Indoline Derivatives as Serotonergic Agents Useful for the Treatment of Disorders Associated with Indoline Derivatives as Serotonergic Agents - Patent application

Abstract

The present application relates to indoline derivatives of general formula (I), processes for their preparation, compositions containing them, and their use in activating serotonin receptors in cells, and treating diseases, disorders, or conditions by activating serotonin receptors in cells, including, for example, psychoses, psychiatric disorders, and CNS disorders, and / or associated endophenotypes and / or symptom clusters, wherein Q is (Q3). TIFF2025513461000132.tif29100

Description

[Technical field]

[0001] Related Applications This application claims the benefit of priority to co-pending U.S. Provisional Patent Application No. 63 / 332,450, filed April 19, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] The present application relates to indoline compounds for the treatment of various conditions, such as psychiatric and neurological disorders, that are treated by activation of serotonin receptors in the fields of psychiatry, neurobiology and pharmacotherapy. [Background technology]

[0003] The applicant has several co-pending applications disclosing novel indole derivatives as serotonergic psychotropic agents for the treatment of various CNS disorders, including PCT Patent Application Publication Nos. WO2021 / 155470, WO2021 / 155468, and WO2021 / 155467, and PCT Application Nos. PCT / CA2022 / -50295, and U.S. Provisional Application Nos. 63 / 260,470 and 63 / 449,715. These applications describe various pharmaceutical uses for such agents, including in the treatment of psychiatric and neurological disorders, as well as uses in the fields of psychiatry, neurobiology, and pharmacotherapy.

[0004] Psychotropic drugs show promise in treating diseases such as major depressive disorder, treatment-resistant depression, post-traumatic stress disorder (PTSD), and substance use disorders, in addition to terminal existential distress and others. To date, hundreds of millions of dollars have been invested in companies developing new psychotropic drugs (see, for example, C&EN March 7, 2022). Thus, psychotropic drugs are intended to become mainstream in modern medicine as a treatment for intractable psychiatric disorders.

[0005] The therapeutic efficacy of classical psychotropic drugs such as mescaline, N,N-dimethyltryptamine (DMT), psilocybin, and lysergic acid diethylamide (LSD) is due to the serotonin 2A (5-HT 2A These drugs are increasingly being evaluated and used to treat neuropsychiatric disorders.

[0006] Many psychotropic agents have side effects, such as hallucinogenic effects, which preclude their use outside of clinical settings.

[0007] Several potential non-hallucinogenic mind-expanding analogs have been reported (Cunningham MJ et al., ACS Chem. Neurosci. 2023, 14, 1, 119-135; Hofman, A. LSD, My Problem Child: Reflections on Sacred Drugs, Mysticism, and Science, MAPS, Multidisciplinary Association for Psychedelic Studies: Santa Cruz, CA, 2009; Weingartner, H. et al., J. Clin. Pharmacol. New Drugs 1971, 11, 103-111; Shulgin. AT2-Amino-1-(2,5-dimethoxyphenyl)butanes, U.S. Patent No. 4,105,695(A); Shulgin, ATSoc. Pharmacol. 1987, 1, 279-290; Cameron, et al. Nature 2021,589(7842)474-479, Lu J.et al.,Molecular Psychiatry,2021,26,6237-6252, Cao et al.,Science 2022,375,403-411, Vargas et al.,Science,2023,379,700-706). These non-hallucinogenic 5-HT 2A Results with agonists have been promising, but non-hallucinogenic, 5-HT 2A The therapeutic development of agonists is still in its early stages.

[0008] For example, new psychoactive and non-hallucinogenic 5-HT 2A There remains a need to provide agonist molecules. Summary of the Invention

[0009] The compounds of the present application inhibit serotonin receptor subtypes, specifically 5-HT 2A Regulates the activity of.

[0010] Thus, the present application relates to a compound of formula I: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 、 SO2R 7 、 C 1-4 Alkylene R 7 , and R 7 is selected from Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently H, halo, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 2a )(R 2b ), and S.C.1-6 alkyl, R 2a and R 2b are independently H and C 1-6 alkyl, R 3 , R 4 , R 5 , and R 6 are independently H, halo, N(R 5’ )(R 6’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl, the latter four groups being selected from OH and C 1-6 optionally substituted with one or two substituents selected from alkoxy; R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-6 Alkyl, C 1-6 Alkoxy, N(R 5’ )(R 6’ ), C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl; or R 3 , R 4 , R 5 , and R 6 One of them is A, OA, and C 1-4 alkylene A; R 4 The other one and R 3 , R 4 , R 5 , and R 6 the remainder of are independently H or halo; R 5’ and R 6’ are independently H and C 1-6 alkyl, A is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from halo, C 1-4 Alkyl, OC 1-4 Alkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), and S.C. 1-4 and optionally substituted with one or more substituents independently selected from alkyl, R 7 , H, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 7 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR 7 ''; and 5-6 membered heteroaryl containing 1-4 hetero moieties independently selected from the following: halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-6 Alkyl is O, C(O), CO2, and NR 57 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 7’ H and C1-6 alkyl, R 7’’ H and C 1-6 alkyl, R 26 , R 27 , R 28 , and R 29 is independently selected from H, halo, and C alkyl; R 30 and R 31 are independent of each other, H, C 1-6 alkyl, and C(O)C1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 54 , R 55 , R 56 , R 57 , and R 58 are independently H and C 1-6 alkyl, R 54a and R 54b are independently H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 But R 7 and R 7 But H, R 2 , R 2’ , R 2’’ , R 3 , R 4, R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0011] In some embodiments, the compound of formula I is defined as follows: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; R 1 is H, Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently selected H, D, and F; R 3 , R 4 , R 5 , and R 6 are independent of each other, H, C1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 or R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-6 Alkyl, and C 1-6 alkoxy; R 26 , R 27 , R 28 , and R 29 are independently H, halo, and C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 58 H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 , R2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0012] In a further embodiment, the compounds of the present application are used as medicaments. Thus, the present application also includes compounds of the present application for use as medicaments.

[0013] The present application also includes a method of treating psychosis or a psychotic symptom, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof.

[0014] The present application also includes a method of treating a psychiatric disorder, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof.

[0015] The present application also includes methods of treating central nervous system (CNS) diseases, disorders, or conditions, and / or neurological diseases, disorders, or conditions.

[0016] The present application also includes methods of treating endophenotypes and / or symptom clusters associated with a disease, disorder, or condition that is treated by activation of a serotonin receptor.

[0017] The present application also relates to a non-hallucinogenic compound of formula II [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, During the ceremony, R 59 is C(O)R 65 , CO2R 65 , C(O)N(R 65 )(' 65’ ), S(O)R 65 , SO2R 65 , C 1-6 Alkylene R 65 , and R 65 is selected from Q' is Q3': [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 60 , R 60’ , and R 60’’ are independently H, halo, and C 1-6 Alkyl and C 1-6 Alkoxy, C 1-6 AlkyleneN(R 60a )(R 60b ), and SC 1-6 alkyl, R 60a and R 60b are independently H and C 1-6 alkyl, R 61 , R 62 , R 63 , and R 64are independently H, halo, N(R 63’ )(R 64’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 63’ )(R 64’ ), and S.C. 1-6 alkyl, the latter four groups being selected from OH and C 1-6 optionally substituted with one or two substituents selected from alkoxy; R 61 , R 62 , R 63 , and R 64 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 61 , R 62 , R 63 , and R 64 The rest are independently H, halo, and C. 1-6 Alkyl and C 1-6 Alkoxy, N(R 63’ )(R 64’ ), C 1-6 AlkyleneN(R 63’ )(R 64’ ), and SC 1-6 alkyl; or R 61 , R 62 , R 63 , and R 64 One of them is A', O-A', and C 1-4 alkylene A'; R 61 , R 62 , R 63 , and R 64 the remainder of are independently H or halo; R 63’ and R 64’ are independently H and C 1-6 alkyl, A' is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 72and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 72 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from halo, C 1-4 Alkyl, OC 1-4 Alkyl, N(R 72a )(R 72b ), C 1-6 AlkyleneN(R 72a )(R 72b ), and S.C. 1-6 and optionally substituted with one or more substituents independently selected from alkyl, R 65 , H, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 65 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR 65 ''; and 5-6 membered heteroaryl containing 1-4 hetero moieties independently selected from the group consisting of halo, OR, 73 , N(R 73 )(R 74 ), and S.R. 73 and / or C 1-6 Alkyl is O, C(O), CO2, and NR 75 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 65’ H and C 1-6 alkyl, R 65’’ H and C 1-6 alkyl, R 66 , R 67 , R 68 , and R 69are independently H, halo, and C 1-6 alkyl, R 70 and R 71 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 70 and R 71 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 76 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 72 , R 73 , R 74 , R 75 , and R 76 are independently H and C 1-6 alkyl, R 72a and R 72b are independently H and C 1-6 alkyl, All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0018] The present application further provides processes for the preparation of the compounds of the present application. General and specific processes are discussed in more detail below and described in the Examples below.

[0019] The present application also provides processes for the preparation of compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof.General and specific processes are discussed in more detail below and described in the examples below.

[0020] Other features and advantages of the present application will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples, while showing embodiments of the present application, are given for the purpose of illustration only, and the claims should not be limited by these embodiments, but should be given the broadest interpretation consistent with the description as a whole. [Brief description of the drawings]

[0021] The present application will now be described in more detail with reference to the accompanying drawings.

[0022] [Figure 1] 1 shows scores for an exemplary compound II-1 in the mouse head twitch assay at doses up to 30 mg / kg. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] I. Definition 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 application described herein where they are suitable, as would be understood by one of ordinary skill in the art.

[0024] As used herein, the terms "compound(s) of the application" or "compound(s) of the present application" and the like refer to compounds of Formula I, including pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, and all stereoisomers and regioisomers thereof.

[0025] As used herein, the terms "composition(s) of the application" or "composition(s) of the present application" and the like refer to compositions, such pharmaceutical compositions, that include one or more compounds of the present application.

[0026] As used herein, the term "and / or" means that the listed items are present or used individually or in combination. In practice, the term means that "at least one of" or "one or more of" the listed items are used or present. The term "and / or" with respect to pharma-ceutically acceptable salts and / or solvates thereof means that the compounds of the present application are present as individual salts and solvates as well as combinations of salts, for example, solvates of the compounds of the present application.

[0027] As used in this application, 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 a particular aspect having one compound, or two or more additional compounds.

[0028] As used in this application and the claims, "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.

[0029] As used herein, the term "comprising" and its derivatives are intended to be closed terminology specifying the presence of stated features, elements, components, groups, integers, and / or steps, and excluding the presence of other unstated features, elements, components, groups, integers, and / or steps.

[0030] As used herein, the term "consisting essentially of" is intended to specify the presence of the described features, elements, components, groups, integers, and / or steps, as well as things that do not materially affect the basic and novel characteristics of those features, elements, components, groups, integers, and / or steps.

[0031] In embodiments that include an "additional" or "second" component, such as an additional or second compound, as used herein, the second component is chemically distinct from the other component or the first component. A "third" component is distinct from the other component, the first component, and the second component, and further recited or "additional" components are similarly distinct.

[0032] As used herein, the term "suitable" means that the selection of a particular compound or condition will depend on the specific synthetic operation being performed, the identity of the molecule being converted, and / or the specific use for the compound, but the selection will be within the skill of one of ordinary skill in the art. All process / method steps described herein are performed under conditions sufficient to provide the indicated product. One of ordinary skill in the art will understand that all reaction conditions, including, for example, reaction solvent, reaction time, reaction temperature, reaction pressure, reactant ratios, and whether the reaction should be performed under anhydrous or inert atmosphere, can be varied to optimize the yield of the desired product, and it is within the skill of one of ordinary skill in the art to do so.

[0033] As used herein, the terms "about," "substantially," and "approximately" refer to a reasonable amount of deviation of the modified term so that the end result is not materially altered. These terms of degree should be interpreted as including at least ±5% deviation of the modified term, unless this deviation negates the meaning of the term it modifies or the context would suggest otherwise to one of ordinary skill in the art.

[0034] This specification references numerous chemical terms and abbreviations used by those of skill in the art. Nonetheless, definitions of selected terms are provided for clarity and consistency.

[0035] As used herein, the term "solvate" means a compound, or a salt and / or prodrug of a compound, wherein molecules of a suitable solvent are incorporated into the crystal lattice.

[0036] As used herein, the term "prodrug" means a compound, or a salt of a compound, that is converted into an active drug after administration.

[0037] As used herein, the term "zwitterion" refers to a molecule that contains an equal number of positively and negatively charged functional groups. Zwitterions are also known as "inner salts" and "zwitterions."

[0038] As used herein, the term "alkyl," whether used alone or as part of another group, means a straight or branched chain saturated alkyl group. The number of carbon atoms possible in the referenced alkyl group is determined by the prefix "C n1-n2 ". So, for example, "C 1-6 The term "alkyl" (or "C1-C6 alkyl") means an alkyl group having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0039] As used herein, the term "alkenyl," whether used alone or as part of another group, means a straight or branched chain unsaturated alkyl group containing at least one double bond. The number of carbon atoms possible in the referenced alkylene group is determined by the prefix "C n1-n2 For example, C 2-6 The term alkenyl refers to an alkenyl group having 2, 3, 4, 5, or 6 carbon atoms and at least one double bond.

[0040] As used herein, the term "alkynyl," whether used alone or as part of another group, means a straight or branched chain unsaturated alkynyl group containing at least one triple bond. The number of carbon atoms possible in the referenced alkyl group is determined by the prefix "C n1-n2 For example, C 2-6 The term alkynyl refers to alkynyl groups having 2, 3, 4, 5 or 6 carbon atoms.

[0041] The term "alkoxy" as used herein, alone or in combination, includes an alkyl group attached to an oxygen-linking atom.

[0042] As used herein, the term "fluoroalkoxy" refers to an alkoxy group, as defined above, in which one or more of the available hydrogen atoms has been replaced with fluorine.

[0043] As used herein, the term "deuteroalkoxy" refers to an alkoxy group, as defined above, in which one or more of the available hydrogen atoms has been replaced with deuterium.

[0044] As used herein, the term "cycloalkyl," whether used alone or as part of another group, means a saturated carbocyclic group containing from 3 to 6 carbon atoms and one or more rings. The number of carbon atoms possible in the referenced cycloalkyl group is determined by the numerical prefix "C". n1-n2 For example, C 3-10 The term cycloalkyl means a cycloalkyl group having 3, 4, 5 or 6 carbon atoms.

[0045] The term "heterocycloalkyl," as used herein, whether used alone or as part of another group, refers to a cyclic group containing at least one non-aromatic ring containing 3 to 6 atoms, where one or more of the atoms is a hetero moiety selected from O, S, S(O), SO2, and N, and the remaining atoms are C. Heterocycloalkyl groups are either saturated or unsaturated (i.e., contain one or more double bonds). Heterocycloalkyl groups are defined as groups that are either heterocyclic or non-cyclic, and may be any combination of the heterocyclic and non-cyclic rings. n1-n2 or "n1-n2", this prefix indicates the number of carbon atoms in the corresponding carbocyclic group in which one or more, preferably one to four, of the ring atoms are replaced with a hetero moiety selected from O, S, S(O), SO2, and N, and the remaining atoms are C.

[0046] The term "heteroaryl" as used herein, whether used alone or as part of another group, refers to a cyclic group containing at least one heteroaromatic ring containing 5-6 atoms, where one or more of the atoms are heteroatoms selected from O, S, and N, and the remaining atoms are C. Heteroaryl groups are defined as groups that are denoted by the prefix C. n1-n2 When the prefix contains a heteroatom, it indicates the number of carbon atoms in the corresponding carbocyclic group where one or more, preferably one to four, of the ring atoms are replaced with a heteroatom as defined above.

[0047] The term "halogen" (or "halo"), whether used alone or as part of another group, refers to a halogen atom and includes fluoro, chloro, bromo, and iodo.

[0048] As used herein, the term "haloalkyl" refers to an alkyl group as defined above in which one or more of the available hydrogen atoms has been replaced with a halogen. Thus, for example, "C 1-6 "Haloalkyl" refers to a C1 to C6 straight or branched chain alkyl group, as defined above, having one or more halogen substituents.

[0049] As used herein, the term "deuteroalkyl" refers to an alkyl group, as defined above, in which one or more of the available hydrogen atoms have been replaced with deuterium. Thus, for example, "C 1-6 "Deuteroalkyl" refers to a C1 to C6 straight or branched chain alkyl group, as defined above, having one or more deuterium substituents.

[0050] The term "available," as in "available hydrogen atom" or "available atom," refers to an atom that would be known to one of ordinary skill in the art to be available for replacement with a substituent.

[0051] As used herein, the term "one or more" items includes a single item selected from a list, as well as mixtures of two or more items selected from a list.

[0052] As used herein, the term "alternate isotope thereof" refers to an isotope of an element other than the isotope that is most abundant in nature.

[0053] As used herein, the term "all available atoms are optionally replaced with alternative isotopes" means that available atoms are optionally replaced with an isotope of that atom having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number primarily found in nature.

[0054] In the compounds of general formula I, and their pharma- ceutically acceptable salts and / or solvates, the atoms may exhibit their natural isotopic abundance, or one or more of the atoms may be artificially enriched with a particular isotope having the same atomic number, but an atomic mass or mass number different from that found predominantly in nature. The present disclosure is intended to include all suitable isotopic variations of the compounds of general formula I, and their pharma- ceutically acceptable salts and / or solvates. For example, different isotopic forms of hydrogen (H) include protium ( 1 H), deuterium ( 2 H), and tritium ( 3 H). Protium is the predominant hydrogen isotope found in nature.

[0055] In the compounds of general formula II, and their pharma- ceutically acceptable salts and / or solvates, the atoms may exhibit their natural isotopic abundance, or one or more of the atoms may be artificially enriched with a particular isotope having the same atomic number, but an atomic mass or mass number different from that found predominantly in nature. The present disclosure is intended to include all suitable isotopic variations of the compounds of general formula II, and their pharma- ceutically acceptable salts and / or solvates. For example, different isotopic forms of hydrogen (H) include protium ( 1 H), deuterium ( 2 H), and tritium ( 3 H). Protium is the predominant hydrogen isotope found in nature.

[0056] The term "compound" refers to a compound and, in certain embodiments, any hydrates or solvates thereof, so long as they are stable. A hydrate is a compound complexed with water, and a solvate is a compound complexed with a solvent, which may be an organic or inorganic solvent. A "stable" compound is one that can be prepared and isolated, and whose structure and properties remain essentially unchanged, or can be made to remain essentially unchanged, for a period of time sufficient to permit the use of the compound for the purposes described herein (e.g., therapeutic administration to a subject). The compounds of the present application are limited to stable compounds encompassed by the general formula I, or pharma- ceutically acceptable salts and / or solvates thereof. The compounds of the present application are limited to stable compounds encompassed by the general formula I, or pharma- ceutically acceptable prodrugs thereof. Further compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, are limited to stable compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof.

[0057] The term "pharmaceutical acceptable" means compatible with the treatment of a subject.

[0058] The term "pharmaceutical acceptable carrier" means a non-toxic solvent, dispersant, excipient, adjuvant, or other material with which an active ingredient is mixed to enable the formation of a pharmaceutical composition, i.e., a dosage form that can be administered to a subject.

[0059] The term "pharmaceutically acceptable salt" means either an acid addition salt or a base addition salt which is suitable or compatible with the treatment of a subject.

[0060] The acid addition salts suitable or compatible for the treatment of a subject are any non-toxic organic or inorganic acid addition salts of any basic compound.

[0061] A base addition salt suitable for or compatible with the treatment of a subject is any non-toxic organic or inorganic base addition salt of any acidic compound.

[0062] As used herein, terms such as "protecting group" or "PG" refer to chemical moieties that protect or mask reactive portions of a molecule to prevent side reactions at those reactive portions of the molecule while manipulating or reacting different portions 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. Selection of a suitable protecting group can be made by one of ordinary skill in the art. Many conventional protecting groups are described, for example, in "Protective Groups in Organic Chemistry" McOmie, JFW Ed., Plenum Press, 1973, in Greene, TW and Wuts, PGM, "Protective Groups in Organic Synthesis", John Wiley & Sons, 3 rd Edition, 1999, and Kocienski, P. Protecting Groups, 3rd Edition, 2003, Georg Thieme Verlag (The Americas).

[0063] As used herein, the term "subject" includes all members of the animal kingdom, including mammals, and preferably refers to humans. Thus, the methods of the present application are applicable to both human therapy and veterinary applications.

[0064] As used herein, and as is well understood in the art, the term "treating" or "treatment" refers to an approach to obtain 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 pathology, whether detectable or undetectable, reduction in the extent of disease, a stabilized (i.e., not worsening) state of disease, prevention of disease spread, delay or slowing of disease progression, improvement or palliative of disease state, reduction in recurrence of disease, and remission (whether partial or complete). "Treating" and "treatment" can also mean prolonging survival compared to expected survival in the absence of treatment. As used herein, "treating" and "treatment" also include prophylactic treatment. For example, a subject with early stage cancer can be treated to prevent progression, or alternatively, a subject in remission can be treated with a compound or composition of the present application to prevent recurrence. A method of treatment includes administering to a subject a therapeutically effective amount of one or more of the compounds of the present application, optionally consisting of a single dose or, alliteratively, including a series of doses.

[0065] As used herein, the term "effective amount" or "therapeutically effective amount" refers to an amount of one or more compounds of the present application that is effective, at dosages and for periods of time necessary, to achieve a desired result. For example, in the context of treating a disease, disorder, or condition mediated or treated by agonism or activation of serotonergic receptors and downstream second messengers, an effective amount is, for example, an amount that increases said activation compared to activation without administration of one or more compounds.

[0066] "Alleviating" a disease, disorder, or condition means that the severity and / or undesirable clinical signs of the disease, disorder, or condition are lessened and / or the time course of progression is slowed or prolonged compared to not treating the disorder.

[0067] As used herein, the term "administered" refers to administration of a therapeutically effective amount of one or more compounds or compositions of the present application to a cell, tissue, organ, or subject.

[0068] As used herein, the terms "prevention" or "prophylaxis," or their equivalents, refer to a reduction in the risk or probability that a patient will suffer from a disease, disorder, or condition, or exhibit symptoms associated with a disease, disorder, or condition.

[0069] As used herein, a "disease, disorder, or condition" refers to an impairment of a serotonin receptor, e.g., 5-HT 2A agonist, particularly by using a serotonin receptor agonist such as one or more of the compounds of the present application described herein.

[0070] As used herein, the term "treating a disease, disorder, or condition through activation of serotonin receptors" means that the disease, disorder, or condition being treated is influenced, regulated, and / or has some biological basis, either directly or indirectly, involving serotonergic activity, specifically increased serotonergic activity. These diseases respond favorably when the serotonergic activity associated with the disease, disorder, or condition is agonized by one or more of the compounds or compositions of the present application.

[0071] As used herein, the term "activation" includes agonism, partial agonism, and positive allosteric modulation of a serotonin receptor.

[0072] "5-HT 1A " and "5-HT 2A " is used herein to refer to the 5-HT2 serotonin receptor 2A and 5-HT 2A Receptor subtypes are meant.

[0073] As used herein, the term "therapeutic agent" refers to any drug or active agent that has a pharmacological effect when administered to a subject.

[0074] As used herein, the term "equivalent dose of psilocybin" means that the compound is administered or used in a dose that is the same molar amount as the corresponding dose of psilocybin.

[0075] II. Compounds The present application relates to a compound of formula I: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , SO2R 7 , C 1-6 Alkylene R 7 , and R 7 is selected from Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently H, halo, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 2a )(R 2b ), and S.C. 1-6 alkyl, R 2a and R 2bare independently H and C 1-6 alkyl, R 3 , R 4 , R 5 , and R 6 are independently H, halo, N(R 5’ )(R 6’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl, the latter four groups being selected from OH and C 1-6 optionally substituted with one or two substituents selected from alkoxy; R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-6 Alkyl, C 1-6 Alkoxy, N(R 5’ )(R 6’ ), C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl; or R 3 , R 4 , R 5 , and R 6 One of them is A, OA, and C 1-4 alkylene A; R 3 , R 4 , R 5 , and R 6 the remainder of are independently H or halo; R 5’ and R 6’ are independently H and C 1-6 alkyl, A is phenyl, C3-6 Cycloalkyl, O, S, S(O), SO 2 , N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from halo, C 1-4 Alkyl, OC 1-4 Alkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), and S.C. 1-4 and optionally substituted with one or more substituents independently selected from alkyl, R 7 , H, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 7 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR 7 ''; and 5-6 membered heteroaryl containing 1-4 hetero moieties independently selected from the following: halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-6 Alkyl is O, C(O), CO2, and NR 57 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 7’ H and C 1-6 alkyl, R 7’’ H and C 1-6 alkyl, R 26 , R 27 , R 28 , and R 29 are independently H, halo, and C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 54 , R 55 , R 56 , R 57 , and R 58 are independently H and C 1-6 alkyl, R 54a and R 54b are independently H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 But R 7and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0076] The present application relates to a compound of formula I: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is H,C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , and SO2R 7 is selected from Q is Q1, Q2, Q3, Q4, and Q5: [ka] and [ka] is a single bond or a double bond, provided that in Q1 [ka] If is a double bond, R 9 and R 15 does not exist and in Q2 [ka] If is a double bond, R 17 and R 25 does not exist, R 2 , R 2’ , R 2’’ , R 3 , and R 6 are independently H, halo, and C 1-6 Alkyl, and C 1-6 alkoxy; R 4 and R 5 One or both of the groups are independently selected from H, halo, C, 1-6 Alkyl, and C 1-6 alkoxy; or R 4 and R 5 are linked together to form O-(CH2) 1-2 Form O, or R 4 and R 5 One of A, OA, and C 1-4 alkylene A; R 4 and R 5 the other of which is H; A is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from halo, C 1-4 Alkyl and OC 1-4 and optionally substituted with one or more substituents independently selected from alkyl, R7 H and C 1-6 alkyl, C 1-6 Alkyl, halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or O, C(O), CO, and NR 57 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 7’ H and C 1-6 alkyl, R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 32 , R 33 , R 34 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , R 52 , and R 53 are independently H, halo, and C 1-6 alkyl, R 12 , R 20 , R35 , and R 45 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 54 , R 55 , R 56 , R 57 , and R 58 are independently H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, Q is Q3 and R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0077] In some embodiments, when all available hydrogen atoms in a group are optionally replaced with halogen atoms, the halogen atom is F, Cl, or Br. In some embodiments, when all available hydrogen atoms in a group are optionally replaced with halogen atoms, the halogen atom is F or Br. In some embodiments, when all available hydrogen atoms in a group are optionally replaced with halogen atoms, the halogen atom is F or Cl. In some embodiments, when all available hydrogen atoms in a group are optionally replaced with halogen atoms, the halogen atom is F.

