 5, 6, or 7 ring carbon atoms. A cycloalkyl is optionally fused to another ring, including fused to an aryl ring (e.g., benzofused) or heteroaryl ring.

[0037] The term “deuteroalkenyl,” as used herein, refers to an alkenyl group as defined above in which one or more of the available hydrogen atoms have been independently replaced with one or more deuterium atoms, respectively. Thus, for example, “C2-C6deuteroalkenyl” (or “C2-6deuteroalkenyl”) refers to a two-carbon to six-carbon linear or branched alkenyl group as defined above with one or more deuterium substituents, and optionally one or more non-deuterium substitutes.

[0038] The term “deuteroalkyl,” as used herein, refers to an alkyl group as defined above in which one or more of the available hydrogen atoms have been independently replaced with one or more deuterium atoms, respectively. Thus, for example, “C1-C6deuteroalkyl” (or “C1-6deuteroalkyl”) refers to a one-carbon to six-carbon linear or branched alkyl group as defined above with one or more deuterium substituents, and optionally one or more non-deuterium substitutes.

[0039] The term “deuterohaloalkenyl,” as used herein, refers to an alkenyl group as defined above in which one or more of the available hydrogen atoms have been independently replaced with one or more deuterium atoms and one or more of the available hydrogen atoms have been independently replaced with one or more halogen atoms. Thus, for example, “C2- C6deuterohaloalkenyl” (or “C2-6deuterohaloalkenyl”) refers to a two-carbon to six-carbon linear or branched alkenyl group as defined above with one or more deuterium substituents and one or more halogen substituents, and optionally one or more non-deuterohalo substitutes.

[0040] The term “deuterohaloalkyl,” as used herein, refers to an alkyl group as defined above in which one or more of the available hydrogen atoms have been independently replaced with one or more deuterium atoms and one or more of the available hydrogen atoms have beenindependently replaced with one or more halogen atoms. Thus, for example, “C1- C6deuterohaloalkyl” (or “C1-edeuterohaloalkyl") refers to a one-carbon to six-carbon linear or branched alkyl group as defined above with one or more deuterium substituents and one or more halogen substituents, and optionally one or more non-deuterohalo substitutes.

[0041] The term “disease, disorder, or condition,” as used herein, refers to a disease, disorder, or condition treated or treatable using one or more compounds of the disclosure herein described.

[0042] The term “effective amount” or “therapeutically effective amount,” as used herein, means an amount of one or more compounds of the disclosure that is effective, at dosages and for periods of time necessary to achieve the desired result. For example, in the context of treating a disease, disorder, or condition, an effective amount is an amount that, for example, treats, palliates, and / or prevents said disease, disorder, or condition compared to the non-treatment, non-palliation, or non-prevention without administration of the one or more compounds.

[0043] The suffix “ene” at the end of a group (for example “alkylene”) means that the group is bivalent, that is that it is bonded to two variables each on a different end of or location on the group. An alkylene may be substituted or unsubstituted, straight or branched chain. The number of carbon atoms that are possible in the referenced alkylene group are indicated by the prefix “Cn- Cm” and “Co” where n, m, and o are integers. Thus, for example, the term “C1-C6alkylene” (or “C1-6alkylene”) means an alkylene group having 1 , 2, 3, 4, 5, or 6 carbon atoms and includes, for example, any of the hexylene and pentylene isomers as well as n-, iso-, sec-, and tert-butylene, n- and iso-propylene, ethylene, and methylene. Unless otherwise stated, an “alkylene” group includes all isomers. As another example, “C1alkylene” refers to a methylene group; “C2alkylene” refers to an ethylene group; “C3alkylene” refers to a propylene group (e.g., n-propylene or isopropylene); “C4alkylene” refers to a butylene group (e.g., n-butylene, sec-butylene, isobutylene, or tert-butylene); “C5alkylene” refers to a pentylene group and any of its isomers; and “C6alkylene” refers to a hexylene group and any of its isomers. As another example, “propylene” includes n- propylene and iso-propylene; “butylene” includes n-butylene, sec-butylene, isobutylene, and tertbutylene; etc.

[0044] The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any implementation described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other implementations. Reference throughout this specification to “a select embodiment,” “one embodiment,” “an exemplary embodiment,” “exemplary embodiments,” “an embodiment,” “some embodiments,” or “embodiments” means that a particular feature, structure, or characteristic described in connection with theembodiment(s) is included in at least one embodiment. Thus, appearances of the phrases “in a select embodiment,” “in one embodiment,” “in an exemplary embodiment,” “in exemplary embodiments,” “in some embodiments,” “in an embodiment,” “some embodiments,” or “in embodiments” in various places throughout this specification are not necessarily referring to the same embodiment(s) or only a single embodiment. The embodiments may be, for example, combined with one another in various combinations and modified to include features of one another.

[0045] A first ring being “fused” with a second ring means the first ring and the second ring share two adjacent atoms there between.

[0046] The term “halo” (or “halogen”) whether it is used alone or as part of another group, refers to a halogen atom and includes fluoro, chloro, bromo, and iodo.

[0047] The term “haloalkenyl,” as used herein, refers to an alkenyl group as defined above in which one or more of the available hydrogen atoms have been independently replaced with one or more halogen atoms. Thus, for example, “C2-C6haloalkenyl” (or “C2-ehaloalkenyl”) refers to a two-carbon to six-carbon linear or branched alkenyl group as defined above with one or more halogen substituents, and optionally one or more non-halogen substitutes.

[0048] The term “haloalkyl,” as used herein, refers to an alkyl group as defined above in which one or more of the available hydrogen atoms have been independently replaced with one or more halogen atoms. Thus, for example, “C1-C6h aloalkyl” (or “C1-ehaloalkyl”) refers to a one-carbon to six-carbon linear or branched alkyl group as defined above with one or more halogen substituents , and optionally one or more non-halogen substitutes.

[0049] The term “heteroaryl,” as used herein, whether it is used alone or as part of another group, refers to substituted or unsubstituted aromatic ring or multi-ring structures (e.g., bi-cyclic), in which one or more of the atoms of the aromatic ring are a heteromoiety independently selected from O, S, and N, including oxidized or substituted versions thereof (e.g., S(O) and S(O)2), and the remaining atoms are C, unless otherwise specified. When a heteroaryl group contains the prefix of, for example, C5-C10, this prefix indicates that the corresponding carbocyclic group(s) contains 5, 6, 7, 8, 9, or 10 carbon atoms in the ring, in which one or more, suitably 1 to 5, of the ring atoms is replaced with a heteroatom as defined above. Heteroaryl groups may also be preceded by, for example, “5- to 10-membered” which refers to the total number of ring atoms (in this example, 5, 6, 7, 8, 9, or 10 atoms) in the aromatic ring or multi-ring structures, including the heteroatom(s). Heteroaryl groups may be benzofused.

[0050] The term “heterocycle" or “heterocyclic” refers to a cyclic group which contains at least one heteroatom, e.g., N, O, or S, and may be aromatic (heteroaryl) or non-aromatic. Thus, the heteroaryl moieties and the heterocycloalkyl moieties are subsumed under the definition of heterocycle, depending on the context of its use. The term “heterocyclic” also includes bicyclic groups in which any of the heterocyclic rings is fused to a benzene ring or a cyclohexane ring or another heterocyclic ring.

[0051] The term “heterocycloalkyl” as used herein, whether it is used alone or as part of another group, refers to substituted or unsubstituted, saturated or non -saturated, non-aromatic ring or non-aromatic multi-ring structures (e.g., bi-cyclic), in which one or more of the ring atoms of the non-aromatic ring or non-aromatic multi-ring structure are independently selected from O, S, and N, including oxidized or substituted versions thereof (e.g., S(O) and S(O)2), and the remaining atoms are C, unless otherwise specified. Heterocycloalkyl groups are either saturated or unsaturated (i.e., contain one or more double bonds) and / or optionally comprise one or more C=O groups (i.e., one or more carbon atoms in the ring is oxidized to C=O). When a heterocycloalkyl group contains a prefix, such as C3-C10, this prefix indicates that the corresponding carbocyclic group contains 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms in the ring, in which one or more, suitably 1 to 5, of the ring atoms are replaced with a heteromoiety independently selected from O, S, and N including oxidized or substituted versions thereof, and the remaining atoms are C. Similarly, heterocycloalkyl groups may also be preceded by a prefix, such as “3- to 10-membered,” which refers to the total number of atoms in the ring(s) (in this example, 3, 4, 5, 6, 7, 8, 9, or 10 atoms). Heterocycloalkyl groups are optionally fused to another ring, including fused to an aryl ring (e.g., benzofused) or heteroaryl ring.

[0052] As used herein, the term “one or more" items includes a single item selected from the list as well as two or more items (e.g., combinations and mixtures) selected from the list.

[0053] The term “one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms,” and the like, as used herein, means that at least one available hydrogen atom is replaced with at least one deuterium atom, or two or more hydrogen atoms are replaced with two or more deuterium atoms, respectively, or optionally that each and every available hydrogen atom is replaced with a respective deuterium atom. When a compound comprises one or more available hydrogen atoms that have been replaced with one or more deuterium atoms, the compound comprises that deuterium isotope in greater amounts than would otherwise be present in the compound if said replacement had not taken place.

[0054] The term “one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms,” and the like as used herein, means that at least one available hydrogen atom is replaced with at least one halogen atom, or two or more hydrogen atoms are replaced with two or more halogen atoms, respectively, or optionally that each and every available hydrogen atom is replaced with a respective halogen atom, and that the replacements are independent of one another.

[0055] The term “one or more available hydrogen atoms are optionally and independently replaced with one or more fluorine atoms," and the like, as used herein, means that at least one available hydrogen atom is replaced with at least one fluorine atom, or two or more hydrogen atoms are replaced with two or more fluorine atoms, respectively, or optionally that each and every available hydrogen atom is replaced with a respective fluorine atom.

[0056] The term “optionally substituted,” as used herein, means that the subject group is unsubstituted or substituted and the terms “optionally substituted” and “unsubstituted or substituted” are used interchangeably herein. As used herein, when referring to more than one item or “each” item, “optionally substituted" and “unsubstituted or substituted" means that the items are independently unsubstituted or substituted with respect to one another, e.g., for item A and item B that are optionally substituted, both may be substituted, both may be un substituted, or one may be substituted and the other unsubstituted. Additionally, as used herein, the term “optionally substituted” when referring to more than one item means that if more than one of the items is substituted, the substitutions may be independent from one another, e.g., for item A and item B that are both substituted, item A may have a first substitution and item B may have a second substitution that is the same or different from the first substitution of item A.

[0057] “Palliating” a disease, disorder, or condition means that the extent and / or undesirable clinical manifestations of a disease, disorder, or condition are lessened and / or time course of the progression is slowed or lengthened, as compared to not treating the disorder.

[0058] The term “pharmaceutically acceptable” means compatible with the treatment of subjects.

[0059] The term “pharmaceutically acceptable carrier" means a non-toxic solvent, dispersant, excipient, adjuvant, or other material which is mixed or otherwise combined with the active ingredient in order to permit the formation of a pharmaceutical composition, i.e., a dosage form capable of administration to a subject.

[0060] The term “pharmaceutically acceptable salt” means either an acid addition salt or a base addition salt which is suitable for, or compatible with, the treatment of subjects. An acid addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic acid addition salt of any basic compound. A base addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic base addition salt of any acidic compound.

[0061] The term “prevention” or “prophylaxis,” or synonym thereto, as used herein, refers to a reduction in the risk or probability of a patient becoming afflicted with a disease, disorder, or condition or manifesting a symptom associated with a disease, disorder, or condition.

[0062] The term “prodrug,” as used herein, means a compound, or salt of a compound, that, after administration, is converted into an active drug.

[0063] The term “protecting group” or “PG” and the like, as used herein, refers to a chemical moiety which protects or masks a reactive portion of a molecule to prevent side reactions in those reactive portions of the molecule, while manipulating or reacting a different portion of the molecule. After the manipulation or reaction is complete, the protecting group is removed under conditions that do not degrade or decompose the remaining portions of the molecule. The selection of a suitable protecting group can be made by a person skilled in the art. Many conventional protecting groups are known in the art, for example as described in “Protective Groups in Organic Chemistry,” McOmie, J.F.W. Ed., Plenum Press, 1973, in Greene, T.W. and Wuts, P.G.M., “Protective Groups in Organic Synthesis,” John Wiley & Sons, 3rdEdition, 1999 and in Kocienski, P. Protecting Groups, 3rd Edition, 2003, Georg Thieme Verlag (The Americas).

[0064] The term “solvate,” as used herein, means a compound, or a salt or prodrug of a compound, wherein molecules of a suitable solvent are incorporated in the crystal lattice. A suitable solvent is physiologically tolerable at the dosage administered.

[0065] A first ring being “spirofused" with a second ring means the first ring and the second ring share one atom there between.

[0066] The term “subject,” as used herein, includes all members of the animal kingdom including mammals, and suitably refers to humans. Thus, the methods of the present disclosure are applicable to both human therapy and veterinary applications.

[0067] The term “substituted,” as used herein, means, unless otherwise indicated, that the referenced group is substituted with one or more independently selected substituents. When a group is substituted with more than one substituent selected from a list of substituents, each ofthe substituents is independently selected from the listed group of substituents unless otherwise indicated.

[0068] The term “suitable,” as used herein, means that the selection of the particular compound or conditions would depend on the specific synthetic manipulation to be performed, the identity of the molecule(s) to be transformed and / or the specific use for the compound, but the selection would be well within the skill of a person trained in the art. All process / method steps described herein are to be conducted under conditions sufficient to provide the product shown. A person skilled in the art would understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reactant ratio, and whether or not the reaction should be performed under an anhydrous or inert atmosphere, can be varied to control the yield of the desired product and it is within their skill to do so.

[0069] The term “therapeutic agent,” as used herein, refers to any drug or active agent that has a pharmacological effect when administered to a subject.

[0070] The term “treating” or “treatment,” as used herein, and as is well understood in the art, means an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, preventing spread of disease, delay, or slowing of disease progression, amelioration or palliation of the disease state, diminishment of the reoccurrence of disease and remission (whether partial or total), whether detectable or undetectable. “Treating” and “treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. “Treating” and “treatment,” as used herein, also include prophylactic treatment. Treatment methods comprise administering to a subject a therapeutically effective amount of one or more of the compounds of the disclosure and optionally consist of a single administration, or alternatively comprise a series of administrations.

[0071] The term “treating a disease, disorder, or condition,” as used herein, means that the disease, disorder, or condition to be treated is affected by, modulated by, and / or has some biological basis.II. Compounds

[0072] The present disclosure includes a compound of Formula (I) or a stereoisomer thereof:

[0073] In some embodiments, one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms independently selected from fluorine, chlorine, and bromine and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0074] In some embodiments, one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms independently selected from fluorine and chlorine and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0075] In some embodiments, one or more available hydrogen atoms are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0076] In some embodiments, one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0077] In some embodiments, X1is selected from O and S and X2is selected from O and S, including any member, combination, subset thereof, e.g., X1is O and X2is O, X1is S and X2is S, X1is O and X2is S, and X1is S and X2is O.

[0078] In some embodiments, Y is CR14. In some embodiments, Y is N.

[0079] In some embodiments, R14is selected from H, D, halo, and optionally substituted C1-C4alkyl. In some embodiments, R14has one or more available hydrogen atoms independentlyreplaced with one or more halogen atoms and / or one or more available hydrogen atoms independently replaced with one or more deuterium atoms. In some embodiments, R14has no hydrogen atoms independently replaced with halogen atoms and / or no hydrogen atoms replaced with deuterium atoms.

[0080] In some embodiments, R14is unsubstituted. In some embodiments, R14is substituted.In some embodiments, R14is substituted with one or more members independently selected from halo, Ci.C4alkyl, OCi.C4alkyl, and C(O)Ci.C4alkyl, including any member, combination, or subset thereof.

[0081] In some embodiments, R14is selected from H and D, including any member, combination, subset thereof, e.g., H and D, H alone, and D alone.

[0082] In some embodiments, R14is halogen, i.e., is selected from F, Cl, Br, and I, including any member, combination, or subset thereof. In some embodiments, R14is a halogen selected from fluorine, chlorine, and bromine. In some embodiments, R14is a halogen selected from fluorine and bromine. In some embodiments, R14is a halogen selected from fluorine and chlorine. In some embodiments, R14is a halogen selected from chlorine and bromine. In some embodiments, R14is fluorine. In some embodiments, R14is chlorine. In some embodiments, R14is bromine. In some embodiments, R14is iodine. In some embodiments, R14is not halogen.

[0083] In some embodiments, R14is C1-C4alkyl. In some embodiments, R14is C1-CsalkyL In some embodiments, R14is C1-C2alkyl. In some embodiments, R14is C2-C4alkyl. In some embodiments, R14is C2-C3alkyl. In some embodiments, R14is C3-C4alkyl. In some embodiments, R14is selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0084] In some embodiments, R14is selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl group of R14are replaced with deuterium atoms. In some embodiments, none of the available hydrogens of the alkyl group of R14are replaced with halogen atoms. In some embodiments, none of the hydrogen atoms of the alkyl group of R14are replaced with halogen atoms and none of the hydrogen atoms of the alkyl group of R14are replaced with deuterium atoms.

[0085] In some embodiments, R14includes at least one deuterium atom. In some embodiments, R14includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more halogen atoms (i.e. , F,Cl, Br, and / or I) and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R14are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of R14are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of R14are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of R14are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of R14are replaced with a halogen atom and none of the available hydrogen atoms of R14are replaced with a deuterium atom.

[0086] In some embodiments, Y is OR14and R14is selected from CH, CH2, and a heteroatom linked with R2to form a 5-membered heterocyclic ring including R2, R14, and X2, and R2is selected from CH and CH2 linked with R14to form the 5-membered heterocyclic ring including R2, R14, and X2, as shown below.

[0087] In some embodiments, R14of the 5-membered heterocyclic ring including R2, R14, and X2is CH or CH2. In some embodiments, R14of the 5-membered heterocyclic ring including R2, R14, and X2is a heteroatom, such as a member selected from O, S, and N (including oxidized versions of the heteroatom, i.e., S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R2, R14, and X2contains one heteroatom. In some embodiments, the heterocyclic ring including R2, R14, and X2contains two heteroatoms, such as members independently selected from O, S, and N (including oxidized versions of the heteroatom, i.e., S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R2, R14, and X2contains one double bond, and in some embodiment the heterocyclic ring includes two double bonds. In some embodiments, the heterocyclic ring including R2, R14, and X2contains one double bond and one heteroatom, in some embodiments, the heterocyclic ring includes two double bonds and one heteroatom, and in some embodiments, the heterocyclic ring includes two double bonds and two heteroatoms. In some embodiments, the 5-membered heterocyclic ring including R2, R14, and X2is unsubstituted. A person skilled in the art would appreciate that when R14is a heteroatom selected from N and the heterocyclic ring including R2, R14, and X2contains one double bond that the N would be present in the form of NH.

[0088] In some embodiments, R14is linked with R2to form a 5-membered heterocyclic ring including R2, R14, and X2to provide a structure for Formula (I) selected from:including any member, combination, or subset thereof. For the purposes of this disclosure, the 5- membered heterocyclic rings of the first two compounds each contain one double bond, and the 5-membered heterocyclic rings of the latter two compounds each contain two double bonds.

[0089] In some embodiments, the heterocyclic ring including R2, R14, and X2includes at least one deuterium atom. In some embodiments, the heterocyclic ring including R2, R14, and X2includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independentlyreplaced with one or more bromine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are replaced with a halogen atom and none of the available hydrogen atoms of the heterocyclic ring including R2, R14, and X2are replaced with a deuterium atom.

[0090] In some embodiments, R1is C1-C6alkyl. In some embodiments, R1is C1-Csalkyl. In some embodiments, R1is C1-C4alkyl. In some embodiments, R1is C1-C3alkyl. In some embodiments, R1is C1-C2alkyl. In some embodiments, R1is Ca2-lkCy6l. In some embodiments, R1is C2-Csalkyl. In some embodiments, R1is C2-C4alkyl. In some embodiments, R1is C2-C3alkyl. In some embodiments, R1is Cs-CgalkyL In some embodiments, R1is Cs-CsalkyL In some embodiments, R1is C3-C4alkyl. In some embodiments, R1is C4-C6alkyl. In some embodiments, R1is C4-Csalkyl. In some embodiments, R1is Cs-C6alkyl. In some embodiments, none of the available hydrogens of the alkyl moiety of R1are replaced with halogen atoms. In some embodiments, none of the available hydrogen atoms of the alkyl moiety of R1are replaced with halogen atoms and none of the available hydrogen atoms of the alkyl moiety of R1are replaced with deuterium atoms. In some embodiments, the alkyl moiety of R1has one or more available hydrogen atoms independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms independently replaced with one or more deuterium atoms (e.g., alkyl, deuteroalkyl, haloalkyl, deuterohaloalkyl). In some embodiments, R1is selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0091] In some embodiments, R1is selected from CH3, CD2H, CDH2, CDs, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3 CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2ICH(CHF2)2, CH(CFH2)2, CH(CD3)2ICH(CHD2)2, CH(CDH2)2, C(CH3)3,C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3,C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CF3)2,CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3JCH2CH(CH3)CD3,CH2C(CH3)3,CH2C(CF3)3, CH2C(CD3)3,CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, R1is selected from CH3, CH2D, CHD2, CDs, CH2F, CHF2, CF3, CH2CH3, CD2CD3, CF2CF3, CH(CH3)2, CH(CD3)2, CH(CF3)2, CD(CD3)2, CF(CF3)2, C(CH3)3, C(CD3)3,and C(CF3)3, including any member, combination, or subset thereof. In some embodiments, R1is selected from Ch3, CHF2, CF3,CD3,CH2CH3, CH(CH3)2, CH(CD3)2, and C(CH3)3, including any member, combination, or subset thereof. In some embodiments, R1is selected from Ch3, CH2D, CHD2, CD3, CH2F, CHF2JCF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof. In some embodiments, R1is selected from CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0092] In some embodiments, the alkyl of R1is unsubstituted. In some embodiments, the alkyl of R1is substituted. In some embodiments, the alkyl of R1is substituted with one or more members independently selected from halo, Ci.C4alkyl, OCiXLUalkyl, and C(O)Ci.C4alkyl, including any member, combination, or subset thereof.