[0078] In some embodiments, the compound of formula I has the following structure: [ka] or a pharma- ceutically acceptable salt or solvate thereof, During the ceremony, R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , R 6 , R 26 , R 27 , R 28 , R 29 , R 30 , and R 31 is as defined for formula I, All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0079] In some embodiments, R 1 , R 2 , R 2’ , R 3 , R 5 , and R 6 are all H, and the compound formula [ka] or a pharma- ceutically acceptable salt and / or solvate thereof, During the ceremony, R 4 and Q is as defined for formula I; All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0080] In some embodiments, R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , and R 6 are all H, and compound formula I has the following structure: [ka] or a pharma- ceutically acceptable salt and / or solvate thereof, During the ceremony, R 5 and Q is as defined for formula I; All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0081] In some embodiments, R 1 , R2 , R 2’ , R 2’’ , R 3 , and R 6 are all H, and compound formula I has the following structure: [ka] or a pharma- ceutically acceptable salt and / or solvate thereof, During the ceremony, R 4 , R 5 and Q are as defined for formula I; All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0082] In some embodiments, R 1 , R 2 , R 2’ , and R 2’’ are all H and R 3 , R 4 , R 5 , and R 6 are all D, and the compound of formula I has the following structure: [ka] or a pharma- ceutically acceptable salt and / or solvate thereof, During the ceremony, Q is as defined for formula I, All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0083] In some embodiments, R 26 , R 27 , R 28 , and R 29 are independently H, D, F, Cl, and C. 1-6alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 26 , R 27 , R 28 , and R 29 are independently H, D, F, Cl, and C. 1-6 Alkyl, C 1-6 Fluoroalkyl, and C 1-6 In some embodiments, R 26 , R 27 , R 28 , and R 29 is independently selected from H, F, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 26 , R 27 , R 28 , and R 29 is independently selected from H, F, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CHCHD, CHCDH, and CDCD. 26 , R 27 , R 28 , and R 29 is independently selected from H and D.

[0084] In some embodiments, Q is the following group: [ka] wherein R 30 and R 31 is as defined in formula I. In some embodiments, Q is the following group: [ka] wherein R 30 and R 31 is as defined in formula I.

[0085] In some embodiments, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 30 and R 31 are independent of each other, H, D, and C. 1-6 Alkyl, C 1-6 Fluoroalkyl, C 1-6 Deuteroalkyl, C(O)C 1-6 Fluoroalkyl and C(O)C 1-6 In some embodiments, R 30 and R 31 are independent of each other, H, D, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C(O)C 1-4 Alkyl, C(O)C 1-4 Fluoroalkyl and C(O)C 1-4 In some embodiments, R 30 and R 31 is independently selected from H, D, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3C(O), CD2HC(O), CDH2C(O), CD3C(O), CF3C(O), CHF2C(O), CH3CH2C(O), CH(CH3)2C(O), CH2DCH2C(O), CD2HCH2C(O), and CD3CH2C(O).

[0086] In some embodiments, R 30 and R 31 is independently selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 30 and R 31is independently selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, and CH(CH). 30 and R 31 is independently selected from H, D, CH, CD, CFH, CF, and CH(CH). 30 and R 31 is independently selected from H, D, CH, CF, and CH(CH). In some embodiments, R 30 and R 31 is independently selected from H, D, CH3, and CD3. In some embodiments, R 30 and R 31 is independently selected from H, CH, and CD. In some embodiments, R 30 and R 31 is independently selected from CH3 and CD3. In some embodiments, R 30 and R 31 is independently selected from H and CH(CH). In some embodiments, R 30 and R 31 are both CH(CH3)2.

[0087] In some embodiments, R 30 and R 31 is independently selected from H, D, H, D, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH3C(O), CD2HC(O), CDH2C(O), CD3C(O), CF3C(O), CHF2C(O), CH3CH2C(O), CH(CH3)2C(O), CH2DCH2C(O), CD2HCH2C(O), and CD3CH2C(O). 30 and R 31 is independently selected from H, D, CHC(O), CDHC(O), CDHC(O), CDC(O), CFC(O), CHFC(O), CHCHC(O), CH(CH)C(O), CHDCHC(O), CDHCHC(O), and CDCDC(O). 30 and R31 is independently selected from H, CHC(O), CDC(O), CFHC(O), and CFC(O).

[0088] In some embodiments, Q is the following group: [ka] wherein R 30 and R 31 are independent of each other, H, D, and C. 1-6 Alkyl, C 1-6 Fluoroalkyl, and C 1-6 In some embodiments, R 30 and R 31 are independent of each other, H, C 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 30 and R 31 is independently selected from H, CH, CD, CFH, and CF. In some embodiments, R 30 and R 31 is independently selected from CH3 and CD3.

[0089] In some embodiments, R 30 and R 31 together with the N atom to which they are attached, O, N, and NR 58 In some embodiments, R 30 and R 31 together with the N atom to which they are attached, O, N, and NR 58 Forms a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from:

[0090] In some embodiments, the 3-6 membered heterocycle is selected from aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolinyl, piperidinyl, piperazinyl, and morpholinyl. In some embodiments, the 3-6 membered heterocycle is selected from azetidinyl, pyrrolidinyl, pyrazolinyl, piperidinyl, and piperazinyl. In some embodiments, the 3-6 membered heterocycle is pyrrolidinyl.

[0091] In some embodiments, R 1 is C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , SO2R 7 , C 1-4 Alkylene R 7 , and R 7 wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0092] In some embodiments, R 1 is C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , and SO2R 7 In some embodiments, R 1 is C(O)R 7 , CO2R 7 , and C(O)N(R 7 )(R 7’ In some embodiments, R 1 is C(O)R 7 and CO2R 7 is selected from.

[0093] In some embodiments, R 7’ H and C 1-4alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7’ H, D, C 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 7’ is selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 7’ is selected from H, CH, CD, CFH, and CF. In some embodiments, R 7’ is selected from H, CH3, and CD3.

[0094] In some embodiments, R 1 is R 7 and C 1-4 Alkylene R 7 In some embodiments, R 1 is R 7 and C 1-2 Alkylene R 7 In some embodiments, R 1 is R 7 In some embodiments, R 1 is C 1-4 Alkylene R 7 In some embodiments, R 1 is C1 alkylene R 7 (CH2R 7 ).

[0095] In some embodiments, R 7 , H, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 7’’ and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR7’’ and wherein the seven latter groups are selected from halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-4 Alkyl is O, C(O), CO2, and NR 57 and any available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0096] In some embodiments, R 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 Phenyl optionally substituted with one or more substituents independently selected from 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 7’’ and 3-6 membered heterocycloalkyl containing 1-3 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 7’’ and 3-6 membered heterocycloalkyl containing 1-3 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is phenyl, C 3-6Cycloalkyl, O, S, S(O), SO2, N, and NR 7’’ and 5-6 membered heterocycloalkyl containing 1-2 hetero moieties independently selected from O, S, N, and NR 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0097] In some embodiments, R 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is phenyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0098] In some embodiments, R 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 C optionally substituted with one or more substituents independently selected from 3-6 In some embodiments, R is a cycloalkyl group, and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is C 3-6 In some embodiments, R is a cycloalkyl group, and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 C in 3-6 Cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. In some embodiments, R 7 C in 3-6Cycloalkyl is selected from cyclopropyl, cyclobutyl, and cyclopentyl. In some embodiments, R 7 C in 3-6 Cycloalkyl is cyclopropyl.

[0099] In some embodiments, R 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 O, S, S(O), SO2, N, and NR, optionally substituted with one or more substituents independently selected from 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 are O, S, S(O), SO2, N, and NR 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 O, S, S(O), SO2, N, and NR 7’’ and R is selected from aziridinyl, oxiranyl, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thianyl, thianyloxide, and thianyldioxide. 7 O, S, S(O), SO2, N, and NR 7’’ The 3-6 membered heterocycloalkyl containing 1-2 heteromoieties independently selected from is selected from azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thianyl, and thianyl dioxide.7 O, S, S(O), SO2, N, and NR 7’’ The 3-6 membered heterocycloalkyl containing 1-2 heteromoieties independently selected from is selected from tetrahydropyranyl, thianyl, and thianyl dioxide.

[0100] In some embodiments, R 7 are independent, halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 O, S, N, and NR optionally substituted with one or more substituents selected from 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 are O, S, N, and NR 7’’ and wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 O, S, N, and NR in 7’’ The 5-6 membered heteroaryl containing 1-3 heteromoieties independently selected from is selected from pyrrolyl, furanyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, pyrazolyl, thiophenyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and triazinyl. 7 O, S, N, and NR in 7’’ The 5-6 membered heteroaryl containing 1-3 hetero moieties independently selected from is selected from pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, pyrazolyl, thiophenyl, pyrazolyl, and pyridinyl.

[0101] In some embodiments, R 7 , Halo, OR 55 , N(R 55)(R 56 ), and S.R. 55 C optionally substituted with one or more substituents independently selected from 2-6 Alkenyl and C 2-6 alkynyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 C optionally substituted with one or more substituents independently selected from 2-4 Alkenyl and C 2-4 alkynyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0102] In some embodiments, R 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 C optionally substituted with one or more substituents independently selected from 2-4 alkenyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is C 2-4 alkenyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0103] In some embodiments, R 7 , Halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 C optionally substituted with one or more substituents independently selected from 2-4 alkynyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is C 2-4alkynyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 is selected from C≡CH, C≡CCH3, CH2C≡CH, C≡CCH2CH3, CH2C≡CCH3. In some embodiments, R 7 is CH2C≡CH.

[0104] In some embodiments, R 7 H and C 1-4 alkyl, C 1-4 Alkyl, halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-4 Alkyl is O, C(O), CO2, and NR 57 and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 H and C 1-4 alkyl, C 1-4 Alkyl, halo, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-4 Alkyl is O, C(O), CO2, and NR 57 and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 H and C 1-4 alkyl, C 1-4 Alkyl is F, Cl, OR 55 , N(R 55 )(R 56 ), and S.R. 55and / or C 1-4 Alkyl is O, C(O), CO2, and NR 57 and any available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0105] In some embodiments, R 7 H and C 1-4 alkyl, C 1-4 Alkyl is F, Cl, OR 55 , N(R 55 )(R 56 ), and S.R. 55 and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 H and C 1-4 alkyl, C 1-4 Alkyl is optionally substituted OR 55 wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0106] In some embodiments, R 7 H and C 1-4 alkyl, C 1-4 Alkyl is O, C(O), CO2, and NR 57 and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 H and C 1-4 alkyl, C 1-4 Alkyl is optionally interrupted O, and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0107] In some embodiments, R 7 H and C 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 7 H, D, C 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 7 H, D, C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, OC 1-4 Alkyl, OC 1-4 Fluoroalkyl and OC 1-4 In some embodiments, R 7 is selected from H, D, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH(CD3)2, CH2CD2H, and CD2CD3. 7 is selected from H, CH, CD, CFH, CF, and CH(CH). In some embodiments, R 7 is selected from H, CH, CD, CFH, and CF. In some embodiments, R 7 is selected from H, CH, CD, and CH(CH). In some embodiments, R 7 is selected from H, CH3, and CD3. In some embodiments, R 7 is H.

[0108] In some embodiments, R 1 is R 7 Thus, in some embodiments, R 1 H and C 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 1 H, D, C 1-4Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 1 H, D, C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, OC 1-4 Alkyl, OC 1-4 Fluoroalkyl and OC 1-4 In some embodiments, R 1 is selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 7 are H, D, CH3, CD3, CF3, CH2CH3, CH(CD3)2, and CH(CH3)2, and R 1 is selected from H, D, CH, CD, CF, CHCH, and CH(CH). 1 is selected from H, CH, CD, CFH, CF, and CH(CH). In some embodiments, R 1 is selected from H, CH, CD, CFH, and CF. In some embodiments, R 1 is selected from H, CH, CD, and CH(CH). In some embodiments, R 1 is R 7 and R 7 is selected from H, CH, CD, and CH(CH). In some embodiments, R 1 is selected from H, CH3, and CD3. In some embodiments, R 1 is selected from CH3 and CD3. In some embodiments, R 1 R 7 and R 7 When is H, R 1 is H. Thus, in some embodiments, R 1 is H.

[0109] In some embodiments, R 7’’ H and C 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. ’’ H, D, C 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 7’’ is selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 7’’ is selected from H, CH, CD, CFH, and CF. In some embodiments, R 7’’ is selected from H, CH3, and CD3.

[0110] In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, halo, and C 1-4 Alkyl, C 1-4 Alkoxy, C 1-3 AlkyleneN(R 2a )(R 2b ), and S.C. 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms.

[0111] In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, D, F, Cl, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, C 1-4 Deuteroalkoxy, C 1-3 AlkyleneN(R 2a )(R 2b ), C1-3 Fluoroalkylene N(R 2a )(R 2b ), C 1-3 DeuteroalkyleneN(R 2a )(R 2b ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, D, F, Cl, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, C 1-4 Deuteroalkoxy, C 1-3 AlkyleneN(R 2a )(R 2b ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 Deuteroalkyl is selected from the group consisting of aryl, aryloxy ...

[0112] In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, D, F, Cl, Br, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CHD2CH2O, CD2HCH2O, and CD3CD2O, C 1-2 AlkyleneN(R 2a )(R 2b ), C 1-2 Fluoroalkylene N(R 2a )(R 2b ), C 1-2 DeuteroalkyleneN(R 2a )(R 2b), CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S. In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, D, F, Cl, Br, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CHD2CH2O, CD2HCH2O, and CD3CD2O, C 1-2 AlkyleneN(R 2a )(R 2b ), CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S.

[0113] In some embodiments, R 2 , R 2’ , and R 2’’ is independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CHD2CH2O, CD2HCH2O, CD3CD2O, CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S. 2 , R 2’ , and R 2’’ is independently selected from H, D, CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S.

[0114] In some embodiments, R2 , R 2’ , and R 2’’ are independent, H, D, F, C 1-2 AlkyleneN(R 2a )(R 2b ), C 1-2 Fluoroalkylene N(R 2a )(R 2b ), and C 1-2 DeuteroalkyleneN(R 2a )(R 2b ) is selected.

[0115] In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, D, F, Cl, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R 2 , R 2’ , and R 2’’ are independently H, D, F, Cl, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R 2 , R 2’ , and R 2’’ is independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CHD2CH2O, CD2HCH2O, and CD3CD2O.

[0116] In some embodiments, R 2 , R2’ , and R 2’’ is independently selected from H, F, D, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O. 2 , R 2’ , and R 2’’ is independently selected from H, D, F, CH3O, CD3O, CF2HO, and CF3O.

[0117] In some embodiments, R 2 , R 2’ , and R 2’’ is independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, and CD2CD3. 2 , R 2’ , and R 2’’ is independently selected from H, D, F, CH, CDH, CDH, CD, CF, CHF, CHCH, and CH(CH). 2 , R 2’ , and R 2’’ is independently selected from H, F, D, CH, CD, CFH, and CF. In some embodiments, R 2 , R 2’ , and R 2’’ is independently selected from H, F, D, CH3, and CD3.

[0118] In some embodiments, R 2’’ is selected from H, F, D, CH, CD, CFH, and CF. In some embodiments, R 2’’ is selected from H, D, or F. In some embodiments, R 2’’ is selected from H or F. In some embodiments, R 2’’ is H.

[0119] In some embodiments, R 2 and R2’ is independently selected from H, F, D, CH, CD, CFH, and CF. In some embodiments, R 2 and R 2’ is independently selected from H, D, or F. In some embodiments, R 2 and R 2’ are both H or R 2 and R 2’ and R are both D. 2 and R 2’ are both H.

[0120] In some embodiments, R 2 , R 2’ , and R 2’’ is independently H, D, or F. In some embodiments, R 2 , R 2’ , and R 2’’ are all H or all D. In some embodiments, R 2 , R 2’ , and R 2’’ are all H.

[0121] In some embodiments, R 2a and R 2b are independently H and C 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 2a and R 2b are independent of each other, H, D, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 2a and R 2b is independently selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 2a and R 2bis independently selected from H, CH, CD, CFH, and CF. In some embodiments, R 2a and R 2b is independently selected from H, CH3, and CD3.

[0122] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, halo, N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-4 alkyl, the latter four groups being selected from OH and C 1-4 and all available hydrogen atoms are optionally and independently replaced with fluorine atoms or deuterium atoms. 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, C 1-4 Deuteroalkoxy, C 1-4 AlkyleneN(R 5’ )(R 6’ ), C 1-4 DeuteroalkyleneN(R 5’ )(R 6’ ), C 1-4 Fluoroalkylene N(R 5’ )(R 6’ ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4deuteroalkyl, the latter 12 groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R is optionally substituted with one or two substituents selected from deuteroalkoxy. 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, C 1-4 Deuteroalkoxy, C 1-4 AlkyleneN(R 5’ )(R 6’ ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 deuteroalkyl, the latter ten groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 Optionally substituted with one or two substituents selected from deuteroalkoxy.

[0123] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 AlkyleneN(R 5’ )(R 6’ ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4deuteroalkyl, the latter seven groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R is optionally substituted with one or two substituents selected from deuteroalkoxy. 3 , R 4 , R 5 , and R 6 are independent of H, D, and N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 AlkyleneN(R 5’ )(R 6’ ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 Deuteroalkyl is selected from the group consisting of aryl, aryloxy ...

[0124] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, and C 1-4 AlkyleneN(R 5’ )(R 6’ ), the latter four groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R is optionally substituted with one or two substituents selected from deuteroalkoxy. 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, N(R 5’ )(R 6’ ), C 1-4 Alkyl, C1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, and C 1-2 AlkyleneN(R 5’ )(R 6’ In some embodiments, R 3 , R 4 , R 5 , and R 6 One to three of the following are independently selected: H, D, F, N(R 5’ )(R 6’ ), CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, and C 1-2 AlkyleneN(R 5’ )(R 6’ ) and R 3 , R 4 , R 5 , and R 6 The remainder of R is selected from H and D. 3 , R 4 , R 5 , and R 6 One to three of the following are independently selected: H, D, F, N(R 5’ )(R 6’ ), CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, and CH2 alkylene N(R 5’ )(R 6’ ) and R 3 , R 4 , R 5 , and R 6 The remainder of R is selected from H and D. 3 , R 4 , R 5 , and R 6 are independent of H, D, and N(R 5’ )(R 6’ ), C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, and C 1-2 AlkyleneN(R 5’ )(R 6’In some embodiments, R 3 , R 4 , R 5 , and R 6 One to three of the following are independently selected: H, D, N(R 5’ )(R 6’ ), CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, and C 1-2 AlkyleneN(R 5’ )(R 6’ ) and R 3 , R 4 , R 5 , and R 6 The remainder of are selected from H and D.

[0125] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, SC 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 deuteroalkyl, the latter six groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R is optionally substituted with one or two substituents selected from deuteroalkoxy. 3 , R 4 , R 5 , and R 6 One to three of these are independently H, D, F, Cl, or C. 1-3 Alkyl, C 1-3 Fluoroalkyl, C 1-3 Deuteroalkyl, SC 1-3 Alkyl, SC 1-3 Fluoroalkyl and SC 1-3 deuteroalkyl; R 3 , R 4 , R5 , and R 6 The remainder of R is selected from H and D. 3 , R 4 , R 5 , and R 6 one to three of are independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S; R 3 , R 4 , R 5 , and R 6 The remainder of R is selected from H and D. 3 , R 4 , R 5 , and R 6 One to three of them are independently H, D, and C. 1-3 Alkyl, C 1-3 Fluoroalkyl, C 1-3 Deuteroalkyl, SC 1-3 Alkyl, SC 1-3 Fluoroalkyl and SC 1-3 deuteroalkyl; R 3 , R 4 , R 5 , and R 6 The remainder of R is selected from H and D. 3 , R 4 , R 5 , and R 6 one to three of are independently selected from H, D, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S; R 3 , R 4 , R 5 , and R 6The remainder of are selected from H and D.

[0126] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, halo, and C 1-4 Alkyl, and C 1-4 alkoxy, the latter two groups being selected from OH and C 1-4 and all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 deuteroalkoxy, the latter six groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 Optionally substituted with one or two substituents selected from deuteroalkoxy.

[0127] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, and C. 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 deuteroalkoxy, the latter three groups being selected from OH, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R is substituted with one or two substituents selected from deuteroalkoxy. 3 , R 4, R 5 , and R 6 One of them is OH,C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 C substituted with one or two substituents selected from deuteroalkoxy 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 R is selected from deuteroalkoxy; 3 , R 4 , R 5 , and R 6 The rest are independently H, D, F, Cl, Br, and C. 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R 3 , R 4 , R 5 , and R 6 One of them is OH,C 1-3 Alkoxy, C 1-3 Fluoroalkoxy, and C 1-3 C substituted with one or two substituents selected from deuteroalkoxy 1-3 Alkoxy, C 1-3 Fluoroalkoxy, and C 1-3 R is selected from deuteroalkoxy; 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H, D, CH3O, CD3O, and CF3O. 3 and R 4 One of them is OH,C 1-3 Alkoxy, C 1-3 Fluoroalkoxy, and C 1-3 C substituted with one or two substituents selected from deuteroalkoxy 1-3 Alkoxy, C 1-3 Fluoroalkoxy, and C 1-3 R is selected from deuteroalkoxy; 3 , R 4 , R 5, and R 6 The remainder of are independently selected from H, D, CH3O, CD3O, and CF3O. 3 and R 4 One of them is C. 1-3 Alkoxy-substituted C 1-3 alkoxy; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H, D, CH3O, CD3O, and CF3O. 3 and R 4 one of which is C substituted with one substituent selected from CH3O, CD3O, and CF3O; 1-3 Alkoxy, R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H, D, CH3O, CD3O, and CF3O. 4 is a C substituted with one substituent selected from CH3O, CD3O, and CF3O; 1-3 Alkoxy, R 3 , R 5 , and R 6 the remainder of which are independently selected from H, D, CH3O, CD3O, and CF3O.

[0128] In some embodiments, R 3 , R 4 , R 5 , and R 6 are independently H, D, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R 3 , R 4 , R 5 , and R 6One to three of these are independently H, D, F, Cl, Br, or C. 1-3 Alkyl, C 1-3 Fluoroalkyl, C 1-3 Deuteroalkyl, C 1-3 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 R is selected from deuteroalkoxy; 3 , R 4 , R 5 , and R 6 The remainder of are selected from H and D.

[0129] In some embodiments, R 3 , R 4 , R 5 , and R 6 one to three of are independently selected from H, D, F, Cl, Br, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH3CH2O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O; R 3 , R 4 , R 5 , and R 6 The remainder of are selected from H and D.

[0130] In some embodiments, R 3 , R 4 , R 5 , and R 6 one to three of are independently selected from H, D, F, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O; R 3 , R 4 , R 5 , and R 6 The remainder of are selected from H and D.

[0131] In some embodiments, R 3 , R 4 , R5 , and R 6 1 to 3 of them are F and R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 3 , R 4 , R 5 , and R 6 One or two of the groups are F, and R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 3 and R 4 One of them is F and the other is R 3 , R 4 , R 5 , and R 6 R of 5 the remainder are independently selected from H and D.

[0132] In some embodiments, R 3 , R 4 , R 5 , and R 6 one to three of are independently selected from CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 3 , R 4 , R 5 , and R 6 one to three of are independently selected from CH3O, CD2HO, CDH2O, CD3O, CF3O, and CHF2O; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 3 , R4 , R 5 , and R 6 one or two of are independently selected from CH3O, CD2HO, CDH2O, CD3O, CF3O, and CHF2O; R 3 , R 4 , R 5 , and R 6 the remainder of are independently selected from H and D.

[0133] In some embodiments, R 4 and R 5 one or both of are independently selected from H, F, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O; 3 , R 4 , R 5 , and R 6 The remainder of R is selected from H and D. 4 and R 5 one or both of are independently selected from CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH2CH3O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O; 3 , R 4 , R 5 , and R 6 The remainder of R is selected from H and D. 4 and R 5 one or both of are independently selected from OCH3, OCD2H, OCDH2, OCD3, OCF3, and OCHF2; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 4 and R 5 are both independently selected from OCH3, OCD2H, OCDH2, OCD3, OCF3, and OCHF2; R 3 and R 6is independently selected from H and D.

[0134] In some embodiments, R 3 , R 4 , R 5 , and R 6 is independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, and CD2CD3; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 3 , R 4 , R 5 , and R 6 one or two of are independently selected from CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, and CD2CD3; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 4 and R 5 one or both of are independently selected from CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, and CD2CD3; 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H and D. In some embodiments, R 3 , R 4 , R 5 , and R 6 is selected from H and D. In some embodiments, R 3 , R 4 , R 5 , and R 6 All of are D or R 3 , R 4 , R 5 , and R 6All of them are H.

[0135] In some embodiments, R 3 and R 6 are independently H, D, Cl, F, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 3 and R 6 are independently H, D, Cl, F, and C. 1-2 Alkyl, C 1-2 Fluoroalkyl, and C 1-2 In some embodiments, R 3 and R 6 is independently selected from H, D, F, Cl, Br, CH, CDH, CDH, CD, CF, and CHF. 3 and R 6 is independently selected from H, D, F, CH3, CF3, and CD3.