[0093] In some embodiments, R1includes at least one deuterium atom. In some embodiments, R1includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of R1are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R1are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R1are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R1are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R1are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or moreavailable hydrogen atoms of R1are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R1are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of R1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of R1are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of R1are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of R1are replaced with a halogen atom and none of the available hydrogen atoms of R1are replaced with a deuterium atom.

[0094] In some embodiments, R4is selected from CH, CH2, and a heteroatom linked with R1to form a 5-membered heterocyclic ring including R1, R4, and X1, and R1is selected from CH and CH2 linked with R4to form the 5-membered heterocyclic ring including R1, R4, and X1, as shown below.

[0095] In some embodiments, R4of the 5-membered heterocyclic ring including R1, R4, and X1is CH or CH2. In some embodiments, R4of the 5-membered heterocyclic ring including R1, R4, and X1is a heteroatom, such as a member selected from O, S, and N (including oxidized versions of the heteroatom, i.e., S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R1, R4, and X1contains one heteroatom. In some embodiments, the heterocyclic ring including R1, R4, and X1contains two heteroatoms, such as members independently selected from O, S, and N (including oxidized versions of the heteroatom, i.e., S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R1, R4, and X1contains one double bond, and in some embodiments the heterocyclic ring includes two double bonds. In some embodiments, the heterocyclic ring including R1, R4, and X1contains one double bond and one heteroatom, in some embodiments, the heterocyclic ring includes twodouble bonds and one heteroatom, and in some embodiments, the heterocyclic ring includes two double bonds and two heteroatoms. In some embodiments, the 5-membered heterocyclic ring including R1, R4, and X1is unsubstituted. A person skilled in the art would appreciate that when R4is a heteroatom selected from N and the heterocyclic ring including R1, R4, and X1contains one double bond that the N would be present in the form of NH.

[0096] In some embodiments, the 5-membered heterocyclic ring including R1, R4, and X1has a structure for Formula (I) selected from:including any member, combination, or subset thereof. For the purposes of this disclosure, the 5- membered heterocyclic rings of the first two compounds each contain one double bond, and the 5-membered heterocyclic rings of the latter two compounds each contain two double bonds.

[0097] In some embodiments, the heterocyclic ring including R1, R4, and X1includes at least one deuterium atom. In some embodiments, the heterocyclic ring including R1, R4, and X1includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more fluorine atoms and / or one or moreavailable hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are replaced with a halogen atom and none of the available hydrogen atoms of the heterocyclic ring including R1, R4, and X1are replaced with a deuterium atom.

[0098] In some embodiments, Y is CR14and R14is selected from CH, CH2, and a heteroatom linked with R2, and R2is selected from CH and CH2 linked with R14to form the 5-membered heterocyclic ring including R2, R14, and X2, and R4is selected from CH, CH2, and a heteroatom linked with R1, and R1is selected from CH and CH2 linked with R4to form the 5-membered heterocyclic ring including R1, R4, and X1, as shown below.wherein Y, X1, X2, R1, R2, R3, R4, R5, R14, and Q are as defined herein.

[0099] In some embodiments, R2is C1-C6alkyl. In some embodiments, R2is C1-CsalkyL In somemore available hydrogen atoms independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms independently replaced with one or more deuterium atoms (e.g., alkyl, deuteroalkyl, haloalkyl, deuterohaloalkyl). In some embodiments, R2is selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0100] In some embodiments, R2is selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moiety of R2are replaced with deuterium atoms. In some embodiments, none of the available hydrogens of the alkyl moiety of R2are replaced with halogen atoms. In some embodiments, none of the available hydrogen atoms of the alkyl moiety of R2are replaced with halogen atoms and none of the available hydrogen atoms of the alkyl moiety of R2are replaced with deuterium atoms.

[0101] In some embodiments, R2is selected from CH3, CD2H, CDH2, CD3, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2, CH(CHF2)2ICH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2, C(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3, C(CHD2)3,C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CCHH22CCHH22CCHH22CCDD33,, CH2CH(CH3)2, CCHH22CCHH((CCDD33))22,, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3,CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, R2is selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CH2CH3, CD2CD3, CF2CF3, CH(CH3)2, CH(CD3)2, CH(CF3)2, CD(CD3)2, CF(CF3)2, C(CH3)3, C(CD3)3, and C(CF3)3, including any member, combination, or subset thereof. In some embodiments, R2is selected from CH3, CHF2, CF3,CD3,CH2CH3JCH(CH3)2, CH(CD3)2, and C(CH3)3, including any member, combination, or subset thereof. In some embodiments, R2is selected from Ch3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subsetthereof. In some embodiments, R2is selected from CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0102] In some embodiments, the alkyl of R2is unsubstituted. In some embodiments, the alkyl of R2is substituted. In some embodiments, the alkyl of R2is substituted with one or more members independently selected from halo, C1-C4alkyl, OC1-C+alkyl, and C(O)Ci-C4alkyl, including any member, combination, or subset thereof.

[0103] In some embodiments, R2includes at least one deuterium atom. In some embodiments, R2includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R2are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of R2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of R2are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of R2are replaced with a deuterium atom. In some embodiments, noneof the available hydrogen atoms of R2are replaced with a halogen atom and none of the available hydrogen atoms of R2are replaced with a deuterium atom.

[0104] In some embodiments, R2is selected from CH and CH2 linked with R14to form the 5- membered heterocyclic ring including R2, R14, and X2exemplified above.

[0105] In some embodiments, R3is selected from CH, CH2, and a heteroatom linked with R2to form a 5-membered heterocyclic ring including R2, R3, and X2. In some embodiments, the heterocyclic ring including R2, R3, and X2contains one heteroatom. In some embodiments, the heterocyclic ring including R2, R3, and X2contains two heteroatoms, such as members independently selected from O, S, and N (including oxidized versions of the heteroatom, i.e. , S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R2, R3, and X2contains one double bond, in some embodiments the heterocyclic ring includes two double bonds. In some embodiments, the heterocyclic ring including R2, R3, and X2contains one double bond and one heteroatom, in some embodiments two double bonds and one heteroatom. In some embodiments, the 5-membered heterocyclic ring including R2, R3, and X2is unsubstituted.

[0106] In some embodiments, R2is selected from CH and CH2 linked with R3to form a 5- membered heterocyclic ring including R2, R3, and X2, and R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2, as shown below.

[0107] In some embodiments, R3of the 5-membered heterocyclic ring including R2, R3, and X2is CH or CH2. In some embodiments, R3of the 5-membered heterocyclic ring including R2, R3, and X2is a heteroatom, such as a member selected from O, S, and N (including oxidized versions of the heteroatom, i.e., S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R2, R3, and X2contains one heteroatom. In some embodiments, the heterocyclic ring including R2, R3, and X2contains two heteroatoms, such as membersindependently selected from O, S, and N (including oxidized versions of the heteroatom, i.e. , S(O), S(O)2, unless otherwise indicated). In some embodiments, the heterocyclic ring including R2, R3, and X2contains one double bond, and in some embodiments the heterocyclic ring includes two double bonds. In some embodiments, the heterocyclic ring including R2, R3, and X2contains one double bond and one heteroatom, in some embodiments, the heterocyclic ring includes two double bonds and one heteroatom, and in some embodiments, the heterocyclic ring includes two double bonds and two heteroatoms. In some embodiments, the 5-membered heterocyclic ring including R2, R3, and X2is unsubstituted. A person skilled in the art would appreciate that when R3is a heteroatom selected from N and the heterocyclic ring including R2, R3, and X2contains one double bond that the N would be present in the form of NH.

[0108] In some embodiments, the 5-membered heterocyclic ring including R2, R3, and X2has a structure for Formula (I) selected from:g any member, combination, or subset thereof. Forthe purposes of this disclosure, the 5-membered heterocyclic rings of the first four compounds each contain one double bond, and the 5-membered heterocyclic rings of the latter two compounds each contain two double bonds.

[0109] In some embodiments, the heterocyclic ring including R2, R3, and X2includes at least one deuterium atom. In some embodiments, the heterocyclic ring including R2, R3, and X2includesat least one halogen atom. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are replaced with a halogen atom and none of the available hydrogen atoms of the heterocyclic ring including R2, R3, and X2are replaced with a deuterium atom.

[0110] In some embodiments, R3is selected from SH, CN, NO2, 1, optionally substituted S(O)Cr C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyl, optionally substituted OC1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted -

[0111] In some embodiments, the alkyl moieties of R3(e.g., of optionally substituted S(O)Cr C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyl, optionally

[0112] In some embodiments, the alkyl moieties of R3are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moiety of R3are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moiety of R3are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moiety of R3are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moiety of R3are replaced with a deuterium atom. In some embodiments, the alkyl moieties of R3are independently unsubstituted. In some embodiments, the alkyl moieties of R3are independently substituted.

[0113] In some embodiments, the alkylene moieties of R3(e.g., of optionally substituted C1- CsalkyleneOC1-C8alkyl and optionally substituted C1-C8alkyleneSC1-C8alkyl) are independently C1-Csalkylene. In some embodiments, the alkylene moieties of R3are independently C1- C?alkylene. In some embodiments, the alkylene moieties of R3are independently C1-Csalkylene. In some embodiments, the alkylene moieties of R3are independently C1-Csalkylene. In some embodiments, the alkylene moieties of R i3:are independently C1-C4alkylene. In some embodiments, the alkylene moieties of R3are independently C1-Csalkylene. In some embodiments, the alkylene moieties of R3are independently C1-C2alkylene. In some embodiments, the alkylene moieties of R3are independently C2-Csalkylene. In some embodiments, the alkylene moieties of R3are independently Cs-Csalkylene. In some embodiments, the alkylene moieties of R3are independently C^Csalkylene. In some embodiments, the alkylene moieties of R3are independently Cs-Csalkylene. In some embodiments, the alkylene moieties of R i3:are independently Cs-Csalkylene. In some embodiments, the alkylene moieties of R3are independently Cz-Csalkylene. In some embodiments, the alkylene moieties of R3are independently C2-C?alkylene. In some embodiments, the alkylene moieties of R3are independently Cs-Czalkylene. In some embodiments, the alkylene moieties of R3are independently C4-C?alkylene. In some embodiments, the alkylene moieties of R3are independently Cs-Czalkylene. In some embodiments, the alkylene moieties of R3are independently Cs-Czalkylene. In some embodiments, the alkylene moieties of R3are independently C2-C6alkylene. In some embodiments, the alkylene moieties of R3are independently Cs-C6alkylene. In some embodiments, the alkylene moieties of R3are independently C4-C6alkylene. In some embodiments, the alkylene moieties of R3are independently Cs-C6alkylene. In some embodiments, the alkylene moieties of R3are independently C2-Csalkylene. In some embodiments, the alkylene moieties of R3are independently Cs-Csalkylene. In someembodiments, the alkylene moieties of R3are independently C4-Csalkylene. In some embodiments, the alkylene moieties of R3are independently C2-C4alkylene. In some embodiments, the alkylene moieties of R >3 are independently C3-C4alkylene. In some embodiments, the alkylene moieties of R3are independently C2-C3alkylene. In some embodiments, the alkylene moieties of R3are independently -CH2-.

[0114] In some embodiments, the alkylene moieties of R3are independently selected from alkylene, deuteroalkylene, haloalkylene, and deuterohaloalkylene, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkylene moieties of R3are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkylene moieties of R3are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkylene moieties of R3are replaced with a halogen atom and none of the available hydrogen atoms of the alkylene moieties of R3are replaced with a deuterium atom. In some embodiments, the alkylene moieties of R3are independently unsubstituted. In some embodiments, the alkylene moieties of R3are independently substituted.

[0115] In some embodiments, the alkenyl moiety of R3is Ca2-lCke6nyl. In some embodiments,

[0116] In some embodiments, the alkenyl moiety of R3is selected from alkenyl, deuteroalkenyl, haloalkenyl, and deuterohaloalkenyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkenyl moiety of R3are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkenyl moiety of R3are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkenyl moiety of R3are replaced with a halogen atom and none of the available hydrogen atoms of the alkenyl moiety of R3are replaced with a deuterium atom. In some embodiments, the alkenyl moiety of R3is unsubstituted. In some embodiments, the alkenyl moiety of R3is substituted.

[0117] In some embodiments, the alkynyl moiety of R3is C2a-lCky6nyl. In some embodiments, the alkynyl moiety of R3is C2-Csalkynyl. In some embodiments, the alkynyl moiety of R3is C2-C4alkynyl. In some embodiments, the alkynyl moiety of R3is C2-C3alkynyl. In some embodiments,

[0118] In some embodiments, the alkynyl moiety of R3is selected from alkynyl, deuteroalkynyl, haloalkynyl, and deuterohaloalkynyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkynyl moiety of R3are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkynyl moiety of R3are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkynyl moiety of R3are replaced with a halogen atom and none of the available hydrogen atoms of the alkynyl moiety of R3are replaced with a deuterium atom. In some embodiments, the alkynyl moiety of R3is unsubstituted. In some embodiments, the alkynyl moiety of R3is substituted.

[0119] In some embodiments, R3is selected from SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, and optionally substituted S(O)2C1-C8alkyl, including any member, combination, or subset thereof. In some embodiments, R3is selected from SCH3, SCH2D, SCHD2, SCD3JSCH2F, SCHF2, SCF3, SCHDF, SCD2F, and SCDF2, including any member, combination, or subset thereof.

[0120] In some embodiments, R3is selected from optionally substituted C1-Csalkyl. In some embodiments, R3is selected from Ch3, CD2H, CDH2, CD3, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3 CH(CH3)2, CH(CF3)2, CH(CHF2)2, CH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2, C(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3, C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CHS)2, CH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, R3is selected from Ch3, CH2D, CHD2, CD3, CH2F, CHF2JCF3, CH2CH3, CD2CD3, CF2CF3, CH(CH3)2, CH(CD3)2, CH(CF3)2, CD(CD3)2, CF(CF3)2, C(CH3)3,C(CD3)3, and C(CF3)3, including any member, combination, or subset thereof. In some embodiments, R3is selected from Ch3, CHF2, CF3, CD3, CH2CH3, CH(CH3)2, CH(CD3)2, and C(CH3)3, including any member, combination, or subset thereof. Insome embodiments, R3is selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof. In some embodiments, R3is selected from CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0121] In some embodiments, R3is optionally substituted OC1-Cgalkyl. In some embodiments,

[0122] In some embodiments, R3is optionally substituted C1-C8alkyleneOC1-C8alkyl. In some

[0123] In some embodiments, R3is optionally substituted C1-C8alkyleneSC1-CaalkyL In some

[0124] In some embodiments, R3is optionally substituted NHC1-C8alkyl. In some embodiments, R3is selected from optionally substituted NHC1-C8alkyl, NDC1-C8alkyl, and N(halo)C1-C8alkyl, including any member, combination, or subset thereof. In some embodiments, R3is optionally substituted NHC1-C8alkyl wherein none of the available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R3is optionally substituted NHC1-C8alkyl wherein none of the available hydrogen atoms are replaced with a halogen atom. In some embodiments, R3is optionally substituted NHC1-C8alkyl wherein none of the available hydrogen atoms are replaced with a halogen atom and none of the available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R3is unsubstituted NHC1-C8alkyl. In some embodiments, R3is substituted NHC1-C8alkyl. In some embodiments, the NHC1-C8alkyl moiety of R3is unsubstituted. In some embodiments, the NHC1-C8alkyl moiety of R3is substituted.

[0125] In some embodiments, R3is optionally substituted N(C1-C8alkyl)2. In some embodiments, R3is optionally substituted N(C1-C8alkyl)2 wherein none of the available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R3is optionally substituted N(C1-C8alkyl)2 wherein none of the available hydrogen atoms are replaced with a halogen atom. In some embodiments, R3is optionally substituted N(C1-C8alkyl)2wherein none of the available hydrogen atoms are replaced with a halogen atom and none of the available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R3is unsubstituted N(C1-C8alkyl)2. In some embodiments, R3is substituted N(C1-C8alkyl)2. In some embodiments, the N(C1-C8alkyl)2moiety of R3is unsubstituted. In some embodiments, the N(C1-C8alkyl)2moiety of R3is substituted.

[0126] In some embodiments, S(O)C1-C8alkyl, S(O)2C1-C8alkyl, C1-C8alkyl, OC1-C8alkyl, C1- C8alkyleneOC1-C8alkyl, SC1-C8alkyl, C1-C8alkyleneSC1-C8alkyl, NHC1-C8alkyl, N(C1-C8alkyl)2, C2- C8alkenyl, and C2-C8alkynyl of R3are independently unsubstituted. In some embodiments, S(O)C1-C8alkyl, S(O)2C1-C8alkyl, C1-C8alkyl, OC1-C8alkyl, C1-C8alkyleneOC1-C8alkyl, SC1- C8alkyl, C1-C8alkyleneSC1-C8alkyl, NHC1-C8alkyl, N(C1-C8alkyl)2, C2-C8alkenyl, and C2-C8alkynyl, of R3are independently substituted. In some embodiments, R3is independently substituted with one or more members independently selected from halo, C1-C4alkyl, O(C1-C4alkyl), C1- C4haloalkyl, O(C1-C4haloalkyl), CN, OH, NH2, NH(C1-C4alkyl), N(C1-C4alkyl)(C1-C4alkyl), S(C1- C4alkyl), S(O)C1-C4alkyl, S(O)2C1-C4alkyl, CO2H, CO2(C1-C4alkyl), C(O)NH2, C(O)NH(C1-C4alkyl),C(O)N(C1-C4alkyl)(C1-C4alkyl), Cs-Cycycloalkyl, including any member,combination, or subset thereof. In some embodiments, R3is independently substituted with oneor more members independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)Ci-C4alkyl, including any member, combination, or subset thereof.

[0127] In some embodiments, R3includes at least one deuterium atom. In some embodiments, R3includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R3are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of R3are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of R3are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of R3are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of R3are replaced with a halogen atom and none of the available hydrogen atoms of R3are replaced with a deuterium atom.

[0128] In some embodiments, R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2as exemplified above.

[0129] In some embodiments, R4is selected from H, D, and halo, including any member, combination, or subset thereof. In some embodiments, R4is selected from D and halo. In some embodiments, R4is selected from H and D. In some embodiments, R4is hydrogen not replaced with a halogen atom. In some embodiments, R4is not replaced with a deuterium atom. In some embodiments, R4is not replaced with a halogen atom or a deuterium atom.

[0130] In some embodiments, R4is halogen, i.e., selected from F, Cl, Br, and I, including any member, combination, or subset thereof. In some embodiments, R4is a halogen selected from fluorine, chlorine, and bromine. In some embodiments, R4is a halogen selected from fluorine and bromine. In some embodiments, R4is a halogen selected from fluorine and chlorine. In some embodiments, R4is a halogen selected from chlorine and bromine. In some embodiments, R4is fluorine. In some embodiments, R4is chlorine. In some embodiments, R4is bromine. In some embodiments, R4is iodine. In some embodiments, R4is not halogen.

[0131] In some embodiments, R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1exemplified above.

[0132] In some embodiments, R5is selected from optionally substituted C1-C6alkylene, optionally substituted Cs-Cecycloalkylene, CH(halo) (i.e., F, Cl, Br, and I), CH(OH), CH(SH), CH(NH2), optionally substituted CH(C1-C4alkyl), optionally substituted CH(OC1-C4alkyl), optionally substituted CH(SC1-C4alkyl), optionally substituted CH(NH(C1-C4alkyl)), and optionally substituted CH(N(C1-C4alkyl)2). In some embodiments, R5is optionally and independently substituted with one or more members independently selected from C1-Csalkyl, OC1-Cgalkyl, and SC1-C6alkyl, including any member, combination, or subset thereof. In some embodiments, R5is selected from a carbonyl group having a structure and a thionyl group having a structure. In some embodiments, R5is selected from CH2, CH2CH2, CH(CH3), CH(halo), CH(OH),CH(OCH3), CH(SH), a carbonyl group having a structure, and a thionyl group having astructure . In some embodiments, R5is not optionally substituted. In some embodiments,R5is absent to provide a direct bond between the phenyl ring and Q.