[0136] In some embodiments, R 3 and R 6 is independently selected from H and D. In some embodiments, R 3 and R 6 At least one of R is D. 3 and R 6 Each of R is D. 3 and R 6 Each of is H.

[0137] In some embodiments, R 4 and R 5 One or both of the groups are independently H, D, F, Cl, C 1-6 Alkyl, C 1-6 Fluoroalkyl, C 1-6 Deuteroalkyl, C 1-6 Alkoxy, C 1-6 Fluoroalkoxy, and C 1-6In some embodiments, R 4 and R 5 One or both of are independently selected from H, D, F, Cl, CH3, CF3, CF2H, CD3, CH3O, CF3O, CHF2O, and CD3O.

[0138] In some embodiments, R 4 and R 5 Both are independent of D, F, Cl, C 1-6 Alkyl, C 1-6 Fluoroalkyl, C 1-6 Deuteroalkyl, C 1-6 Alkoxy, C 1-6 Fluoroalkoxy, and C 1-6 In some embodiments, R 4 and R 5 are independently selected from D, F, Cl, CH3, CF3, CF2H, CD3, CH3O, CF3O, CHF2O, and CD3O.

[0139] In some embodiments, R 4 is H or D, R 5 are H, D, F, Cl, and C. 1-6 Alkyl, C 1-6 Fluoroalkyl, C 1-6 Deuteroalkyl, C 1-6 Alkoxy, C 1-6 Fluoroalkoxy, and C 1-6 In some embodiments, R 4 is H or D, R 5 is selected from D, F, Cl, CH3, CF3, CF2H, CD3, CH3O, CF3O, CHF2O, and CD3O.

[0140] In some embodiments, R 5 is H or D, R 4 are H, D, F, Cl, and C. 1-6 Alkyl, C 1-6 Fluoroalkyl, C 1-6 Deuteroalkyl, C1-6 Alkoxy, C 1-6 Fluoroalkoxy, and C 1-6 In some embodiments, R 5 is H or D, R 4 is selected from D, F, Cl, CH3, CF3, CF2H, CD3, CH3O, CF3O, CHF2O, and CD3O.

[0141] In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-4 Alkyl, C 1-4 Alkoxy, N(R 5’ )(R 6’ ), C 1-4 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, C 1-4 Deuteroalkoxy, N(R 5’ )(R 6’ ), C1-4 AlkyleneN(R 5’ )(R 6’ ), C 1-4 DeuteroalkyleneN(R 5’ )(R 6’ ), C 1-4 Fluoroalkylene N(R 5’ )(R 6’ ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, C 1-4 Deuteroalkoxy, N(R 5’ )(R 6’ ), C 1-4 AlkyleneN(R 5’ )(R 6’ ), S.C. 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 Deuteroalkyl is selected from the group consisting of aryl, aryloxy ...

[0142] In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, D, F, Cl, Br, and C.1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, N(R 5’ )(R 6’ ), and C 1-4 AlkyleneN(R 5’ )(R 6’ In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, D, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, N(R 5’ )(R 6’ ), and C 1-2 AlkyleneN(R 5’ )(R 6’ In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The remainder of the groups are independently H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, N(R 5’ )(R 6’ ), and CH2 alkyleneN(R 5’ )(R 6’ In some embodiments, R 4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6are independently H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, N(R 5’ )(R 6’ ), and CH2 alkyleneN(R 5’ )(R 6’ ) is selected.

[0143] In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, D, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, SC 1-4 Alkyl, SC 1-4 Fluoroalkyl and SC 1-4 In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, D, F, Cl, and C. 1-3 Alkyl, C 1-3 Fluoroalkyl, C 1-3 Deuteroalkyl, SC 1-3 Alkyl, SC 1-3 Fluoroalkyl and SC 1-3 In some embodiments, R 3 , R 4 , R 5 , and R 6Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 the remainder are independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S. 4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6 is independently selected from H, D, F, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3S, CD2HS, CDH2S, CD3S, CF3S, CHF2S, CH2CH3S, CH(CH3)2S, CHD2CH2S, CD2HCH2S, and CD3CD2S.

[0144] In some embodiments, R 5’ and R 6’ are independently H and C 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 5’ and R 6’ are independent of each other, H, D, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 5’ and R 6’ is independently selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 5’ and R 6’is independently selected from H, CH, CD, CFH, and CF. In some embodiments, R 5’ and R 6’ is independently selected from H, CH3, and CD3.

[0145] In some embodiments, R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-6 Alkyl, and C 1-6 alkoxy, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-4 Alkyl, and C 1-4 alkoxy, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, F, Cl, Br, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R 3 , R 4 , R 5 , and R 6 two adjacent ones of are linked together to form O-(CH2)O, and R 3 , R 4 , R 5 , and R 6 the remainder are independently selected from H, D, F, Cl, Br, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH3CH2O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O.

[0146] In some embodiments, R 4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6 are independently H, F, Cl, Br, C 1-4 Alkyl, C 1-4 Fluoroalkyl, C 1-4 Deuteroalkyl, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 In some embodiments, R 4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6 is independently selected from H, D, F, Cl, Br, CH3, CD2H, CDH2, CD3, CF3, CHF2, CH2CH3, CH(CH3)2, CH2CH2D, CH2CD2H, CD2CD3, CH3O, CD2HO, CDH2O, CD3O, CF3O, CHF2O, CH3CH2O, CH(CH3)2O, CH2DCH2O, CD2HCH2O, and CD3CD2O.4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6 is independently selected from H, D, F, CH3O, CD2HO, CDH2O, CD3O, CF3O, and CHF2O. 4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6 are both H or R 3 and R 6 and R are both D. In some embodiments, R 4 and R 5 are linked together to form O-(CH2)O, and R 3 and R 6 are both H.

[0147] In some embodiments, R 4 and R 5 are linked together to form O-CH2O.

[0148] In some embodiments, R 3 , R 4 , R 5 , and R 6 One of them is A, OA, and C. 1-2 alkylene A; R 3 , R 4 , R 5 , and R 6 The remainder of are independently H or halo, and any available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , R 5 , and R 6 One of them is A, OA, and C. 1-2 alkylene A; R 3 , R 4 , R 5 , and R 6The remainder of are independently H, F, Br, or Cl, and any available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , R 5 , and R 6 is selected from A, OA, CH2A, CF2A, and CD2A; R 3 , R 4 , R 5 , and R 6 The remainder of are independently H, D, or F. In some embodiments, R 3 , R 4 , R 5 , and R 6 is selected from A, OA, CH2A, CF2A, and CD2A; R 3 , R 4 , R 5 , and R 6 the remainder of are independently selected from H and D.

[0149] In some embodiments, R 3 , R 4 , and R 5 One of them is A, OA, and C. 1-2 alkylene A; R 3 , R 4 , R 5 , and R 6 The remainder of are independently H or halo, and any available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 3 , R 4 , and R 5 is selected from A, OA, CH2A, CF2A, and CD2A; R 3 , R 4 , R 5 , and R 6 The remainder of are independently selected from H, Cl, F, Br, D, and F. In some embodiments, R 3 , R 4 , and R 5is selected from A, OA, CH2A, CF2A, and CD2A; R 3 , R 4 , R 5 , and R 6 the remainder of are independently selected from H, D, and F.

[0150] In some embodiments, R 4 and R 5 One of them is A, OA, and C. 1-2 alkylene A; R 4 and R 5 The other of R is H or D, and any available hydrogen atom is optionally and independently replaced with a fluorine atom or a deuterium atom. 4 and R 5 is selected from A, OA, CH2A, CF2A, and CD2A; R 4 and R 5 The other of R is H or D. 4 A, OA, and C 1-2 alkylene A; R 5 is H or D, and all available hydrogen atoms are optionally and independently replaced with fluorine atoms or deuterium atoms. 4 is selected from A, OA, CH2A, CF2A, and CD2A; R 5 is H or D. In some embodiments, R 5 A, OA, and C 1-2 alkylene A; R 4 is H or D, and all available hydrogen atoms are optionally and independently replaced with fluorine atoms or deuterium atoms. 5 is selected from A, OA, CH2A, CF2A, and CD2A; R 4 is H or D.

[0151] In some embodiments, A is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR54 and 3-6 membered heterocycloalkyl containing 1-3 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from F, Cl, Br, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl, OC 1-4 Fluoroalkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), C 1-4 DeuteroalkyleneN(R 54a )(R 54b ), C 1-4 Fluoroalkylene N(R 54a )(R 54b ), S.C. 1-4 Alkyl, SC 1-4 Deuteroalkyl and SC 1-4 In some embodiments, A is optionally substituted with 1 or 2 substituents independently selected from phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-3 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from F, Cl, Br, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4Deuteroalkyl, OC 1-4 Fluoroalkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), S.C. 1-4 Alkyl, SC 1-4 Deuteroalkyl and SC 1-4 In some embodiments, A is optionally substituted with 1 or 2 substituents independently selected from phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 5-6 membered heterocycloalkyl containing 1-2 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl and OC 1-4 Optionally substituted with 1 or 2 substituents independently selected from fluoroalkyl.

[0152] In some embodiments, A is F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl, OC 1-4 Fluoroalkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), S.C. 1-4 Alkyl, SC 1-4 Deuteroalkyl and SC 1-4In some embodiments, A is phenyl, optionally substituted with one or two substituents independently selected from fluoroalkyl. In some embodiments, A is phenyl, optionally substituted with one or two substituents independently selected from F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl and OC 1-4 Optionally substituted with 1 or 2 substituents independently selected from fluoroalkyl.

[0153] In some embodiments, A is F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl, OC 1-4 Fluoroalkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), S.C. 1-4 Alkyl, SC 1-4 Deuteroalkyl and SC 1-4 C optionally substituted with 1 or 2 substituents independently selected from fluoroalkyl 3-6 In some embodiments, A is cycloalkyl. 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl and OC 1-4 C optionally substituted with 1 or 2 substituents independently selected from fluoroalkyl 3-6 In some embodiments, C in A is cycloalkyl. 3-6 Cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. 3-6Cycloalkyl is selected from cyclopropyl, cyclobutyl, and cyclopentyl. 3-6 Cycloalkyl is cyclopropyl.

[0154] In some embodiments, A is F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl, OC 1-4 Fluoroalkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), S.C. 1-4 Alkyl, SC 1-4 Deuteroalkyl and SC 1-4 O, S, S(O), SO2, N, and NR optionally substituted with one or two substituents independently selected from fluoroalkyl 54 In some embodiments, A is a 5-6 membered heterocycloalkyl containing 1-2 hetero moieties independently selected from F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl and OC 1-4 O, S, S(O), SO2, N, and NR optionally substituted with one or two substituents independently selected from fluoroalkyl 54 In some embodiments, O, S, S(O), SO2, N, and NR 54The 3-6 membered heterocycloalkyl containing 1-2 heteromoieties independently selected from is selected from aziridinyl, oxiranyl, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thianyl, thianyloxide, and thianyldioxide. In some embodiments, O, S, S(O), SO2, N, and NR 54 In some embodiments, the 5-6 membered heterocycloalkyl containing 1-2 hetero moieties independently selected from is selected from piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thianyl, and thianyl dioxide. In some embodiments, O, S, S(O), SO2, N, and NR 54 The 5-6 membered heterocycloalkyl containing 1-2 heteromoieties independently selected from is selected from tetrahydropyranyl, thianyl, and thianyl dioxide.

[0155] In some embodiments, A is F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl, OC 1-4 Fluoroalkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), S.C. 1-4 Alkyl, SC 1-4 Deuteroalkyl and SC 1-4 Optionally substituted with one or two substituents independently selected from fluoroalkyl, O, S, N, and NR 54 In some embodiments, A is a 5-6 membered heteroaryl containing 1-3 hetero moieties independently selected from F, Cl, C 1-4 Alkyl, C 1-4 Deuteroalkyl, C 1-4 Fluoroalkyl, OC 1-4 Alkyl, OC1-4 Deuteroalkyl and OC 1-4 O, S, N, and NR, optionally substituted with one or two substituents independently selected from fluoroalkyl 54 In some embodiments, O, S, N, and NR 54 The 5-6 membered heteroaryl containing 1-3 heteromoieties independently selected from is selected from pyrrolyl, furanyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, pyrazolyl, thiophenyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and triazinyl. In some embodiments, O, S, N, and NR in A are each independently selected from the group consisting of aryl, ... 54 The 5-6 membered heteroaryl containing 1-3 hetero moieties independently selected from is selected from pyrrolyl, imidazolyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, pyrazolyl, thiophenyl, pyrazolyl, and pyridinyl. In some embodiments, the 5-6 membered heteroaryl is selected from F, OC 1-4 Alkyl, OC 1-4 Deuteroalkyl and OC 1-4 Optionally substituted with 1 or 2 substituents independently selected from fluoroalkyl.

[0156] In some embodiments, R 54a and R 54b are independently H and C 1-4 alkyl, wherein all available hydrogen atoms are optionally and independently replaced with fluorine or deuterium atoms. 54a and R 54b are independent of each other, H, D, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 54a and R 54bis independently selected from H, D, CH, CDH, CDH, CD, CF, CHF, CHCH, CH(CH), CHCHD, CHCDH, and CDCD. 54a and R 54b is independently selected from H, CH, CD, CFH, and CF. In some embodiments, R 54a and R 54b is independently selected from H, CH3, and CD3.

[0157] In some embodiments, R 54 , R 55 , R 56 , R 57 , and R 58 are independent of each other, H, D, and C. 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 In some embodiments, R 54 , R 55 , R 56 , R 57 , and R 58 is independently selected from H, D, F, CH, CDH, CDH, CD, CF, and CHF. 54 , R 55 , R 56 , R 57 , and R 58 is independently selected from H, D, CH3, CF3, and CD3. In some embodiments, R 54 , R 55 , R 56 , R 57 , and R 58 is independently selected from CH3 and CD3.

[0158] In some embodiments, the compound of formula I is defined as follows: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is H, Q3: [ka] and R 2 , R 2’ , R 2’’ , R 3 , and R 6 is independently selected from H, D and F; R 4 and R 5 One or both of the 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 deuteroalkoxy; or R 4 and R 5 are linked together to form O-(CH2) 1-2 Forming O R 26 , R 27 , R 28 , and R 29 is independently selected from H and D; R 30 and R 31 are independent of each other, H, C 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 is selected from deuteroalkyl, However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’, R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0159] [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is H, Q is Q1, Q2, Q3, Q4, and Q5: [ka] and [ka] is a single bond or a double bond, provided that in Q1 [ka] If is a double bond, R 9 and R 15 does not exist and in Q2 [ka] If is a double bond, R 17 and R 25 does not exist, R 2 , R 2’ , R 2’’ , R 3, and R 6 is independently selected from H, D and F; R 4 and R 5 One or both of the 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 deuteroalkoxy; or R 4 and R 5 are linked together to form O-(CH2) 1-2 Forming O R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 29 , R 32 , R 33 , R 34 , R 36 , R 37 , R 38 , R 39 , R 40 , R 41 , R 42 , R 43 , R 44 , R 46 , R 47 , R 48 , R 49 , R 50 , R 51 , R 52 , R 54 , R 55 , R 56 , and R 57 is independently selected from H and D; R 12 , R 20 , R 30 , R 31, R 35 , and R 45 are independent of each other, H, C 1-4 Alkyl, C 1-4 Fluoroalkyl, and C 1-4 is selected from deuteroalkyl, However, Q is Q3 and R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0160] In some embodiments, the compound of formula I is defined as follows: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1is H, Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently selected H, D, and F; R 3 , R 4 , R 5 , and R 6 are independently selected H, C 1-4 Alkoxy, C 1-4 Fluoroalkoxy, and C 1-4 deuteroalkoxy, or R 3 , R 4 , R 5 , and R 6 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-6 Alkyl, and C 1-6 alkoxy; R 26 , R 27 , R 28 , and R 29 are independently H, halo, and C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 alkyl, and C(O)C1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 58 are independently H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0161] In some embodiments, the compound of formula I is defined as follows: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 But, C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , SO2R 7 , C 1-6 Alkylene R 7 , and R 7 is selected from Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently H, halo, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 2a )(R 2b ), and S.C. 1-6 alkyl, R 2a and R 2b are independently H and C 1-6 alkyl, R 3 and R 6 are independently H, halo, N(R 5’ )(R 6’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl, the latter four groups being selected from OH and C 1-6 Optionally substituted with 1 or 2 substituents selected from alkoxy; R4 and R 5 are independently H, halo, N(R 5’ )(R 6’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl, the latter four groups being selected from OH and C 1-6 optionally substituted with one or two substituents selected from alkoxy; R 4 and R 5 are linked together to form O-(CH2) 1-2 Form O, or R 4 and R 5 One of A, OA, and C 1-4 alkylene A; R 4 and R 5 the other of is H or halo; R 5’ and R 6’ are independently H and C 1-6 alkyl, and A is selected from phenyl, Ccycloalkyl, O, S, S(O), SO, N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C3- 10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from halo, C 1-4 Alkyl, OC 1-4 Alkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b ), and S.C. 1-4 and optionally substituted with one or more substituents independently selected from alkyl, R 7 , H, C1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 7 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR 7 ''; and 5-6 membered heteroaryl containing 1-4 hetero moieties independently selected from the group consisting of halo, OR, 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-6 Alkyl is O, C(O), CO2, and NR 57 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 7’ H and C 1-6 alkyl, R 7’’ H and C 1-6 alkyl, R 26 , R 27 , R 28 , and R 29 are independently H, halo, and C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 54 , R 55 , R 56 , R 57 , and R 58 are independently H and C1-6 alkyl, R 54a and R 54b are independently H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0162] In some embodiments, the compound of formula I is defined as follows: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is H, Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently H, halo, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 2a )(R 2b ), and S.C. 1-6 alkyl, R 2a and R 2b are independently H and C 1-6 alkyl, R 3 , R 4 , R 5 , and R 6 are independent of each other, H, halo, N(R 5’ )(R 6’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl, the latter two groups being selected from OH and C 1-6 optionally substituted with one or two substituents selected from alkoxy; R 3 , R4 , R 5 , and R 6 The two adjacent ones are linked together to form O-(CH2). 1-2 Form O and R 3 , R 4 , R 5 , and R 6 The rest are independently H, halo, and C. 1-6 Alkyl, C 1-6 AlkoxyN(R 5’ )(R 6’ ), C 1-6 AlkyleneN(R 5’ )(R 6’ ), and S.C. 1-6 alkyl, R 5’ and R 6’ are independently H and C 1-6 alkyl, R 26 , R 27 , R 28 , and R 29 are independently H, halo, and C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 58 H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R30 and R 31 is H or CH3, and R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 , R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5 If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0163] In some embodiments, the compound of formula I is defined as follows: [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof; During the ceremony, R 1 is C(O)R 7 , CO2R 7 , C(O)N(R 7 )(R 7’ ), S(O)R 7 , SO2R 7 , C 1-6 Alkylene R 7 , and R 7 is selected from Q3: [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 2 , R 2’ , and R 2’’ are independently H, halo, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 2a )(R 2b ), and S.C. 1-6 alkyl, R 2a and R 2b are independently H and C 1-6 alkyl, R 3 , R 4 , R 5 , and R 6 One of them is A, OA, and C. 1-4 alkylene A; R 3 , R 4 , R 5 , and R 6 the remainder of are independently H or halo; A is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 54 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 54 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are also included, including halo, C 1-4 Alkyl, OC 1-4 Alkyl, N(R 54a )(R 54b ), C 1-4 AlkyleneN(R 54a )(R 54b), and S.C. 1-4 and optionally substituted with one or more substituents independently selected from alkyl, R 7 But, H, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 7 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR 7 ''; and 5-6 membered heteroaryl containing 1-4 hetero moieties independently selected from the group consisting of halo, OR, 55 , N(R 55 )(R 56 ), and S.R. 55 and / or C 1-6 Alkyl is O, C(O), CO2, and NR 57 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 7’ But H and C 1-6 alkyl, R 7’’ But H and C 1-6 alkyl, R 26 , R 27 , R 28 , and R 29 are independently H, halo, and C 1-6 alkyl, R 30 and R 31 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 30 and R 31 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 58 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 54 , R 55 , R 56 , R 57 , and R 58 are independently H and C 1-6 alkyl, R 54a and R 54b are independently H and C 1-6 alkyl, all available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes; However, R 26 , R 27 , R 28 , and R 29 are all H and R 30 and R 31 is H or CH3, and R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H or R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 5 , and R 6 are all H and R 4 is OCH3, or R 1 But R 7 and R 7 is H and R 2 , R 2’ , R 2’’ , R 3 , R 4 , R 5 , and R 6 are all H and R 5If OCH3, Provided that the compound of formula I is either the (R)- or the (S)-enantiomer of the carbon to which Q is attached.

[0164] One of ordinary skill in the art will appreciate that the carbon to which Q is attached is chiral. Thus, in some embodiments, the carbon to which Q is attached is racemic. In some embodiments, the stereochemistry at the carbon to which Q is attached is R. In some embodiments, the stereochemistry at the carbon to which Q is attached is S. Thus, in some embodiments, the compound of formula I has the following structure: [ka] One of the or a mixture thereof.

[0165] Those skilled in the art will recognize that R 2 and R 2’ If different, R 2 and R 2’ It will be further understood that the carbon to which is attached is also chiral, and therefore the present application also includes all stereoisomers at this carbon center and mixtures thereof.

[0166] In some embodiments, the compound of formula I is selected from the compounds listed in Table A below, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof. Table A [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9] [Table 10] [Table 11] [Table 12] [Table 13] [Table 14]

[0167] In some embodiments, the compound of formula I is selected from the compounds listed below, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof. [Table 15] [Table 16] [Table 17] [Table 18]

[0168] In some embodiments, the compound of formula I is a zwitterion, and the present application includes compounds of formula I, as well as pharma- ceutically acceptable salts, solvates, zwitterions, and / or prodrugs thereof.

[0169] In some embodiments, the pharma- ceutically acceptable salt is an acid addition salt or a base addition salt.The selection of suitable salt can be performed by those skilled in the art.Suitable salts include, for example, acid addition salts that can be formed by mixing a solution of a compound with a solution of a pharma- ceutically acceptable acid such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, or benzoic acid. Additionally, acids generally considered suitable for the formation of pharma- ceutically 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) 33 201-217, Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York, and The Orange Book (website of the Food & Drug Administration, Washington, DC).

[0170] The acid addition salt suitable for or compatible with the treatment of the subject is any non-toxic organic or inorganic acid addition salt of any basic compound.Basic compounds that form acid addition salts include, for example, compounds that contain amine groups.Exemplary inorganic acids that form suitable salts include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, as well as acid metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate.Exemplary organic acids that form suitable salts include mono-, di-, and tri-carboxylic acids. Illustrative of such organic acids are, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, mandelic acid, salicylic acid, 2-phenoxybenzoic acid, 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 acetate, ascorbate, benzoate, benzenesulfonate, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, fumarate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, methanesulfonate ("mesylate"), naphthalenesulfonate, nitrate, oxalate, phosphate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate (also known as tosylate), and the like. In some embodiments, mono- or di-acid salts are formed, and such salts exist in either hydrated, solvated, or substantially anhydrous form. In general, acid addition salts are more soluble in water and various hydrophilic organic solvents, and generally exhibit higher melting points compared to their free base forms. The criteria for selecting an appropriate salt will be known to those skilled in the art. Other non-pharmaceutical acceptable salts, such as, but not limited to, oxalates, may be used, for example, in the isolation of compounds of the present application for laboratory use or for subsequent conversion to a pharmaceutically acceptable acid addition salt.

[0171] The base addition salt suitable for or compatible with the treatment of the subject is any non-toxic organic or inorganic base addition salt of any acidic compound. Acidic compounds that form base addition salts include, for example, compounds that contain a carboxylic acid group. Exemplary inorganic bases that form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide, as well as ammonia. Exemplary organic bases that 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, purine, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. The selection of an appropriate salt may be useful, for example, to prevent hydrolysis when there is an ester functionality elsewhere in the compound. The criteria for selecting an appropriate salt will be known to those skilled in the art. In some embodiments, exemplary basic salts also include alkali metal salts such as ammonium salts, sodium salts, lithium salts, and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, salts with organic bases (e.g., organic amines) such as dicyclohexylamine, A-butylamine, choline, and salts with amino acids such as arginine and lysine. Basic nitrogen-containing groups may be quaternized with agents such as lower alkyl halides (e.g., methyl, ethyl, and butyl chlorides, bromides, and iodides), dialkyl sulfates (e.g., dimethyl sulfate, diethyl sulfate, and dibutyl sulfate), longer chain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides, and iodides), aralkyl halides (e.g., benzyl and phenethyl bromides).Compounds bearing an acidic moiety can be mixed with a suitable pharma- ceutically acceptable salt to provide, for example, salts formed with suitable organic ligands, such as alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., calcium or magnesium salts), and quaternary ammonium salts. Also, when an acid (-COOH) or alcohol group is present, pharma- ceutically acceptable esters can be used to modify the solubility or hydrolysis characteristics of the compound.

[0172] All such acid salts and base salts are intended to be pharma- ceutically acceptable salts within the scope of this application, and all acid salts and base salts are considered equivalent to the free form of the corresponding compound for the purposes of this application. Furthermore, when a compound of this application contains both a basic moiety, such as, but not limited to, an aliphatic primary, secondary, tertiary, or cyclic amine, an aromatic or heteroaryl amine, a pyridine, or an imidazole, and an acidic moiety, such as, but not limited to, a tetrazole or a carboxylic acid, a zwitterion ("inner salt") may be formed and is included in the term "salt" as used herein. It is understood that certain compounds of this application may exist in zwitterionic form, with both an anionic and cationic center within the same compound, and a net neutral charge. Such zwitterions are included within this application.

[0173] The solvates of the compounds of the present application include, for example, those prepared with pharma- ceutically acceptable solvents. Examples of such solvents include water (the resulting solvates are called hydrates) and ethanol. Suitable solvents are physiologically tolerated at the dosage administered.