[0133] In some embodiments, R5includes an alkylene moiety (e.g., of optionally substituted C1- C6alkylene). In some embodiments, the alkylene moiety of R5is C1-C6alkylene. In some embodiments, the alkylene moiety of R5is C1-Csalkylene. In some embodiments, the alkylene moiety of R5is C1-C4alkylene. In some embodiments, the alkylene moiety of R5is C1-Csalkylene. In some embodiments, the alkylene moiety of R5is C1-C2alkylene. In some embodiments, the alkylene moiety of R5is C2-Ca6lkylene. In some embodiments, the alkylene moiety of R5is C2- Csalkylene. In some embodiments, the alkylene moiety of R5is C2-C4alkylene. In some embodiments, the alkylene moiety of R5is C2-C3alkylene. In some embodiments, the alkylene moiety of R5is Cs-C6alkylene. In some embodiments, the alkylene moiety of R5is Cs-Csalkylene. In some embodiments, the alkylene moiety of R5is C3-C4alkylene. In some embodiments, the alkylene moiety of R5is C4-C6alkylene. In some embodiments, the alkylene moiety of R5is C4- Csalkylene. In some embodiments, the alkylene moiety of R5is Cs-C6alkylene. In some embodiments, R5is selected from -CH2-, -CH(CH3)-, and -CH2CH2-, including any member, combination, or subset thereof.

[0134] In some embodiments, the alkylene moiety of R5is selected from alkylene, deuteroalkylene, haloalkylene, and deuterohaloalkylene, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkylene moiety of R5are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkylene moiety of R5are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkylene moiety of R5are replaced with a halogen atom and none of the available hydrogen atoms of the alkylene moiety of R5are replaced with a deuterium atom. In some embodiments, the alkylene moiety of R5is unsubstituted. In some embodiments, the alkylene moiety of R5is substituted.

[0135] In some embodiments, R5includes a cycloalkylene moiety (e.g., of optionally substituted Cs-Cecycloalkylene). In some embodiments, the cycloalkylene moiety of R5is Cs-C6alkylene. In some embodiments, the cylcoalkylene moiety of R5is Cs-Csalkylene. In some embodiments, the cycloalkylene moiety of R5is C3-C4alkylene. In some embodiments, the cycloalkylene moiety of R5is Czi-C6alkylene. In some embodiments, the cycloalkylene moiety of R5is C4-C5alkylene. In some embodiments, the cycloalkylene moiety of R5is Cs-C6alkylene. In some embodiments, the

[0136] In some embodiments, the cycloalkylene moiety of R5is selected from cycloalkylene, deuterocycloalkylene, halocycloalkylene, and deuterohalocycloalkylene, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the cycloalkylene moiety of R5are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the cycloalkylene moiety of R5are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the cycloalkylene moiety of R5are replaced with a halogen atom and none of the available hydrogen atoms of the cycloalkylene moiety of R5are replaced with a deuterium atom. In some embodiments, the cycloalkylene moiety of R5is unsubstituted. In some embodiments, the alkylene moiety of R5is substituted.

[0137] In some embodiments, the alkyl moieties of R5(e.g., of optionally substituted CH(C1-

[0138] In some embodiments, the alkyl moieties of R5have one or more available hydrogen atoms independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms replaced with one or more deuterium atoms. In some embodiments, the alkyl moieties of R5are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of alkyl moieties of R5are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R5are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R5are replaced with a halogen atom and none of the available hydrogenatoms of the alkyl moieties of R5are replaced with a deuterium atom. In some embodiments, the alkyl moieties of R5are independently unsubstituted. In some embodiments, the alkyl moieties of R5are independently substituted.

[0139] In some embodiments, R5is selected from CH(alkyl), CH(deuteroalkyl), CH(haloalkyl), and CH(deuterohaloalkyl), including any member, combination, or subset thereof. In some embodiments, R5is CH(alkyl), wherein no available hydrogen atoms are replaced with a halogen. In some embodiments, R5is CH(alkyl), wherein no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is CH(alkyl), wherein no available hydrogen atoms are replaced with a halogen and no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is unsubstituted CH(alkyl). In some embodiments, R5is substituted CH(alkyl).

[0140] In some embodiments, R5is selected from CH(OH) (i.e.,) and optionally

[0141] In some embodiments, R5is selected from CH(SH) (i.e.) and optionally substituted CH(SC1-C4alkyl). In some embodiments, R5is selected from CH(SC1-C4alkyl),available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is unsubstituted CH(SC1-C4alkyl). In some embodiments, R5is substituted CH(SC1-C4alkyl). In some embodiments, R5is -CH(SCH3)-.

[0142] In some embodiments, R5is selected from CH(NH2) (i.e.,) and optionally substituted CH(NH(C1-C4alkyl)). In some embodiments, R5is selected from CH(NH(C1-C4alkyl)), CH(NH(C1-C4deuteroalkyl)), CH(NH(C1-C4haloalkyl)), and CH(NH(C1-C4deuterohaloalkyl)), including any member, combination, or subset thereof. In some embodiments, R5is selected from CH(NH2) and CH(NH(C1-C4alkyl)), wherein no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is selected from CH(NH2) and CH(NH(C1-C4alkyl)), wherein no available hydrogen atoms are replaced with a halogen. In some embodiments, R5is selected from CH(NH2) and CH(NH(C1-C4alkyl)), wherein no available hydrogen atoms are replaced with a halogen and no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is unsubstituted CH(NH(C1-C4alkyl)). In some embodiments, R5is substituted CH(NH(C1-C4alkyl)).

[0143] In some embodiments, R5is optionally substituted CH(N(C1-C4alkyl)2). In some embodiments, R5is selected from CH(N(C1-C4alkyl)2), CH(N(C1-C4deuteroalkyl)2), CH(N(C1- C4haloalkyl)2), and CH(N(C1-C4deuterohaloalkyl)2), including any member, combination, or subset thereof. In some embodiments, R5is CH(N(C1-C4alkyl)2), wherein no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is CH(N(C1-C4alkyl)2), wherein no available hydrogen atoms are replaced with a halogen. In some embodiments, R5is CH(N(C1- C4alkyl)2), wherein no available hydrogen atoms are replaced with a halogen and no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is unsubstituted CH(N(C1-C4alkyl)2). In some embodiments, R5is substituted CH(N(C1-C4alkyl)2).

[0144] In some embodiments, R5is optionally substituted Cs-Cscycloalkylene. In some embodiments, R5is selected from Cs-Cecycloalkylene, Cs-C6deuterocycloalkylene, C3- C6h alocycloalkylene, and Cs-C6deuterohalocycloalkylene, including any member, combination, or subset thereof. In some embodiments, R5is Cs-Cecycloalkylene, wherein no available hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is Cs-Cecycloalkylene, wherein no available hydrogen atoms are replaced with a halogen. In some embodiments, R5is Cs-Cscycloalkylene, wherein no available hydrogen atoms are replaced with a halogen and noavailable hydrogen atoms are replaced with a deuterium atom. In some embodiments, R5is unsubstituted Cs-Cecycloalkylene. In some embodiments, R5is substituted Cs-Cecycloalkylene.

[0145] In some embodiments, the alkylene (e.g., of optionally substituted C1-C6alkylene) and cycloalkylene (e.g., of optionally substituted C3-C6cycloalkylene) moieties of R5are substituted with one or more members independently selected from C1-Csalkyl, OC1-Csalkyl, and SC1-Csalkyl, including any member, combination, or subset thereof.

[0146] In some embodiments, R5includes at least one deuterium atom. In some embodiments, R5includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of R5are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of R5are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of R5are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of R5are replaced with a deuterium atom. In some embodiments, noneof the available hydrogen atoms of R5are replaced with a halogen atom and none of the available hydrogen atoms of R5are replaced with a deuterium atom.

[0147] In some embodiments, Q is selected from:H (R8)or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof, including the enantiomers:wherein Y, X1, X2, R1, R2, R3, R4, R5, R6, R14, and m are as defined (and provisos and exclusions provided for) herein.

[0149] In some embodiments, the compound has the structure of Formula (l)-A, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl group o shaving a structure , and a thionyl group having a structureeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; m is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1and X2are independently selected from O and S, Y is CR14, R1is CH3, R2is selected from CH3 and CH2CH3, R4is selected from H and halo, R5is selected from CH2and C(OH), R14is selected from H and halo, and m is 0, then R3is not selected from C1-C4alkyl, OC1- C3alkyl, SCH3, S(O)2CH3,CH2OCH3,N(CH3)2Iand CHF2; and provided when X1is O, X2is O, Y is CR14, R1and R2are eachH, and m is 0, then R3is not selected from CH3, CH2CH3, and OCH3.

[0150] In some embodiments, the compound of Formula (l)-A is as defined above, further provided: (1 ) when X1and X2are independently selected from O and S, Y is CR14, R1and R2are independently C1-C6alkyl, R4is selected from H, D, and halo, R5is selected from CH2and C(OH),R14is selected from H, D, and halo, and m is 0, then R3is not selected from C1-Caalkyl, OC1-Csalkyl, SC1-Csalkyl, S(O)2C1-C8alkyl, CH2OC1-C8alkyl, N(C1-C8alkyl)2, and C1-C8fluoroalkyl; and(2) when X1is O, X2is O, Y is CR14, R1and R2are independently C1-C6alkyl, R5is, R4is selected from H and D, R14is selected from H and D, and m is 0, then R3is not selected from C1- Caalkyl and OC1-Caalkyl.

[0151] In some embodiments, the compound has the structure of Formula (l)-A, wherein:Y is CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2 linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted Cz-C6alkenyl, and optionally substituted Cz-C6alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupJ having a structure , and a thionyl group having a structureeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, X2, and R14; m is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, and m is 0, then R3is not CH3 or OCH3.

[0152] In some embodiments, the compound has the structure of Formula (I )-A, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl group having a structure and a thionyl group having a structureeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; m is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0153] In some embodiments, the compound has the structure of Formula (I )-A, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl group having a structure and a thionyl group having a structureeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; m is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is selected from O and S, Y is CR14, R4is selected from H and Br, R5is CH2, R14is H, and m is 0, then R1is optionally substituted alCky2-lC.6

[0154] In some embodiments, Formula (l)-A is as defined in the immediately preceding embodiment, provided when X1is O, X2is selected from O and S, Y is CR14, R4is selected from H, D and halo, R5is CH2, R14is selected from H and D, and m is 0, then R1is optionally substituted C2-C6alkyl.

[0155] In some embodiments, the compound has the structure of Formula (l)-A, wherein X1is selected from O and S, X2is S, Y is CR14, R1is Ch3, R2is CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2, R3is S, R4is H, R5is CH2, R14is H, and m is 0.

[0156] In some embodiments, each R6is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0157] In some embodiments, the alkyl moieties of R6(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R6are independently C1-Csalkyl. In some embodiments, the alkyl moieties of R6are independently C1- C4alkyl. In some embodiments, the alkyl moieties of R6are independently C1-C3alkyl. In some embodiments, the alkyl moieties of R6are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R6are independently C2-aClk6yl. In some embodiments, the alkyl moieties of R6are independently C2-C5alkyl. In some embodiments, the alkyl moieties of R6are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R6are independently C2-C3alkyl. In some embodiments, the alkyl moieties of R6are independently C3-C6alkyl. In some embodiments, thealkyl moieties of R6are independently Cs-Csalkyl. In some embodiments, the alkyl moieties of R6are independently C3-C4alkyl. In some embodiments, the alkyl moieties of R6are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R6are independently C4-Csalkyl. In some embodiments, the alkyl moieties of R6are independently Cs-C6alkyL In some embodiments, the alkyl moieties of R6are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0158] In some embodiments, the alkyl moieties of R6(e.g., C1-C6alkyl, OC1-C6alkyl, SCr C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R6are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R6are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R6are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R6are replaced with a deuterium atom.

[0159] In some embodiments, either or each R6is independently selected from CH3, CD2H, CDH2, CDs, CF2H, CFH2, CFS, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3 CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3 CH(CH3)2, CH(CF3)2, CH(CHF2)2, CH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2, C(CH3)3, C(CF3)3,C(CHF2)3, C(CFH2)3, C(CD3)3,C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R6is independently selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0160] In some embodiments, either or each R6is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3, OCH2CH3, OCD2CD3, OCF2CF3, OCH(CH3)2, OCH(CD3)2, OCH(CF3)2, OCD(CD3)2, OCF(CF3)2, OC(CH3)3, OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R6is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2, and OCD3, including any member, combination, or subset thereof.

[0161] In some embodiments, either or each R6is independently selected from SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0162] In some embodiments, either or each R6is independently unsubstituted. In some embodiments, either or each R6is independently substituted. In some embodiments, either or each R6is independently substituted with one or more members independently selected from halo, C1-C4alkyl, OCi-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0163] In some embodiments, either or each R6independently includes at least one deuterium atom. In some embodiments, either or each R6independently includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more halogen atoms (i.e. , F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R6are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atomsof either or each R6are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R6are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R6are replaced with a halogen atom and none of the available hydrogen atoms of either or each R6are replaced with a deuterium atom.

[0164] In some embodiments, m is selected from 0, 1 , and 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2.

[0165] In some embodiments, R1and / or R2are independently selected from CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof. In some embodiments, R3is selected from I, CH3, CHF2, CF3, CH2CH2CH3, CH2OCHF2,CH2OCH2CH2CH3, CH2SCH3, CH2SCH2CH2CH3, OCHF2, OCF3,SCHs, SCF3, NO2, and CN.

[0166] In some embodiments, R1is selected from CH3and CHF2, R2is selected from CH3, CHF2, and CF3, R3is selected from I, CH3, CHF2, CF3, CH2CH2CH3, CH2OCHF2, CH2OCH2CH2CH3, CHECKS, CH2SCH2CH2CH3, OCHF2IOCF3, SCHS, SCF3,NO2Iand CN, R4is H, R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupor a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R7, R14, and n are as defined (and provisos and exclusions provided for) herein.

[0168] In some embodiments in which the compound has the structure of Formula (l)-B:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OCr C8alkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R7is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;RU is selected from H, D, halo, and optionally substituted C1-C4alkyl; n is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0169] In some embodiments in which the compound has the structure of Formula (l)-B:Y is CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2 linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R7is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; n is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0170] In some embodiments in which the compound has the structure of Formula (l)-B:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted aClk2-yCn6yl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is selected from CH2, CH(halo), CH(CHs), CH(OH), CH(SH), CHtOCHs), a carbonyl groupeach R7is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; n is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0171] In some embodiments in which the compound has the structure of Formula (l)-B:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH),each R7is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; n is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0172] In some embodiments, each R7is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0173] In some embodiments, the alkyl moieties of R7(e.g., of C1-C6alkyl, OC1-C6alkyl, SCr C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R7are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R7are independently Cr C4alkyl. In some embodiments, the alkyl moieties of R7are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R7are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R7are independently C2-aClk6yl. In some embodiments, the alkyl moieties of R7are independently C2-Csalkyl. In some embodiments, the alkyl moieties of R7are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R7are independently C2-C3alkyl. In some embodiments, the alkyl moieties of R7are independently Cs-C6alkyl. In some embodiments, the alkyl moieties of R7are independently Cs-Csalkyl. In some embodiments, the alkyl moieties of R7are independently Cs-C4alkyl. In some embodiments, the alkyl moieties of R7are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R7are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R7are independently Cs-C6alkyL In some embodiments, the alkyl moieties of R7are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0174] In some embodiments, the alkyl moieties of R7(e.g., of C1-C6alkyl, OC1-C6alkyl, SCr C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R7are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R7are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R7are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R7are replaced with a deuterium atom.

[0175] In some embodiments, either or each R7is independently selected from CH3, CD2H, CDH2, CDS, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3JCF2CF3,CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2ICH(CHF2)2, CH(CFH2)2, CH(CD3)2ICH(CHD2)2, CH(CDH2)2, C(CH3)3,C(CF3)3, C(CHF2)3,C(CFH2)3, C(CD3)3,C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3JCH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3,CH2C(CF3)3JCH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R7is independently selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0176] In some embodiments, either or each R7is independently selected from OC1-C6alkyL In some embodiments, either or each R7is independently selected from Oalkyl, Odeuteroalkyl, Ohaloalkyl, Odeuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, either or each R7is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3, OCH2CH3, OCD2CD3,OCF2CF3, OCH(CH3)2, OCH(CD3)2JOCH(CF3)2, OCD(CD3)2, OCF(CF3)2, OC(Ch3)3, OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R7is independently selected from OCH2F, OCHF2IOCF3, OCH2D, OCHD2Iand OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R7is independently selected from SCr C6alkyl. In some embodiments, either or each R7is independently selected from S-alkyl, S- deuteroalkyl, S-haloalkyl, and S-deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, either or each R7is independently selected from non-halogenated non-deuterated SC1-C3alkyl. In some embodiments, either or each R7is independently selectedfrom SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0177] In some embodiments, either or each R7is independently unsubstituted. In some embodiments, either or each R7is independently substituted. In some embodiments, either or each R7is independently substituted with one or more members independently selected from halo, C1-C4alkyl, OCi-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0178] In some embodiments, either or each R7includes at least one deuterium atom. In some embodiments, either or each R7includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R7are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or eachR7are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R7are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R7are replaced with a halogen atom and none of the available hydrogen atoms of either or each R7are replaced with a deuterium atom.

[0179] In some embodiments, n is selected from 0, 1 , and 2. In some embodiments, n is 0. In some embodiments, n is 1 . In some embodiments, n is 2.

[0180] In some embodiments for Q2, R1is CH3, R2is CH3, R3is CH2OCHF2, R4is hydrogen, R5is CH2, and n is 0, wherein none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0181] In some embodiments, Q is selected as Q3 to provide a compound having the structure of Formula (l)-C:or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R8, R14, and o are as defined (and provisos and exclusions provided for) herein.

[0182] In some embodiments in which the compound has the structure of Formula (l)-C:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-Csalkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R8is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; o is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1and X2are independently selected from O and S, Y is CR14, R1is CH3, R2is selected from CH3and CH2CH3, R4is selected from H and halo, R5is selected from Ch2and C(OH), R14is selected from H and halo, and o is 0, then R3is not selected from C1-C4alkyl, OC1- C3alkyl, SCH3, S(O)2CH3, CH2OCH3, and N(CH3)2; and provided when X1is O, X2is O, Y is CR14, R1and R2are each CH3, R4is H, R5isH, and o is 0, then R3is not Ch3.

[0183] In some embodiments, the compound of Formula (l)-C is as defined above, further provided: (1 ) when X1and X2are independently selected from O and S, Y is CR14, R1and R2are independently C1-C6alkyl, R4is selected from H, D, and halo, R5is selected from CH2 and C(OH),R14is selected from H, D, and halo, and o is 0, then R3is not selected from C1-C8alkyl, OC1-Csalkyl, SCq-Caalkyl, S(O)2C1-C8alkyl, CFWC1-Cgalkyl, and N(C1-C8alkyl)2; and (2) when X1is O, X2is O, Y is CR14, R1and R2are independently C1-C6alkyl, R4is selected from H and D, R5is

[0184] In some embodiments in which the compound has the structure of Formula (l)-C:Y is CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C3alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R8is independently selected from optionally substituted C1-Cgalkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-Csalkyl;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; o is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms,provided when X1is 0, X2is O, R5is CH2, and o is 0, then R3is not selected from CH3 and OCH3.

[0185] In some embodiments in which the compound has the structure of Formula (l)-C:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- C8alkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C8alkenyl, and optionally substituted C2-C8alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R8is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C8alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; o is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0186] In some embodiments in which the compound has the structure of Formula (l)-C:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R® is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; o is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, Y is CR14, R4is selected from H and halo, R5is CH2, R14is H, and o is 0, then R1is not CH3.

[0187] Some embodiments include Formula (l)-C as defined in the immediately preceding embodiment, provided when X1is O, X2is O, Y is CR14, R4is selected from H, D, and halo, R5is CH2, R14is selected from H and D, and o is 0, then R1is not CH3.

[0188] In some embodiments, each R® is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0189] In some embodiments, the alkyl moieties of R® (e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R® are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R® are independently C1- C4alkyl. In some embodiments, the alkyl moieties of R® are independently C1-C3alkyl. In some embodiments, the alkyl moieties of R® are independently C1-C2alkyl. In some embodiments, thealkyl moieties of R8are independently C2-C6alkyl. In some embodiments, the alkyl moieties of R8are independently C2-C5alkyl. In some embodiments, the alkyl moieties of R8are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R8are independently C2-C3alkyl. In some embodiments, the alkyl moieties of R8are independently Cs-C6alkyL In some embodiments, the alkyl moieties of R8are independently Cs-CsalkyL In some embodiments, the alkyl moieties of R8are independently C3-C4alkyl. In some embodiments, the alkyl moieties of R8are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R8are independently C4-Csalkyl. In some embodiments, the alkyl moieties of R8are independently Cs-C6alkyl. In some embodiments, the alkyl moieties of R8are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0190] In some embodiments, the alkyl moieties of R8(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R8are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R8are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R8are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R8are replaced with a deuterium atom.

[0191] In some embodiments, either or each R8is independently selected from CH3, CD2H, CDH2, CD3,CF2H, CFH2, CF3,CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3,CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2ICH(CHF2)2, CH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2, C(CH3)3, C(CF3)3,C(CHF2)3, C(CFH2)3, C(CD3)3,C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3JCH2CH2CH2CD3, CH2CH(CH3)2ICH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R8is independently selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0192] In some embodiments, either or each R8is independently unsubstituted. In some embodiments, either or each R8is independently substituted. In some embodiments, either or each R8is independently substituted with one or more members independently selected fromhalo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0193] In some embodiments, either or each R8is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3, OCH2CH3, OCD2CD3, OCF2CF3, OCH(CH3)2, OCH(CD3)2, OCH(CF3)2, OCD(CD3)2, OCF(CF3)2IOC(CH3)3, OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R8is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2, and OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R8is independently selected from SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0194] In some embodiments, either or each R8includes at least one deuterium atom. In some embodiments, either or each R8includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R8are optionally and independently replaced with one or more iodine atoms and / or one or more availablehydrogen atoms of either or each R8are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or each R8are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R8are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R8are replaced with a halogen atom and none of the available hydrogen atoms of either or each R8are replaced with a deuterium atom.

[0195] In some embodiments, o is selected from 0, 1 , and 2. In some embodiments, o is 0. In some embodiments, o is 1. In some embodiments, o is 2.

[0196] In some embodiments, Q is selected as Q3, R1is CHs, R2is CHa or CHF2, R3is CF3, R4is hydrogen, R5is CH2, and 0 is 0, wherein none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0197] In some embodiments, Q is selected as Q4 to provide a compound having the structure of Formula (l)-D:or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R9, R14, and p are as defined (and provisos and exclusions provided for) herein.

[0198] In some embodiments, the compound has the structure of Formula (I )-D, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from H, D, and halo;R5is a direct bond; each R9is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; p is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, R1is C1-C2alkyl, R2is C1-C2alkyl, and R4is H, then R3is not selected from I, CN, fluoromethyl, C1-C4alkyl, OCHs, and SCHs.

[0199] In some embodiments, the compound has the structure of Formula (l)-D as defined in the immediately preceding embodiment, provided when X1is O, X2is O, R1is C1-C6alkyl, R2is C1-Cgalkyl, and R4is selected from H and D, then R3is not selected from I, CN, C1-Cgalkyl, C1- Csfluoroalkyl, OC1-C8alkyl, and SC1-CaalkyL

[0200] In some embodiments, the compound has the structure of Formula (l)-D, wherein:Y is selected from CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond; each R9is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; p is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, then R3is not selected from CN, NO2, and CH3.

[0201] In some embodiments, the compound has Formula (l)-D as defined in the immediately preceding embodiment, provided when X1is O, X2is O, then R3is not selected from CN, NO2, and C1-C8alkyl.

[0202] In some embodiments, the compound has the structure of Formula (l)-D, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionallysubstituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-Cgalkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond; each R9is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; p is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0203] In some embodiments, the compound has the structure of Formula (l)-D, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is a direct bond; each R9is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; p is selected from 0, 1 , and 2; andone or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, and R14is H, then R1is not CH3.

[0204] In some embodiments, each R9is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0205] In some embodiments, the alkyl moieties of R9(e.g., of C1-C6alkyl, OC1-C6alkyl, SCr C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R9are independently C1-Csalkyl. In some embodiments, the alkyl moieties of R9are independently C1- C4alkyl. In some embodiments, the alkyl moieties of R9are independently C1-C3alkyl. In some embodiments, the alkyl moieties of R9are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R9are independently C2-aClk6yl. In some embodiments, the alkyl moieties of R9are independently C2-Csalkyl. In some embodiments, the alkyl moieties of R9are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R9are independently C2-C3alkyl. In some embodiments, the alkyl moieties of R9are independently Cs-C6alkyl. In some embodiments, the alkyl moieties of R9are independently Cs-Csalkyl. In some embodiments, the alkyl moieties of R9are independently C3-C4alkyl. In some embodiments, the alkyl moieties of R9are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R9are independently C4-Csalkyl. In some embodiments, the alkyl moieties of R9are independently Cs-C6alkyl. In some embodiments, the alkyl moieties of R9are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0206] In some embodiments, the alkyl moieties of R9(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R9are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R9are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R9are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R9are replaced with a deuterium atom.

[0207] In some embodiments, either or each R9is independently selected from CH3, CD2H, CDH2, CD3, CF2H, CFH2, CF3, CH2CH3,CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3,CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2, CH(CHF2)2JCH(CFH2)2JCH(CD3)2, CH(CHD2)2, CH(CDH2)2, C(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3,C(CD3)3, C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3,CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2ICH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3,CH2C(CH3)3JCH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R9is independently selected from Ch3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0208] In some embodiments, either or each R9is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3, OCH2CH3, OCD2CD3JOCF2CF3, OCH(CH3)2IOCH(CD3)2IOCH(CF3)2IOCD(CD3)2, OCF(CF3)2, OC(CH3)3, OC(CD3)3,and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R9is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2Iand OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R9is independently selected from SCH2F, SCHF2, SCF3JSCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0209] In some embodiments, either or each R9is independently unsubstituted. In some embodiments, either or each R9is independently substituted. In some embodiments, either or each R9is independently substituted with one or more members independently selected from halo, Ci.C4alkyl, OCi-C4alkyl, and C(O)Ci.C4alkyl, including any member, combination, or subset thereof.

[0210] In some embodiments, either or each R9independently includes at least one deuterium atom. In some embodiments, either or each R9independently includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more halogen atoms (i.e., F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R9are optionallyand independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R9are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or each R9are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R9are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R9are replaced with a halogen atom and none of the available hydrogen atoms of either or each R9are replaced with a deuterium atom.

[0211] In some embodiments, p is selected from 0, 1 , and 2. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2.

[0212] In some embodiments, Q is Q4, R1is CHs, R2is CHs, R3is CH2OCHF2, R4is hydrogen, R5is CH2, and p is 0, wherein none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0213] In some embodiments, Q is selected as Q5 to provide a compound having the structure of Formula (l)-E:p )

[0214] In some embodiments, the compound has the structure of Formula (l)-D, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-Caalkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from H, D, and halo;R5is a direct bond; each R10is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; q is selected from 0, 1 , and 2;one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms; andprovided when R1is CH3, R2is C1-C2alkyl, R4is selected from H and halo, R14is selected from H and halo, and q is 0, then R3is not selected from CN, C1-C4alkyl, OC1-Csalkyl, SCH3, S(O)2CH3, CH2OCH3, and N(CH3)2; and provided when X1is selected from O and S, X2is O, Y is CR14, R1is selected from C1-C2alkyl and fluoromethyl, R2is selected from C1-C2alkyl, R4is H, R5is a direct bond, R10is CH3, R14is H, and q is 0, 1 , or 2, then R3is not selected from I, C1-C4alkyl, CF3, and CN.

[0215] In some embodiment, the compound has the structure of Formula (l)-E as described in the immediately preceding embodiment, provided: (1 ) when R1is C1-C6alkyl, R2is C1-C6alkyl, R4is selected from H, D, and halo, R is selected from H, D, and halo, and q is 0, then R3is not selected from CN, C1-Caalkyl, OC1-C6alkyl, SC1-C8alkyl, S(O)2C1-C8alkyl, C^OC1-C8alkyl, and N(C1-C8alkyl)2; and (2) provided when X1is selected from O and S, X2is O, Y is CR14, R1is selected from C1-C6alkyl and C1-C6fluoroalkyl, R2is selected from C1-C6alkyl, R4is selected from H and D, R5is a direct bond, R10is C1-C6alkyl, R14is selected from H and D, and q is 0, 1 , or 2, then R3is not selected from I, C1-C8alkyl, C1-Csfluoroalkyl, and CN.

[0216] In some embodiments, the compound has the structure of Formula (l)-E, wherein:Y is CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond; each R10is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; q is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, and q is 0, then R3is not selected from CHs, OCH3, and CN.

[0217] In some embodiments, the compound has the structure of Formula (l)-E as described in the immediately preceding embodiment, provided when X1is O, X2is O, and q is 0, then R3is not selected from C1-C8alkyl, OC1-C8alkyl, and CN.

[0218] In some embodiments, the compound has the structure of Formula (l)-E, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionallysubstituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-Cgalkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted aClk2y-Cny6l;R5is a direct bond; each R10is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; q is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0219] In some embodiments, the compound has the structure of Formula (l)-E, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is a direct bond; each R10is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; q is selected from 0, 1 , and 2; andone or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, Y is CR14, R14is H, and q is 0, then R1is optionally substituted Ca-Csalkyl.

[0220] In some embodiments, Q is selected as Q5 andprovide a compound having the structure of Formula (l)-E(i):or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R10, and q are as defined (and provisos and exclusions provided for) herein.

[0221] In some embodiments, Q is selected as Q5 andprovide a compound having the structure of Formula (l)-E(ii):or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R10, and q are as defined (and provisos and exclusions provided for) herein.

[0222] In some embodiments, each R10is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0223] In some embodiments, the alkyl moieties of R10(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R10are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R10are independently C1- C4alkyl. In some embodiments, the alkyl moieties of R10are independently C1-C3alkyl. In some embodiments, the alkyl moieties of R10are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R10are independently C2-C6alkyl. In some embodiments, the alkyl moieties of R10are independently C2-Csalkyl. In some embodiments, the alkyl moieties of R10are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R10are independently C2- C3alkyl. In some embodiments, the alkyl moieties of R10are independently C3-C6alkyl. In some embodiments, the alkyl moieties of R10are independently C3-C6alkyl. In some embodiments, the alkyl moieties of R10are independently C3-C4alkyl. In some embodiments, the alkyl moieties of R10are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R10are independently C4-Csalkyl. In some embodiments, the alkyl moieties of R10are independently C5- C6alkyL In some embodiments, the alkyl moieties of R10are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0224] In some embodiments, the alkyl moieties of R10(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R10are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R10are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R10are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R10are replaced with a deuterium atom.

[0225] In some embodiments, either or each R10is independently selected from CH3, CD2H, CDH2, CD3, CF2H, CFH2, CF3,CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2, CH(CHF2)2, CH(CFH2)2ICH(CD3)2, CH(CHD2)2, CH(CDH2)2, C(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3, C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3,CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R10is independently selected from CHs, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0226] In some embodiments, either or each R10is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3, OCH2CH3, OCD2CD3, OCF2CF3, OCH(CH3)2, OCH(CD3)2, OCH(CF3)2, OCD(CD3)2, OCF(CF3)2IOC(CH3)3, OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R10is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2, and OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R10is independently selected from SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0227] In some embodiments, either or each R10is independently unsubstituted. In some embodiments, either or each R10is independently substituted. In some embodiments, either or each R10is independently substituted with one or more members independently selected from halo, C1-C4alkyl, OC1-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0228] In some embodiments, either or each R10independently includes at least one deuterium atom. In some embodiments, either or each R10independently includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more halogen atoms (i.e. , F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In someembodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R10are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or each R10are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R10are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R10are replaced with a halogen atom and none of the available hydrogen atoms of either or each R10are replaced with a deuterium atom.

[0229] In some embodiments, q is selected from 0, 1 , and 2. In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, q is 2.

[0230] In some embodiments, Q is selected as Q5 to provide a compound having the structure of Formula (l)-E, wherein R1is CHs, R2is CH3, R3is CH2OCHF2, R4is hydrogen, R5is a direct bond, and none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0231] In some embodiments, Q is selected as Q6 to provide a compound having the structure of Formula (l)-F:or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R11, R14, and r are as defined (and provisos and exclusions provided for) herein.

[0232] In some embodiments, the compound has the structure of Formula (l)-F, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C8alkyl;R2is optionally substituted C1-C8alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- C8alkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from H, D, and halo;each R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C8alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; r is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, Y is CR14, R1is Ch3, R2is Ch3, R4is H, R5is CH2CH2, R14is H, and r is 0, then R3is not Ch3.

[0233] In some embodiments, the compound has the structure of Formula (l)-F of the immediately preceding embodiment, provided when X1is O, X2is O, Y is CR14, R1is C1-C6alkyl, R2is C1-C6alkyl, R4is selected from H and D, R5is CH2CH2, R14is selected from H and D, and r is 0, then R3is not C1-C8alkyl.

[0234] In some embodiments, the compound has the structure of Formula (l)-F, wherein:Y is CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-Csalkenyl, and optionally substituted aClk2y-Cny6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;each R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; r is selected from 0, 1 , and 2; andone or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0235] In some embodiments, the compound has the structure of Formula (l)-F, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- C8alkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C8alkenyl, and optionally substituted C2-C8alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1; seach R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C8alkyl, and optionally substituted SC1-C8alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; r is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0236] In some embodiments, the compound has the structure of Formula (l)-F, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;each R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; r is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, R4is H, R5is CH2CH2, and R14is H, then R3is not O.

[0237] In some embodiments, each R11is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0238] In some embodiments, the alkyl moieties of R11(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- Csalkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R11are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R11are independently C1- C4alkyl. In some embodiments, the alkyl moieties of R11are independently C1-CsalkyL In someembodiments, the alkyl moieties of R11are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R11are independently C2-C6alkyl. In some embodiments, the alkyl moieties of R11are independently C2-Csalkyl. In some embodiments, the alkyl moieties of R11are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R11are independently C2- C3alkyl. In some embodiments, the alkyl moieties of R11are independently C3-C6alkyl. In some embodiments, the alkyl moieties of R11are independently Cs-Csalkyl. In some embodiments, the alkyl moieties of R11are independently C3-C4alkyl. In some embodiments, the alkyl moieties of R11are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R11are independently C^Csalkyl. In some embodiments, the alkyl moieties of R11are independently C5- C6alkyl. In some embodiments, the alkyl moieties of R11are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0239] In some embodiments, the alkyl moieties of R11(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R11are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R11are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R11are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R11are replaced with a deuterium atom.

[0240] In some embodiments, either or each R11is independently selected from CH3, CD2H, CDH2, CDS, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3 CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3 CH(CH3)2, CH(CF3)2, CH(CHF2)2, CH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2IC(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3, C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R11is independently selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0241] In some embodiments, either or each R11is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3,OCH2CH3, OCD2CD3, OCF2CF3, OCH(CH3)2, OCH(CD3)2,OCH(CF3)2, OCD(CD3)2, OCF(CF3)2, OC(CH3)3, OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R11is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2, and OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R11is OCHF2. In some embodiments, either or each R11is independently selected from SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof. In some embodiments, either or both R11is SCHF2.

[0242] In some embodiments, either or each R11is independently unsubstituted. In some embodiments, either or each R11is independently substituted. In some embodiments, either or each R11is independently substituted with one or more members independently selected from halo, C1-C4alkyl, OCi-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0243] In some embodiments, either or each R11independently includes at least one deuterium atom. In some embodiments, either or each R11independently includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more halogen atoms (i.e. , F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more bromine atoms and / or one or moreavailable hydrogen atoms of R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R11are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or each R11are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R11are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R11are replaced with a halogen atom and none of the available hydrogen atoms of either or each R11are replaced with a deuterium atom.

[0244] In some embodiments, r is selected from 0, 1 , and 2. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, r is 2.

[0245] In some embodiments, Q is selected as Q6, wherein to provide a compound having the structure of Formula (l)-F as defined above, wherein r is 1 , and R11is OCHF2 or SCHF2.

[0246] In some embodiments, Q is selected as Q6 to provide a compound having the structure of Formula (l)-F as defined above, wherein:Y is CR14;R1is CH3, or R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is CH3, or R2is selected from CH and CH2 linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from CF3, CH2OCH3, CH2OCF3, OCH3, and CH2SCF3;R4is hydrogen, or R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5- membered heterocyclic ring including R1, R4, and X1;R11is selected from OCHF2 and SCHF2; andR14is selected from H, D, halo, and optionally substituted C1-C4alkyl, or R14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, R14, and X2; none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0247] In some embodiments, Q is selected as Q6 to provide a compound having the structure of Formula (l)-F as defined above, wherein:Y is CR14;R1is CH3;R2is CH3, or R2is selected from CH and CH2 linked with R14and to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from CF3, CH2OCH3, CH2OCF3, OCH3, and CH2SCF3;R4is hydrogen;r is selected from 0 and 1 ;R11is selected from OCHF2 and SCHF2; andR14is selected from H, D, halo, and optionally substituted C1-C4alkyl, or R14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, R14, and X2; none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0248] In some embodiments, Q is selected as Q6 to provide a compound having the structure of Formula (l)-F as defined above, wherein:Y is CR14;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is CH3, or R2is selected from CH and CH2 linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from CF3, CH2OCH3, CH2OCF3, OCH3, and CH2SCF3;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;r is selected from 0 and 1 ;R11is selected from OCHF2 and SCHF2; andR14is selected from H, D, halo, and optionally substituted C1-C4alkyl, or R14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, R14, and X2; none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0249] In some embodiments, Q is selected as Q6 to provide a compound having the structure of Formula (l)-F as defined above, wherein:R1is CH3, or R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is CH3;R3is selected from CF3, CH2OCH3, CH2OCF3, OCH3, and CH2SCF3;R4is hydrogen, or R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5- membered heterocyclic ring including R1, R4, and X1;r is selected from 0 and 1 ;R11is selected from OCHF2 and SCHF2; andR14is selected from H, D, and halo; none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0250] In some embodiments, Q is selected as Q6 to provide a compound having the structure of Formula (l)-F as defined above, wherein:R1is CH3, or R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2 linked with R14and Y is CR14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from CF3, CH2OCH3, CH2OCF3, OCH3, and CH2SCF3;R4is hydrogen, or R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5- membered heterocyclic ring including R1, R4, and X1;r is selected from 0 and 1 ;R11is selected from OCHF2 and SCHF2; andR14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, R14, and X2; none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0251] In some embodiments, Q is selected as Q6, Y is CR14, R1is CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1with one double bond, R2is CH2 linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2with one double bond, and R5is CH2CH2.

[0252] In some embodiments, Q is selected as Q6, Y is CR14, R1is CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1with one double bond, R2is CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2with one double bond, r is 1 , and R11is OCHF2.

[0253] In some embodiments, including modifications of other Formula (l)-F embodiments described herein, Q is selected from Q6, and R5is an optionally substituted bivalent linking group. In some embodiments, the optionally substituted bivalent linking group is an optionally substituted bivalent cycloalkyl. In some embodiments, the optionally substituted bivalent cycloalkyl is selected

[0254] In some embodiments, Q is selected as Q7 to provide a compound having the structure of Formula (l)-G:or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; whereinY, X1, X2, R1, R2, R3, R4, R5, R12,R14, and s are as defined (and provisos and exclusions provided for) herein.

[0255] In some embodiments for Formula (I )-G, R5is absent to provide a direct bond.

[0256] In some embodiments, the compound has the structure of Formula (l)-G, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, ON, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted 02-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from H, D, and halo;R5is a direct bond; each R12is independently selected from optionally substituted C1-Csalkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-Cgalkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; s is selected from 0, 1, and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when R1is C1-C2alkyl, R2is C1-C2alkyl, R4is selected from H and halo, R14is selected from H and halo, and s is 0, then R3is not selected from C1-C4alkyl, OC1-Csalkyl, SCH3, S(O)2CH3, CH2OCH3, and N(CH3)2.

[0257] In some embodiments, the compound has the structure of Formula (l)-G of the immediately preceding embodiment, provided when R1is C1-C6alkyl, R2is C1-C6alkyl, R4is selected from H, D, and halo, R14is selected from H, D, and halo, and s is 0, then R3is not selected from C1-C8alkyl, OC1-C8alkyl, SC1-Csalkyl, S(O)2C1-C8alkyl, CFhOC1-C8alkyl, and N(C1- C8alkyl)2.

[0258] In some embodiments, the compound has the structure of Formula (l)-G, wherein:Y is selected from CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-Caalkyl)2, optionally substituted C2-aCl6kenyl, and optionally substituted C2-C6alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond;each R12is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; s is selected from 0, 1, and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, and s is 0, then R3is not selected from CH3 and OCH3.

[0259] In some embodiments, the compound has the structure of Formula (l)-G of the immediately preceding embodiment, provided when X1is O, X2is O, and s is 0, then R3is not selected from C1-C8alkyl and OC1-C8alkyl.

[0260] In some embodiments, the compound has the structure of Formula (l)-G, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, GN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-Csalkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted aClk2y-nCy6l;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond; each R12is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; s is selected from 0, 1, and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0261] In some embodiments, the compound has the structure of Formula (l)-G, wherein:Y is selected from CR14;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is selected from CH and CH2linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is a direct bond; each R12is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; s is selected from 0, 1, and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, R4is selected from H and halo, R14is H, and s is 0, then R1is not C1-C2alkyl.

[0262] In some embodiments, the compound has the structure of Formula (l)-G of the immediately preceding paragraph, provided when X1is O, X2is O, R4is selected from H, D, and halo, R14is selected from H and D, and s is 0, then R1is not C1-C2alkyl.

[0263] In some embodiments, Q is selected as Q7, andprovide a compound having the structure of Formula (l)-G(i):or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R3, R5, R12, R14, and s are as defined (and provisos and exclusions provided for) herein.

[0264] In some embodiments, Q is selected as Q7, and " is a double bond > to provide a compound having the structure of Formula (l)-G(ii):or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R3, R5, R12, R14, and s are as defined (and provisos and exclusions provided for) herein.

[0265] In some embodiments, each R12is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0266] In some embodiments, the alkyl moieties of R12(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R12are independently C1-Csalkyl. In some embodiments, the alkyl moieties of R12are independently Cr C4alkyl. In some embodiments, the alkyl moieties of R12are independently C1-CaalkyL In someembodiments, the alkyl moieties of R12are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R12are independently C2-C6alkyl. In some embodiments, the alkyl moieties of R12are independently C2-Csalkyl. In some embodiments, the alkyl moieties of R12are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R12are independently C2- C3alkyl. In some embodiments, the alkyl moieties of R12are independently C3-C6alkyl. In some embodiments, the alkyl moieties of R12are independently C3-C5alkyl. In some embodiments, the alkyl moieties of R12are independently C3-C4alkyl. In some embodiments, the alkyl moieties of R12are independently C4-C6alkyl. In some embodiments, the alkyl moieties of R12are independently C^Csalkyl. In some embodiments, the alkyl moieties of R12are independently C5- C6alkyl. In some embodiments, the alkyl moieties of R12are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0267] In some embodiments, the alkyl moieties of R12(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R12are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R12are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R12are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R12are replaced with a deuterium atom.