[0174] Prodrugs of the compounds of the present application include, for example, conventional esters formed at available hydroxy, thiol, amino, or carboxyl groups. Some common esters utilized as prodrugs are phenyl esters, aliphatic (C1-C 24) esters, acyloxymethyl esters, carbamates, and amino acid esters.

[0175] It is understood and appreciated that in some embodiments, the compounds of the present application may have at least one chiral center and therefore may exist as enantiomers and / or diastereomers. It should be understood that all such isomers and mixtures thereof in any proportion are encompassed within the scope of the present application. It should be further understood that the stereochemistry of the compounds may be as shown for any given compound listed herein, but such compounds may also contain a certain amount (e.g., less than 20%, preferably less than 10%, more preferably less than 5%) of compounds of the present application having alternative stereochemistry. Any optical isomers, as separated, pure or partially purified optical isomers or racemic mixtures thereof, are intended to be encompassed within the scope of the present application.

[0176] In some embodiments, the compounds of the present application may also include tautomeric forms, such as keto-enol tautomers. The tautomeric forms may be in equilibrium or may be sterically locked into one form by appropriate substitution. Any tautomeric forms that the compounds form, as well as mixtures thereof, are intended to be included within the scope of the present application.

[0177] The compounds of the present application may further exist in various amorphous and polymorphic forms, and any amorphous form, polymorph, or mixture thereof formed is contemplated to be included within the scope of the present application.

[0178] The compounds of the present application may further be radiolabeled, and therefore all radiolabeled forms of the compounds of the present application are included within the scope of the present application. Thus, the compounds of the present application also include those that have one or more radioactive atoms incorporated within their structure.

[0179] III. Composition The compounds of the present application are suitably formulated in a conventional manner into a composition using one or more carriers. Thus, the present application also includes a composition comprising one or more compounds of the present application and a carrier. The compounds of the present application are suitably formulated into a pharmaceutical composition for administration to a subject in a biologically compatible form suitable for administration in vivo. Thus, the present application further includes a pharmaceutical composition comprising one or more compounds of the present application and a pharma- ceutically acceptable carrier. In an embodiment of the present application, the pharmaceutical composition is used in the treatment of any of the diseases, disorders, or conditions described herein.

[0180] The compounds of the present application may be administered to a subject in various forms depending on the route of administration selected, as will be understood by those skilled in the art. For example, the compounds of the present application may be administered by oral, inhalation, parenteral, buccal, sublingual, insufflation, epidural, nasal, rectal, vaginal, patch, pump, minipump, topical, or transdermal administration, and pharmaceutical compositions formulated accordingly. In some embodiments, administration is by 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 The United States Pharmacopeia: The National Formulary (USP 24 NF19), published in 1999.

[0181] Parenteral administration includes systemic delivery routes other than the gastrointestinal (GI) tract, and includes, for example, intravenous, intraarterial, intraperitoneal, subcutaneous, intramuscular, transepithelial, nasal, pulmonary (e.g., by use of an aerosol), intrathecal, rectal, and topical (including use of a patch or other transdermal delivery device) methods of administration. Parenteral administration may also be by continuous infusion over a selected period of time.

[0182] In some embodiments, the compounds of the present application are administered orally, for example, with an inert diluent or with an assimilable edible carrier, or are enclosed in hard or soft shell gelatin capsules, or are compressed into tablets, or are directly incorporated with dietary foods. In some embodiments, the compounds are incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, caplets, pellets, granules, lozenges, chewing gum, powders, syrups, elixirs, wafers, aqueous solutions, and suspensions. In the case of tablets, carriers used include lactose, corn starch, sodium citrate, and salts of phosphoric acid. Pharmaceutically acceptable excipients include binders (e.g., pregelatinized maize starch, polyvinylpyrrolidone, or hydroxypropylmethylcellulose), 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), or wetting agents (e.g., sodium lauryl sulfate), or solvents (e.g., medium chain triglycerides, ethanol, water). In embodiments, the tablets are coated by methods well known in the art. For 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, e.g., immediate release and timed release formulations. Examples of modified release formulations include, for example, sustained release (SR), extended release (ER, XR, or XL), timed or timed release, controlled release (CR), or continuous release (CR or Contin), used, for example, in the form of coated tablets, osmotic delivery devices, coated capsules, microencapsulated microspheres, agglomerated particles, for example, molecular sieving type particles, or fine hollow permeable fiber bundles, or chopped hollow permeable fibers aggregated or held within a fibrous packet.The timed release composition is formulated, for example, as liposomes, or where the active compound is protected with a differentially degradable coating, such as by microencapsulation, multiple coatings, etc. Liposomal delivery systems include, for example, small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. In some embodiments, liposomes are formed from various phospholipids, such as cholesterol, stearylamine, or phosphatidylcholine. For oral administration in capsule form, useful carriers, solvents, or diluents include lactose, medium chain triglycerides, ethanol, and dry cornstarch.

[0183] In some embodiments, liquid preparations for oral administration may take the form of, for example, a solution, syrup, or suspension, or may be 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 compounds of the present application are suitably suspended or dissolved in an oily phase combined with an emulsifying and / or suspending agent. If necessary, certain sweetening and / or flavoring and / or coloring agents are added. Such liquid preparations for oral administration are prepared by conventional means using pharma- ceutically acceptable additives, such as suspending agents (e.g., sorbitol syrup, methylcellulose, 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 preservatives (e.g., methyl or propyl p-hydroxybenzoate, or sorbic acid). Useful diluents include lactose and high molecular weight polyethylene glycols.

[0184] It is also possible to lyophilize the compounds of the present application and use the resulting lyophilizates, for example, for the preparation of injectable products.

[0185] In some embodiments, the compounds of the present application are administered parenterally. For example, solutions of the compounds of the present application 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 normal conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. Those skilled in the art will know how to prepare suitable formulations. For parenteral administration, sterile solutions of the compounds of the present application are usually prepared, and the pH of the solution is suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled to make the preparation isotonic. For ophthalmic administration, ointments or instillable liquids are delivered by ophthalmic delivery systems known in the art, such as applicators or eyedroppers. In some embodiments, such compositions include a viscosity mimic such as hyaluronic acid, chondroitin sulfate, hydroxypropylmethylcellulose, or polyvinyl alcohol, a preservative such as sorbic acid, EDTA, or benzyl chromium chloride, and a diluent or carrier in the usual amount. For pulmonary administration, the diluent or carrier is selected to be appropriate to allow the formation of an aerosol.

[0186] In some embodiments, the compounds of the present application are formulated for parenteral administration by injection, including the use of conventional catheter insertion techniques or infusion. Preparations for injection are presented, for example, in unit dosage form, for example, in ampoules or in multi-dose containers, with added preservatives. In some embodiments, the compositions take the form of a sterile suspension, solution, or emulsion in an oily or aqueous vehicle, 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 of the present application are preferably in sterile powder form for reconstitution with a suitable vehicle, for example, sterile pyrogen-free water, before use.

[0187] 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 present application are conveniently delivered in the form of a solution, dry powder formulation, or suspension from a pump spray container that is pressed or pumped by the patient, or as an aerosol spray presentation from a pressurized container or nebulizer. Aerosol formulations typically include a solution or fine suspension of an active substance in a physiologically acceptable aqueous or non-aqueous solvent, and are usually presented in single or multiple doses in a sterile form in a sealed container, for example in the form of a cartridge or refill for use in a nebulizing device. Alternatively, the sealed container is a unit-dispensing device, such as a single-dose nasal inhaler, or an aerosol dispenser with a metering valve that is intended for disposal after use. When the dosage form includes an aerosol dispenser, it contains a propellant, which is, for example, a compressed gas such as compressed air or an organic propellant such as a fluorochlorohydrocarbon. Suitable propellants include, but are 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 (e.g., made from gelatin) for use in an inhaler or insufflator are formulated, for example, containing a powder mix of the compound of the present application and a suitable powder base, such as lactose or starch. The aerosol dosage form can also take the form of a pump-atomizer.

[0188] Compositions suitable for buccal or sublingual administration include tablets, lozenges, and pastilles, in which the compounds of the present application are formulated with carriers 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.

[0189] Suppository forms of the compounds of the present application are useful for vaginal, urethral and rectal administration. Such suppositories are generally constructed from a mixture of materials that are solid at room temperature but melt at body temperature. Materials commonly used to produce 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. For example, see Remington's Pharmaceutical Sciences, 16th Ed., Mack Publishing, Easton, PA, 1980, pp.1530-1533, for further discussion of suppository dosage forms.

[0190] In some embodiments, the compounds of the present application are coupled to soluble polymers as targetable drug carriers. Such polymers include, for example, polyvinylpyrrolidone, pyran copolymers, polyhydroxypropylmethacrylamide-phenol, polyhydroxy-ethylaspartamide-phenol, or polyethylene oxide-polylysine substituted with palmitoyl residues. Furthermore, in some embodiments, the compounds of the present application are coupled to classes of biodegradable polymers useful for achieving controlled release of drugs, such as polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polyepsilon caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates, and crosslinked or amphiphilic block copolymers of hydrogels.

[0191] The compounds of the present application are particularly suitable for administration with the air of nanocarrier systems, such as liposomes, micelles, nanoparticles, nanoemulsions, lipid nanosystems, etc. (see, for example, Bhat, M. et al. Chem. and Phys. of Lipids, 2021, 236, 105053). Thus, the present application includes compositions comprising one or more compounds of the present application and one or more components of a nanocarrier system.

[0192] Although the compounds of the present application (including their pharma- ceutically acceptable salts and / or solvates) are suitably used per se, they are generally administered in the form of a pharmaceutical composition in which one or more compounds of the present application (the active ingredient) are associated with a pharma- ceutically acceptable carrier. Depending on the method of administration, the pharmaceutical composition contains about 0.05% to about 99% by weight, or about 0.10% to about 70% by weight of the active ingredient, and about 1% to about 99.95% by weight, or about 30% to about 99.90% by weight of the pharma- ceutical acceptable carrier, all weight percentages being based on the total composition.

[0193] In some embodiments, the compounds of the present application (including their pharma- ceutically acceptable salts and / or solvates) are administered in a composition comprising an additional therapeutic agent. Thus, the present application also includes pharmaceutical compositions comprising one or more compounds of the present application, or their pharma- ceutically acceptable salts and / or solvates, an additional therapeutic agent, and optionally one or more pharma- ceutical acceptable excipients. In some embodiments, the additional therapeutic agent is another known agent useful for treating a disease, disorder, or condition caused by activation of serotonin receptors, such as those listed in the methods and uses section below. In some embodiments, the additional therapeutic agent is a psychotropic drug.

[0194] As used above, the term "compound" also includes embodiments where one or more compounds are referenced.

[0195] IV. Methods and Uses of the Compounds of the Present Application The compounds of the present application are 5-HT 2A These compounds are serotonergic binding agents that act as agonists, partial agonists, or positive allosteric modulators at serotonin receptors, including

[0196] Accordingly, the present application includes a method for activating serotonin receptors in a cell, either in a biological sample or in a subject, comprising administering to the cell an effective amount of one or more compounds of the present application.

[0197] The present application also includes the use of the present application for activating serotonin receptors in cells, and the use of one or more compounds of the present application for the preparation of a medicament for activating serotonin receptors in cells. The present application further includes one or more compounds of the present application for use in activating serotonin receptors in cells. In some embodiments, the method or use is for activating serotonin receptors in and / or on cells, either in a biological sample or in a patient.

[0198] In some embodiments, activation of serotonin receptors has no hallucinogenic effect in a subject or has a reduced hallucinogenic effect in a subject compared to the hallucinogenic effect from administration of an equivalent dose of a hallucinogenic agent, such as, for example, psilocybin, DMT, or 5-MeO-DMT. In some embodiments, activation of serotonin receptors has no hallucinogenic effect in a subject or has a reduced hallucinogenic effect in a subject compared to the hallucinogenic effect from administration of an equivalent dose of psilocybin.

[0199] The compounds of the present application are useful for treating diseases, disorders, or conditions by activating serotonin receptors. Thus, the compounds of the present application are useful as pharmaceuticals. Thus, the present application also includes the compounds of the present application for use as pharmaceuticals.

[0200] The present application also includes a method of treating a disease, disorder, or condition treatable by activation of a serotonin receptor, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof.The present application also includes a method of treating a disease, disorder, or condition treatable by activation of a serotonin receptor, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof.

[0201] The present application also includes the use of one or more compounds of the present application for the treatment of a disease, disorder, or condition treatable by activation of a serotonin receptor, as well as the use of one or more compounds of the present application for the preparation of a medicament for the treatment of a disease, disorder, or condition treatable by activation of a serotonin receptor. The present application further includes one or more compounds of the present application for use in the treatment of a disease, disorder, or condition treatable by activation of a serotonin receptor.

[0202] The present application also includes the use of one or more compounds of the present application for the treatment of a disease, disorder, or condition caused by activation of a serotonin receptor, as well as the use of one or more compounds of the present application for the preparation of a medicament for the treatment of a disease, disorder, or condition caused by activation of a serotonin receptor. The present application further includes one or more compounds of the present application for use in the treatment of a disease, disorder, or condition caused by activation of a serotonin receptor.

[0203] In some embodiments, the serotonin receptor is 5-HT 2A Thus, the present application relates to the detection of intracellular 5-HT in either a biological sample or a patient. 2A The present application also includes a method for activating 5-HT in cells, the method comprising administering to the cells an effective amount of one or more compounds of the present application. 2A The use of one or more compounds of the present application to activate 5-HT 2A The present application includes the use of one or more compounds of the present application for the preparation of a medicament for activating intracellular 5-HT 2A In some embodiments, the method or use is for activating 5-HT2 in and / or on cells, either in a biological sample or in a patient.

[0204] The present application also provides 5-HT 2A The present invention also includes a method for treating a disease, disorder, or condition treatable by activation of the agonist, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof.

[0205] The present application also provides 5-HT 2A The present application also includes a method of treating a disease, disorder, or condition treatable by activation of 5-HT, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of the present application. 2A Use of one or more compounds of the present application for the treatment of a disease, disorder, or condition treatable by activation of 5-HT 2A The present application includes the use of one or more compounds of the present application for the preparation of a medicament for the treatment of a disease, disorder, or condition treatable by activation of 5-HT 2A The present invention further includes one or more compounds of the present application for use in the treatment of a disease, disorder, or condition treatable by activation of the

[0206] The present application also provides 5-HT 2A The present application also provides a method for treating a disease, disorder, or condition caused by activation of 5-HT, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of the present application. 2A Use of one or more compounds of the present application for the treatment of a disease, disorder, or condition resulting from activation of 5-HT 2A The present application includes the use of one or more compounds of the present application for the preparation of a medicament for the treatment of a disease, disorder, or condition resulting from activation of 5-HT 2A The present invention further includes one or more compounds of the present application for use in the treatment of a disease, disorder, or condition via activation of

[0207] In some embodiments, the treatment of a disease, disorder, or condition treatable by activation of a serotonin receptor does not have a hallucinogenic effect in the subject, or has a reduced hallucinogenic effect in the subject, as compared to the hallucinogenic effect from administration of an equivalent dose of a hallucinogenic agent, such as, for example, psilocybin, DMT, or 5-MeO-DMT. In some embodiments, the hallucinogenic agent is psilocybin. In some embodiments, 5-HT 2ATreatment of a disease, disorder, or condition treatable by activation of serotonin receptors, including those having no hallucinogenic effect in the subject, or having a reduced hallucinogenic effect in the subject compared to the hallucinogenic effect from administration of an equivalent dose of psilocybin.

[0208] In some embodiments, the compounds of the present application are useful for preventing, treating, and / or reducing the severity of psychiatric diseases, disorders, and / or conditions in a subject. Thus, in some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a psychiatric disease. Thus, the present application also includes a method of treating a psychiatric disease, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof. The present application also includes the use of one or more compounds of the present application for treating a psychiatric disease, as well as the use of one or more compounds of the present application for the preparation of a medicament for treating a psychiatric disease. The present application further includes one or more compounds of the present application for use in treating a psychiatric disease.

[0209] In some embodiments, the psychiatric illness is an anxiety disorder such as generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia; depression such as hopelessness, loss of pleasure, fatigue, and suicidal ideation; mood disorders such as depression, bipolar disorder, cancer-related depression, anxiety, and cyclothymic disorder; psychotic disorders such as hallucinations, delusions, and schizophrenia; impulse control and addiction disorders such as pyromania (pyromania), kleptomania (kleptomania), and compulsive gambling; alcoholism; drug addiction such as opioid addiction; antisocial personality disorder, obsessive-compulsive personality disorder, and delusions. The psychiatric disorder is selected from personality disorders such as sexual personality disorder; obsessive-compulsive disorder (OCD), such as thoughts or fears that cause a subject to perform a certain ritual or routine; post-traumatic stress disorder (PTSD); stress response disorder (formerly known as adjustment disorder); dissociative disorders, formerly known as multiple personality disorder or "split personality," and depersonalization disorder; factitious disorder; sexual and gender disorders, such as sexual dysfunction, gender identity disorder, and paraphilia; somatic symptom disorders, formerly known as psychosomatic or somatoform disorders; and combinations thereof. In some embodiments, the psychiatric disorder is postpartum depression.

[0210] In some embodiments, treating a disease, disorder, or condition treatable by activation of serotonin receptors does not have a hallucinogenic effect in the subject, or has a reduced hallucinogenic effect in the subject, compared to the hallucinogenic effect from administration of an equivalent dose of a hallucinogenic agent, such as, for example, psilocybin, DMT, or 5-MeO-DMT. In some embodiments, the hallucinogenic agent is psilocybin. In some embodiments, treating a psychiatric disorder does not have a hallucinogenic effect in the subject, or has a reduced hallucinogenic effect in the subject, compared to the hallucinogenic effect from administration of an equivalent dose of psilocybin.

[0211] In some embodiments, diseases, disorders, or conditions treated by activation of serotonin receptors include cognitive disorders: ischemia, including stroke; neurodegeneration; refractory substance use disorders; sleep disorders; pain, such as social pain, acute pain, cancer pain, chronic pain, breakthrough pain, bone pain, soft tissue pain, neuralgia, referred pain, phantom limb pain, neuropathic pain, cluster headaches, and migraines; obesity and eating disorders; epilepsy and seizure disorders; neuronal cell death; excitotoxic cell death; or combinations thereof.

[0212] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is neurodegeneration. In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is reduced brain-derived neurotrophic factor (BDNF), mammalian target of rapamycin (mTOR) activation, and / or inflammation.

[0213] In some embodiments, the psychiatric disorder is selected from hallucinations and delusions, and combinations thereof.

[0214] In some embodiments, the hallucinations are selected from visual hallucinations, auditory hallucinations, olfactory hallucinations, gustatory hallucinations, tactile hallucinations, proprioceptive hallucinations, balance hallucinations, nociceptive hallucinations, thermosensory hallucinations, time-sensory hallucinations, and combinations thereof.

[0215] In some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is psychosis or a psychotic condition. Thus, the present application also includes a method for treating a psychosis or a psychotic condition, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof. The present application also includes the use of one or more compounds of the present application for treating a psychosis or a psychotic condition, as well as the use of one or more compounds of the present application for preparing a medicament for treating a psychosis or a psychotic condition. The present application further includes one or more compounds of the present application for use in treating a psychosis or a psychotic condition.

[0216] In some embodiments, administering a therapeutically effective amount of a compound of the present application to a subject in need thereof does not result in a worsening of psychosis or psychotic symptoms, such as, but not limited to, hallucinations and delusions. In some embodiments, administering a therapeutically effective amount of a compound of the present application to a subject in need thereof results in an improvement of psychosis or psychotic symptoms, such as, but not limited to, hallucinations and delusions. In some embodiments, administering a therapeutically effective amount of a compound of the present application to a subject in need thereof results in an improvement of psychosis or psychotic symptoms.

[0217] In some embodiments, the compounds of the present application are useful for treating a central nervous system (CNS) disorder in a subject in need of therapy, comprising administering to the subject a therapeutically effective amount of a compound of formula I, or a pharma- ceutically acceptable salt thereof.

[0218] Thus, in some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a central nervous system (CNS) disease, disorder, or condition, and / or a neurological disease, disorder, or condition. Thus, the present application also includes a method of treating a CNS disease, disorder, or condition, and / or a neurological disease, disorder, or condition, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof. The present application also includes the use of one or more compounds of the present application for the treatment of a CNS disease, disorder, or condition, and / or a neurological disease, disorder, or condition, as well as the use of one or more compounds of the present application for the preparation of a medicament for the treatment of a CNS disease, disorder, or condition, and / or a neurological disease, disorder, or condition. The present application further includes one or more compounds of the present application for use in the treatment of a CNS disease, disorder, or condition, and / or a neurological disease, disorder, or condition.

[0219] In some embodiments, the CNS disease, disorder, or condition, and / or the neurological disease, disorder, or condition is a neurodevelopmental and neurodegenerative disease, such as Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; dementia with Lewy bodies; cognitive disorders, Parkinson's disease, and Parkinson's disease-related disorders, such as Parkinson's dementia, corticobasal degeneration, and progressive supranuclear palsy; epilepsy; CNS trauma; CNS infection; CNS inflammation; stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; fragile X syndrome; Angelman syndrome; hereditary ataxias; neuro-otopathies. The present invention is selected from neurological disorders including neurodegenerative diseases of the retina, amyotrophic lateral sclerosis, tardive dyskinesia, hyperactivity disorder, attention deficit hyperactivity disorder and attention deficit disorder, restless legs syndrome, Tourette's disorder, schizophrenia, autism spectrum disorders, tuberous sclerosis, Rett's syndrome, cerebral palsy, disorders of the reward system including eating disorders, e.g., anorexia nervosa ("AN") and bulimia nervosa ("BN"), and binge eating disorder ("BED"), trichotillomania, self-injurious dermatosis, onychopathia, migraine, fibromyalgia, and peripheral neuropathies of any etiology, and combinations thereof.

[0220] In some embodiments, the compounds of the present application are useful for treating endophenotypes and / or symptom clusters across a variety of neuropsychiatric and CNS disorders in a subject in need of therapy, comprising administering to the subject a therapeutically effective amount of a compound of general formula (IA) or a pharma- ceutical acceptable salt thereof.

[0221] Thus, in some embodiments, the disease, disorder, or condition treated by activation of the serotonin receptor is an endophenotype or symptom cluster associated with the disease, disorder, or condition. Thus, the present application also includes a method of treating an endophenotype and / or symptom cluster associated with a disease, disorder, or condition treated by activation of the serotonin receptor, comprising administering a therapeutically effective amount of one or more compounds of the present application to a subject in need thereof. The present application also includes the use of one or more compounds of the present application for the treatment of an endophenotype and / or symptom cluster associated with a disease, disorder, or condition treated by activation of the serotonin receptor, as well as the use of one or more compounds of the present application for the preparation of a medicament for the treatment of an endophenotype and / or symptom cluster associated with a disease, disorder, or condition treated by activation of the serotonin receptor. The present application further includes one or more compounds of the present application for use in the treatment of an endophenotype and / or symptom cluster associated with a disease, disorder, or condition treated by activation of the serotonin receptor.

[0222] In some embodiments, the endophenotype and / or symptom cluster is associated with a disease, disorder, or condition selected from a neuropsychiatric disease, disorder, or condition, and / or a nervous system disease, disorder, or condition. In some embodiments, the nervous system disease is a CNS disease, disorder, or condition.

[0223] In some embodiments, the endophenotypes and / or symptom clusters are associated with neurodevelopmental and neurodegenerative disorders, such as apathy, anhedonia, attention disorders, memory disorders, negative affect bias, hypomania, impaired executive function, impulsivity, decreased mood, decreased libido, sensory gating, impaired prepulse inhibition, aggressive behavior, suicidal ideation, obesity, increased arousal, decreased arousal, hypersexuality, decreased seeking, hyperactivity, hypoactivity, sleep disorders, incontinence, impaired social perception, ruminative thinking, and combinations thereof.

[0224] In some embodiments, the endophenotypes and / or symptom clusters are selected from apathy, anhedonia, attention disorders, memory disorders, negative affect bias, hypomania, impaired executive function, impulsivity, decreased mood, decreased libido, sensory gating, impaired prepulse inhibition, aggressive behavior, suicidal ideation, obesity, increased arousal, decreased arousal, hypersexuality, decreased seeking, hyperactivity, hypoactivity, sleep disorders, incontinence, impaired social perception, and ruminative thoughts.

[0225] In some embodiments, the subject is a mammal. In another embodiment, the subject is a human. In some embodiments, the subject is a non-human animal. In some embodiments, the subject is a dog. In some embodiments, the subject is a cat. Thus, the compounds, methods, and uses of the present application are directed to both human and veterinary diseases, disorders, and conditions.

[0226] In some embodiments, a "subject in need of treatment" is a subject having a disease, disorder, or condition that is to be treated.

[0227] In some embodiments, the compounds of the present application are useful for treating behavioral problems in subjects that are cats or dogs.

[0228] Thus, in some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is behavioral problems in a cat or dog subject.Thus, the present application also includes a method for treating behavioral problems, comprising administering a therapeutically effective amount of one or more compounds of the present application to a non-human subject in need thereof.The present application also includes the use of one or more compounds of the present application for treating behavioral problems in non-human subjects, as well as the use of one or more compounds of the present application for preparing a medicament for treating behavioral problems in non-human subjects.The present application further includes one or more compounds of the present application for use in treating behavioral problems in non-human subjects.

[0229] In some embodiments, the behavioral problem is selected from, but is not limited to, anxiety, fear, stress, sleep disorders, cognitive dysfunction, aggressive behavior, excessive fussing, scratching, biting, and combinations thereof.

[0230] In some embodiments, the non-human subject is a dog. In some embodiments, the non-human subject is a cat.

[0231] The present application also includes a method of treating a disease, disorder, or condition by activating a serotonin receptor, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of the present application in combination with another known agent useful for treating a disease, disorder, or condition by activating a serotonin receptor. The present application also includes the use of one or more compounds of the present application in combination with another known agent useful for treating a disease, disorder, or condition by activating a serotonin receptor for treating a disease, disorder, or condition by activating a serotonin receptor, as well as the use of one or more compounds of the present application in combination with another known agent useful for treating a disease, disorder, or condition by activating a serotonin receptor for preparing a medicament for treating a disease, disorder, or condition by activating a serotonin receptor. The present application further includes one or more compounds of the present application in combination with another known agent useful for treating a disease, disorder, or condition by activating a serotonin receptor for use in treating a disease, disorder, or condition by activating a serotonin receptor.