[0268] In some embodiments, either or each R12is independently selected from CH3, CD2H, CDH2, CDS, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3CH(CH3)2, CH(CF3)2, CH(CHF2)2, CH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2IC(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3, C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CFS)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R12is independently selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3,CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0269] In some embodiments, either or each R12is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3,OCH2CH3, OCD2CD3,OCF2CF3, OCH(CH3)2JOCH(CD3)2,OCH(CF3)2, OCD(CD3)2, OCF(CF3)2, OC(CH3)3, OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R12is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2, and OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R12is independently selected from SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0270] In some embodiments, either or each 12 is independently unsubstituted. In some embodiments, either or each R12is independently substituted. In some embodiments, either or each R12is independently substituted with one or more members independently selected from halo, C1-C4alkyl, OCi-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0271] In some embodiments, either or each R12independently includes at least one deuterium atom. In some embodiments, either or each R12independently includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more halogen atoms (i.e. , F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced withone or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R12are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or each R12are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R12are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R12are replaced with a halogen atom and none of the available hydrogen atoms of either or each R12are replaced with a deuterium atom.

[0272] In some embodiments, s is selected from 0, 1 , and 2. In some embodiments, s is 0. In some embodiments, s is 1. In some embodiments, s is 2.

[0273] In some embodiments, Q is selected as Q7 to provide a compound having the structure of Formula (l)-G as defined above, wherein R1is CHs, R2is CH3, R3is CH2OCHF2, R4is hydrogen, R5is a direct bond, t is 0, and none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0274] In some embodiments, Q is selected as Q8 to provide a compound having the structure of Formula (I )-H:or a stereoisomer, pharmaceutically acceptable salt, solvate, and / or prodrug thereof; wherein Y, X1, X2, R1, R2, R3, R4, R5, R13, R14, and t are as defined (and provisos and exclusions provided for) herein.

[0275] In some embodiments for Formula (I )-H, R5is absent to provide a direct bond.

[0276] In some embodiments, the compound has the structure of Formula (l)-H, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-Csalkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-Csalkenyl, and optionally substituted C2-Csalkynyl;R4is selected from H, D, and halo;R5is a direct bond; each R13is independently selected from optionally substituted C1-Csalkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; t is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when R1is C1-C2alkyl, R2is C1-C2alkyl, R4is selected from H and halo, R14is selected from H and halo, and t is 0, then R3is not selected from I, CN, C1-C4alkyl, OC1-C3alkyl, SCr C3alkyl, S(O)2CH3, CH2OCH3,and N(CH3)2; and provided when X1is selected from O and S, X2is 0, Y is CR14, R1is selected from C1-C2alkyl and fluoromethyl, R2is C1-C2alkyl, R4is H, R5is a direct bond, R13is Ch3, R14is H, and t is 0, 1 , or 2, then R3is not selected from I, C1-C4alkyl, CF3, and CN.

[0277] In some embodiments, the compound has the structure of Formula (l)-H according to the immediately preceding embodiment, provided: (1 ) when R1is C1-Csalkyl, R2is C1-Csalkyl, R4is selected from H, D, and halo, R14is selected from H, D, and halo, and t is 0, then R3is not selected from I, CN, C1-C8alkyl, OC1-C8alkyl, SC1-Csalkyl, S(O)2C1-C8alkyl, CH2OC1-C8alkyl, andN(C1-C8alkyl)2; and (2) when X1is selected from O and S, X2is O, Y is CR14, R1is selected from C1-C6alkyl and C1-Cefluoroalkyl, R2is Ci -C6a Iky I, R4is selected from H and D, R5is a direct bond, R13is CH3, R14is selected from H and D, and t is 0, 1 , or 2, then R3is not selected from I, CrCsalkyl, C1-C8fluoroalkyl, and CN.

[0278] In some embodiments, the compound has the structure of Formula (l)-H, wherein:Y is selected from CR14;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is selected from CH and CH2linked with R14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CaalkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-Caalkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted C2-C6alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond;R14is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R14, and X2; each R13is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-Csalkyl; t is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, and t is 0, then R3is not selected from CH3 and OCH3.

[0279] In some embodiments, the compound has the structure of Formula (l)-H, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is selected from CH and CH2 linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C8alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C8alkenyl, and optionally substituted C2-C8alkynyl;R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is a direct bond; each R13is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14 is selected from H, D, halo, and optionally substituted C1-C4alkyl; t is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0280] In some embodiments, the compound has the structure of Formula (l)-H, wherein:Y is selected from CR14;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C8alkyl;R2is selected from CH and CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2;R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo;R5is a direct bond; each R13is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; t is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, R4is selected from H and halo, R14is H, and t is 0, then R1is not C1-C2alkyl.

[0281] In some embodiments, the compound has the structure of Formula (l)-H of the immediately preceding embodiment, provided when X1is O, X2is O, R4is selected from H, D, and halo, R14is selected from H and D, and t is 0, then R1is not C1-Czalkyl.

[0282] In some embodiments, each R13is independently selected from C1-C6alkyl, OC1-C6alkyl, and SC1-C6alkyl, including any member, combination, or subset thereof.

[0283] In some embodiments, the alkyl moieties of R13(e.g., of C1-C6alkyl, OC1-C6alkyl, SCr C6alkyl) are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R13are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R13are independently Cr C4alkyl. In some embodiments, the alkyl moieties of R13are independently C1-C6alkyl. In some embodiments, the alkyl moieties of R13are independently C1-C2alkyl. In some embodiments, the alkyl moieties of R13are independently C2-C6alkyl. In some embodiments, the alkyl moieties of R13are independently C2-C6alkyl. In some embodiments, the alkyl moieties of R13are independently C2-C4alkyl. In some embodiments, the alkyl moieties of R13are independently C2- CsalkyL In some embodiments, the alkyl moieties of R13are independently Ce-C6alkyL In some embodiments, the alkyl moieties of R13are independently Ce-C6alkyL In some embodiments, the alkyl moieties of R13are independently Ce-C4alkyl. In some embodiments, the alkyl moieties ofR13are independently C^C6alkyl. In some embodiments, the alkyl moieties of R13are independently C^Csalkyl. In some embodiments, the alkyl moieties of R13are independently C5- C6alkyL In some embodiments, the alkyl moieties of R13are independently selected from methyl, ethyl, isopropyl, and tert-butyl, including any member, combination, or subset thereof.

[0284] In some embodiments, the alkyl moieties of R13(e.g., of C1-C6alkyl, OC1-C6alkyl, SC1- C6alkyl) are independently selected from alkyl, deuteroalkyl, haloalkyl, and deuterohaloalkyl, including any member, combination, or subset thereof. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R13are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R13are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of the alkyl moieties of R13are replaced with a halogen atom and none of the available hydrogen atoms of the alkyl moieties of R13are replaced with a deuterium atom.

[0285] In some embodiments, either or each R13is independently selected from CH3, CD2H, CDH2, CD3, CF2H, CFH2, CF3, CH2CH3, CH2CH2F, CH2CF2H, CH2CF3, CF2CF3, CH2CH2D, CH2CD2H, CH2CD3CD2CD3, CH2CH2CH3, CH2CH2CHF2, CH2CH2CFH2, CH2CH2CF3, CH2CH2CHD2, CH2CH2CDH2, CH2CH2CD3 CH(CH3)2, CH(CF3)2, CH(CHF2)2, CH(CFH2)2, CH(CD3)2, CH(CHD2)2, CH(CDH2)2IC(CH3)3, C(CF3)3, C(CHF2)3, C(CFH2)3, C(CD3)3, C(CHD2)3, C(CDH2)3, CH2CH2CH2CH3, CH2CH2CH2CF3, CH2CH2CH2CD3, CH2CH(CH3)2, CH2CH(CD3)2, CH2CH(CF3)2, CH(CH3)CH2CH3, CH(CH3)CH2CF3, CH(CH3)CH2CD3, CH2CH(CH3)CH3, CH2CH(CH3)CF3, CH2CH(CH3)CD3, CH2C(CH3)3, CH2C(CF3)3, CH2C(CD3)3, CH2CH2C(CH3)3, CH2CH2C(CF3)3, and CH2CH2C(CD3)3, including any member, combination, or subset thereof. In some embodiments, either or each R13is independently selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3, CHDF, CD2F, and CDF2, including any member, combination, or subset thereof.

[0286] In some embodiments, either or each R13is independently selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3,OCH2CH3, OCD2CD3, OCF2CF3, OCH(CH3)2, OCH(CD3)2, OCH(CF3)2, OCD(CD3)2, OCF(CF3)2, OC(CH3)3,OC(CD3)3, and OC(CF3)3, including any member, combination, or subset thereof. In some embodiments, either or each R13is independently selected from OCH2F, OCHF2, OCF3, OCH2D, OCHD2, and OCD3, including any member, combination, or subset thereof. In some embodiments, either or each R13is independently selected from SCH2F, SCHF2, SCF3, SCH2D, SCHD2, and SCD3, including any member, combination, or subset thereof.

[0287] In some embodiments, either or each R13is independently unsubstituted. In some embodiments, either or each R13is independently substituted. In some embodiments, either or each R13is independently substituted with one or more members independently selected from halo, C1-C4alkyl, OCi-C4alkyl, and C(O)C1-C4alkyl, including any member, combination, or subset thereof.

[0288] In some embodiments, either or each R13independently includes at least one deuterium atom. In some embodiments, either or each R13independently includes at least one halogen atom. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more halogen atoms (i.e. , F, Cl, Br, and / or I) and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more fluorine atoms, one or more chlorine atoms, and / or one or more bromine atoms, and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more fluorine atoms and / or one or more chlorine atoms, and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more chlorine atoms and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more bromine atoms and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more iodine atoms and / or one or more available hydrogen atoms of either or each R13are optionally and independently replaced with one or more deuterium atoms. In some embodiments, none of the available hydrogen atoms of either or each R13are replaced with a halogen atom. In some embodiments, none of the available hydrogen atoms of either or each R13are replaced with a deuterium atom. In some embodiments, none of the available hydrogen atoms of either or each R13are replacedwith a halogen atom and none of the available hydrogen atoms of either or each R13are replaced with a deuterium atom.

[0289] In some embodiments, t is selected from 0, 1 , and 2. In some embodiments, t is 0. In some embodiments, t is 1. In some embodiments, t is 2.

[0290] In some embodiments, Q is selected as Q8 to provide a compound having the structure of Formula (l)-H as defined above (and provisos and exclusions provided for), wherein R5is absent to provide a direct bond.

[0291] In some embodiments, Q is selected as Q8 to provide a compound having the structure of Formula (l)-H as defined above (and provisos and exclusions provided for), wherein R1is CHs, R2is CH3, R3is CH2OCHF2, R4is hydrogen, R5is a direct bond, t is 0, and none of the hydrogen atoms are optionally and independently replaced with one or more halogen atoms and none of the available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0292] In some embodiments, the compound is selected from one or more of the following compounds of Table 1 below.

[0293] Table 1

[0294] In some embodiments, the compound is selected from one or more of the following compound of Table 2 below.

[0295] Table 2or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

[0296] In some embodiments, the compound is selected from one or more of the following compounds of Table 3 below.

[0297] Table sor a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

[0298] IUPAC names were generated with CHEMDRAW Professional 22.2.0 64-bit.

[0299] Some embodiments relate to pharmaceutically acceptable salts, solvates, and / or prodrugs of compounds disclosed herein.

[0300] In some embodiments, the pharmaceutically acceptable salt is an acid addition salt or a base addition salt. The selection of a suitable salt may be made by a person skilled in the art.Suitable salts include acid addition salts that may, for example, be formed by mixing a solution of a compound with a solution of a pharmaceutically acceptable acid, such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, or benzoic acid. Additionally, acids that are generally considered suitable for the formation of pharmaceutically useful salts from basic pharmaceutical compounds are discussed, for example, by P. Stahl et aL, Camille G. (eds.) and Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley VCH; S. Berge et al., Journal of Pharmaceutical Sciences 1977 66(1 ) 1 -19; P. Gould, International J. of Pharmaceutics (1986) 33201-217; Anderson et al., The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food and Drug Administration, Washington, D.C. on their website).

[0301] An acid addition salt suitable for, or compatible with, the treatment of subjects is any non-toxic organic or inorganic acid addition salt of any basic compound. Basic compounds that form an acid addition salt include, for example, compounds comprising an amine group. Illustrative inorganic acids which form suitable salts include hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acids, as well as acidic metal salts, such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate. Illustrative organic acids which form suitable salts include mono-, di-, and tricarboxylic acids. Illustrative of such organic acids are, for example, acetic, trifluoroacetic, propionic, glycolic, lactic, pyruvic, malonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, benzoic, hydroxybenzoic, phenylacetic, cinnamic, mandelic, salicylic, 2-phenoxybenzoic, p-toluenesulfonic acid, and other sulfonic acids, such as methanesulfonic acid, ethanesulfonic acid, and 2-hydroxyethanesulfonic acid. In some embodiments, exemplary acid addition salts also include acetates, ascorbates, besylates, gentisates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates, camphorsulfonates, fumarates, hydrochlorides, hydrobromides, hydroiodides, lactates, maleates, methanesulfonates (“mesylates”), naphthalenesulfonates, nitrates, oxalates, phosphates, propionates, salicylates, succinates, sulfates, tartarates, thiocyanates, toluenesulfonates (also known as tosylates), and the like. In some embodiments, the mono- or di-acid salts are formed and such salts exist in either a hydrated, solvated, or substantially anhydrous form. In general, acid addition salts are more soluble in water and various hydrophilic organic solvents and generally demonstrate higher melting points in comparison to their free base forms. The selection criteria for the appropriate salt will be known to one skilled in the art. Other non -pharmaceutically acceptable salts, such as, but not limited to, oxalates may be used, for example in the isolation of compounds of the disclosure for laboratory use, or for subsequent conversion to a pharmaceutically acceptable acid addition salt.

[0302] A base addition salt suitable for, or compatible with, the treatment of subjects is any nontoxic organic or inorganic base addition salt of any acidic compound. Acidic compounds that form a basic addition salt include, for example, compounds comprising a carboxylic acid group. Illustrative inorganic bases which form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide as well as ammonia. Illustrative organic bases which form suitable salts include aliphatic, alicyclic, or aromatic organic amines, such as isopropylamine, methylamine, trimethylamine, picoline, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. The selection of the appropriate salt may be useful, for example, so that an ester functionality, if any, elsewhere in a compound is not hydrolyzed. The selection criteria for the appropriate salt will be known to one skilled in the art. In some embodiments, exemplary basic salts also include ammonium salts, alkali metal salts, such as sodium, lithium, and potassium salts, alkaline earth metal salts, such as calcium and magnesium salts, salts with organic bases (for example, organic amines), such as dicyclohexylamine, butyl amine, choline, and salts with amino acids, such as arginine, lysine, and the like. Basic nitrogen containing groups may be quartemized with agents, such as lower alkyl halides (e.g., methyl, ethyl, and butyl chlorides, bromides, and iodides), dialkyl sulfates (e.g., dimethyl, diethyl, and dibutyl sulfates), long chain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides, and iodides), aralkyl halides (e.g., benzyl and phenethyl bromides), and others. Compounds carrying an acidic moiety can be mixed with suitable pharmaceutically acceptable salts to provide, for example, alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., calcium or magnesium salts), and salts formed with suitable organic ligands, such as quaternary ammonium salts. Also, in the case of an acid (-COOH) or alcohol group being present, pharmaceutically acceptable esters can be employed to modify the solubility or hydrolysis characteristics of the compound.

[0303] All such acid salts and base salts are intended to be pharmaceutically acceptable salts within the scope of the disclosure and all acid and base salts are considered equivalent to the free forms of the corresponding compounds for purposes of the disclosure. In addition, when a compound of the disclosure contains both a basic moiety, such as, but not limited to, an aliphatic primary, secondary, tertiary, or cyclic amine, an aromatic or heteroaryl amine, pyridine, or imidazole and an acidic moiety, such as, but not limited to, tetrazole or carboxylic acid, zwitterions(“inner salts”) may be formed and are included within the terms “salt(s),” as used herein. It is understood that certain compounds of the disclosure may exist in zwitterionic form, having both anionic and cationic centers within the same compound and a net neutral charge. Such zwitterions are included within the disclosure.

[0304] Solvates of compounds of the disclosure include, for example, those made with solvents that are pharmaceutically acceptable. Examples of such solvents include water (resulting solvate is called a hydrate) and ethanol and the like. Suitable solvents are physiologically tolerable at the dosage administered.

[0305] Prodrugs of the compounds of the present disclosure include, for example, conventional esters formed with available hydroxy, thiol, amino, or carboxyl groups. Some common esters which have been utilized as prodrugs are phenyl esters, aliphatic (C1-C24) esters, acyloxymethyl esters, carbamates, and amino acid esters.

[0306] It is understood and appreciated that in some embodiments, compounds of the present disclosure may have at least one chiral center and therefore can exist as enantiomers and / or diastereomers. It is to be understood that all such isomers and mixtures thereof in any proportion are encompassed within the scope of the present disclosure. It is to be further understood that while the stereochemistry of the compounds may be as shown in any given compound listed herein, such compounds may also contain certain amounts (for example, less than 20%, suitably less than 10%, more suitably less than 5%) of compounds of the present disclosure having an alternate stereochemistry. It is intended that any optical isomers, as separated, pure, or partially purified optical isomers or racemic mixtures thereof are included within the scope of the present disclosure.

[0307] In some embodiments, the compounds of the present disclosure can also include tautomeric forms. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. It is intended that any tautomeric forms which the compounds form, as well as mixtures thereof, are included within the scope of the present disclosure.

[0308] The compounds of the present disclosure may further exist in varying amorphous and polymorphic forms and it is contemplated that any amorphous forms, polymorphs, or mixtures thereof, which form are included within the scope of the present disclosure.

[0309] In the compounds of general Formula (I) and pharmaceutically acceptable salts, solvates, and / or prodrugs thereof, the atoms may exhibit their natural isotopic abundances, or one or more of the atoms may be artificially enriched in a particular isotope having the sameatomic number, but an atomic mass or mass number different from the atomic mass or mass number predominantly found in nature. The present disclosure is meant to include all suitable isotopic variations of the compounds of the disclosure and pharmaceutically acceptable salts, solvates, and / or prodrugs thereof. For example, different isotopic forms of hydrogen (H) include protium (1 H), deuterium (2H), and tritium (3H). Protium is the predominant hydrogen isotope found in nature.

[0310] The compounds of the present disclosure may further be radiolabeled and accordingly all radiolabeled versions of the compounds of the disclosure are included within the scope of the present disclosure. Therefore, the compounds of the disclosure also include those in which one or more radioactive atoms are incorporated within their structure.III. Compositions

[0311] The compounds of the present disclosure are suitably formulated in a conventional manner into compositions using one or more carriers. Accordingly, the present disclosure also includes a composition comprising one or more compounds of the disclosure and a carrier. The compounds of the disclosure are suitably formulated into pharmaceutical compositions for administration to subjects in a biologically compatible form suitable for administration in vivo. Accordingly, the present disclosure further includes a pharmaceutical composition comprising one or more compounds of the disclosure and a pharmaceutically acceptable carrier. In embodiments of the disclosure the pharmaceutical compositions are used in the treatment of any of the diseases, disorders, or conditions described herein.

[0312] In embodiments, compounds and / or compositions of the disclosure are administered to a subject in one or more of a variety of forms depending on the selected route of administration, as will be understood by those skilled in the art. For example, a compound and / or composition of the disclosure is administered by oral, inhalation, parenteral, buccal, sublingual, insufflation, epidurally, nasal, rectal, vaginal, patch, pump, minipump, topical, or transdermal administration and the pharmaceutical compositions formulated accordingly. In some embodiments, administration is by means of a pump for periodic or continuous delivery. Conventional procedures and ingredients for the selection and preparation of suitable compositions are described, for example, in Remington's Pharmaceutical Sciences (2000 - 20th edition) and in The United States Pharmacopeia: The National Formulary (USP 24 NF19) published in 1999.

[0313] Parenteral administration includes systemic delivery routes other than the gastrointestinal (Gl) tract and includes, for example intravenous, intra-arterial, intraperitoneal,subcutaneous, intramuscular, transepithelial, nasal, intrapulmonary (for example, by use of an aerosol), intrathecal, rectal, and topical (including the use of a patch or other tran6dermal delivery device) modes of administration. Parenteral administration may be by continuous infusion over a selected period of time.

[0314] In some embodiments, a compound and / or composition of the disclosure is orally administered, for example, with an inert diluent or with an assimilable edible carrier, or it is enclosed in hard- or soft-shell gelatin capsules, or it is compressed into tablets, or it is incorporated directly with the food of the diet. In some embodiments, the compound and / or composition is incorporated with excipient(s) and used in the form of ingestible tablets, buccal tablets, troches, capsules, caplets, pellets, granules, lozenges, chewing gum, powders, syrups, elixirs, wafers, aqueous solutions, suspensions, and the like. In the case of tablets, carriers that are used include lactose, corn starch, sodium citrate, and salts of phosphoric acid. Pharmaceutically acceptable excipients include binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone, or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose, or calcium phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrants (e.g., potato starch or sodium starch glycolate); wetting agents (e.g., sodium lauryl sulphate); and / or solvents (e.g., medium chain triglycerides, ethanol, or water). In embodiments, the tablets are coated by methods well known in the art. In the case of tablets, capsules, caplets, pellets, or granules for oral administration, pH sensitive enteric coatings, such as Eudragits™, designed to control the release of active ingredients are optionally used. Oral dosage forms also include modified release, for example immediate release and timed-release, formulations. Examples of modified-release formulations include, for example, sustained-release (SR), extended-release (ER, XR, or XL), time-release or timed-release, controlled-release (CR), or continuous-release (CR or Contin), employed, for example, in the form of a coated tablet, an osmotic delivery device, a coated capsule, a microencapsulated microsphere, an agglomerated particle, e.g., as of molecular sieving type particles, or, a fine hollow permeable fiber bundle, or chopped hollow permeable fibers, agglomerated or held in a fibrous packet. Timed-release compositions are formulated, for example, as liposomes or those wherein the active compound is protected with differentially degradable coatings, such as by microencapsulation, multiple coatings, etc. Liposome delivery systems include, for example, small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. In some embodiments, liposomes are formed from a variety of phospholipids, such as cholesterol, stearylamine, or phosphatidylcholines. For oral administration in a capsule form, useful carriers, solvents, or diluents include lactose, medium chain triglycerides, ethanol, and dried corn starch.