[0232] In some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is a psychiatric disorder. In some embodiments, the psychiatric disorder is selected from hallucinations and delusions, and combinations thereof. In some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is a central nervous system (CNS) disorder. In some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is a psychosis or psychotic symptom. In some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is a behavioral problem in a non-human subject.

[0233] In some embodiments, the disease, disorder, or condition treated by activating serotonin receptors is a psychiatric disorder, and one or more compounds of the present application are administered in combination with one or more additional treatments for the psychiatric disorder. In some embodiments, the additional treatment for the psychiatric disorder is selected from antipsychotics, including typical antipsychotics and atypical antipsychotics; antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs) (e.g., bupropion); anxiolytics, including benzodiazepines such as alprazolam; mood stabilizers, such as lithium, and anticonvulsants, such as carbamazepine, divalproex (valproic acid), lamotrigine, gabapentin, and topiramate. In some embodiments, the anticonvulsant is leviteracetam or brivaracetam.

[0234] In some embodiments, the disease, disorder or condition that is treated by activating serotonin receptor is selected from attention deficit hyperactivity disorder and attention deficit disorder, and combinations thereof.In some embodiments, the disease, disorder or condition that is treated by activating serotonin receptor is attention deficit hyperactivity disorder and / or attention deficit disorder, and combinations thereof, and one or more compounds of the present application are administered in combination with one or more additional treatments for attention deficit hyperactivity disorder and / or attention deficit disorder, and combinations thereof.In some embodiments, the additional treatments for attention deficit hyperactivity disorder and / or attention deficit disorder, and combinations thereof are selected from methylphenidate, atomoxetine, and amphetamine, and combinations thereof.

[0235] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is dementia or Alzheimer's disease, and one or more compounds of the present application are administered in combination with one or more additional treatments for dementia or Alzheimer's disease. In some embodiments, the additional treatments for dementia and Alzheimer's disease are selected acetylcholinesterase inhibitors, NMDA antagonists, and muscarinic agonists and antagonists, and nicotinic agonists.

[0236] In some embodiments, the acetylcholinesterase inhibitor is selected from donepezil, galantamine, rivastigmine, and phenserine, and combinations thereof.

[0237] In some embodiments, the NMDA antagonist is selected from MK-801, ketamine, phencilidine, and memantine, and combinations thereof.

[0238] In some embodiments, the nicotinic agonist is nicotine, nicotinic acid, a nicotinic alpha 7 agonist, or an alpha 2 beta 4 agonist, or a combination thereof.

[0239] In some embodiments, the muscarinic agonist is a muscarinic M1 agonist or a muscarinic M4 agonist, or a combination thereof.

[0240] In some embodiments, the muscarinic antagonist is a muscarinic M2 antagonist.

[0241] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is psychosis or a psychotic condition, and one or more compounds of the present application are administered in combination with one or more additional treatments for the psychosis or psychotic condition. In some embodiments, the additional treatment for the psychosis or psychotic condition is a selected typical antipsychotic and an atypical antipsychotic.

[0242] In some embodiments, the typical antipsychotic is acepromazine, acetophenazine, benperidol, bromperidol, butaperazine, carphenazine, chlorproethazine, chlorpromazine, chlorprothixene, clopenthixol, cyamemazine, dixyrazine, droperidol, fluanisone, flupenthixol, fluphenazine, fluspirilene, haloperidol, levomepromazine, lenperone, loxapine, mesoridazine, methythepin, molindone, mope The active ingredient is selected from the group consisting of thiazepam, oxypertine, oxyprothepin, penfluridol, perazine, pericyazine, perphenazine, pimozide, pipamperone, piperacetazine, pipotiazine, prochlorperazine, promazine, prothipendyl, spiperone, sulforidazine, thiopropazate, thioproperazine, thioridazine, thiothixene, timiperone, trifluoperazine, trifluperidol, triflupromazine, and zuclopenthixol, and combinations thereof.

[0243] In some embodiments, the atypical antipsychotic is selected from amoxapine, amisulpride, aripiprazole, asenapine, blonanserin, brexpiprazole, cariprazine, carpipramine, clocapramine, chlorothepine, clothiapine, clozapine, iloperidone, levosulpiride, lurasidone, melperone, mosapramine, nemonapride, olanzapine, paliperidone, perospirone, quetiapine, remoxipride, reserpine, risperidone, sertindole, sulpiride, sultopride, tiapride, veralipride, ziprasidone, and zotepine, and combinations thereof.

[0244] In some embodiments, the disease, disorder, or condition treated by activation of serotonin receptors is a psychiatric disorder, and one or more compounds of the present application are administered in combination with one or more additional treatments for the psychiatric disorder. In some embodiments, the additional treatment for the psychiatric disorder is a selected typical antipsychotic and an atypical antipsychotic.

[0245] In some embodiments, the compound of formula I is a zwitterion, and the methods and uses of the present application include administration of the compound of formula I, as well as pharma- ceutically acceptable salts, solvates, zwitterions, and / or prodrugs thereof.

[0246] In some embodiments, a "subject in need of treatment" is a subject having a disease, disorder, or condition that is to be treated.

[0247] In some embodiments, a "subject in need of treatment" is a subject who expresses the endophenotype and / or symptom cluster being treated.

[0248] In some embodiments, the effective amount will vary depending on factors such as the condition, age, sex, and / or weight of the subject or species. In some embodiments, the amount of a given compound that corresponds to an effective amount will vary depending on factors such as the given drug or compound, pharmaceutical formulation, route of administration, type of condition, disease, or disorder, identity of the subject being treated, etc., but may nevertheless be routinely determined by one of skill in the art.

[0249] In some embodiments, the compounds of the present application are administered 1, 2, 3, or 4 times per year. In some embodiments, the compounds of the present application are administered at least once a week. However, in other embodiments, the compounds are administered to the subject about once every two weeks, three weeks, or month. In other embodiments, the compounds are administered about once per week to about once a day. In other embodiments, the compounds are administered 1, 2, 3, 4, 5, or 6 times a day. The length of the treatment period depends on various factors, such as the severity of the disease, disorder, or condition, the age of the subject, the concentration and / or activity of the compounds of the present application, and / or combinations thereof. It is also understood that the effective dosage of the compounds used for treatment may increase or decrease over the course of a particular treatment regimen. Changes in dosage may occur and be evident by standard diagnostic assays known in the art. In some cases, long-term administration is required. For example, the compounds are administered to the subject in an amount and for a duration sufficient to treat the subject.

[0250] In some embodiments, the compounds of the present application are administered at doses that are hallucinogenic or psychotomimetic and are administered in conjunction with psychotherapy or therapy, which may occur 1, 2, 3, or 4 times per year. However, in some embodiments, the compounds are administered to a subject at doses that are not hallucinogenic or psychotomimetic, once per day, once every 2 days, once every 3 days, once per week, once every 2 weeks, once per month, once every 2 months, or once every 3 months.

[0251] The compounds of the present application are used alone or in combination with other known agents useful for treating diseases, disorders, or conditions through activation of serotonin receptors, such as the compounds of the present application. When used in combination with other known agents useful for treating diseases, disorders through activation of serotonin receptors, it is an embodiment in which the compounds of the present application are administered simultaneously with those agents. As used herein, "co-administration" of two substances to a subject means providing each of the two substances so that both are active in an individual at the same time. The exact details of administration depend on the pharmacokinetics of the two substances in the presence of each other, and may even include administering the two substances within a few hours of each other, or administering one substance within 24 hours of administration of the other, if the pharmacokinetics are favorable. Designing suitable administration regimens is routine for those skilled in the art. In certain embodiments, the two substances are administered substantially simultaneously, i.e., within minutes of each other, or in a single composition containing both substances. It is a further embodiment of the present application that the combination of agents is administered to a subject in a non-simultaneous manner. In some embodiments, the compounds of the present application are administered simultaneously or sequentially with another therapeutic agent, either in separate unit dosage forms or together in a single unit dosage form. Thus, the present application provides a single unit dosage form that includes one or more compounds of the present application, an additional therapeutic agent, and a pharma- ceutically acceptable carrier.

[0252] The dosage of the compounds of the present application varies depending on many factors, such as the pharmacodynamic properties of the compounds, the method of administration, the age, health, and weight of the recipient, the nature and extent of the symptoms, the frequency of treatment, and the type of concurrent treatment, if any, as well as the clearance rate of the compounds in the subject being treated. Those skilled in the art can determine the appropriate dosage based on the above factors. In some embodiments, one or more compounds of the present application are initially administered at a suitable dosage, which is adjusted as necessary depending on the clinical response. The dosage is generally selected to maintain a serum level of one or more compounds of the present application of about 0.01 μg / cc to about 1000 μg / cc, or about 0.1 μg / cc to about 100 μg / cc. As a representative example, the oral dosage of one or more compounds of the present application ranges from about 10 μg per day to about 1000 mg per day for an adult, preferably about 10 μg per day to about 1000 mg per day, more preferably about 10 μg per day to about 500 mg per day. For parenteral administration, a representative amount is about 0.0001 mg / kg to about 10 mg / kg, about 0.001 mg / kg to about 100 mg / kg, about 0.1 mg / kg to about 1000 mg / kg, or about 1 mg / kg to about 10000 mg / kg. For oral administration, a representative amount is about 0.001 μg / kg to about 10 mg / kg, about 0.1 μg / kg to about 100 mg / kg, about 0.01 μg / kg to about 1000 mg / kg, or about 1 μg / kg to about 10000 mg / kg. For administration in the form of a suppository, a representative amount is about 0.1 mg / kg to about 10 mg / kg or about 0.1 mg / kg to about 100 mg / kg.

[0253] In some embodiments, dosages are generally selected to maintain serum levels of one or more compounds of the present application of about 0.01 μg / cc to about 1000 μg / cc, or about 0.1 μg / cc to about 100 μg / cc. As a representative example, oral dosages of one or more compounds of the present application range from about 10 μg per day to about 1000 mg per day for adults, preferably about 10 μg per day to about 500 mg per day, and more preferably about 10 μg per day to about 200 mg per day. For parenteral administration, representative amounts are administered 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. For oral administration, a representative amount is about 0.001 μg / kg to about 10 mg / kg, about 0.1 μg / kg to about 10 mg / kg, about 0.01 μg / kg to about 1 mg / kg, or about 0.1 μg / kg to about 1 mg / kg. For administration in suppository form, a representative amount is about 0.1 mg / kg to about 10 mg / kg or about 0.1 mg / kg to about 1 mg / kg.

[0254] In some embodiments of the present application, the 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 present application) per tablet. In some embodiments of the present application, one or more compounds of the present application are administered in a single daily, weekly, or monthly dose, or the total daily dose is divided into two, three, or four doses.

[0255] In some embodiments, the compounds of the present application are used or administered in an effective amount, including a dose or dosing regimen that lacks clinically significant psychotropic / psychotomimetic effects. ... 2A As indicated by human CNS receptor occupancy or human plasma psilocin Cmax of 1ng / mL or less and / or human 5-HT 2A The compounds of the present application are used or administered in effective amounts, including doses or dosing regimens that provide clinical efficacy similar to that indicated by human CNS receptor occupancy. In some embodiments, the compounds of the present application provide a human plasma psilocin Cmax of 4 ng / mL or greater and / or a human 5-HT 2A As indicated by human CNS receptor occupancy or human plasma thyroxine Cmax of 10 ng / mL or greater and / or human 5-HT 2A It is used or administered in an effective amount, including a dosage administration or dosing regimen that provides a clinical effect similar to that demonstrated by human CNS receptor occupancy.

[0256] In some embodiments, the compounds of the present application are used or administered in an effective amount, including administration of a dose or dosing regimen that provides a clinical effect similar to that demonstrated by human plasma psilocin Tmax at greater than 60 minutes, greater than 120 minutes, or greater than 180 minutes.

[0257] For clarity, in the above, the term "compound" also includes embodiments in which one or more compounds are referenced. Similarly, the term "compounds of the application" also includes embodiments in which only one compound is referenced.

[0258] In some embodiments, the above methods and uses comprise administering to a subject a subject a compound comprising an effective amount of 2-(5-methoxyindolin-3-yl)-N,N-dimethylethan-1-amine (II-1): [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, and / or 2-(indolin-3-yl)-N,N-dimethylethan-1-amine (II-2): [ka] or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, either by themselves, or in combination with one of more compounds of Formula I, and / or a salt, solvate, and / or prodrug thereof, and / or one or more other therapeutic agents.

[0259] V. Methods and Uses of Compounds of Formula II The compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is a compound having a 5-HT 2A These compounds are serotonergic binding agents that act as agonists, partial agonists, or positive allosteric modulators at serotonin receptors, including

[0260] Accordingly, the present application includes a method for activating serotonin receptors in and / or on cells, either in a biological sample or in a subject, comprising administering to the cells an effective amount of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof.

[0261] The present application also includes the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for activating serotonin receptors in and / or on cells, and the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for the preparation of a medicament for activating serotonin receptors in and / or on cells. The present application further includes one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for use in activating serotonin receptors in and / or on cells.

[0262] The compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, may also be used to inhibit other psychoactive 5-HT receptors, such as psilocybin. 2A Unlike agonists, they show a significant reduction in their risk of causing hallucinogenic effects.Thus, in some embodiments, the treatment of disease, disorder, or condition treatable by the activation of serotonin receptors does not have hallucinogenic effects in subjects, or has reduced hallucinogenic effects in subjects, compared to the hallucinogenic effects from the administration of an equivalent dose of hallucinogenic agent, such as, for example, psilocybin, DMT, or 5-MeO-DMT.In some embodiments, the hallucinogenic agent is psilocybin.In some embodiments, the activation of serotonin receptors does not have hallucinogenic effects in subjects, or has reduced hallucinogenic effects in subjects, compared to the hallucinogenic effects from the administration of an equivalent dose of psilocybin.

[0263] The present application also includes the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for activating serotonin receptors in and / or on cells, and the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for the preparation of a medicament for activating serotonin receptors in and / or on cells. The present application further includes one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for use in activating serotonin receptors in and / or on cells. In some embodiments, the treatment of a disease, disorder, or condition treatable by activation of a serotonin receptor does not have a hallucinogenic effect in the subject, or has a reduced hallucinogenic effect in the subject, as compared to the hallucinogenic effect from administration of an equivalent dose of a hallucinogenic agent, such as, for example, psilocybin, DMT, or 5-MeO-DMT. In some embodiments, the hallucinogenic agent is psilocybin. In some embodiments, activation of the serotonin receptors has no hallucinogenic effect in the subject, or has a reduced hallucinogenic effect in the subject compared to the hallucinogenic effect from administration of an equivalent dose of psilocybin.

[0264] The application also includes a method of treating a disease, disorder, or condition treatable by activation of a serotonin receptor, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, wherein treating the disease, disorder, or condition treatable by activation of a serotonin receptor does not have a hallucinogenic effect in the subject or has a reduced hallucinogenic effect in the subject compared to the hallucinogenic effect from administration of an equivalent dose of a hallucinogenic agent. In some embodiments, the hallucinogenic agent is selected from psilocybin, DMT, or 5-MeO-DMT. Accordingly, the application also includes methods of treating a disease, disorder, or condition treatable by activation of a serotonin receptor, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, wherein treating the disease, disorder, or condition treatable by activation of a serotonin receptor does not have a hallucinogenic effect in the subject, or has a reduced hallucinogenic effect in the subject compared to the hallucinogenic effect from administration of an equivalent dose of psilocybin.

[0265] The application also includes the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for the treatment of a disease, disorder, or condition due to activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to an equivalent dose of a hallucinogenic agent, as well as the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for the preparation of a medicament for the treatment of a disease, disorder, or condition due to activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to an equivalent dose of a hallucinogenic agent. The present application further includes one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for use in treating a disease, disorder, or condition due to activation of a serotonin receptor, wherein the use has no hallucinogenic effect or has a reduced hallucinogenic effect compared to an equivalent dose of a hallucinogenic agent. In some embodiments, the hallucinogenic agent is selected from psilocybin, DMT, or 5-MeO-DMT. Thus, the present application also includes the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for the treatment of a disease, disorder, or condition through activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of psilocybin, as well as the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for the preparation of a medicament for the treatment of a disease, disorder, or condition through activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of psilocybin.The application further includes one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, for use in the treatment of a disease, disorder, or condition through activation of a serotonin receptor, wherein the use has no hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of psilocybin.

[0266] In some embodiments, the serotonin receptor is 5-HT 2A It is.

[0267] The present application also includes a method of treating a disease, disorder, or condition by activation of a serotonin receptor, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, in combination with another known agent useful for treating the disease, disorder, or condition by activation of a serotonin receptor, wherein treating the disease, disorder, or condition by activation of a serotonin receptor does not have a hallucinogenic effect in the subject or has a reduced hallucinogenic effect in the subject compared to the hallucinogenic effect from administration of an equivalent dose of a hallucinogenic agent. In some embodiments, the hallucinogenic agent is selected from psilocybin, DMT, or 5-MeO-DMT. Accordingly, the application also includes a method of treating a disease, disorder, or condition through activation of a serotonin receptor, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, in combination with another known agent useful for treating the disease, disorder, or condition through activation of a serotonin receptor, wherein treating the disease, disorder, or condition through activation of a serotonin receptor does not have a hallucinogenic effect in the subject or has a reduced hallucinogenic effect in the subject compared to the hallucinogenic effect from administration of an equivalent dose of psilocybin.

[0268] The application also includes the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, in combination with another known agent useful for treating a disease, disorder, or condition through activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of the hallucinogenic agent, for the treatment of a disease, disorder, or condition through activation of a serotonin receptor, as well as the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, in combination with another known agent useful for treating a disease, disorder, or condition through activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of the hallucinogenic agent, for the preparation of a medicament for the treatment of a disease, disorder, or condition through activation of a serotonin receptor. The present application further includes one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, in combination with another known agent useful in the treatment of a disease, disorder, or condition due to activation of a serotonin receptor, wherein the use has no hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of the hallucinogenic agent, for use in the treatment of a disease, disorder, or condition due to activation of a serotonin receptor. In some embodiments, the hallucinogenic agent is selected from psilocybin, DMT, or 5-MeO-DMT.Thus, the present application also includes the use of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, in combination with another known agent useful in the treatment of a disease, disorder, or condition through activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of psilocybin, for the preparation of a medicament for the treatment of a disease, disorder, or condition through activation of a serotonin receptor, which does not have a hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of psilocybin. The application further includes one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, in combination with another known agent useful in the treatment of a disease, disorder, or condition due to activation of a serotonin receptor, wherein the use has no hallucinogenic effect or has a reduced hallucinogenic effect compared to the hallucinogenic effect from the use of an equivalent dose of psilocybin.

[0269] The embodiments for diseases, disorders, or conditions treatable by activation of serotonin receptors are the same as the embodiments for diseases, disorders, or conditions treatable by activation of serotonin receptors described above with respect to one or more compounds of the invention, i.e., compounds of Formula I, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof.

[0270] In some embodiments, the disease, disorder, or condition treated by activation of a serotonin receptor is an endophenotype or symptom cluster associated with a disease, disorder, or condition described above with respect to one or more compounds of the invention, i.e., a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

[0271] The embodiments for "known agents useful for treating a disease, disorder, or condition through activation of serotonin receptors" are the same as the embodiments for "known agents useful for treating a disease, disorder, or condition through activation of serotonin receptors" described above with respect to one or more compounds of the invention, i.e., a compound of Formula I, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof.

[0272] In some embodiments, a "subject in need of treatment" is a subject having a disease, disorder, or condition that is to be treated.

[0273] The embodiments for the "subject" are the same as the embodiments for the "subject" described above for administration or use with one or more compounds of the invention.

[0274] The compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, [ka] where: R 59 is C(O)R 65 , CO2R 65 , C(O)N(R 65 )(R 65’ ), S(O)R 65 , SO2R 65 , C 1-6 Alkylene R 65 , and R 65 is selected from Q' is Q3': [ka] and on the bond [ka] means that the bond connects it to the rest of the compound, R 60 , R 60’ , and R 60’’ are independently H, halo, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 60a )(R 60b ), and S.C. 1-6 alkyl, R 60a and R 60b are independently H and C 1-6 alkyl, R 61 , R 62 , R 63 , and R 64 are independently H, halo, N(R 63’ )(R 64’ ), C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 AlkyleneN(R 63’ )(R 64’ ), and S.C. 1-6 alkyl, the latter four groups being selected from OH and C 1-6 optionally substituted with one or two substituents selected from alkoxy; R 61 , R 62 , R 63 , and R 64 Two adjacent ones of the are linked together to form O-(CH2) 1-2 Form O and R 61 , R 62 , R 63 , and R 64 The rest are independently H, halo, and C. 1-6 Alkyl and C 1-6 Alkoxy, N(R 63’ )(R 64’ ), C 1-6 AlkyleneN(R 63’ )(R64’ ), and SC 1-6 alkyl; or R 61 , R 62 , R 63 , and R 64 One of them is A', O-A', and C 1-4 alkylene A'; R 61 , R 62 , R 63 , and R 64 the remainder of are independently H or halo; R 63’ and R 64’ are independently H and C 1-6 alkyl, A is phenyl, C 3-6 Cycloalkyl, O, S, S(O), SO2, N, and NR 72 and 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, S(O), SO2, N, and NR 72 phenyl, C 3-10 Cycloalkyl, 3- to 6-membered heterocycloalkyl, and 5- to 6-membered heteroaryl are selected from halo, C 1-4 Alkyl, OC 1-4 Alkyl, N(R 63’ )(R 64’ ), C 1-6 AlkyleneN(R 63’ )(R 64’ ), and S.C. 1-6 and optionally substituted with one or more substituents independently selected from alkyl, R 65 , H, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, Phenyl, C 3-6 Cycloalkyl, O, S, N, and NR 65 3-6 membered heterocycloalkyl containing 1-4 hetero moieties independently selected from O, S, N, and NR 65''; and 5-6 membered heteroaryl containing 1-4 hetero moieties independently selected from the group consisting of halo, OR, 73 , N(R 73 )(R 74 ), and S.R. 73 and / or C 1-6 Alkyl is O, C(O), CO2, and NR 75 and optionally interrupted by 1 to 3 heteroaryl moieties independently selected from R 65’ H and C 1-6 alkyl, R 65’’ H and C 1-6 alkyl, R 66 , R 67 , R 68 , and R 69 are independently H, halo, and C 1-6 alkyl, R 70 and R 71 are independent of each other, H, C 1-6 Alkyl, and C(O)C 1-6 alkyl; or R 70 and R 71 together with the N atom to which they are attached, they form O, S, S(O), SO2, N, and NR 76 forming a 3-6 membered heterocycle optionally containing one or two additional hetero moieties independently selected from R 72 , R 73 , R 74 , R 75 , and R 76 are independently H and C 1-6 alkyl, R 72a and R 72b are independently H and C 1-6 alkyl, All available hydrogen atoms are optionally and independently replaced with fluorine or chlorine atoms, and all available atoms are optionally replaced with their alternative isotopes.

[0275] R in the compound of formula II 59 , R 60 , R 60’ , R 60’’ , R 60a , R 60b 、 R 61 , R 62 , R 63 , R 64 , R 63’ and R 64’ , R 65 , R 65’ , R 65’’ , R 66 , R 67 , R 68 , R 69 , R 70 , R 71 , R 72 , R 72a , R 72b R 73 , R 74 , R 75 , R 76 The embodiments for Q′, Q′, and A′ are the same as those for R for formula I above, except that the proviso in formula I does not apply to formula II. 1 , R 2 , R 2’ , R 2’’’ , R 2a , R 2b 、 R 3 , R 4 , R 5 , R 6 , R 5’ , R 6’ , R 7 , R 7’ , R 7’’ , R 26 , R 27 , R 28 , R 29 , R 30 , R 31 , R 54 , R 54a , R 54b R 55, R 56 , R 57 , R 58 , Q, and A. Further, in some embodiments of Formula II, the compound of Formula II is selected from 2-(5-methoxyindolin-3-yl)-N,N-dimethylethan-1-amine (II-1) and 2-(indolin-3-yl)-N,N-dimethylethan-1-amine (II-2), and pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof.

[0276] In some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is a compound of formula I, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof. In some embodiments, the compound of formula II is selected from the compounds of formula I listed in Table A, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof.

[0277] Further, in some embodiments, the compound of formula II is selected from the compounds listed below, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof. [Table 19]

[0278] In some embodiments, the compound of formula II is a zwitterion, and the present application includes compounds of formula II, as well as pharma- ceutically acceptable salts, solvates, zwitterions, and / or prodrugs thereof.

[0279] In some embodiments, the pharma- ceutically acceptable salt is an acid addition salt or a base addition salt.The selection of suitable salt can be performed by those skilled in the art.Suitable salts include, for example, acid addition salts that can be formed by mixing a solution of a compound with a solution of a pharma- ceutically acceptable acid such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, or benzoic acid. Additionally, acids generally considered suitable for the formation of pharma- ceutically 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) 33 201-217, Anderson et al, The Practice of Medicinal Chemistry (1996), Academic Press, New York, and The Orange Book (website of the Food & Drug Administration, Washington, DC).