[0315] In some embodiments, liquid preparations for oral administration take the form of, for example, solutions, syrups, or suspensions, or they are suitably presented as a dry product for constitution with water or other suitable vehicle before use. When aqueous suspensions and / or emulsions are administered orally, the compound of the disclosure is suitably suspended or dissolved in an oily phase that is combined with emulsifying and / or suspending agents. If desired, certain sweetening and / or flavoring and / or coloring agents are added. Such liquid preparations for oral administration are prepared by conventional means with pharmaceutically acceptable additives, such as suspending agents (e.g., sorbitol syrup, methyl cellulose, or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., medium chain triglycerides, almond oil, oily esters, or ethyl alcohol); and / or preservatives (e.g., methyl or propyl p-hydroxybenzoates or sorbic acid). Useful diluents include lactose and high molecular weight polyethylene glycols.

[0316] It is also possible to freeze-dry the compounds of the disclosure and use the lyophilizates obtained, for example, for the preparation of products for injection.

[0317] In some embodiments, a compound and / or composition of the disclosure is administered parenterally. For example, solutions of a compound of the disclosure are prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. In some embodiments, dispersions are prepared in glycerol, liquid polyethylene glycols, DMSO, and mixtures thereof with or without alcohol and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. A person skilled in the art would know how to prepare suitable formulations. For parenteral administration, sterile solutions of the compounds and / or compositions of the disclosure are usually prepared and the pH's of the solutions are suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled to render the preparation isotonic. For ocular administration, ointments, or droppable liquids are delivered, for example, by ocular delivery systems known to the art, such as applicators or eye droppers. In some embodiments, such compositions include mucomimetics, such as hyaluronic acid, chondroitin sulfate, hydroxypropyl methylcellulose, or polyvinyl alcohol, preservatives, such as sorbic acid, EDTA, or benzyl chromium chloride, and the usual quantities of diluents or carriers. For pulmonary administration, diluents or carriers may be selected to be appropriate to allow the formation of an aerosol.

[0318] In some embodiments, a compound and / or composition of the disclosure is formulated for parenteral administration by injection, including using conventional catheterization techniques or infusion. Formulations for injection are, for example, presented in unit dosage form, e.g., inampoules or in multi-dose containers, with an added preservative. In some embodiments, the compositions take such forms as sterile suspensions, solutions, or emulsions in oily or aqueous vehicles and contain formulating agents, such as suspending, stabilizing, and / or dispersing agents. In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. Alternatively, the compounds and / or compositions of the disclosure are suitably in a sterile powder form for reconstitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

[0319] In some embodiments, compositions for nasal administration are conveniently formulated as aerosols, drops, gels, and powders. For intranasal administration or administration by inhalation, the compounds of the disclosure are conveniently delivered in the form of a solution, dry powder formulation, or suspension from a pump spray container that is squeezed or pumped by the patient or as an aerosol spray presentation from a pressurized container or a nebulizer. Aerosol formulations typically comprise a solution or fine suspension of the active substance in a physiologically acceptable aqueous or non-aqueous solvent and are usually presented in single or multidose quantities in sterile form in a sealed container, which, for example, take the form of a cartridge or refill for use with an atomising device. Alternatively, the sealed container is a unitary dispensing device, such as a single dose nasal inhaler or an aerosol dispenser fitted with a metering valve which is intended for disposal after use. Where the dosage form comprises an aerosol dispenser, it may contain a propellant which is, for example, a compressed gas, such as compressed air, or an organic propellant, such as fluorochlorohydrocarbon. Suitable propellants include but aarree not limited to dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, heptafluoroalkanes, carbon dioxide, or another suitable gas. In the case of a pressurized aerosol, the dosage unit is suitably determined by providing a valve to deliver a metered amount. In some embodiments, the pressurized container or nebulizer contains a solution or suspension of the active compound. Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator are, for example, formulated containing a powder mix of a compound and / or composition of the disclosure and a suitable powder base, such as lactose or starch. The aerosol dosage forms can also take the form of a pump-atomizer.

[0320] Compositions suitable for buccal or sublingual administration include tablets, lozenges, and pastilles, wherein a compound of the disclosure is formulated with a carrier, such as sugar, acacia, tragacanth, or gelatin, and glycerin. Compositions for rectal administration are conveniently in the form of suppositories containing a conventional suppository base, such as cocoa butter.

[0321] Suppository forms of the compounds and / or compositions of the disclosure are useful for vaginal, urethral, and rectal administrations. Such suppositories may generally be constructed of a mixture of substances that is solid at room temperature but melts at body temperature. The substances commonly used to create such vehicles include but are not limited to theobroma oil (also known as cocoa butter), glycerinated gelatin, other glycerides, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights and fatty acid esters of polyethylene glycol. See, for example: Remington's Pharmaceutical Sciences, 16th Ed., Mack Publishing, Easton, PA, 1980, pp. 1530-1533 for further discussion of suppository dosage forms.

[0322] In some embodiments, a compound of the disclosure is coupled with soluble polymers as targetable drug carriers. Such polymers include, for example, polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxy-ethylaspartamide-phenol, or polyethyleneoxide-polylysine substituted with palmitoyl residues. Furthermore, in some embodiments, a compound of the disclosure is coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates, and crosslinked or amphipathic block copolymers of hydrogels.

[0323] A compound of the disclosure including pharmaceutically acceptable salts, solvates, and / or prodrugs thereof is suitably used on their own but may generally be administered in the form of a pharmaceutical composition in which the one or more compounds of the disclosure (the active ingredient) is in association with a pharmaceutically acceptable carrier. Depending on the mode of administration, the pharmaceutical composition may comprise from about 0.05 wt% to about 99 wt%, or about 0.10 wt% to about 70 wt%, of the active ingredient and from about 1 wt% to about 99.95 wt%, or about 30 wt% to about 99.90 wt% of a pharmaceutically acceptable carrier, all percentages by weight being based on the total composition.

[0324] In some embodiments, the compounds of the disclosure including pharmaceutically acceptable salts, solvates, and / or prodrugs thereof are used are administered in a composition comprising an additional therapeutic agent. Therefore, the present disclosure also includes a pharmaceutical composition comprising one or more compounds of the disclosure, or pharmaceutically acceptable salts, solvates, and / or prodrugs thereof and an additional therapeutic agent, and optionally one or more pharmaceutically acceptable excipients. In some embodiments, the additional therapeutic agent is another known agent useful for treatment of a disease, disorder, or condition, for example those listed in the Methods and Uses section below.

[0325] In the above, the term “a compound” also includes embodiments wherein one or more compounds are referenced.IV. Methods and Uses of the Disclosure

[0326] Compounds and / or compositions disclosed herein may be administered alone or in combination with other compounds and / or compositions to treat a wide range of disorders, diseases, and conditions that include, but are not limited to, depressive disorder, bipolar disorder, eating disorder, impulse control disorder, personality disorder, substance abuse disorder, behavioral addiction disorder, alcohol use disorder, post-traumatic stress disorder, anxiety disorder, stress disorder, neurodevelopmental disorder, pain disorder, headache disorder, inflammatory disorder, injury-related disorder, neurodegenerative disorder, functional disorder, psychotic disorder, hyperkinetic movement disorder, age-related macular degeneration, atherosclerosis, dissociative disorders, genetic brain disorders, hyperprolactinemia, hypersomnia, obesity, phobias, apathy disorders, burnout, and a combination thereof.

[0327] The compounds and / or compositions of the present disclosure are useful as medicaments. Accordingly, the disclosure also includes a compound and / or composition of the disclosure for use as, among other things, a medicament.

[0328] The present disclosure also includes a method of treating a disease, disorder, or condition by administering a therapeutically effective amount of one or more compounds and / or compositions of the disclosure to a subject in need thereof. The present disclosure also includes use of one or more compounds and / or compositions of the disclosure to manufacture a medicine or medicament that in a therapeutically effect amount treats a disease, disorder, or condition.

[0329] The present disclosure also includes use of one or more compounds and / or compositions of the disclosure for treatment of a disease, disorder, or condition as well as use of one or more compounds and / or compositions of the disclosure for the preparation and manufacture of a medicine or medicament for treatment of a disease, disorder, or condition.

[0330] In some embodiments, the compounds and / or compositions of the disclosure are useful for preventing, treating, and / or reducing the severity of a disease, disorder, and / or condition in a subject. Accordingly, the present disclosure also includes a method of preventing, treating, and / or reducing the severity of a disease, disorder, and / or condition comprising administering a therapeutically effective amount of one or more compounds and / or compositions of the disclosure to a subject in need thereof. The present disclosure also includes use of one or more compounds and / or compositions of the disclosure for treatment a disease, disorder, and / or condition, as wellas use of one or more compounds and / or compositions of the disclosure for the preparation of a medicament for preventing, treating, and / or reducing the severity of a disease, disorder, and / or condition in a subject.

[0331] Some embodiments disclosed herein are directed to a method of treating a depressive disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the depressive disorder is selected from major depressive disorder (MDD), MDD with suicidal ideation, persistent depressive disorder, dysthymia, dysthymic disorder, seasonal affective disorder, pre-menstrual dysphoric disorder, antenatal depression, postpartum depression, postnatal depression, treatment-resistant depression, depression related to a medical condition, depression in bipolar disorder, depression related to substance use, depression related to medicine use, psychotic depression, and a combination thereof.

[0332] Some embodiments disclosed herein are directed to a method of treating a bipolar disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the bipolar disorder is selected from Bipolar I disorder, Bipolar II disorder, cyclothymia, cyclothymic disorder, bi-polar related to a medicinal condition, and a combination thereof.

[0333] Some embodiments disclosed herein are directed to a method of treating an eating disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the eating disorder is selected from anorexia nervosa, bulimia nervosa, avoidant restrictive food intake disorder, other specified feeding and eating disorder, pica, rumination disorder, avoidant / restrictive food intake disorder, and a combination thereof.

[0334] Some embodiments disclosed herein are directed to a method of treating an impulsecontrol disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the impulse-control disorder is selected from binge-eating disorder, obsessive compulsive disorder, and a combination thereof.

[0335] Some embodiments disclosed herein are directed to a method of treating a personality disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the personality disorder is selected from avoidant personality disorder, dependent personalitydisorder, borderline personality disorder, histrionic personality disorder, narcissistic personality disorder, paranoid personality disorder, and a combination thereof.

[0336] Some embodiments disclosed herein are directed to a method of treating a substance use / abuse and / or behavioral addiction disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the substance abuse and / or behavioral addiction disorder is selected from alcohol use disorder, stimulant use disorder, cannabis use disorder, opioid use disorder, tobacco use disorder, nicotine use disorder, inhalant use disorder, sedative-hypnotic use disorder, anxiolytic use disorder, gambling disorder, gaming disorder, compulsive sexual behavior disorder, and a combination thereof.

[0337] Some embodiments disclosed herein are directed to a method of treating an anxiety and / or stress disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the anxiety disorder and / or the stress disorder is selected from acute stress disorder, adjustment disorder in chronic illness, body dysmorphic disorder, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, prolonged grief disorder, social anxiety disorder, agoraphobia, separation anxiety disorder, specific phobias, anxiety due to a medical condition, anxiety in advanced stage illness, selective mutism, and a combination thereof.

[0338] Some embodiments disclosed herein are directed to a method of treating a neurodevelopmental disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the neurodevelopmental disorder is selected from attention deficit hyperactivity disorder and subtypes, autism spectrum disorder, behavioral symptoms of Fragile X syndrome, and a combination thereof.

[0339] Some embodiments disclosed herein are directed to a method of treating a pain disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the pain disorder is selected from fibromyalgia, neuropathic pain, phantom limb pain, chronic pain, and a combination thereof.

[0340] Some embodiments disclosed herein are directed to a method of treating a headache disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, theheadache disorder is selected from cluster headaches, short-lasting unilateral neuralgiform headaches, tension-type headaches, chronic daily headache syndrome, migraine headaches, and a combination thereof.

[0341] Some embodiments disclosed herein are directed to a method of treating an inflammatory disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the inflammatory disorder is selected from inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, vasculitis, and a combination thereof.

[0342] Some embodiments disclosed herein are directed to a method of treating an injury- related disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the injury-related disorder is selected from cognitive and / or behavioral symptoms of TBI, functional recovery in stroke, and a combination thereof.

[0343] Some embodiments disclosed herein are directed to a method of treating a neurodegenerative disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the neurodegenerative disorder is selected from Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), behavioral symptoms in ALS, frontotemporal dementia, Parkinson’s disease, vascular dementia, Huntington’s disease, and a combination thereof.

[0344] Some embodiments disclosed herein are directed to a method of treating a functional disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the functional disorder is selected from chronic fatigue syndrome, functional neurological disorder, irritable bowel syndrome, long COVID, post-treatment Lyme, and a combination thereof.

[0345] Some embodiments disclosed herein are directed to a method of treating a psychotic disorder comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof. In some embodiments, the psychotic disorder is selected from schizophrenia, delusional disorder, schizoaffective disorder, and a combination thereof.

[0346] Some embodiments disclosed herein are directed to a method of treating a hyperkinetic disorder comprising administering a therapeutically effective amount of one or more compoundsand / or compositions disclosed herein to a subject in need thereof. In some embodiments, the hyperkinetic movement disorder is selected from chorea, akathisia, asterixis, dystonia, tremor, myoclonus, tics, stereotypies, movement disorders caused by neurodegenerative disease, metabolic derangements, vascular and autoimmune disease, infections, medications, recreational drugs, and / or pregnancy, and a combination thereof.

[0347] The present disclosure also includes a method of treating age-related macular degeneration, atherosclerosis, dissociative disorders, genetic brain disorders, hyperprolactinemia, hypersomnia, obesity, phobias, apathy disorders, and / or burnout, comprising administering a therapeutically effective amount of one or more compounds and / or compositions disclosed herein to a subject in need thereof.

[0348] In some embodiments, the subject is a non-human mammal. In other embodiments, the subject is human. Accordingly, the compounds, compositions, methods, and uses of the present disclosure are directed to human and non-human diseases, disorders, and conditions.

[0349] In some embodiments, the “subject in need thereof’ is a subject having the disease, disorder, or condition to be treated.

[0350] The present disclosure also includes a method of treating a disease, disorder, or condition comprising administering a therapeutically effective amount of one or more compounds and / or compositions of the disclosure in combination with another known agent useful for treatment of a disease, disorder, or condition to a subject in need thereof. The present disclosure also includes use of one or more compounds and / or compositions of the disclosure in combination with another known agent useful for treatment of a disease, disorder, or condition for treatment of a disease, disorder, or condition, as well as use of one or more compounds and / or compositions of the disclosure in combination with another known agent useful for treatment of a disease, disorder, or condition for the preparation of a medicament for treatment of a disease, disorder, or condition. The disclosure further includes one or more compounds and / or compositions of the disclosure in combination with another known agent useful for treatment of a disease, disorder, or condition for use in treating a disease, disorder, or condition.

[0351] In some embodiments, the one or more compounds and / or compositions of the disclosure are administered in combination with one or more additional treatments for a disease, disorder, or condition.

[0352] In some embodiments, the one or more compounds and / or compositions of the disclosure are administered in combination with one or more additional medicaments for the treatment of the disease, disorder, or condition.

[0353] In some embodiments, effective amounts vary according to factors such as the disease state, age, sex, and / or weight of the subject or species. In some embodiments, the amount of a given compound or compounds that will correspond to an effective amount may vary depending upon factors, such as the given drug(s) or compound(s), the pharmaceutical formulation, the route of administration, the type of condition, disease, or disorder, the identity of the subject being treated, and the like, but can nevertheless be routinely determined by one skilled in the art.

[0354] In some embodiments, the compounds and / or compositions of the disclosure are administered one, two, three, or four times a year. In some embodiments, the compounds and / or compositions of the disclosure are administered at least once a week. However, in another embodiment, the compounds and / or compositions are administered to the subject from about one time per one week, two weeks, three weeks, or one month. In another embodiment, the compounds and / or compositions are administered about one time per week to about once daily. In another embodiment, the compounds and / or compositions are administered 1 , 2, 3, 4, 5, or 6 times daily. The length of the treatment period depends on a variety of factors, such as the severity of the disease, disorder, or condition, the age of the subject, the concentration and / or the activity of the compounds of the disclosure and / or a combination thereof. It will also be appreciated that the effective dosage of the compound and / or compositions used for the treatment may increase or decrease over the course of a particular treatment regime. Changes in dosage may result and become apparent by standard diagnostic assays known in the art. In some instances, chronic administration is required. For example, the compounds and / or compositions are administered to the subject in an amount and for duration sufficient to treat the subject.

[0355] In some embodiments, the compounds and / or compositions of the disclosure are administered at doses that may occur once, twice, three, or four times a year. However, in some embodiments, the compounds and / or compositions and / or compositions are administered to the subject once daily, once every two days, once every 3 days, once a week, once every two weeks, once a month, once every two months, or once every three months at doses.

[0356] A compound and / or composition of the disclosure is either used alone or in combination with other known agent(s) useful for treating diseases, disorders, or conditions. When used in combination with other known agents useful in treating diseases, disorders, or conditions, it is an embodiment that a compound and / or composition of the disclosure is administeredcontemporaneously with those agents. As used herein, “contemporaneous administration” of two substances to a subject means providing each of the two substances so that they are both active in the individual at the same time. The exact details of the administration may depend on the pharmacokinetics of the two substances in the presence of each other and can include administering the two substances within a few hours of each other, or even administering one substance within 24 hours of administration of the other, if the pharmacokinetics are suitable. The design of suitable dosing regimens is routine for one skilled in the art. In particular embodiments, two substances may be administered substantially simultaneously, i.e., within minutes of each other, or in a single composition that contains both substances. It is a further embodiment of the present disclosure that a combination of agents is administered to a subject in a noncontemporaneous fashion. In some embodiments, a compound and / or composition of the present disclosure is administered with another therapeutic agent simultaneously or sequentially in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present disclosure provides a single unit dosage form comprising one or more compounds of the disclosure, an additional therapeutic agent and / or a pharmaceutically acceptable carrier.

[0357] The dosage of a compound and / or composition of the disclosure varies depending on many factors, such as the pharmacodynamic properties of the compound, the mode of administration, the age, health, and weight of the recipient, the nature and extent of the symptoms, the frequency of the treatment, and the type of concurrent treatment, if any, and the clearance rate of the compound in the subject to be treated. One of skill in the art can determine the appropriate dosage based on the above factors. In some embodiments, one or more compounds and / or compositions of the disclosure are administered initially in a suitable dosage that is adjusted as required, depending on the clinical response. Dosages may generally be selected to maintain a serum level of the one or more compounds of the disclosure from about 0.01 pg / cc to about 1000 pg / cc, or about 0.1 pg / cc to about 100 pg / cc. As a representative example, oral dosages of one or more compounds of the disclosure may range between about 10 pg per day to about 1000 mg per day for an adult, suitably about 10 pg per day to about 500 mg per day, more suitably about 10 pg per day to about 200 mg per day. For parenteral administration, a representative amount is from about 0.0001 mg / kg to about 10 mg / kg, about 0.0001 mg / kg to about 1 mg / kg, about 0.01 mg / kg to about 0.1 mg / kg, or about 0.0001 mg / kg to about 0.01 mg / kg may be administered. For oral administration, a representative amount is from about 0.001 pg / kg to about 10 mg / kg, about 0.1 pg / kg to about 10 mg / kg, about 0.01 pg / kg to about 1 mg / kg, or about 0.1 pg / kg to about 1 mg / kg. For administration in suppository form , a representative amount is from about 0.1 mg / kg to about 10 mg / kg or about 0.1 mg / kg to about 1 mg / kg. In someembodiments of the disclosure, compositions are formulated for oral administration and the one or more compounds are suitably in the form of tablets containing 0.1 , 0.25, 0.5, 0.75, 1.0, 5.0, 10.0, 20.0, 25.0, 30.0, 40.0, 50.0, 60.0, 70.0, 75.0, 80.0, 90.0, 100.0, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 mg of active ingredient (one or more compounds of the disclosure) per tablet. In some embodiments of the disclosure, the one or more compounds of the disclosure are administered in a single daily, weekly, or monthly dose or the total daily dose is divided into two, three, or four daily doses.

[0358] To be clear, in the above, the term “a compound" also includes embodiments wherein one or more compounds are referenced. Likewise, the term “compounds of the disclosure” also includes embodiments wherein only one compound is referenced.V. Preparation of Compounds

[0359] Compounds of the present disclosure can be synthesized by various synthetic processes. The choice of particular structural features and / or substituents may influence the selection of one process over another. The selection of a particular process to prepare a given compound of the disclosure is within the purview of the person of skill in the art. Some starting materials for preparing compounds of the present disclosure are available from commercial chemical sources or may be extracted from cells, plants, animals, or fungi. Other starting materials, for example as described below, are readily prepared from available precursors using straightforward transformations that are well known in the art. In the Schemes below showing some embodiments of methods of preparation of compounds of the disclosure, all variables are as defined in Formula (I), unless otherwise stated.

[0360] A person skilled in the art would appreciate that further manipulation of the substituent groups using known chemistry can be performed on the intermediates and final compounds in the Schemes below to provide alternative compounds of the disclosure.

[0361] Compounds of Formula (I) wherein Q is Q1 can be prepared as shown in Scheme I.

[0362] A phenyl compound can be treated with a prolinoyl chloride in the presence of AICI3 to obtain the corresponding ketone, following a similar procedure as described in J. Org. Chem. 1984, 49, 22, 4107-4111. The obtained ketone is reduced with triethylsilane in CF3COOH or lithium aluminum hydride to give the desired compound of Formula (I) wherein Q is Q1.

[0363] Alternatively, a compound of Formula (I) wherein Q is Q1 can be obtained according to Scheme II, as shown below.

[0364] In Scheme II, a bromine phenyl derivative is treated in the presence of BuLi with a proline derivative, following a similar procedure as described in WO2001 / 005758. The methanol derivative obtained can be reduced in the presence of LiAIH4 in THF to yield the corresponding compound of Formula (I) wherein Q is Q1 .

[0365] Compounds of Formula (I) wherein Q is Q2 can be prepared as shown in Scheme III.

[0366] Friedel-Crafts acylation reaction conditions as described in J. Org. Chem. 1984, 49, 22, 4107-4111 , can be applied to obtain compounds of Formula (I) wherein Q is Q2. A phenyl compound can be treated with an acyl chloride in the presence of AICIs to give the corresponding ketone. The ketone obtained may be reduced in the presence of triethylsilane in CF3COOH or lithium aluminum hydride to afford the desired compound.

[0367] Scheme IV shows another synthetic route to compounds of Formula (I) wherein Q is Q2, starting with a bromo phenyl derivative.

[0368] The bromo phenyl derivative is reacted in the presence of BuLi with an azetidine derivative following a similar procedure described in W02001 / 005758. The resulting methanol derivative can be reduced to the corresponding compound of Formula (I) wherein Q is Q2, in the presence of LiAIFL in THF.

[0369] Compounds of Formula (I) wherein Q is Q3 can be prepared as shown in Scheme V.

[0370] Friedel-Crafts acylation reaction conditions as described in J. Org. Chem. 1984, 49, 22, 4107-4111 , can be applied to obtain compounds of Formula (I) wherein Q is Q3. A phenyl compound can be treated with an acyl chloride in the presence of AICI3 to give the corresponding ketone. The ketone obtained may be reduced in the presence of triethylsilane in CF3COOH or lithium aluminum hydride to afford the desired compound.

[0371] Scheme VI shows another synthetic route to compounds of Formula (I) wherein Q is Q3, starting with a bromo phenyl derivative.

[0372] The bromo phenyl derivative is reacted in the presence of BuLi with an piperidine derivative following a similar procedure described in W02001 / 005758. The resulting methanol derivative can be reduced to the corresponding compound of Formula (I) wherein Q is Q3, in the presence of LiAIFL in THF.

[0373] Compounds of Formula (I) wherein Q is Q4 can be prepared as shown in Scheme VII .

[0374] A bromo phenyl derivative may be coupled with an iodo azetidine in a solution of Zn in DMF, using Pd2(dba)3 as catalyst. Such Negishi type coupling conditions are described in WO2022 / 221774.

[0375] Scheme VIII shows an alternative synthetic route to compounds of Formula (I) wherein Q is Q4.

[0376] In this scheme an azetidinone derivative may react with tosyl hydrazine to give the corresponding hydrazine azetidine derivative. The desired compound of Formula (I) wherein Q is Q4 is generated during the coupling of the hydrazine azetidine compound with a phenyl boronic acid derivative. General conditions for such cross couplings are described in Bioorg. Med. Chem. Lett. 2017, 27(23), 5179-5184.

[0377] Compounds of Formula (I) wherein Q is Q5 can be prepared as shown in Scheme IX.Scheme IX

[0378] A bromo phenyl derivative may be treated in the presence of BuLi with a proline derivative, to give the corresponding pyrrole phenyl derivative. A general procedure for such a reaction is described in Eur. J. Med. Chem. 2014, 74, 246-257. The pyrrole phenyl derivative may be reduced to the corresponding pyrrolidine compound in the presence of Pd / Fb in MeOH in suitable reducing conditions known in the art, such as, for examples, the reducing conditions described in W02006 / 047277.

[0379] Scheme X shows another procedure suitable for obtaining a compound of Formula (I) wherein Q is Q5.

[0380] A bromo phenyl derivative may be treated in the presence of BuLi with a pyrrole boronic acid derivative, in similar conditions as described in Eur. J. Med. Chem. 2014, 74, 246-257. The corresponding pyrrole phenyl derivative obtained can be reduced to the corresponding pyrrolidine in suitable reducing conditions known in the art.

[0381] Compounds of Formula (I) wherein Q is Q6 can be prepared as shown in Scheme XI. A brominated phenyl derivative may be obtained following known bromination reactions conditions, such as, for example as described in J. Chem. Am. Soc. (1949) 71 , 2901-2. Further, the brominated moiety may be treated with magnesium and then with an appropriately substituted ethylene oxide, in similar reaction conditions as those described in W02001 / 046121 , to give the corresponding hydroxy phenyl derivative. The hydroxy derivative is converted to the corresponding chloride in the presence of thionyl chloride in toluene. The desired compound of Formula (I) with Q = Q6 results from the reaction of the chloride with the desired cyclic secondary amine in the presence of potassium phthalimide and hexadecyltributylphosphonium bromide hydrazine hydrate (1 :1 ).

[0382] Compounds of Formula (I) wherein Q is Q7 can be prepared as shown in Scheme XII .

[0383] A bromo phenyl may be coupled with a tetrahydropyridine boronate ester in the presence of Pd(PPh3)4 following Suzuki coupling conditions as the ones described in W02006 / 047277. The corresponding phenyl tetrahydropyridine derivative obtained may be reduced, in reducing conditions known in the art, to the corresponding piperidine compound of Formula (I) wherein Q is Q7.

[0384] Compounds of Formula (I) wherein Q is Q8 can be prepared as shown in Scheme XIII.

[0385] A bromo phenyl may be coupled with a tetrahydropyridine boronate ester in the presence of Pd(PPh3)4 following Suzuki coupling conditions as the ones described in W02006 / 047277. The corresponding phenyl tetrahydropyridine derivative obtained may be reduced, in reducing conditions known in the art, to the corresponding piperidine compound of Formula (I) wherein Q is Q8.VI. Further preparation discussion

[0386] Salts of compounds of the disclosure may be formed by methods known to those of ordinary skill in the art, for example, by reacting a compound of the disclosure with an amount of acid or base, such as an equivalent amount, in a medium such as one in which the salt precipitates or in aqueous medium followed by lyophilization.

[0387] The formation of solvates may vary depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in the appropriate solvent and isolatingthe solvate by cooling or using an antisolvent. The solvate is typically dried or azeotroped under ambient conditions. The selection of suitable conditions to form a particular solvate can be made by a person skilled in the art. Examples of suitable solvents are ethanol, water, and the like. When water is the solvent, the molecule is referred to as a “hydrate.” The formation of solvates of the compounds of the disclosure may vary depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in the appropriate solvent and isolating the solvate by cooling or using an antisolvent. The solvate is typically dried or azeotroped under ambient conditions. The selection of suitable conditions to form a particular solvate can be made by a person skilled in the art.

[0388] Isotopically-enriched compounds of the disclosure and pharmaceutically acceptable salts, solvates, and / or prodrug thereof, can be prepared by conventional techniques well known to those skilled in the art or by processes analogous to those described in the Schemes and Examples herein using suitable isotopically-enriched reagents and / or intermediates.

[0389] Throughout the processes described herein it is to be understood that, where appropriate, suitable protecting groups may be added to and subsequently removed from, the various reactants and intermediates in a manner that will be readily understood by one skilled in the art. Conventional procedures for using such protecting groups as well as examples of suitable protecting groups are described, for example, in “Protective Groups in Organic Synthesis,” T.W. Green, P.G.M. Wuts, Wiley-lnterscience, New York, (1999). It is also to be understood that a transformation of a group or substituent into another group or substituent by chemical manipulation can be conducted on any intermediate or final product on the synthetic path toward the final product, in which the possible type of transformation is limited only by inherent incompatibility of other functionalities carried by the molecule at that stage to the conditions or reagents employed in the transformation. Such inherent incompatibilities and ways to circumvent them by carrying out appropriate transformations and synthetic steps in a suitable order, will be readily understood to one skilled in the art. Examples of transformations are given herein and it is to be understood that the described transformations are not limited only to the generic groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations are given in “Comprehensive Organic Transformations - A Guide to Functional Group Preparations,” R.C. Larock, VHC Publishers, Inc. (1989). References and descriptions of other suitable reactions are described in textbooks of organic chemistry, for example, “Advanced Organic Chemistry,” March, 4th ed. McGraw Hill (1992) or, “Organic Synthesis,” Smith, McGraw Hill, (1994). Techniques for purification of intermediates and finalproducts include, for example, straight and reversed phase chromatography on column or rotating plate, recrystallisation, distillation and liquid-liquid or solid-liquid extraction, which will be readily understood by one skilled in the art.

[0390] It is also to be understood that a transformation of a group or substituent into another group or substituent by chemical manipulation can be conducted on any intermediate or final product on the synthetic path toward the final product, in which the possible type of transformation is limited only by inherent incompatibility of other functionalities carried by the molecule at that stage to the conditions or reagents employed in the transformation. Such inherent incompatibilities, and ways to circumvent them by carrying out appropriate transformations and synthetic steps in a suitable order, will be readily understood to one skilled in the art. Examples of transformations are given herein, and it is to be understood that the described transformations are not limited only to the generic groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations are given in “Comprehensive Organic Transformations - A Guide to Functional Group Preparations,” R.C. Larock, VHC Publishers, Inc. (1989). References and descriptions of other suitable reactions are described in textbooks of organic chemistry, for example, “Advanced Organic Chemistry,’’ March, 4th ed. McGraw Hill (1992) or, “Organic Synthesis," Smith, McGraw Hill, (1994).

[0391] Techniques for purification of intermediates and final products include, for example, straight and reversed phase chromatography on column or rotating plate, recrystallisation, distillation, and liquid-liquid or solid-liquid extraction, which will be readily understood by one skilled in the art.

[0392] The products of processes disclosed in the disclosure may be isolated according to known methods, for example, the compounds may be isolated by evaporation of the solvent, by filtration, centrifugation, chromatography, or other suitable method.

[0393] Prodrugs of the compounds of the present disclosure may be, for example, conventional esters formed with available hydroxy, thiol, amino, or carboxyl groups. For example, available hydroxy or amino groups may be acylated using an activated acid in the presence of a base, and optionally, in inert solvent (e.g., an acid chloride in pyridine).

[0394] One skilled in the art will recognize that where a reaction step of the present disclosure is carried out in a variety of solvents or solvent systems, said reaction step may also be carried out in a mixture of the suitable solvents or solvent systems.VII. Biological Testing

[0395] Compounds of the invention are tested in binding assays and in functional assays of the human 5-hydroxytryptamine receptor subfamilies.

[0396] Human 5-Hydroxytryptamine Receptor 1A (5-HTIA) cAMP assay

[0397] Compounds of the invention are tested for potency (ECso) and efficacy (Max response) against the human 5-HTIA receptor in a cAMP assay using stably transfected CHO-K1 cells. The results are expressed as a percent efficacy relative to the maximum response of the control ligand (serotonin).

[0398] Human 5-Hydroxytryptamine Receptor 1A (5-HTIA) Functional FLIPR assay

[0399] Compounds of the invention are tested to assess the potential excitatory effects of compounds targeting on 5-HT1Aunder agonist mode, using FLIPR functional assay.

[0400] The results are expressed in ECso (nM) concentrations. This assay confirms compounds of the disclosure are effective agonists of the target human 5-HTIA receptors.

[0401] Human 5-Hydroxytryptamine Receptor 1A (5-HTIA) Radioligand binding assay.

[0402] Compounds of the invention are tested to evaluate the binding properties in radioligand binding assay on human 5-HTIA receptor.

[0403] Human 5-Hydroxytryptamine Receptor 2A (5-HT2A) 0-arrestins Assay

[0404] Compounds of the invention are tested for potency (ECso) and efficacy (Max response) against the human 5-HT2Areceptor in stably transfected U2OS cells in a GPCR cell based p- arrestins reporter assay. The results are expressed as a percent efficacy relative to the maximum response of the control ligand (serotonin).

[0405] Human 5-Hydroxytryptamine Receptor 2A (5-HT2A) Functional FLIPR Assay

[0406] Compounds of the invention are tested to assess the potential excitatory effects of compounds targeting human 5-HT2Aunder agonist mode, using FLIPR functional assay.

[0407] The results are expressed in ECso (nM) concentrations This assay confirms compounds of the disclosure are effective agonists of the target human 5-HT2Areceptors.

[0408] Human 5-Hydroxytryptamine Receptor 2A (5-HT2A) Radioligand binding assay

[0409] Compounds of the invention are tested in the human 5-HT2A, by radioligand binding assay, to evaluate the binding properties of compounds targeting on 5-HT2A. Ketanserin, known 5-HT2A antagonist, is used as reference compound. The results are expressed in % inhibition IC50.

[0410] Human 5-Hydroxytryptamine Receptor 2B (5-HT2B) FLIPR assay

[0411] Compounds of the invention are tested for potency (EC50) and efficacy (Max response) against the human 5-HT2B receptor in stably transfected HEK293 cells, in a calcium mobilizationbased assay.

[0412] The results are expressed as a percent efficacy relative to the maximum response of the control ligand (serotonin).

[0413] Human 5-Hydroxytryptamine Receptor 2B (5-HT2B) Positive Allosteric Modulator (PAM) Assay

[0414] Compounds of the invention are tested for potency (EC50) and efficacy (Max response) against the human 5-HT2B receptor in stably transfected HEK293 cells, in a GPCR cell-based assay. The results are expressed as a percent efficacy relative to the maximum response of the control ligand (serotonin).

[0415] Human 5-Hydroxytryptamine Receptors 2B (5-HT2B) Radioligand binding assay

[0416] Compounds of the invention are tested in the 5-HT2B, by radioligand binding assay. Yohimbine, known 5-HT2B antagonist, are used as a reference compound. The results are expressed as % inhibition IC50.

[0417] Human 5-Hydroxytryptamine Receptors 2C (5-HT2c) FLIPR assay

[0418] Compounds of the invention are tested for potency (EC50) and efficacy (Max response) against the human 5-HT2C receptor in stably transfected U2OS cells, in a calcium mobilizationbased assay.

[0419] The results are expressed as a percent efficacy relative to the maximum response of the control ligand (serotonin).VIII. Exemplary Embodiments

[0420] E1 . A compound of Formula (I) or a stereoisomer thereof:or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl, or R1is selected from CH and CH2linked with R4to form a 5-membered heterocyclic ring including R1, R4, and X1;R2is optionally substituted C1-C6alkyl, or R2is selected from CH and CH2 linked with R3to form a 5-membered heterocyclic ring including R2, R3, and X2, or R2is selected from CH and CH2 linked with R14and Y is CR14to form a 5-membered heterocyclic ring including R2, R14, and X2;R3is selected from SH, CN, NO2, I, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-C8alkyl, optionally substituted OC1-C8alkyl, optionally substituted C1-C8alkyleneOC1-C8alkyl, optionally substituted SC1-C8alkyl, optionally substituted C1-C8alkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(Cr C8alkyl)2, optionally substituted C2-C8alkenyl, and optionally substituted C2-C8alkynyl, or R3is selected from CH, CH2, and a heteroatom linked with R2to form the 5-membered heterocyclic ring including R2, R3, and X2;R4is selected from H, D, and halo, or R4is selected from CH, CH2, and a heteroatom linked with R1to form the 5-membered heterocyclic ring including R1, R4, and X1;R5is absent to provide a direct bond with the Q group or is selected from C1-C2alkylene (including CH2, CH2CH2, and CH(CH3)), CH(halo), CH(OH), CH(SH), CH(OCH3), a carbonyl group having aeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R7is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R8is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;each R9is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R10is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R12is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl; each R13is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl, or R14is selected from CH, CH2, and a heteroatom linked to R2to form the 5-membered heterocyclic ring including R2, X2, and R14; m is selected from 0, 1 , and 2; n is selected from 0, 1 , and 2; o is selected from 0, 1 , and 2; p is selected from 0, 1 , and 2; q is selected from 0, 1 , and 2; r is selected from 0, 1 , and 2; s is selected from 0, 1 , and 2; t is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0421] E2. The compound of E1 , wherein one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms independently selected from fluorine and chlorine and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0422] E3. The compound of E1 or E2, wherein one or more available hydrogen atoms are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

[0423] E4. The compound of any one of E1 to E3, wherein X1is O and X2is O.

[0424] E5. The compound of any one of E1 to E3, wherein X1is S and X2is S.

[0425] E6. The compound of any one of E1 to E3, wherein X1is O and X2is S.

[0426] E7. The compound of any one of E1 to E3, wherein X1is S and X2is O.

[0427] E8. The compound of any one of E1 to E7, wherein Y is CR14and R14is H without an available hydrogen replaced with a halogen atom or a deuterium atom.

[0428] E9. The compound of any one of E1 to E7, wherein Y is CR14and R14is H or D.

[0429] E10. The compound of any one of E1 to E7, wherein Y is CR14and R14is halo.

[0430] E11 . The compound of any one of E1 to E7, wherein Y is CR14and R14is C(C1-C4alkyl).

[0431] E12. The compound of any one of E1 to E7, wherein Y is N.

[0432] E13. The compound of any one of E1 to E12, wherein R1is optionally substituted C1- C3alkyl.

[0433] E14. The compound of E13, wherein R1is selected from optionally substituted C1-C3alkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0434] E15. The compound of E13, wherein R1is optionally substituted C1-C3fluoroalkyl.

[0435] E16. The compound of E13, wherein R1is optionally substituted C1-C3deuteroalkyl.

[0436] E17. The compound of E13, wherein R1is optionally substituted C1-C3deuterofluoroalkyl.

[0437] E18. The compound of E13, wherein R1is selected from CH3, CH2D, CHD2, CDs, CH2F, CHF2, CF3,CHDF, CD2F, and CDF2.

[0438] E19. The compound of any one of E1 to E12, wherein R1is selected from CH and CH2 linked with R4to form the 5-membered heterocyclic ring including R1, R4, and X1.

[0439] E20. The compound of E19, wherein the 5-membered heterocyclic ring including R1, R4, and X1contains one double bond.

[0440] E21. The compound of E20, wherein the compound of Formula (I) has a structure selected from:

[0441] E22. The compound of E19, wherein the 5-membered heterocyclic ring including R1, R4, and X1contains two double bonds.

[0442] E23. The compound of E22, wherein the compound of Formula (I) has a structure selected from:

[0443] E24. The compound of E19 or E20, wherein the 5-membered heterocyclic ring including R1, R4, and X1contains two heteroatoms independently selected from O and S.

[0444] E25. The compound of any one of E1 to E24, wherein R2is optionally substituted C1- Caalkyl.

[0445] E26. The compound of E25, wherein R2is selected from optionally substituted C1-Csalkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0446] E27. The compound of E25, wherein R2is optionally substituted C1-Csfluoroalkyl.

[0447] E28. The compound of E25, wherein R2is optionally substituted C1-C6deuteroalkyL

[0448] E29. The compound of E25, wherein R2is optionally substituted C1-C6deuterofluoroalkyl.

[0449] E30. The compound of E25, wherein R2is selected from CH3, CH2D, CHD2, CD3, CH2F, CHF2, CF3,CHDF, CD2F, and CDF2.

[0450] E31 . The compound of any one of E1 to E24, wherein R2is selected from CH and CH2 linked with R3to form the 5-membered heterocyclic ring including R2, R3, and X2.

[0451] E32. The compound of E31 , wherein the 5-membered heterocyclic ring including R2, R3, and X2contains one double bond.

[0452] E33. The compound of E32, wherein the compound of Formula (I) has a structure selected from:

[0453] E34. The compound of E31 , wherein the 5-membered heterocyclic ring including R2, R3, and X2contains two double bonds.

[0454] E35. The compound of E34, wherein the compound of Formula (I) has a structure selected from:

[0455] E36. The compound of E31 or E32, wherein the 5-membered heterocyclic ring including R2, R3, and X2contains two heteroatoms independently selected from O and S.

[0456] E37. The compound of any one of E1 to E24, wherein R2is selected from CH and CH2linked with R14to form the 5-membered heterocyclic ring including R2, X2, and R14.

[0457] E38. The compound of E37, wherein the 5-membered heterocyclic ring including R2, X2, and R14contains one double bond.

[0458] E39. The compound of E38, wherein the compound of Formula (I) has a structure selected from:

[0459] E40. The compound of E37, wherein the 5-membered heterocyclic ring including R2, X2, and R14contains two double bonds.

[0460] E41. The compound of E40, wherein the compound of Formula (I) has a structure selected from:

[0461] E42. The compound of E37 or E38, wherein the 5-membered heterocyclic ring including R2, X2, and R14contains two heteroatoms independently selected from O and S.