[0280] The acid addition salt suitable for or compatible with the treatment of the subject is any non-toxic organic or inorganic acid addition salt of any basic compound.Basic compounds that form acid addition salts include, for example, compounds that contain amine groups.Exemplary inorganic acids that form suitable salts include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid, as well as acid metal salts such as sodium monohydrogen orthophosphate and potassium hydrogen sulfate.Exemplary organic acids that form suitable salts include mono-, di-, and tri-carboxylic acids. Illustrative of such organic acids are, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, mandelic acid, salicylic acid, 2-phenoxybenzoic acid, 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 acetate, ascorbate, benzoate, benzenesulfonate, bisulfate, borate, butyrate, citrate, camphorate, camphorsulfonate, fumarate, hydrochloride, hydrobromide, hydroiodide, lactate, maleate, methanesulfonate ("mesylate"), naphthalenesulfonate, nitrate, oxalate, phosphate, propionate, salicylate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate (also known as tosylate), and the like. In some embodiments, mono- or di-acid salts are formed, and such salts exist in either hydrated, solvated, or substantially anhydrous form. In general, acid addition salts are more soluble in water and various hydrophilic organic solvents, and generally exhibit higher melting points compared to their free base forms. The criteria for selecting an appropriate salt will be known to those skilled in the art. Other non-pharmaceutical acceptable salts, such as, but not limited to, oxalates, may be used, for example, in the isolation of compounds of formula II for laboratory use or for subsequent conversion to a pharmaceutical acceptable acid addition salt.

[0281] The base addition salt suitable for or compatible with the treatment of the subject is any non-toxic organic or inorganic base addition salt of any acidic compound. Acidic compounds that form base addition salts include, for example, compounds that contain a carboxylic acid group. Exemplary inorganic bases that form suitable salts include lithium, sodium, potassium, calcium, magnesium, or barium hydroxide, as well as ammonia. Exemplary organic bases that 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, purine, piperazine, piperidine, N-ethylpiperidine, polyamine resins, etc. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine. The selection of an appropriate salt may be useful, for example, to prevent hydrolysis when there is an ester functionality elsewhere in the compound. The criteria for selecting an appropriate salt will be known to those skilled in the art. In some embodiments, exemplary basic salts also include alkali metal salts such as ammonium salts, sodium salts, lithium salts, and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, salts with organic bases (e.g., organic amines) such as dicyclohexylamine, A-butylamine, choline, and salts with amino acids such as arginine and lysine. Basic nitrogen-containing groups may be quaternized with agents such as lower alkyl halides (e.g., methyl, ethyl, and butyl chlorides, bromides, and iodides), dialkyl sulfates (e.g., dimethyl sulfate, diethyl sulfate, and dibutyl sulfate), longer chain halides (e.g., decyl, lauryl, and stearyl chlorides, bromides, and iodides), aralkyl halides (e.g., benzyl and phenethyl bromides).Compounds bearing an acidic moiety can be mixed with a suitable pharma- ceutically acceptable salt to provide, for example, salts formed with suitable organic ligands, such as alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., calcium or magnesium salts), and quaternary ammonium salts. Also, when an acid (-COOH) or alcohol group is present, pharma- ceutically acceptable esters can be used to modify the solubility or hydrolysis characteristics of the compound.

[0282] All such acid salts and base salts are intended to be pharma- ceutically acceptable salts of the compounds of formula II within the scope of this application, and all acid salts and base salts are considered equivalent to the free form of the corresponding compounds for the purposes of this application. Furthermore, when a compound of formula II contains both a basic moiety, such as, but not limited to, an aliphatic primary, secondary, tertiary, or cyclic amine, an aromatic or heteroaryl amine, a pyridine, or an imidazole, and an acidic moiety, such as, but not limited to, a tetrazole or a carboxylic acid, a zwitterion ("inner salt") may be formed and is included within the scope of this application. It is understood that certain compounds of formula II may exist in zwitterionic form, with both an anionic and cationic center within the same compound, and a net neutral charge. Such zwitterions are included within the scope of this application.

[0283] The solvates of the compound of formula II, or its salts and / or prodrugs, include, for example, those prepared with pharma- ceutically acceptable solvents. Examples of such solvents include water (the resulting solvates are called hydrates) and ethanol. Suitable solvents are physiologically tolerated at the dosage administered.

[0284] Prodrugs of compounds of formula II, or salts and / or solvates thereof, include, for example, conventional esters formed at available hydroxy, thiol, amino, or carboxyl groups. Some common esters utilized as prodrugs are phenyl esters, aliphatic (C1-C 24) esters, acyloxymethyl esters, carbamates, and amino acid esters.

[0285] In some embodiments, it is understood and appreciated that the compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, may have at least one chiral center and therefore may exist as enantiomers and / or diastereomers. It should be understood that all such isomers and mixtures thereof in any proportion are encompassed within the scope of this application. It should be further understood that the stereochemistry of the compound may be as shown for any given compound listed herein, but such compounds may also contain a certain amount (e.g., less than 20%, preferably less than 10%, more preferably less than 5%) of compounds of formula II having alternative stereochemistry. Any optical isomer, as an isolated, pure, or partially purified optical isomer or racemic mixture thereof, is intended to be encompassed within the scope of this application.

[0286] In some embodiments, the compound of formula II may also include tautomeric forms, such as keto-enol tautomers. The tautomeric forms may be in equilibrium or may be sterically locked into one form by appropriate substitution. Any tautomeric form that the compound forms, as well as mixtures thereof, are intended to be included within the scope of this application.

[0287] The compound of formula II, or salts and / or solvates thereof, may further exist in various amorphous and polymorphic forms, and any amorphous forms, polymorphs, or mixtures thereof formed are contemplated to be included within the scope of this application.

[0288] The compounds of formula II, or salts, solvates, and / or prodrugs thereof, may further be radiolabeled, and therefore all radiolabeled forms of the compounds of the present application are included within the scope of the present application. Thus, compounds of formula II also include those having one or more radioactive atoms incorporated within their structure.

[0289] The compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, is suitably formulated in a conventional manner into a composition using one or more carriers. The compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, is suitably formulated into a pharmaceutical composition for administration to a subject in a biologically compatible form suitable for administration in vivo. Thus, the present application further includes a pharmaceutical composition comprising one or more compounds of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, and a pharma- ceutically acceptable carrier, wherein the one or more compounds of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, are present in an amount effective to treat any of the diseases, disorders, or conditions described herein.

[0290] The compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, may be administered to a subject in a variety of forms depending on the selected route of administration, as will be appreciated by those skilled in the art. For example, the compound of formula II may be administered by oral, inhalation, parenteral, buccal, sublingual, insufflation, epidural, nasal, rectal, vaginal, patch, pump, minipump, topical, or transdermal administration, and pharmaceutical compositions formulated accordingly. In some embodiments, administration is by pump for periodic or continuous delivery. Conventional procedures and ingredients for the selection and preparation of suitable compositions may be found, for example, in Remington's Pharmaceutical Sciences (2000-2003), 1999, 1998, 1999, 1999, 1990, 1992, 1993, 1994, 1995, 1996, 1997, 1999, 1998, 1999, 1999, 1990, 1991, 1992, 1993, 1994, 1995, 1996, 1997, 1998, 1999, 1999, 1999, 1999, 1998, 1999, 1990, 1991, 1992, 1993, 1994, 1995, 1996, 1997, 1998, 1999, 1999, 1999, 1999, 1999, 1999, 1990, 1991, 1992, 1993, 1994, 1995, 1996, 1997, th edition) and The United States Pharmacopeia: The National Formulary published in 1999 (USP 24 NF19).

[0291] Parenteral administration includes systemic delivery routes other than the gastrointestinal (GI) tract, and includes, for example, intravenous, intraarterial, intraperitoneal, subcutaneous, intramuscular, transepithelial, nasal, pulmonary (e.g., by use of an aerosol), intrathecal, rectal, and topical (including use of a patch or other transdermal delivery device) methods of administration. Parenteral administration may also be by continuous infusion over a selected period of time.

[0292] In some embodiments, the compound of formula II or its pharma- ceutically acceptable salt, solvate, and / or prodrug is orally administered, for example, with an inert diluent or with an assimilable edible carrier, or is enclosed in a hard or soft shell gelatin capsule, or is compressed into a tablet, or is directly incorporated with dietary food. In some embodiments, the compound is incorporated with an excipient and used in the form of ingestible tablets, buccal tablets, troches, capsules, caplets, pellets, granules, lozenges, chewing gum, powders, syrups, elixirs, wafers, aqueous solutions, and suspensions. For tablets, carriers used include lactose, corn starch, sodium citrate, and salts of phosphoric acid. Pharmaceutically acceptable excipients include binders (e.g., pregelatinized maize starch, polyvinylpyrrolidone, or hydroxypropylmethylcellulose), 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), or wetting agents (e.g., sodium lauryl sulfate), or solvents (e.g., medium chain triglycerides, ethanol, water). In embodiments, the tablets are coated by methods well known in the art. For 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, e.g., immediate release and timed release formulations. Examples of modified release formulations include, for example, sustained release (SR), extended release (ER, XR, or XL), timed or timed release, controlled release (CR), or continuous release (CR or Contin), used, for example, in the form of coated tablets, osmotic delivery devices, coated capsules, microencapsulated microspheres, agglomerated particles, for example, molecular sieving type particles, or fine hollow permeable fiber bundles, or chopped hollow permeable fibers aggregated or held within a fibrous packet.The timed release composition is formulated, for example, as liposomes, or where the active compound is protected with a differentially degradable coating, such as by microencapsulation, multiple coatings, etc. Liposomal delivery systems include, for example, small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles. In some embodiments, liposomes are formed from various phospholipids, such as cholesterol, stearylamine, or phosphatidylcholine. For oral administration in capsule form, useful carriers, solvents, or diluents include lactose, medium chain triglycerides, ethanol, and dry cornstarch.

[0293] In some embodiments, liquid preparations for oral administration may take the form of, for example, a solution, syrup, or suspension, or may be 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 formula II, or its pharma- ceutically acceptable salt, solvate, and / or prodrug, is suitably suspended or dissolved in an oily phase combined with an emulsifying and / or suspending agent. If necessary, certain sweetening and / or flavoring and / or coloring agents are added. Such liquid preparations for oral administration are prepared by conventional means using pharma- ceutically acceptable additives, such as suspending agents (e.g., sorbitol syrup, methylcellulose, 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 preservatives (e.g., methyl or propyl p-hydroxybenzoate, or sorbic acid). Useful diluents include lactose and high molecular weight polyethylene glycols.

[0294] It is also possible to lyophilize the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, and use the resulting lyophilizate, for example, for the preparation of an injectable product.

[0295] In some embodiments, the compound of formula II, or its pharma- ceutically acceptable salt, solvate, and / or prodrug, is administered parenterally. For example, a solution of the compound of formula II, or its pharma- ceutically acceptable salt, solvate, and / or prodrug, is prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. In some embodiments, dispersions are prepared in glycerol, liquid polyethylene glycol, DMSO, and mixtures thereof with or without alcohol, and in oils. Under normal conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. A person skilled in the art will know how to prepare suitable formulations. For parenteral administration, a sterile solution of the compound of formula II, or its pharma- ceutically acceptable salt, solvate, and / or prodrug, is usually prepared, and the pH of the solution is suitably adjusted and buffered. For intravenous use, the total concentration of solutes should be controlled to make the preparation isotonic. For ocular administration, ointments or droppable liquids are delivered by ocular delivery systems known in the art, such as applicators or eyedroppers.In some embodiments, such compositions include viscosity mimetics such as hyaluronic acid, chondroitin sulfate, hydroxypropylmethylcellulose, or polyvinyl alcohol, preservatives such as sorbic acid, EDTA, or benzyl chromium chloride, and diluents or carriers in the usual amounts.For pulmonary administration, diluents or carriers are selected to be suitable for allowing the formation of aerosols.

[0296] In some embodiments, the compound of formula II or its pharma- ceutically acceptable salt, solvate, and / or prodrug is formulated for parenteral administration by injection, including the use of conventional catheter insertion techniques or infusion. Formulations for injection are presented, for example, in unit dosage form, for example, in ampoules or in multi-dose containers, with added preservatives. In some embodiments, the composition takes the form of a sterile suspension, solution, or emulsion in an oily or aqueous vehicle, and contains formulating agents such as suspending, stabilizing, and / or dispersing agents. In any case, the form should be sterile and fluid to the extent that easy syringability exists. Alternatively, the compound of formula II or its pharma-ceutically acceptable salt, solvate, and / or prodrug is preferably in sterile powder form for reconstitution with a suitable vehicle, for example, sterile pyrogen-free water, before use.

[0297] In some embodiments, the composition for nasal administration is conveniently formulated as aerosols, drops, gels, and powders. For intranasal administration or administration by inhalation, the compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, is conveniently delivered in the form of a solution, dry powder formulation, or suspension from a pump spray container that is pressed or pumped by the patient, or as an aerosol spray presentation from a pressurized container or nebulizer. Aerosol formulations typically comprise a solution or fine suspension of an active substance in a physiologically acceptable aqueous or non-aqueous solvent, and are usually presented in single or multiple doses in a sealed container in sterile form, for example in the form of a cartridge or refill for use in a nebulizing device. Alternatively, the sealed container is a unit-dispensing device, such as a single-dose nasal inhaler, or an aerosol dispenser with a metering valve that is intended for disposal after use. When the dosage form comprises an aerosol dispenser, it contains a propellant, for example a compressed gas such as compressed air, or an organic propellant such as a fluorochlorohydrocarbon. Suitable propellants include, but are not limited to, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, heptafluoroalkane, carbon dioxide, or another suitable gas. In the case of pressurized aerosol, 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 (e.g., made of gelatin) for use in an inhaler or insufflator are formulated to contain, for example, a powder mix of the compound of formula II, or its pharma-ceutically acceptable salt, solvate, and / or prodrug, and a suitable powder base, such as lactose or starch. Aerosol dosage forms can also take the form of a pump-atomizer.

[0298] Compositions suitable for buccal or sublingual administration include tablets, lozenges, and pastilles, in which the compound of formula II or its pharma- ceutically acceptable salts, solvates, and / or prodrugs are 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.

[0299] Suppository forms of the compound of formula II or its pharma- ceutically acceptable salts, solvates, and / or prodrugs are useful for vaginal, urethral, ​​and rectal administration. Such suppositories are generally constructed from a mixture of materials that are solid at room temperature but melt at body temperature. Materials commonly used to produce 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. For further discussion of suppository dosage forms, see, for example, Remington's Pharmaceutical Sciences, 16 th Ed., Mack Publishing, Easton, PA, 1980, pp. 1530-1533.

[0300] In some embodiments, the compound of formula II or its pharma- ceutically acceptable salt, solvate, and / or prodrug is coupled to a soluble polymer as a targetable drug carrier. Such polymers include, for example, polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide-phenol, polyhydroxy-ethylaspartamide-phenol, or polyethylene oxide-polylysine substituted with palmitoyl residues. Furthermore, in some embodiments, the compound of formula II or its pharma- ceutically acceptable salt, solvate, and / or prodrug is coupled to a class of biodegradable polymers useful for achieving controlled release of drugs, such as polylactic acid, polyglycolic acid, copolymers of polylactic acid and polyglycolic acid, polyepsilon caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates, and crosslinked or amphiphilic block copolymers of hydrogels.

[0301] Compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, are particularly suitable for administration with the air of nanocarrier systems, such as liposomes, micelles, nanoparticles, nanoemulsions, lipid nanosystems, etc. (see, e.g., Bhat, M. et al. Chem. And Phys. Of Lipids, 2021, 236, 105053). Thus, the present application includes compositions comprising one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, and one or more components of a nanocarrier system.

[0302] Although the compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, are suitably used per se, they are generally administered in the form of a pharmaceutical composition in which one or more compounds (active ingredients) are associated with a pharma- ceutically acceptable carrier. Depending on the method of administration, the pharmaceutical composition contains about 0.05% to about 99% by weight, or about 0.10% to about 70% by weight, of the active ingredient, and about 1% to about 99.95% by weight, or about 30% to about 99.90% by weight of the pharma- ceutically acceptable carrier, all weight percentages being based on the total composition.

[0303] In some embodiments, the compound of formula II or its pharma- ceutically acceptable salt, solvate, and / or prodrug is administered in a composition comprising an additional therapeutic agent. Thus, the present application also includes pharmaceutical compositions comprising one or more compounds of formula II or their pharma- ceutically acceptable salt, solvate, and / or prodrug, an additional therapeutic agent, and optionally one or more pharma- ceutically acceptable excipients. In some embodiments, the additional therapeutic agent is another known agent useful for treating a disease, disorder, or condition caused by activation of serotonin receptors, such as those listed in the above method and use section for the compounds of the present application. In some embodiments, the additional therapeutic agent is a psychotropic drug.

[0304] In some embodiments, an effective amount of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, will vary depending on factors such as the condition, age, sex, and / or weight of the subject or species. In some embodiments, the amount of a given compound that corresponds to an effective amount will vary depending on factors such as the given drug or compound, pharmaceutical formulation, route of administration, type of condition, disease, or disorder, identity of the subject being treated, and the like, but may nevertheless be routinely determined by one of skill in the art.

[0305] In some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered 1, 2, 3, or 4 times per year. In some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered at least once per week. However, in other embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered to the subject about once every two weeks, three weeks, or month. In other embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered about once per week to about once per day. In other embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered 1, 2, 3, 4, 5, or 6 times per day. The length of the treatment period depends on various factors, such as the severity of the disease, disorder, or condition, the age of the subject, the concentration and / or activity of the compound of formula II, or its pharmaceutically acceptable salt, solvate, and / or prodrug, and / or a combination thereof. It is also understood that the effective dosage of the compound of formula II, or its pharmaceutically acceptable salt, solvate, and / or prodrug used in the treatment may increase or decrease over the course of a particular treatment regimen. The change in dosage may be consequential and evident by standard diagnostic assays known in the art. In some cases, long-term administration is required. For example, the compound of formula II, or its pharmaceutically acceptable salt, solvate, and / or prodrug is administered to the subject in an amount and duration sufficient to treat the subject.

[0306] In some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered at a dose that is non-hallucinogenic or non-psychotomimetic, is administered in conjunction with psychotherapy or therapy, and may occur 1, 2, 3, or 4 times per year. However, in some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered at a dose that is not hallucinogenic or psychotomimetic to a subject once a day, once every 2 days, once every 3 days, once a week, once every 2 weeks, once a month, once every 2 months, or once every 3 months.

[0307] The compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, is used either alone or in combination with other known agents useful for treating diseases, disorders, or conditions by activating serotonin receptors. When used in combination with other known agents useful for treating diseases, disorders by activating serotonin receptors, it is an embodiment in which the compound of formula II, or its pharma- ceutically acceptable salts, solvates, and / or prodrugs, are administered simultaneously with those agents. As used herein, "co-administration" of two substances to a subject means providing each of the two substances so that both are active in the individual at the same time. The exact details of administration depend on the pharmacokinetics of the two substances in the presence of each other, and may even include administering the two substances within a few hours of each other, or administering one substance within 24 hours of administering the other, if the pharmacokinetics are favorable. Designing suitable administration regimens is routine for those skilled in the art. In certain embodiments, the two substances are administered substantially simultaneously, i.e., within minutes of each other, or in a single composition containing both substances. It is a further embodiment of the present application that the combination of drugs is administered to the subject in a non-simultaneous manner.In some embodiments, the compound of formula II, or its pharmaceutically acceptable salt, solvate, and / or prodrug, is administered simultaneously or sequentially with another therapeutic agent in separate unit dosage forms or together in a single unit dosage form.Thus, the present application provides a single unit dosage form comprising one or more compounds of formula II, or its pharmaceutically acceptable salt, solvate, and / or prodrug, an additional therapeutic agent, and a pharmaceutically acceptable carrier.

[0308] The dosage of the compound of formula II, or its pharmacologic acceptable salt, solvate, and / or prodrug, varies depending on many factors, such as the pharmacodynamic properties of the compound, the method of administration, the age, health, and weight of the recipient, the nature and extent of symptoms, the frequency of treatment, and the type of concurrent treatment, if any, and the clearance rate of the compound in the subject being treated. Those skilled in the art can determine the appropriate dosage based on the above factors. In some embodiments, one or more compounds of formula II, or its pharmacologic acceptable salt, solvate, and / or prodrug, are initially administered at a suitable dosage, which is adjusted as necessary depending on the clinical response.

[0309] In some embodiments, dosages are generally selected to maintain serum levels of one or more compounds of the present application of about 0.01 μg / cc to about 1000 μg / cc, or about 0.1 μg / cc to about 100 μg / cc. As a representative example, oral dosages of one or more compounds of formula II range from about 10 μg per day to about 1000 mg per day for adults, preferably about 10 μg per day to about 500 mg per day, more preferably about 10 μg per day to about 500 mg per day. For parenteral administration, representative amounts are administered from about 0.0001 mg / kg to about 10 mg / kg, about 0.001 mg / kg to about 100 mg / kg, about 0.1 mg / kg to about 1000 mg / kg, or about 1 mg / kg to about 10,000 mg / kg. For oral administration, a representative amount is about 0.001 μg / kg to about 10 mg / kg, about 0.1 μg / kg to about 100 mg / kg, about 0.01 μg / kg to about 1000 mg / kg, or about 1 μg / kg to about 10000 mg / kg. For administration in suppository form, a representative amount is about 0.1 mg / kg to about 10 mg / kg or about 0.1 mg / kg to about 100 mg / kg.

[0310] In some embodiments, dosages are generally selected to maintain serum levels of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, of about 0.01 μg / cc to about 1000 μg / cc, or about 0.1 μg / cc to about 100 μg / cc. As a representative example, oral dosages of one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof, range from about 10 μg per day to about 1000 mg per day, preferably about 10 μg per day to about 500 mg per day, and more preferably about 10 μg per day to about 200 mg per day for adults. For parenteral administration, a representative amount is 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. For oral administration, a representative amount is about 0.001 μg / kg to about 10 mg / kg, about 0.1 μg / kg to about 10 mg / kg, about 0.01 μg / kg to about 1 mg / kg, or about 0.1 μg / kg to about 1 mg / kg. For administration in the form of a suppository, a representative amount is about 0.1 mg / kg to about 10 mg / kg or about 0.1 mg / kg to about 1 mg / kg. In some embodiments of the present application, the 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 the active ingredient (one or more compounds of Formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof) per tablet. In some embodiments of the application, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is administered in a single daily, weekly, or monthly dose, or the total daily dose is divided into two, three, or four doses.

[0311] In some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is used or administered in an effective amount, including a dose or dosing regimen lacking clinically significant psychotropic / psychotomimetic effects. ... 2A As indicated by human CNS receptor occupancy or human plasma psilocin Cmax of 1ng / mL or less and / or human 5-HT 2A It is used or administered in an effective amount, including a dosage administration or dosing regimen that provides a clinical effect similar to that demonstrated by human CNS receptor occupancy.

[0312] In some embodiments, the compound of formula II has a human plasma psilocin Cmax of 4 ng / mL or more and / or a human 5-HT 2A As indicated by human CNS receptor occupancy or human plasma thyroxine Cmax of 10 ng / mL or greater and / or human 5-HT 2A It is used or administered in an effective amount, including a dosage administration or dosing regimen that provides a clinical effect similar to that demonstrated by human CNS receptor occupancy.

[0313] In some embodiments, the compound of formula II, or a pharma- ceutically acceptable salt, solvate, and / or prodrug thereof, is used or administered in an effective amount, including administration of a dose or dosing regimen that provides a clinical effect similar to that exhibited by a human plasma psilocin Tmax of greater than 60 minutes, greater than 120 minutes, or greater than 180 minutes.

[0314] For clarity, in the above, the term "compound" also includes embodiments in which reference is made to one or more compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof. Similarly, the term "compound" also includes embodiments in which reference is made to only one compound of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof.

[0315] VI. Preparation of Compounds The compounds of the present application can be prepared by various synthetic processes. The selection of certain structural features and / or substituents may also influence the selection of one process over another. The selection of a particular process for preparing a given compound of the present application is within the purview of a person skilled in the art. Some starting materials for preparing the compounds of the present application can be obtained from commercial chemical sources or extracted from cells, plants, animals, or fungi. Other starting materials are easily prepared from available precursors using simple transformations that are well known in the art, for example, as described below. In the following schemes showing some embodiments of the method for preparing the compounds of the present application, all variables are as defined in formula I unless otherwise indicated.

[0316] In some embodiments, R 2’ and R 2’’ Compounds of formula I, in which R is H or D, can be prepared by reduction of the corresponding indole compound A, 1 , R 2 , R 3 , R 4 , R 5 , and R 6 is as defined in Formula I, as shown in Scheme 1. [ka]

[0317] In some embodiments, the reduction is carried out using a silane reducing agent, such as triethylsilane, in an acid, such as trifluoroacetic acid, or a deuterated version thereof. In some embodiments, the reaction is made enantioselective or diastereoselective through the use of a chiral reducing agent or chiral auxiliary. In some embodiments, the reduction is carried out using any suitable reduction conditions known in the art, such as, for example, those described in He, Yi; et al: Tetrahedron Letters (2014), 55(29), 3938-3941, and Somei, Masanori; et al: Heterocycles (1995), 40(1), 119-22.

[0318] In some embodiments, compounds of formula A are available as shown in Scheme 2. [ka]

[0319] Thus, in some embodiments, an ortho-iodoaniline compound of formula B, 1 and R 3 ~R 6 is as defined in formula I) can be reacted with an alkyne of formula C, 2 and Q are as defined in formula I) in the presence of a palladium catalyst using conditions described, for example, in Fricke et al., Chem. Eur. J., 2019, 25(4):897-903 to obtain a compound of formula A. One skilled in the art can easily prepare a compound of formula B (wherein R 1 It will be appreciated that compounds of formula A can be obtained by using a suitable protecting group, such as 2-(2-methyl-1,2-diphenyl-2-propanediol), followed by removal of the protecting group to obtain compounds of formula A.

[0320] In some embodiments, Q is [ka] and R 26 ~R31 When is either H or D, compounds of formula A are prepared as shown in Scheme 3. [ka]

[0321] Thus, in some embodiments, a compound of formula D, 1 ~R 6 is as defined in formula I) is reacted with oxalyl chloride followed by the amine NHR 30 R 31 (In the formula, R 30 and R 31 is as defined in formula I) to give a compound of formula E. Subsequent Al-based reduction of the compound of formula E, for example in the presence of lithium borohydride, lithium aluminum hydride, or lithium aluminum deuteride, gives a compound of formula A, where Q is [ka] and R 26 ~R 27 is either H or D, and R 1 ~R 6 and R 30 ~R 31 is as defined in formula I).