[0462] E43. The compound of any one of E1 to E30 and E37 to E42, wherein R3is optionally substituted C1-C3alkyl.

[0463] E44. The compound of E43, wherein R3is selected from optionally substituted C1-C3alkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0464] E45. The compound of E43, wherein R3is optionally substituted C1-C3fluoroalkyl.

[0465] E46. The compound of E43, wherein R3is optionally substituted C1-C3deuteroalkyl.

[0466] E47. The compound of E43, wherein R3is optionally substituted C1-C3deuterofluoroalkyl.

[0467] E48. The compound of E43, wherein R3is selected from CH3, CFW, CHD2, CD3, CH2F, CHF2, CF3,CHDF, CD2F, and CDF2.

[0468] E49. The compound of any one of E1 to E30 and E37 to E42, wherein R3is optionally substituted OC1-C3alkyl.

[0469] E50. The compound of E49, wherein R3is selected from optionally substituted OC1- C3alkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0470] E51 . The compound of E49, wherein R3is optionally substituted OC1-C3fluoroalkyl.

[0471] E52. The compound of E49, wherein R3is optionally substituted OC1-C3deuteroalkyl.

[0472] E53. The compound of E49, wherein R3is optionally substituted OC1-C3deuterofluoroalkyl.

[0473] E54. The compound of E49, wherein R3is selected from OCH3, OCH2D, OCHD2, OCD3, OCH2F, OCHF2, OCF3,OCHDF, OCD2F, and OCDF2.

[0474] E55. The compound of any one of E1 to E30 and E37 to E42, wherein R3is optionally substituted SC1-C3alkyl.

[0475] E56. The compound of E55, wherein R3is optionally substituted SC1-Csalkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0476] E57. The compound of E55, wherein R3is optionally substituted SC1-CsfluoroalkyL

[0477] E58. The compound of E55, wherein R3is optionally substituted SC1-C6deuteroalkyl.

[0478] E59. The compound Of E55, wherein R3is optionally substituted SC1- C3deuterofluoroalkyl.

[0479] EGO. The compound of E55, wherein R3is selected from SCH3, SCH2D, SCHD2, SCD3, SCH2F, SCHF2, SCF3,SCHDF, SCD2F, and SCDF2.100480] E61. The compound of any one of E1 to E30 and E37 to E42, wherein R3is optionally substituted C1-C6alkyleneOC1-Csalkyl.

[0481] E62. The compound of E61 , wherein R3is optionally substituted C1-CsalkyleneOC1- Csalkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0482] E63. The compound of E61 , wherein R3is selected from optionally substituted C1- C6alkyleneOC1-Csfluoroalkyl and optionally substituted C1-CefluoroalkyleneOC1-Csfluoroalkyl.

[0483] E64. The compound of E61 , wherein R3is selected from optionally substituted C1- CsalkyleneOC1-C6deuteroalkyl aanndd optionally substituted C1-C6deuteroalkyleneOC1- C6deuteroalkyl.

[0484] E65. The compound of E61 , wherein R3is selected from optionally substituted C1- CsalkyleneOC1-C6deuterofluoroalkyl and optionally substituted C1-C6deuterofluoroalkyleneOC1- C6deuterofluoroalkyl.

[0485] EGG. The compound of E61 , wherein R3is selected from optionally substituted C1- C6alkyleneOCHs, optionally substituted C1-CsalkyleneOCFW, optionally substituted C-|-C6alkyleneOCHD2, optionally substituted C1-C6alkyleneOCDs, optionally substituted C1-CsalkyleneOCFfeF, optionally substituted C1-C6alkyleneOCHF2, optionally substituted C1-C6alkyleneOCFs, optionally substituted C1-C6alkyleneOCHDF, optionally substituted Cr C6alkyleneOCD2F, and optionally substituted C1-C6alkyleneOCDF2.

[0486] E67. The compound of any one of E1 to E30 and E37 to E42, wherein R3is optionally substituted C1-C6alkyleneSC1-C3alkyl.

[0487] E68. The compound of E67, wherein R3is selected from optionally substituted C1- C6alkyleneSC1-Csalkyl without an available hydrogen replaced with a halogen atom and / or an available hydrogen atom replaced with a deuterium atom.

[0488] E69. The compound of E67, wherein R3is selected from optionally substituted Cr C6alkyleneSC1-Csfluoroalkyl and optionally substituted C1-CefluoroalkyleneSC1-Csfluoroalkyl.

[0489] E70. The compound of E67, wherein R3is selected from optionally substituted C1- C6alkyleneSC1-C3deuteroalkyl and optionally substituted C1-C6deuteroalkyleneSC1- C3deuteroalkyl.

[0490] E71. The compound of E67, wherein R3is selected from optionally substituted C1- C6alkyleneSC1-C6deuterofluoroalkyl and optionally substituted C1-C6deuterofluoroalkyleneSCr C3deuterofluoroalkyl.

[0491] E72. The compound of E67, wherein R3is selected from optionally substituted C1- C6alkyleneSCH3, optionally substituted C1-C6alkyleneSCH2D, optionally substituted C1- C6alkyleneSCFIDz, optionally substituted C1-C6alkyleneSCDs, optionally substituted C1- C6alkyleneSCF^F, optionally substituted C1-C6alkyleneSCHF2, optionally substituted C1- C6alkyleneSCFg, optionally substituted C1-C6alkyleneSCHDF, optionally substituted C1- C6alkyleneSCD2F, and optionally substituted C1-C6alkyleneSCDF2.

[0492] E73. The compound of any one of E1 to E30 and E37 to E42, wherein R3is selected from optionally substituted C1-C3alkyleneOC1-C3alkyl, optionally substituted C1-C3alkyleneOC1- C3fluoroalkyl, optionally substituted C1-C3alkyleneOC1-C3deuteroalkyl, optionally substituted C1- C3alkyleneOC1-C3deuterofluoroalkyl, optionally substituted C1-C3fluoroalkyleneOC1-C3alkyl, optionally substituted C1-C3deuteroalkyleneOC1-C3alkyl, optionally substituted C1- C3deuterofluoroalkyleneOC1-C3alkyl, optionally substituted C1-C3fluoroalkyleneOC1- Csfluoroalkyl, optionally substituted C1-C3deuteroalkyleneOC1-C3deuteroalkyl, optionally substituted C1-C3deuterofluoroalkyleneOC1-C3deuterofluoroalkyl, optionally substituted Cr C3alkyleneSC1-C3fluoroalkyl, optionally substituted C1-C3alkyleneSC1-C3deuteroalkyl, optionally substituted C1-C3alkyleneSC1-C3deuterofluoroalkyl, optionally substituted C1- C3fluoroalkyleneSC1-C3alkyl, optionally substituted C1-C3deuteroalkyleneSC1-C3alkyl, optionallysubstituted C1-C3deuterofluoroalkyleneSC1-C3alkyl, optionally ssuubbssttiittuutteedd C1-C3fluoroalkyleneSC1-C3fluoroalkyl, optionally substituted C1-C3deuteroalkyleneSC1-C6deuteroalkyl, and optionally substituted C1-C3deuterofluoroalkyleneSC1-C3deuterofluoroalkyl.

[0493] E74. The compound of any one of E1 to E30 and E37 to E42, wherein R3is NO2.

[0494] E75. T...

Claims

WHAT IS CLAIMED IS:

1. A compound of Formula (l)-A or a stereoisomer thereof:or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-C6alkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-C6alkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C6alkyl, optionally substituted C1-CsalkyleneOC1-C8alkyl, optionally substituted C1-CgalkyleneSC1-C8alkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-C6alkenyl, and optionally substituted aClk2y-Cny6l;R4is selected from H, D, and halo;R5is selected from CH2, CH(halo), CH(CH3), CH(OH), CH(SH), CH(OCH3), a carbonyl groupeach R6is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-Csalkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; m is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1and X2are independently selected from O and S, Y is CR14, R1is CH3, R2is selected from CH3 and CH2CH3, R4is selected from H and halo, R5is selected from CH2 and C(OH), R14is selected from H and halo, and m is 0, then R3is not selected from C1-C4alkyl, OC1- C3alkyl, SCH3, S(O)2CH3,CH2OCH3, N(CH3)2, and CHF2; and provided when X1is O, X2is O, Y is CR14, R1and R2are each CH3, R4is H, R5is R isH, and m is 0, then R3is not selected from CH3, CH2CH3, and OCH3.

2. The compound of claim 1 , provided when X1and X2are independently selected from O and S, Y is CR14, R1and R2are independently C1-C6alkyl, R4is selected from H, D, and halo, R5is selected from CH2 and C(OH), R14is selected from H, D, and halo, and m is 0, then R3is not selected from C1-C8alkyl, OC1-Csalkyl, SC1-Csalkyl, S(O)2C1-C8alkyl, CFkOC1-C8alkyl, N(C1- Csalkyl)2, and C1-C8fluoroalkyL3. The compound of claim 1 or claim 2, provided when X1is O, X2is O, Y is CR14, R1and R2are independently C1-C6alkyl, R5is R4is selected from H and D, R14is selected from Hand D, and m is 0, then R3is not selected from C1-C8alkyl and OC1-C8alkyL4. The compound of any one of claims 1 to 3, wherein one or more available hydrogen atoms are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

5. The compound of any one of claims 1 to 4, wherein at least one member selected from X1and X2is S.

6. The compound of any one of claims 1 to 5, wherein Y is CR14and R14is H.

7. The compound of any one of claims 1 to 5, wherein Y is N.

8. The compound of any one of claims 1 to 7, wherein R3is selected from I, CH3, CHF2, CF3, CH2CH2CH3, CH2OCHF2, CH2OCH2CH2CH3, CH2SCH3, CH2SCH2CH2CH3, OCHF2, OCF3, SCH3, SCF3, NO2Iand CN.

9. The compound of any one of claims 1 to 8, wherein R5is selected from CH2, CH(halo), CH(OH), CH(SH), and CH(OCH3).

10. The compound of any one of claims 1 to 8, wherein R5is selected from and11. The compound of claim 1 , wherein the compound is selected from:2-(2,5-dimethoxy-4-(trifluoromethyl)benzyl)pyrrolidine;(R)-2-(2,5-dimethoxy-4-(trifluoromethyl)benzyl)pyrrolidine;(S)-2-(2,5-dimethoxy-4-(trifluoromethyl)benzyl)pyrrolidine;2-((2,5-dimethoxy-4-(trifluoromethyl)phenyl)(methoxy)methyl)pyrrolidine;(S)-2-((S)-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)(methoxy)methyl)pyrrolidine;(R)-2-((R)-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)(methoxy)methyl)pyrrolidine;2-(2 , 5-d imethoxy-4-(propoxymethyl )benzyl )pyrrol id i ne ;(S)-2-(2 , 5-d imethoxy-4-(propoxymethyl )benzyl )pyrrol id i ne;2-(5-(difluoromethoxy)-4-(difluoromethyl)-2-methoxybenzyl)pyrrolidine;(R)-2-(2,5-dimethoxy-4-((propylthio)methyl)benzyl)pyrrolidine;(S)-2-(5-(difluoromethoxy)-4-(difluoromethyl)-2-methoxybenzyl)pyrrolidine;(R)-2-(5-(difluoromethoxy)-4-(difluoromethyl)-2-methoxybenzyl)pyrrolidine;2 , 5-d i methoxy-4-(pyrro I id i n -2 -y I m ethyl )be nzon itri le ;(S)-2,5-dimethoxy-4-(pyrrolidin-2-ylmethyl)benzonitrile;(R)-2,5-dimethoxy-4-(pyrrolidin-2-ylmethyl)benzonitrile;2-(5-(difluoromethoxy)-2-meth oxy-4-(trifluoromethyl)benzyl)pyrrolidine;(R)-2-(5-(difluoromethoxy)-2-methoxy-4-(trifluoromethyl)benzyl)pyrrolidine;(S)-2-(5-(difluoromethoxy)-2-methoxy-4-(trifluoromethyl)benzyl)pyrrolidine;2-(2,5-bis(difluoromethoxy)-4-(trifluoromethyl)benzyl)pyrrolidine;(S)-2-(2,5-bis(difluoromethoxy)-4-(trifluoromethyl)benzyl)pyrrolidine;(R)-2-(2,5-bis(difluoromethoxy)-4-(trifluoromethyl)benzyl)pyrrolidine;2-(1-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;(S)-2-((S)-1-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;(R)-2-((R)-1 -(2,5-dimethoxy-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;(S)-2-((R)-1-(2,5-dimeth oxy-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;(S)-2-((S)-1-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;(R)-2-((S)-1-(2,5-dimeth oxy-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;2-(2-methoxy-5-(methylthio)-4-(trifluoromethyl)benzyl)pyrrolidine;(R)-2-(2-methoxy-5-(methylthio)-4-(trifluoromethyl)benzyl)pyrrolidine;(S)-2-(2-methoxy-5-(methylthio)-4-(trifluoromethyl)benzyl)pyrrolidine;2-(2-methoxy-4-(trifluoromethyl)-5-((trifluoromethyl)thio)benzyl)pyrrolidine;(R)-2-(2-methoxy-4-(trifluoromethyl)-5-((trifluoromethyl)thio)benzyl)pyrrolidine;(S)-2-(2-methoxy-4-(trifluoromethyl)-5-((trifluoromethyl)thio)benzyl)pyrrolidine;2-(2-methoxy-5-(methylthio)-4-(trifluoromethoxy)benzyl)pyrrolidine;(S)-2-(2-m ethoxy-5-(methylth io)-4-(trifluoromethoxy)benzyl )pyrrol id i ne ;(R)-2-(2-methoxy-5-(methylthio)-4-(trifluoromethoxy)benzyl)pyrrolidine;(R)-2-(2,5-bis(methylthio)-4-(trifluoromethyl)benzyl)pyrrolidine;(R)-2-(5-methoxy-2-(methylthio)-4-(trifluoromethyl)benzyl)pyrrolidine;2-(4-((difluoromethoxy)methyl)-2,5-dimethoxybenzyl)pyrrolidine;2-(1-(2,5-bis(methylthio)-4-(trifluoromethyl)phenyl)ethyl)pyrrolidine;2-(2,5-bis(methylthio)-4-((trifluoromethyl)thio)benzyl)pyrrolidine;2-(2,5-bis(methylthio)-4-(trifluoromethoxy)benzyl)pyrrolidine;2-(2-methoxy-5-(methylthio)-4-(trifluoromethoxy)benzyl)pyrrolidine;2-(2,5-dimethoxy-4-(trifluoromethoxy)benzyl)pyrrolidine;2-(2,5-dimethoxy-4-((trifluoromethyl)thio)benzyl)pyrrolidine;2-(5-methoxy-2-(methylthio)-4-((trifluoromethyl)thio)benzyl)pyrrolidine;2-(2,5-dimethoxy-4-nitrobenzyl)pyrrolidine;2-(2,5-dimethoxy-4-((propylthio)methyl)benzyl)pyrrolidine;2-(5-methoxy-2-(methylthio)-4-((trifluoromethyl)thio)benzyl)pyrrolidine;2-(2 , 5-d imethoxy-4-((methylthio)methyl )benzyl )pyrrol id i ne;(S)-2-(2,5-dimethoxy-4-((propylthio)methyl)benzyl)pyrrolidine;(R)-2-(2,5-dimethoxy-4-(propoxymethyl)benzyl)pyrrolidine;2-(4-iodo-2,5-dimethoxybenzyl)pyrrolidine;(2,5-dimethoxy-4-(trifluoromethyl)phenyl)(pyrrolidin-2-yl)methanone;(2,5-dimethoxy-4-(trifluoromethyl)phenyl)(pyrrolidin-2-yl)methanethione;(4-(difluoromethyl)-2,5-dimethoxyphenyl)(pyrrolidin-2-yl)methanethione;(4-(difluoromethyl)-2,5-dimethoxyphenyl)(pyrrolidin-2-yl)methanone;(5-(difluoromethoxy)-4-(difluoromethyl)-2-methoxyphenyl)(pyrrolidin-2-yl)methanone;(5-(difluoromethoxy)-4-(difluoromethyl)-2-methoxyphenyl)(pyrrolidin-2-yl)methanethione;(4-(difluoromethyl)-5-((difluoromethyl)thio)-2 -methoxyphenyl )(pyrrolidin-2- yl)methanethione; and(4-(difluoromethyl)-5-((difluoromethyl)thio)-2 -methoxyphenyl )(pyrrolidin-2-yl)methanone, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

12. A compound of Formula (l)-F or a stereoisomer thereof:or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein:Y is selected from CR14and N;X1is selected from O and S;X2is selected from O and S;R1is optionally substituted C1-C6alkyl;R2is optionally substituted C1-Cgalkyl;R3is selected from I, CN, NO2, optionally substituted C1-C8alkyl, optionally substituted OC1- Csalkyl, SH, optionally substituted SC1-Cgalkyl, optionally substituted S(O)C1-C8alkyl, optionally substituted S(O)2C1-C8alkyl, optionally substituted C1-CgalkyleneOC1-C6alkyl, optionallysubstituted C1-C8alkyleneSC1-Csalkyl, optionally substituted NHC1-C8alkyl, optionally substituted N(C1-C8alkyl)2, optionally substituted C2-Csalkenyl, and optionally substituted aClk2y-Cny6l;R4is selected from H, D, and halo; sueach R11is independently selected from optionally substituted C1-C6alkyl, optionally substituted OC1-C6alkyl, and optionally substituted SC1-C6alkyl;R14is selected from H, D, halo, and optionally substituted C1-C4alkyl; r is selected from 0, 1 , and 2; and one or more available hydrogen atoms are optionally and independently replaced with one or more halogen atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms, provided when X1is O, X2is O, Y is CR14, R1is Ch3, R2is CH3, R4is H, R5is CH2CH2, R14is H, and r is 0, then R3is not Ch3.

13. The compound of claim 12, provided when X1is O, X2is O, Y is CR14, R1is C1-C6alkyl, R2is C1-C6alkyl, R4is selected from H and D, R5is CH2CH2, R14is selected from H and D, and r is 0, then R3is not C1-C8alkyL14. The compound of claim 12 or claim 13, wherein one or more available hydrogen atoms are optionally and independently replaced with one or more fluorine atoms and / or one or more available hydrogen atoms are optionally and independently replaced with one or more deuterium atoms.

15. The compound of any one of claims 12 to 14, wherein at least one member selected from X1and X2is S.

16. The compound of any one of claims 12 to 15, wherein Y is CR14and R14is H.

17. The compound of any one of claims 12 to 15, wherein Y is N.

18. The compound of any one of claims 12 to 17, wherein R3is selected from CF3, CH2OCH3, CH2OCF3, CH2SCH3, and CH2SCF3.

19. The compound of any one of claims 12 to 18, wherein R5is CH2CH2.

20. The compound of any one of claims 12 to 18, wherein R5is selected from unsubstituted21. The compound of any one of claims 12 to 20, wherein r is 1 or 2, and wherein each R11is independently selected from OCHF2 and SCHF2.

22. The compound of claim 12, wherein the compound is selected from:3-(difluoromethoxy)-1-(2,5-dimethoxy-4-(methoxymethyl)phenethyl)pyrrolidine;3-((difluoromethyl)thio)-1-(5-methoxy-4-(methoxymethyl)-2- (methylthio)phenethyl)pyrrolidine;3-(d if I u oromethoxy)- 1 -(2 , 5-d imethoxy-4- (((trifluoromethyl)thio)methyl)phenethyl)pyrrolidine;1-(2,5-bis(methylthio)-4-((trifluoromethoxy)methyl)phenethyl)-3-(difluoromethoxy)pyrrolidine;1-(2-(2,5-dimethoxy-4-(((trifluoromethyl)thio)methyl)phenyl)cyclopentyl)pyrrolidine;1-(2-(2,5-dimethoxy-4-(((trifluoromethyl)thio)methyl)phenyl)cyclohexyl)pyrrolidine;3-(difluoromethoxy)-1-(5-methoxy-4-(methoxymethyl)-2- (methylthio)phenethyl)pyrrolidine;3-((difluoromethyl)thio)-1-(2,5-dimethoxy-4-(methoxymethyl)phenethyl)pyrrolidine;3-(difluoromethoxy)-1-(2,5-dimethoxy-4-((trifluoromethoxy)methyl)phenethyl)pyrrolidine;1-(2,5-bis(methylthio)-4-((trifluoromethoxy)methyl)phenethyl)-3-((difluoromethyl)thio)pyrrolidine;1-(2-(2,5-dimethoxy-4-(((trifluoromethyl)thio)methyl)phenyl)cyclobutyl)pyrrolidine; and1-(2-(2,5-dimethoxy-4-(((trifluoromethyl)thio)methyl)phenyl)cyclopropyl)pyrrolidine, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

23. A composition comprising one or more compounds of any one of claims 1 to 22 and a carrier.

24. A method of treating a depressive disorder, bipolar disorder, eating disorder, impulse control disorder, personality disorder, substance abuse disorder, behavioral addiction disorder, anxiety disorder, stress disorder, neurodevelopmental disorder, pain disorder, headache disorder, inflammatory disorder, injury-related disorder, neurodegenerative disorder, functional disorder, psychotic disorder, hyperkinetic movement disorder, age-related macular degeneration, atherosclerosis, dissociative disorders, genetic brain disorders, hyperprolactinemia, hypersomnia, obesity, phobias, apathy disorders, and / or burnout comprising administering a therapeutically effective amount of one or more compounds of any one of claims 1 to 22 and / or the composition of claim 23 to a subject in need thereof.

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