[0322] In some embodiments, Q is [ka] If R 4 is an alkoxy (e.g., C 1-6 alkoxy or OA), and R 1 , R 2 , R 3 , R 5 , R 6 , and R 26 ~R 31 is as defined in Formula I, and compounds of Formula A are prepared as shown in Scheme 4. [ka]

[0323] Thus, in some embodiments, a compound of formula O, where R 4 are OH and A, and R 3 , R 5 , R 6 , and R 26 ~R 31 is as defined in formula I) is reacted with a compound of formula P, where X is a suitable leaving group such as I or Br, and R is alkyl or A, as defined in formula I, under suitable conditions, such as in the presence of a base, such as potassium carbonate, and in a suitable solvent, such as acetone, to provide a compound of formula A. In some embodiments, a compound of formula O, where R 4 are OH and A, and R 1 , R 2 , R 3 , R 5 , R 6 , and R 26 ~R 31 (is as defined in formula I) is reacted with a suitable alcohol under suitable Mitsunobu reaction conditions, such as in the presence of diethyl azodicarboxylate (DEAD) and triphenylphosphine. In some embodiments, the suitable conditions are any suitable conditions known in the art, such as, for example, the coupling conditions described in WO2005 / 009958(A1) and US6133287.

[0324] One skilled in the art can easily prepare compounds of formula I, where R 3 , R 5 , R 5 , and R 6 It will be appreciated that any one of the following is alkoxy.

[0325] Compounds of formula D or A, where R 2 , R 3 ~R 6is deuterium) can be obtained, for example, using a hydrogen-deuterium exchange reaction on a suitable starting substrate (this exchange reaction is catalyzed by Pd / C in DO as described in Esaki, H. et al. Tetrahedron, 2006, 62:10954-10961) and modifications thereof known to those skilled in the art.

[0326] A compound of formula A, wherein R 4 is OCD3), can be obtained, for example, using the methods described in Xu, YZ and Chen, CJ Label Compd. Radiopharm. (2006) 49:897-902, and modifications thereof and known to those skilled in the art.

[0327] Compounds of formulas B, C, D, and F, as well as other reagents used in the above schemes, are available from commercial sources or can be readily prepared using methods known in the art.

[0328] Those skilled in the art will appreciate that further manipulation of the substituents using known chemistry can be carried out on the intermediates and final compounds of the above schemes to provide alternative compounds of the present application.

[0329] Nucleophilic substitution reaction conditions include any known method for the reaction of a nucleophile to transfer a leaving group to form a bond that is compatible with the intermediates and products shown in the schemes above, or that can be used to prepare compounds of Formula I and II, or pharma-ceutically acceptable salts, solvates, zwitterions, and / or prodrugs thereof. In some embodiments, such conditions include combining the reactants in the presence of a base in a suitable solvent.

[0330] Salts of the compounds of the present application can be formed by methods known to those skilled in the art, for example, by reacting the compounds of the present application with an amount of acid or base, e.g., an equivalent amount, in a medium such as a medium in which the salt precipitates, or in an aqueous medium, followed by lyophilization.

[0331] The formation of solvates varies depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in a suitable solvent and isolating the solvate by cooling or using an anti-solvent. The solvate typically dries or azeotropes under ambient conditions. The selection of suitable conditions for forming a particular solvate can be made by one of ordinary skill in the art. Examples of suitable solvents are ethanol, water, etc. When water is the solvent, the molecule is referred to as a "hydrate". The formation of solvates of the compounds of the present application varies depending on the compound and the solvate. In general, solvates are formed by dissolving the compound in a suitable solvent and isolating the solvate by cooling or using an anti-solvent. The solvate typically dries or azeotropes under ambient conditions. The selection of suitable conditions for forming a particular solvate can be made by one of ordinary skill in the art.

[0332] Prodrugs of the compounds of the present application 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 an inert solvent (e.g., an acid chloride in pyridine).

[0333] Isotopically enriched compounds of the present application, as well as pharma- ceutically acceptable salts and / or solvates thereof, may be prepared without undue experimentation by conventional techniques well known to those of skill in the art, or by processes analogous to those described in the Schemes and Examples herein using suitable isotopically enriched reagents and / or intermediates.

[0334] It should be understood that throughout the processes described herein, suitable protecting groups are added to and subsequently removed from the various reactants and intermediates, where appropriate, in a manner that would 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", TW Green, PG M Huts, Wiley-Interscience, New York, (1999). It should also be understood that the conversion of one group or substituent to another group or substituent by chemical manipulation may be performed on any intermediate or final product on the synthetic route toward the final product, with the types of possible transformations being limited only by the inherent incompatibility of other functional groups carried by the molecule at that stage with the conditions or reagents used in the transformation. Such inherent incompatibilities, and how to avoid them by carrying out the appropriate transformations and synthetic steps in a suitable order, will be readily understood by one skilled in the art. It should be understood that examples of transformations are given herein, and that the transformations described are not limited only to the general groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations can be found in "Comprehensive Organic Transformations-A Guide to Functional Group Preparations" RC Larock, VHC Publishers, Inc. (1989). References and descriptions of other suitable reactions can be found in organic chemistry texts, such as "Advanced Organic Chemistry", March, 4th ed. McGraw Hill (1992) or "Organic Synthesis", Smith, McGraw Hill, (1994). Techniques for purification of intermediates and final products include, for example, straight and reverse phase chromatography on columns or spinning plates, recrystallization, distillation, and liquid-liquid or solid-liquid extraction, and will be readily understood by those skilled in the art.

[0335] It should also be understood that the conversion of one group or substituent to another group or substituent by chemical manipulation may be performed on any intermediate or final product on the synthetic route toward the final product, with the types of possible transformations being limited only by the inherent incompatibility of other functional groups carried by the molecule at that stage with the conditions or reagents used in the transformation. Such inherent incompatibilities, and how to avoid them by carrying out appropriate transformations and synthetic steps in a suitable order, will be readily understood by those skilled in the art. Examples of transformations are given herein, and it should be understood that the transformations described are not limited only to the common groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations are found in "Comprehensive Organic Transformations-A Guide to Functional Group Preparations" RC Larock, VHC Publishers, Inc. (1989). Other suitable reaction references and explanations can be found in organic chemistry texts, such as "Advanced Organic Chemistry", March, 4th ed. McGraw Hill (1992) or "Organic Synthesis", Smith, McGraw Hill, (1994).

[0336] Techniques for purification of intermediates and final products include, for example, straight and reverse phase chromatography on columns or spinning plates, recrystallization, distillation, and liquid-liquid or solid-liquid extraction and will be readily understood by those skilled in the art.

[0337] The products of the processes of the present application 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 methods.

[0338] Those skilled in the art will recognize that when reaction steps of the present application are carried out in various solvents or solvent systems, the reaction steps may also be carried out in mixtures of suitable solvents or solvent systems.

[0339] Those skilled in the art will appreciate that the same preparation methods described above for the compounds of the present application can be used to prepare compounds of formula II, or pharma- ceutically acceptable salts, solvates, and / or prodrugs thereof. EXAMPLES

[0340] A. Chemical synthesis Common methods All starting materials used herein were either commercially available or previously described in the literature. 1 H and 13 C NMR spectra were obtained in deuterated chloroform using TMS or residual solvent signals as internal standard unless otherwise indicated. 1 H NMR was recorded on either a Bruker 300, Bruker DPX400, or Varian +400 spectrometer operating at 300, 400, and 400 MHz, respectively. All chemical shifts reported are in ppm on the delta scale, and fine divisions of signals appearing in the recordings are generally indicated as, for example, s: singlet, br s: broad singlet, d: doublet, t: triplet, q: quartet, m: multiplex. Unless otherwise indicated, in the following tables, CDCl3 was used as the solvent, 1 1 H NMR data was obtained at 400 MHz.

[0341] Purification of products was performed using Chem Elut Extraction Columns (Varian, Cat. No. 1219-8002), Mega BE-SI (Bond Elut Silica) SPE Columns (Varian, Cat. Nos. 12256018; 12256026; 12256034) or by flash chromatography on silica-packed glass columns.

[0342] Example 1: 2-(5-Methoxyindolin-3-yl)-N,N-dimethylethan-1-amine (II-1) [ka] Synthesis of 2-(5-methoxyindolin-3-yl)-N,N-dimethylethan-1-amine (2): A solution of 2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethan-1-amine (0.4 g, 1.832 mmol) in trifluoroacetic acid (30 mL) was treated with triethylsilane (0.58 mL, 3.664 mmol) and the resulting solution was stirred at 50 °C overnight (16 h). The reaction was brought to room temperature and the solvent was evaporated. The crude was basified with 4N NaOH solution and the product was extracted into CHCl (3 x 50 mL). The combined CHCl layers were dried (NaSO) and the solvent was evaporated to give the crude product as a brown liquid. The crude was purified by column chromatography on silica gel (2M NH3 in MeOH:CH2Cl2, 5:95) to give the title compound II-1 (0.31 g, 77.5%) as a light brown oil. 1 H NMR (CDCl3): δ 6.76 (s, 1H), 6.65-6.60 (m, 2H), 3.78 (s, 3H), 3.70 (t, 1H, J = 6.0 Hz), 3.35-3.20 (m, 2H), 2.43-2.32 (m, 3H), 2.28 (s, 6H), 2.05-1.99 (m, 1H), 1.78-1.71 (m, 1H); ESI-MS (m / z, %): 221 (MH + , 100).

[0343] Example 2: 2-(indolin-3-yl)-N,N-dimethylethan-1-amine (II-2)] [ka] Synthesis of 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (8): A solution of 1H-indole (5.0 g, 42.698 mmol) in dry THF (50 mL) was treated with oxalyl chloride (3.61 mL, 42.698 mmol) for 5 min at 0° C. The reaction was allowed to reach room temperature and stirred for 3 h. The reaction was treated with dimethylamine (85 mL, 170.0 mmol, 2 M solution in THF) for 15 min and stirred overnight (16 h). The reaction was quenched with water (100 mL) and the product was extracted into ethyl acetate (2×100 mL). The combined ethyl acetate layers were washed with brine (50 mL) and dried (Na2SO4). The solvent was evaporated and the crude was purified by crystallization from ethyl acetate:hexane (1:1) to give the title compound 8 (7.88 g, 85.4%) as a beige solid. 1 H NMR (DMSO-d6): δ 12.28 (brs, 1H), 8.11-8.09 (m, 2H), 7.53 (dd, 1H, J = 3.0 Hz), 7.30-7.23 (m, 2H), 2.99 (s, 3H), 2.91 (s, 3H); ESI-MS (m / z, %): 238 (M+Na, 100).

[0344] Synthesis of 2-(1H-indol-3-yl)-N,N-dimethylethan-1-amine (9): A suspension of lithium aluminum hydride (2.80 g, 74.0 mmol) in dry THF (25 mL) was treated with 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (2.0 g, 9.248 mmol) in dry THF (25 mL) at 0° C. for 10 min. The reaction was allowed to come to room temperature and then refluxed for an additional 16 h. The reaction was worked up and purified as described for compound 5 to give the title compound 9 (1.7 g, quantitative) as an off-white solid. 1H NMR (DMSO-d6): δ 10.76 (s, 1H), 7.50 (d, 1H, J = 3.0 Hz), 7.32 (d, 1H, J = 6.0 Hz), 7.13 (s, 1H), 7.07-7.03 (m, 1H), 6.98-6.95 (m, 1H), 2.82-2.79 (m, 2H), 2.52-2.49 (m, 2H), 2.21 (s, 6H); ESI-MS (m / z, %): 189 (MH + , 100).

[0345] Synthesis of 2-(indolin-3-yl)-N,N-dimethylethan-1-amine (II-2): A solution of 2-(1H-indol-3-yl)-N,N-dimethylethan-1-amine (1.47 g, 7.807 mmol) in trifluoroacetic acid (60 mL) was treated with triethylsilane (2.49 mL, 15.615 mmol) and the resulting solution was stirred overnight (16 h) at 50° C. The reaction was worked up and purified as described for compound II-1 to give the title compound II-2 (1.1 g, 74.3%) as a pale yellow oil. 1 H NMR (DMSO-d6): δ 7.01 (d, 1H, J = 6.0 Hz), 6.90 (t, 1H, J = 6.0 Hz), 6.54 (dd, 1H, J = 1.5, 6.0 Hz), 6.48 (d, 1H, J = 6.0 Hz), 5.41 (s, 1H), 3.55-3.50 (m, 1H), 3.20-3.13 (m, 1H), 3.08-3.03 (m, 1H), 2.31-2.20 (m, 2H), 2.22 (s, 6H), 1.90-1.84 (m, 1H), 1.59-1.50 (m, 1H); ESI-MS (m / z, %): 191 (MH + , 100).

[0346] Example 3: 2-(5-fluoroindolin-3-yl)-N,N-dimethylethan-1-amine (I-2)] [ka] Synthesis of 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (12): A solution of 5-fluoro-1H-indole (5.0 g, 36.999 mmol) in dry THF (50 mL) was treated with oxalyl chloride (3.11 mL, 36.999 mmol) for 5 min at 0° C. The reaction was allowed to come to room temperature and stirred for 3 h. The reaction was treated with dimethylamine (74 mL, 147.996 mmol, 2 M solution in THF) for 15 min and stirred overnight (16 h). The reaction was worked up and purified as described for compound 8 to give the title compound 12 (7.12 g, 82.2%) as a pale yellow solid. 1 H NMR(DMSO-d6):δ 12.40(brs,1H),8.17(s,1H),7.76(dd,1H,J=3.0,4.5Hz),7.55(dd,1H,J= 3.0,6.0Hz),7.16-7.12(m,1H),2.99(s,3H),2.91(s,3H);ESI-MS(m / z,%): 256(M+Na,100).

[0347] Synthesis of 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethylethan-1-amine (13): A suspension of lithium aluminum hydride (2.59 g, 68.308 mmol) in dry THF (25 mL) was treated with 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (2.0 g, 8.538 mmol) in dry THF (25 mL) at 0° C. for 10 min. The reaction was allowed to reach room temperature and then refluxed for an additional 16 h. The reaction was worked up and purified as described for compound 5 to give the title compound 13 (1.7 g, quantitative) as a brown solid. 1H NMR (DMSO-d6): δ 10.87 (s, 1H), 7.30 (dd, 1H, J = 3.0, 6.0 Hz), 7.24 (dd, 1H, J = 3.0, 6.0 Hz), 7.21 (d, 1H, J = 3.0 Hz), 6.90-6.86 (m, 1H), 2.78-2.75 (m, 2H), 2.52-2.47 (m, 2H), 2.20 (s, 6H); ESI-MS (m / z, %): 207 (MH + , 100).

[0348] Synthesis of 2-(5-fluoroindolin-3-yl)-N,N-dimethylethan-1-amine (I-2): A solution of 2-(5-fluoro-1H-indol-3-yl)-N,N-dimethylethan-1-amine (1.51 g, 7.320 mmol) in trifluoroacetic acid (60 mL) was treated with triethylsilane (2.33 mL, 14.641 mmol) and the resulting solution was stirred overnight (16 h) at 50° C. The reaction was worked up and purified as described for compound II-1 to give the title compound I-2 (0.8 g, 52.6%) as a light brown oil. 1 H NMR (DMSO-d6): δ 6.90-6.87 (m, 1H), 6.74-6.69 (m, 1H), 6.45-6.42 (m, 1H), 5.32 (s, 1H), 3.56-3.51 (m, 1H), 3.19-3.05 (m, 2H), 2.30-2.18 (m, 2H), 2.14 (s, 6H), 1.92-1.86 (m, 1H), 1.58-1.51 (m, 1H); ESI-MS (m / z, %): 209 (MH + , 100).

[0349] Example 4: 2-(5-(methoxy-d3)indolin-3-yl)-N,N-dimethylethan-1-amine (I-11)] [ka] Synthesis of 2-(5-(methoxy-d3)-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (16): A solution of 5-(methoxy-d3)-1H-indole (2.5 g, 16.646 mmol) in dry THF (25 mL) was treated with oxalyl chloride (1.40 mL, 16.646 mmol) for 5 min at 0° C. The reaction was allowed to come to room temperature and stirred for 3 h. The reaction was treated with dimethylamine (33.3 mL, 66.584 mmol, 2 M solution in THF) for 15 min and stirred overnight (16 h). The reaction was worked up and purified as described for compound 8 to give the title compound I-11 (3.44 g, 82.9%) as an off-white solid. 1 H NMR (DMSO-d6): δ 12.17 (s, 1H), 8.01 (s, 1H), 7.59 (s, 1H), 7.42 (d, 1H, J = 6.0 Hz), 6.90 (dd, 1H, J = 3.0, 4.5 Hz), 2.98(s, 3H), 2.91 (s, 3H); ESI-MS (m / z, %): 272 (M+Na), 250 (MH + ).

[0350] Synthesis of 2-(5-(methoxy-d3)-1H-indol-3-yl)-N,N-dimethylethan-1-amine (17): A suspension of lithium aluminum hydride (2.43 g, 64.185 mmol) in dry THF (25 mL) was treated with 2-(5-(methoxy-d3)-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (2.0 g, 8.023 mmol) in dry THF (25 mL) at 0° C. for 10 min. The reaction was allowed to come to room temperature and then refluxed for an additional 16 h. The reaction was worked up and purified as described for compound 5 to give the title compound 17 (1.7 g, quantitative) as a brown solid. 1H NMR (DMSO-d6): δ 10.58 (s, 1H), 7.21 (d, 1H, J = 6.0 Hz), 7.08 (d, 1H, J = 3.0 Hz), 6.95 (d, 1H, J = 3.0 Hz), 6.70 (dd, 1H, J = 3.0, 4.5 Hz), 2.78-2.75 (m, 2H), 2.52-2.48 (m, 2H), 2.21 (s, 6H); ESI-MS (m / z, %): 222 (MH + , 100).

[0351] Synthesis of 2-(5-(methoxy-d3)indolin-3-yl)-N,N-dimethylethan-1-amine (I-11): A solution of 2-(5-(methoxy-d3)-1H-indol-3-yl)-N,N-dimethylethan-1-amine (1.34 g, 6.054 mmol) in trifluoroacetic acid (60 mL) was treated with triethylsilane (1.93 mL, 12.109 mmol) and the resulting solution was stirred at 50° C. overnight (16 h). The reaction was worked up and purified as described for compound II-1 to give the title compound I-11 (1.1 g, 81.5%) as a light brown oil. 1 H NMR (DMSO-d6): δ 6.68 (d, 1H, J = 3.0 Hz), 6.53-6.50 (m, 1H), 6.42 (d, 1H, J = 6.0 Hz), 5.02 (brs, 1H), 3.49 (t, 1H, J = 6.0 Hz), 3.17-3.00 (m, 2H), 2.29-2.22 (m, 2H), 2.15 (s, 6H), 1.91-1.86 (m, 1H), 1.55-1.48 (m, 1H); ESI-MS (m / z, %): 224 (MH + , 100).

[0352] Example 5: 2-(indolin-3-yl-4,5,6,7-d4)-N,N-dimethylethan-1-amine (I-24) [ka] Synthesis of 2-(1H-indol-3-yl-2,4,5,6,7-d5)-N,N-dimethyl-2-oxoacetamide (20): A solution of 1H-indole-2,3,4,5,6,7-d6 (2.0 g, 16.236 mmol) in dry THF (25 mL) was treated with oxalyl chloride (1.37 mL, 16.236 mmol) for 5 min at 0° C. The reaction was allowed to come to room temperature and stirred for 3 h. The reaction was treated with dimethylamine (32.4 mL, 64.944 mmol, 2 M solution in THF) for 15 min and stirred overnight (16 h). The reaction was worked up and purified as described for compound 8 to give the title compound 20 (3.0 g, 83.6%) as a light brown solid. 1 H NMR (DMSO-d6): δ 12.30 (s, 1H), 8.12-8.10 (m, 0.43H), 7.55-7.53 (m, 0.09H), 7.30-7.25 (m, 1.43H), 3.00 (s, 3H), 2.92 (s, 3H); ESI-MS (m / z, %): 244 (M+Na), 242 (100).

[0353] Synthesis of 2-(1H-indol-3-yl-2,4,5,6,7-d5)-N,N-dimethylethan-1-amine (21): A suspension of lithium aluminum hydride (2.74 g, 72.310 mmol) in dry THF (25 mL) was treated with 2-(1H-indol-3-yl-2,4,5,6,7-d5)-N,N-dimethyl-2-oxoacetamide (2.0 g, 9.039 mmol) in dry THF (25 mL) at 0° C. for 10 min. The reaction was allowed to come to room temperature and then refluxed for an additional 16 h. The reaction was worked up and purified as described for compound 5 to give the title compound 21 (1.74 g, quantitative) as a brown solid. 1H NMR (DMSO-d6): δ 10.77 (s, 1H), 7.51-7.50 (m, 0.18H), 7.33 (s, 0.04H), 7.14 (d, 0.05H, J = 1.5 Hz), 7.06 (t, 0.27H, J = 3.0 Hz), 6.99-6.96 (m, 0.35H), 2.84-2.80 (m, 2H), 2.54-2.50 (m, 2H), 2.22 (s, 6H); ESI-MS (m / z, %): 194 (MH + ), 193 (100).

[0354] Synthesis of 2-(indolin-3-yl-4,5,6,7-d4)-N,N-dimethylethan-1-amine (I-24): A solution of 2-(1H-indol-3-yl-2,4,5,6,7-d5)-N,N-dimethylethan-1-amine (1.2 g, 6.207 mmol) in trifluoroacetic acid (60 mL) was treated with triethylsilane (1.98 mL, 12.415 mmol) and the resulting solution was stirred overnight (16 h) at 50° C. The reaction was worked up and purified as described for compound II-1 to give the title compound I-24 (1.0 g, 82.6%) as a light brown oil. 1 H NMR (DMSO-d6): δ 7.00 (d, 0.32H, J = 6.0 Hz), 6.90-6.88 (m, 0.41H), 6.53-6.46 (m, 0.88H), 5.38 (s, 1H), 3.53-3.50 (m, 1H), 3.17-3.13 (m, 1H), 3.07-3.03 (m, 1H), 2.31-2.20 (m, 2H), 2.14 (s, 6H), 1.88-1.83 (m, 1H), 1.57-1.51 (m, 1H); ESI-MS (m / z, %): 196 (MH + ), 193 (100).

[0355] Example 6: 2-(5,6-dimethoxyindolin-3-yl)-N,N-dimethylethan-1-amine (I-33) [ka] Synthesis of 2-(5,6-dimethoxy-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (24): A solution of 5,6-dimethoxy-1H-indole (2.0 g, 11.287 mmol) in dry THF (25 mL) was treated with oxalyl chloride (0.95 mL, 11.287 mmol) for 5 min at 0° C. The reaction was allowed to come to room temperature and stirred for 3 h. The reaction was treated with dimethylamine (22.6 mL, 45.148 mmol, 2 M solution in THF) for 15 min and stirred overnight (16 h). The reaction was worked up and purified as described for compound 8 to give the title compound 24 (2.1 g, 67.5%) as a light brown solid. 1 ESI-MS (m / z, %): 299 (M+Na, 100), 277 (MH + ).

[0356] Synthesis of 2-(5,6-dimethoxy-1H-indol-3-yl)-N,N-dimethylethan-1-amine (25): A suspension of lithium aluminum hydride (2.2 g, 57.910 mmol) in dry THF (25 mL) was treated with 2-(5,6-dimethoxy-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (2.0 g, 7.239 mmol) in dry THF (25 mL) at 0° C. for 10 min. The reaction was allowed to come to room temperature and then refluxed for an additional 16 h. The reaction was worked up and purified as described for compound 5 to give the title compound 25 (1.78 g, 99%) as a brown solid. 1 H NMR (DMSO-d6): δ 10.44 (s, 1H), 6.98 (s, 1H), 6.95 (s, 1H), 6.87 (s, 1H), 3.76 (s, 6H), 2.77-2.74 (m, 2H), 2.52-2.48 (m, 2H), 2.22 (s, 6H); ESI-MS (m / z, %): 249 (MH+ , 100).

[0357] Synthesis of 2-(5,6-dimethoxyindolin-3-yl)-N,N-dimethylethan-1-amine (I-33): A solution of 2-(5,6-dimethoxy-1H-indol-3-yl)-N,N-dimethylethan-1-amine (1.41 g, 5.678 mmol) in trifluoroacetic acid (60 mL) was treated with triethylsilane (1.81 mL, 11.356 mmol) and the resulting solution was stirred overnight (16 h) at 50° C. The reaction was worked up and purified as described for compound II-1 to afford the title compound I-33 (0.95 g, 67%) as a light brown oil. 1 H NMR (DMSO-d6): δ 6.72 (s, 1H), 6.22 (s, 1H), 5.02 (s, 1H), 3.66 (s, 3H), 3.63 (s, 3H), 3.52-3.46 (m, 1H), 3.12-2.99 (m, 2H), 2.28-2.17 (m, 2H), 2.14 (s, 6H), 1.88-1.81 (m, 1H), 1.52-1.45 (m, 1H); ESI-MS (m / z, %): 251 (MH + , 100).

[0358] Example 7: 2-(5-Methoxy-1-methylindolin-3-yl)-N,N-dimethylethan-1-amine (I-3) [ka]

[0359] Synthesis of 2-(5-methoxy-1-methylindolin-3-yl)-N,N-dimethylethan-1-amine (48): A solution of 2-(5-methoxyindolin-3-yl)-N,N-dimethylethan-1-amine (1.2 g, 5.447 mmol) in dry CHCl (50 mL) was treated with acetic acid (0.93 mL, 16.341 mmol) followed by formaldehyde (1.21 mL, 16.341 mmol, 37% in water) at 0° C. The reaction was allowed to come to room temperature and stirred for an additional 6 hours. The reaction was cooled to 0° C. and treated with sodium triacetoxyborohydride (3.46 g, 16.341 mmol). The reaction was allowed to come to room temperature and stirred overnight (16 hours). The reaction was quenched with 4N NaOH solution and the product was extracted into dichloromethane (2×100 mL). The combined dichloromethane layers were dried (Na2SO4) and the solvent was evaporated to give the crude product, which was purified by column chromatography on silica gel (2M NH3 in MeOH:CH2Cl2, 3:97) to give the title compound I-3 (0.9 g, 70.8%) as a brown liquid. 1 H NMR (DMSO-d6): δ 6.70 (d, 1H, J = 3.0 Hz), 6.60 (dd, 1H, J = 3.0, 6.0 Hz), 6.41 (d, 1H, J = 6.0 Hz), 3.65 (s, 3H), 3.10-3.04 (m, 1H), 2.78-2.74 (m, 1H), 2.60 (s, 3H), 2.31-2.21 (m, 3H), 2.15 (s, 6H), 1.93-1.87 (m, 1H), 1.58-1.48 (m, 1H); ESI-MS (m / z,%): 235 (MH + , 100).

[0360] B. Biological Testing Example B1: FLIPR Assay: Human 5-HT2A I. Human 5-HT in agonist mode 2A (h5-HT 2A ) Evaluating the Efficacy of Exemplary Compounds of Formula I in Targeting Receptors: Compound Preparation and Assay Controls Ia Reagents and materials: [Table 20]

[0361] Ib Equipment and consumables: [Table 21]

[0362] IC Experimental Methods and Procedures: 1. Cells were cultured in cell culture medium (DMEM containing 10% FBS, 1× penicillin-streptomycin, 300 μg / ml G418, and 100 μg / ml hygromycin B) at 37° C. and 5% (v / v) CO2.

[0363] 2. One day prior to the assay, cells were detached using TrypLE™ Express and counted using a cell counter. Only cells with viability >85% were used in the assay.

[0364] 3. 20000 cells / well were seeded in 384-well cell plates with 30 μl / well culture medium, and the cells were incubated overnight at 37° C., 5% (v / v) CO2.

[0365] 4. On the day of assay, prepare 2x dye solution according to the FLIPR® Calcium 6 Assay Kit manual: i. Dilute dye with assay buffer (20 mM HEPES in 1x HBSS, PH 7.4); ii. Add probenecid to a final concentration of 5 mM; iii. Vortex vigorously for 1-2 minutes.

[0366] 5. Media was removed from the cell plate by tapping the cell plate on a paper towel.

[0367] 6.10 μl of assay buffer and 10 μl of 2× dye solution were added to each well of the cell plate.

[0368] 7. Place the cell plate on a plate shaker and agitate the plate at 600 rpm for 2 minutes. The plate was incubated at 37° C. for 2 hours, followed by 25° C. for an additional 15 minutes.

[0369] 8. Prepared 3x compounds in assay buffer: a. Dilute reference compounds in DMSO to required concentration. Compounds were added to 384-well compound plate; b. Serial dilutions were performed; c. Test compounds were added at 10 mM to compound plate and 3-fold serial dilutions were performed; d. Transfer 60nl / well of compound from source plate to 384-well compound plate (Corning, 3657) by using Echo; e. Add 20μl / well of assay buffer to compound plate; f. Mix plate on plate shaker for 2 minutes.

[0370] 9. The cell plate, compound plate and tip were placed into the FLIPR and the FLIPR transferred 10 μl per well of 3× compound to the cell plate.

[0371] Data analysis i. Normalized fluorescence readings (RFU) were calculated as shown below, where Fmax and Fmin represent the maximum and minimum of the calcium signal during a defined time window: RFU=Fmax-Fmin.

[0372] ii. Calculate the activation rate using the following equation:

number

[0373] III. EC was calculated by fitting the % activation to the logarithm of the compound concentration with the Hill equation using XLfit. 50 Calculate.

[0374] Results and Discussion Exemplary compounds of formula I inhibit h5-HT 2ATheir effects on the receptor were functionally evaluated using the FLIPR assay. Table 2 shows the EC50 (nM) and RFU data for exemplary compounds of the present application. [Table 22] ND: Not detected

[0375] Results and Discussion Exemplary compounds of Formula I and Formula II were functionally evaluated for their effect on the h5-HT2A receptor in agonist mode using the FLIPR assay. EC 50 The concentrations (in nM) and the respective RFU at 10 μM are shown in Table 2. This assay confirms that the compounds of the present application are effective agonists of the target human 5-HT2A receptor.

[0376] II. Human 5-HT 2A Radioligand binding assay: II.1. Materials and Equipment: [Table 23]

[0377] II.2. Equipment and consumables: [Table 24]

[0378] II.3 Experimental Procedure: Prepare assay buffer according to the table below. [Table 25]

[0379] ii. Preparation of 8 doses of reference and test compounds starting from 10 mM stock solutions by 5-fold serial dilution at 100%.

[0380] iii. Prepare DMSO (v / v): a. Add 50 μl / well of 0.5% (v / v) PEI to a UniFilter-96 GF / B plate. Seal the plate and incubate at 4° C. for 3 hours; b. After incubation, wash the plate 3 times with ice-cold wash buffer (50 mM Tris, pH 7.4).

[0381] iv. Assay plate preparation: a. Cell membranes are diluted in assay buffer and 330 μl / well are added to a 96 round deep well plate to reach a concentration of 20 μg / well; b. Eight concentrations of reference or test compound are prepared and 110 μl / well are added to a 96 round deep well plate; c. [3H]-ketanserin is diluted to 5 nM (5× final concentration) in assay buffer and 110 μl / well are added to a 96 round deep well plate.

[0382] v. The plate is centrifuged at 1000 rpm for 30 seconds, then agitated at 600 rpm at room temperature for 5 minutes.

[0383] vi. Seal the plate and incubate at 27° C. for 90 minutes.

[0384] vii. The incubation is terminated by vacuum filtration onto GF / B filter plates, followed by four washes with ice-cold wash buffer (50 mM Tris, pH 7.4).

[0385] viii. Dry the plate at 37° C. for 45 minutes.

[0386] ix. Seal the filter plate and add 40 μl / well of scintillation cocktail.

[0387] x. The plates are read using a Microbeta2 microplate counter.

[0388] Data Analysis: Results are expressed as % inhibition for reference and test compounds using the normalization equation: N=100-100×(U-C2) / (C1-C2), where U is the unknown value, C1 is the mean of the high controls, and C2 is the mean of the low controls. IC50s are determined by fitting the percent inhibition as a function of compound concentration with the Hill equation using XLfit.

[0389] Example B2: Human, rat, and mouse liver microsome stability the purpose The purpose of this study was to estimate the in vitro metabolic stability of representative compounds of the present application in pooled human and male mouse liver microsomes. The concentration of the parent compound in the reaction system was evaluated by LC-MS / MS to estimate the stability in pooled human and male mouse liver microsomes. The in vitro intrinsic clearance of the test compounds was also determined.

[0390] protocol A master solution in an "incubation plate" containing phosphate buffer, ultrapure HO, MgCl solution, and liver microsomes was made according to Table 3. The mixture was pre-warmed in a 37° C. water bath for 5 min. [Table 26]

[0391] 40 μL of 10 mM NADPH solution was added to each well. The final concentration of NADPH was 1 mM. Negative control samples were prepared by replacing NADPH with 40 μL of ultrapure HO. Samples were prepared in duplicate. Negative controls were prepared in singlets.

[0392] The reaction was initiated by adding 4 μL of 200 μM test compound or control compound to each master solution to give a final concentration of 2 μM. The study was performed in duplicate.

[0393] Aliquots of 50 μL were taken from the reaction solution at 0, 15, 30, 45, and 60 min. The reaction solution was stopped by the addition of 4 volumes of cold methanol containing IS (100 nM alprazolam, 200 nM imipramine, 200 nM labetalol, and 2 μM ketoprofen). The samples were centrifuged at 3,220 g for 40 min. An aliquot of 90 μL of the supernatant was mixed with 90 μL of ultrapure HO and then used for LC-MS / MS analysis.

[0394] LC / MS analysis, Deaerator DGU-20A 5R A Shimadzu liquid chromatographic separation system equipped with a solvent delivery unit LC-30AD, a system controller SIL-30AC, a column oven CTO-30A, and a CTC Analytics HTC PAL System was used for all samples from this study. Mass spectrometry was performed using a Triple Quad™ 5500 instrument.

[0395] All calculations were performed using Microsoft Excel. Peak area ratios of test compounds to internal standards (listed in the table below) were determined from extracted ion chromatograms.

[0396] All calculations were performed using Microsoft Excel. Peak areas were determined from extracted ion chromatograms. Slope values, k, were determined by linear regression of the natural logarithm of the percentage of parent drug remaining versus incubation time curve.

[0397] In vitro half-life (in vitro t 1 / 2 ) was determined from the slope value.

number

[0398] In vitro 1 / 2 In vitro specific clearance (in μL / min / mg protein) int ) was performed using the following equation (average of duplicate determinations):

number

[0399] For compounds or control compounds that showed an initial rapid elimination followed by a slower elimination, only time points that were within the initial rate were included in the calculations.

[0400] Results and Discussion Human, rat, and mouse liver microsomes contain a wide variety of drug metabolizing enzymes and are commonly used to support in vitro ADME (absorption, distribution, metabolism, and excretion) studies. These microsomes were used to investigate potential first-pass metabolic by-products of orally administered drugs. Representative compounds of the present application were evaluated for their stability in human, rat, and mouse liver microsomes. Tables 4 and 5 show the results of the stability studies. [Table 27] [Table 28]

[0401] The data in Tables 4 and 5 show that compounds of the present application exhibit a spectrum of stability profiles in liver microsomes across different species, including human, rat, and mouse. Example B3: Psychotropic Effects of Compounds of Formula I

[0402] The effects of different doses of representative compounds of Formula I were evaluated on the head-twitch response (HTR) and other behavioral responses as a behavior-based model of psychotropic activity.

[0403] protocol Mouse head spasm Male C57BL / 6J mice (weight range 20-30 g) were administered the appropriate dose of test substance and, after a 1-minute pretreatment period, were placed into individual observation chambers. Animals were visually assessed for the incidence of head twitches continuously over a 1-hour period. A head twitch was defined as a rapid jerking of the head that was not elicited by external tactile stimulation (Corne and Pickering, Psychopharmacologia, 1967, 11(1):65-78). Each head twitch was counted individually by a trained observer and data were averaged for 6-10 mice per group. + Expressed as SEM. Mice were used in only a single experiment.

[0404] Results and Discussion The head twitch response of exemplary compound II-1 (1-30 mg / kg SC) was compared to 5-MeO DMT and psilocybin (Figure 1, Table 6). [Table 29]

[0405] The data in Table 6 show that psilocybin (0.1-10 mg / kg SC) produced a dose-related increase in the incidence of head twitch responses in male C57BL / 6 mice, which peaked at the 1 mg / kg dose. At the 3 mg / kg and 10 mg / kg SC doses, the incidence of head twitches following psilocybin was reduced, resulting in an inverted U-shaped dose response. The reduction in head twitches at these higher doses was accompanied by reduced locomotor activity and reduced core body temperature.

[0406] 5-MeO DMT (1-30 mg / kg SC) produced a monotonically increasing incidence of head twitches, but across doses from 3 to 30 mg / kg, other behavioral signs associated with 5-HT syndrome (forepaw stamping, tail lift, body twitching, backward walking) appeared and increased in incidence across these doses. As a result, head twitches at 30 mg / kg were somewhat variable, with response conflicts and prominent 5-HT syndrome signs compromising the expression of head twitches in some study subjects.

[0407] In contrast to psilocybin and 5-MeO DMT, exemplary compound II-1 (0.3-30 mg / kg SC) showed a 4.2 + Lower doses were also associated with a higher incidence of head twitches, although only a moderate head twitch response was induced with a peak response of 0.7 twitches. No suppression of locomotor activity or overt signs of 5-HT syndrome were recorded across this dose range, except in 2 / 5 (40%) mice pretreated with the 30 mg / kg dose, although some 5-HT syndrome-related behaviors were noted. Thus, the low incidence of head twitches across at least the 0.3-10 mg / kg dose range did not appear to be the result of alternative competing behaviors.

[0408] Rat behavioral test Male Sprague-Dawley rats (weight range 250-400 g) are administered the appropriate dose of test substance and, after a 1-minute pretreatment period, are placed into locomotor activity boxes (dimensions 17”W x 17”L x 12”H) and monitored continuously for 1 hour, with data collected in 10-minute time bins. The animals are then monitored for 5-HT 2A Receptor activation (shivering, back contraction), 5-HT 2A Receptor activation (yawning, penile grooming) and 5-HT 1A Rats are visually assessed for overt behavioral signs, including behaviors characteristic of the 5-HT syndrome (e.g., tremors, salivation, flat body posture, core temperature changes) (Halberzettl et al, Behav Brain Res. 256:328-345, 2013). Additional behavioral and physical signs characteristic of the 5-HT syndrome (e.g., tremors, salivation, flat body posture, core temperature changes) are also measured. Concurrently, the rats' locomotor activity is measured using an automated tracking system (Med Associates, VT, USA). Activity data collected included total distance traveled, number of rearings, and ambulatory episodes. All data were averaged across 6–10 rats per group. + Expressed as SEM.

[0409] Drug discrimination in rats Male Sprague-Dawley rats are initially food restricted (single housed) by presenting 18-20 g of food at the end of the day. After 7 days of acclimation to the food restriction procedure, mice are trained daily for 1 week to press the lever for food (45 mg Bioserve pellets) in a standard two-lever operant conditioning chamber controlled by Med-PC software (Med. Associates Ins., St. Albans, VT). Rats are trained to press the lever for food up to an FR10 value (i.e., 10 lever presses for a single food reward). Once stable food responding is obtained for both response levers, discrimination training begins. Rats are trained to associate one lever with a psilocybin training dose of 1 mg / kg SC and the second lever with a neutral stimulus (saline, SC) over a period of 20-50 training sessions (Winter et al, Pharmacol Biochem Behav. 87(4):472-480, 2007). Training sessions lasted for 30 min or until delivery of 50 pellets and continued until the animals achieved adequate stimulus control (defined as six consecutive sessions in which the animal pressed the lever 16 or fewer times before delivery of the first reward and at least 95% total responses on the appropriate lever). Rats continued to receive their daily food supply in their home cages at the end of the day.

[0410] Once trained, substitution testing is performed. On test days, both levers are designated active, i.e., every 10th response on either lever results in the delivery of a food pellet. Test sessions continue until 50 pellets are obtained or 30 minutes have elapsed. Response rates are also measured during these sessions.

[0411] Although the present application has been described with reference to examples, it should be understood that the claims should not be limited by the embodiments described in the examples, but should be accorded the broadest interpretation consistent with the description as a whole.

[0412] All patents, patent applications, and publications cited herein are hereby incorporated by reference in their entireties. The disclosures of these publications in their entireties are incorporated by reference into this application in order to more fully describe the state of the art known to those skilled in the art as of the filing date of the application described and claimed herein.

Claims

1. Compound of formula I: 【Chemistry 1】 or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, During the ceremony, R １ is C(O)R ７ CO ２ R ７ C(O)N(R ７ )(R ７’ ), S(O)R ７ SO ２ R ７ C １－６ alkylene R ７ and R ７ is selected from Q is, Q3: 【Chemistry 2】 and, in terms of bonding 【Transformation 3】 However, this means that the bond is connected to the rest of the compound, R ２ , R ２’ , and R ２’’ They became independent as H, Halo, and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkylene N(R) ２ａ ) (Caution ２ｂ ), and SC １－６ Selected from alkyl groups, R ２ａ and R ２ｂ H and C are independent of each other. １－６ Selected from alkyl groups, R ３ , R ４ , R ５ , and R ６ These are independent: H, Halo, N(R) ５’ ) (Caution ６’ ) 、 C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkylene N(R) ５’ ) (Caution ６’ ), and SC １－６ Selected from alkyl groups, the latter four groups are OH and C １－６ They are optionally substituted with one or two substituents selected from alkoxys, or R ３ , R ４ , R ５ , and R ６ Two adjacent ones are linked together, O-(CH ２ ) １－２ Form O, R ３ , R ４ , R ５ , and R ６ The remaining ones are H, Halo, and C, which are independent. １－６ Alkyl, C １－６ Alkoxy, N(R ５’ ) (Caution ６’ ), C １－６ Alkylene N(R) ５’ ) (Caution ６’ ), and SC １－６ Selected from alkyl groups, or R ３ , R ４ , R ５ , and R ６ One of them is A, O-A, and C １－４ Selected from alkylene A, R ３ , R ４ , R ５ , and R ６ The remaining ones are independently H or halo. R ５’ and R ６’ H and C are independent of each other. １－６ Selected from alkyl groups, A is phenyl, C ３－６ Cycloalkyls, as well as O, S, S(O), SO ２ , N, and NR ５４ 3-6 member heterocycloalkyls containing 1-4 heteromolets independently selected from, as well as O, S, S(O), SO ２ , N, and NR ５４ Selected from a 5-6 member heteroaryl comprising 1-4 heteromolets independently selected from, the phenyl, C ３－１０ Cycloalkyl, 3-6 member heterocycloalkyl, and 5-6 member heteroaryl are halos, C １－４ Alkyl, OC １－４ Alkyl, N(R ５４ａ ) (Caution ５４ｂ ), C １－４ Alkylene N(R) ５４ａ ) (Caution ５４ｂ ), and SC １－４ It is optionally substituted with one or more substituents independently selected from the alkyl group. R ７ is H, C １－６ alkyl, C ２－６ alkenyl, C ２－６ alkynyl, phenyl, C ３－６ cycloalkyl, and 3- to 6-membered heterocycloalkyl containing 1 to 4 hetero moieties independently selected from O, S, N, and NR ７’’ and 5- to 6-membered heteroaryl containing 1 to 4 hetero moieties independently selected from O, S, N, and NR ７’’ selected from, wherein the latter seven groups are optionally substituted with one or more substituents independently selected from halo, OR ５５ , N(R ５５ )(R ５６ ), and SR ５５ and / or the C １－６ alkyl is optionally interrupted by 1 to 3 hetero moieties independently selected from O, C(O), CO ２ , and NR ５７ ; R ７’ is selected from H and C １－６ alkyl, R ７’’ However, H and C １－６ Selected from alkyl groups, R ２６ , R ２７ , R ２８ , and R ２９ These are independently H, Halo, and C １－６ Selected from alkyl groups, R ３０ and R ３１ H and C became independent. １－６ Alkyl and C(O)C １－６ Selected from alkyl groups, or R ３０ and R ３１ However, together with the N atoms to which they are bonded, they form O, S, S(O), SO ２ , N, and NR ５８ It forms a 3- to 6-membered heterocycle that optionally includes one or two additional heteromotors independently selected from the original, R ５４ , R ５５ , R ５６ , R ５７ , and R ５８ H and C are independent of each other. １－６ Selected from alkyl groups, R ５４ａ and R ５４ｂ H and C are independent of each other. １－６ Selected from alkyl groups, All available hydrogen atoms are optionally and independently substituted with fluorine or chlorine atoms, and all available atoms are optionally substituted with deuterium. However, R ２６ , R ２７ , R ２８ , and R ２９ All of them are H, and R ３０ and R ３１ However, H or CH ３ and R １ , R ２ , R ２’ , R ２’’ , R ３ , R ４ , R ５ , and R ６ Are all of them H? R １ , R ２ , R ２’ , R ２’’ , R ３ , R ５ , and R ６ All of them are H, and R ４ However, OCH ３ is, or R １ , R ２ , R ２’ , R ２’’ , R ３ , R ４ , R ５ , and R ６ All of them are H, and R ５ However, OCH ３ If that is the case, A compound of formula I, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, provided that the compound of formula I is the (R)- or (S)-enantiomer of the carbon to which Q is attached.

2. R ２６ , R ２７ , R ２８ , and R ２９ A compound according to claim 1, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein H and D are independently selected.

3. Q is based on the following: 【Chemistry 4】 A compound according to claim 1, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, selected from one of the above.

4. R ３０ and R ３１ H and C became independent. １－６ Alkyl and C(O)C １－６ A compound according to claim 3, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, selected from alkyl groups, wherein all available hydrogen atoms are optionally and independently substituted with fluorine or deuterium atoms.

5. R ３０ and R ３１ They became independent: H, D, C １－６ Alkyl, C １－６ Fluoroalkyl, C １－６ Deuteroalkyl, C １－６ Alkoxy, C(O)C １－６ Fluoroalkyl and C(O)C １－６ A compound according to claim 4, selected from deuteroalkyls, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

6. R ３０ and R ３１ They became independent: H, D, CH ３ CF ３ , and CH(CH ３ A compound according to claim 5, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, selected from ).

7. R １ However, C(O)R ７ CO ２ R ７ , C(O)N(R ７ ) (Caution ７’ ), S(O)R ７ SO ２ R ７ , C １－４ Alkilen R ７ , and R ７ Selected from, R ７ However, H, C １－４ Alkyl, C ２－６ Alkenil, C ２－６ Alkinyl, phenyl, C ３－６ Cycloalkyl, as well as O, S, N, and NR ７’’ A 3-6 member heterocycloalkyl comprising 1-4 heteromolets independently selected from, and O, S, N, and NR ７’’ Selected from a 5-6 member heteroaryl containing 1-4 hetero moieties independently selected from, the latter 7 groups being halo, OR ５５ , N(R ５５ ) (Caution ５６ ), and SR ５５ It is optionally substituted with one or more substituents independently selected from and / or the C １－４ Alkyl groups include O, C(O), and CO. ２ , and NR ５７ The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein one to three heteromolets independently selected from thereto are optionally interposed, and all available hydrogen atoms are optionally and independently substituted with fluorine atoms or deuterium atoms.

8. R ７ However, H, D, C １－４ Alkyl, C １－４ Fluoroalkyl and C １－４ A compound according to claim 7, selected from deuteroalkyls, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

9. R ２ , R ２’ , and R ２’’ They became independent as H, Halo, and C １－４ Alkyl, C １－４ Alkoxy, C １－３ Alkylene N(R) ２ａ ) (Caution ２ｂ ), and SC １－４ A compound according to claim 1, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, selected from alkyl groups, wherein all available hydrogen atoms are optionally and independently substituted with fluorine or deuterium atoms.

10. R ２ , R ２’ , and R ２’’ These are H, D, F, Cl, C, and C, respectively. １－４ Alkyl, C １－４ Fluoroalkyl, C １－４ Deuteroalkyl, C １－４ Alkoxy, C １－４ Fluoroalkoxy, C １－４ Deuteroalkoxy, C １－３ Alkylene N(R) ２ａ ) (Caution ２ｂ ), SC １－４ Alkyl, SC １－４ Fluoroalkyl and SC １－４ A compound according to claim 9, selected from deuteroalkyls, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

11. R ２ , R ２’ , and R ２’’ All of them are either H or R ２ , R ２’ , and R ２’’ The compound according to claim 10, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein all of the compounds are D.

12. R ３ , R ４ , R ５ , and R ６ They became independent as H, Halo, and C １－４ Alkyl, C １－４ Alkoxy, C １－４ Alkylene N(R) ５’ ) (Caution ６’ ), and SC １－４ Selected from alkyl groups, the latter four groups are OH and C １－４ The compound according to claim 1, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, wherein it is optionally substituted with one or two substituents selected from alkoxy, and all available hydrogen atoms are optionally and independently substituted with fluorine or deuterium atoms.

13. R ３ , R ４ , R ５ , and R ６ These are independently H, D, F, Cl, Br, N(R ５’ ) (Caution ６’ ), C １－４ Alkyl, C １－４ Fluoroalkyl, C １－４ Deuteroalkyl, C １－４ Alkoxy, C １－４ Fluoroalkoxy, C １－４ Deuteroalkoxy, C １－４ Alkylene N(R) ５’ ) (Caution ６’ ), SC １－４ Alkyl, SC １－４ Fluoroalkyl, SC １－４ Selected from deuteroalkyl groups, the latter 10 groups are OH, C １－４ Alkoxy, C １－４ Fluoroalkoxy, and C １－４ The compound according to claim 12, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, optionally substituted with one or two substituents selected from deuteroalkoxys.

14. R ３ , R ４ , R ５ , and R ６ One of them is OH, C １－３ Alkoxy, C １－３ Fluoroalkoxy, and C １－３ C substituted with one or two substituents selected from deuteroalkoxys １－３ Alkoxy, C １－３ Fluoroalkoxy, and C １－３ Selected from deuteroalkoxys, R ３ , R ４ , R ５ , and R ６ The remaining ones are independently H, D, and CH. ３ O, CD ３ O, and CF ３ A compound according to claim 13, selected from O, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

15. R ３ , R ４ , R ５ , and R ６ One to three of these become independent: H, D, F, CH ３ CD ２ H, CDH ２ CD ３ CF ３ CHF ２ ,CH ２ CH ３ , CH (CH ３ ) ２ ,CH ２ CH ２ D, CH ２ CD ２ H, CD ２ CD ３ ,CH ３ O, CD ２ HO, CDH ２ O, CD ３ O, CF ３ O, CHF ２ O, CH ３ CH ２ O, CH(CH ３ ) ２ O, CH ２ DCH ２ O, CD ２ HCH ２ O, and CD ３ CD ２ Selected from O, R ３ , R ４ , R ５ , and R ６ The remainder of which is selected from H and D, is the compound according to claim 14, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

16. The compound of formula I has the following structure: 【Transformation 5】 A compound according to claim 1, or a mixture thereof, having one of the following.

17. The following table: Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 A compound according to claim 1, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, selected from among.

18. A pharmaceutical composition comprising one or more compounds according to any one of claims 1 to 17, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof, and a pharmaceutically acceptable carrier.

19. An agent for treating a disease, disorder, or condition, comprising one or more compounds according to any one of claims 1 to 17, or a pharmaceutically acceptable salt, solvate, and / or prodrug thereof.

20. Agents for treating central nervous system (CNS) diseases, disorders, or conditions, and / or neurological diseases, disorders, or conditions, comprising one or more compounds according to any one of claims 1 to 17, or pharmaceutically acceptable salts, solvates, and / or prodrugs thereof.

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