WO2025014719A2 - Tropane compounds for treating brain disorders - Google Patents

Abstract

Provided herein are tropane compounds which can be useful for methods of treating a disease or for increasing neural plasticity. The compounds can also be useful for increasing dendritic spine density.

Description

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO TROPANE COMPOUNDS FOR TREATING BRAIN DISORDERS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Application No.63/512,398, filed July 7, 2023, which incorporates herein in its entirety for all purposes. BACKGROUND [0002] Altered synaptic connectivity and plasticity has been observed in the brains of individuals with neuropsychiatric and neurological diseases/disorders. Psychoplastogens promote neuronal growth and improve neuronal architecture through a variety of mechanisms. Modulators of these biological targets, such as, for example, N,N- dimethyltryptamine (DMT), ibogaine, and lysergic acid diethylamide (LSD) have demonstrated psychoplastogenic properties. For example, LSD and other analogs of the ergoline scaffold are capable of rectifying deleterious changes in neuronal structure that are associated with neuropsychiatric and neurological diseases/disorders. Such structural alterations include, for example, the loss of dendritic spines and synapses in the prefrontal cortex (PFC) as well as reductions in dendritic arbor complexity. Furthermore, pyramidal neurons in the PFC exhibit top-down control over areas of the brain controlling motivation, fear, reward, and cognition. Hallucinogenic psychoplastogens have demonstrated antidepressant, anxiolytic, and anti-addictive effects in the clinic. However, their subjective effects have limited their clinical utility. Moreover, hallucinogenic compounds are contraindicated for psychotic illnesses like schizophrenia, which are well known to involve the loss of dendritic spines in the PFC. Thus, non-hallucinogenic psychoplastogens may have distinct advantages over their hallucinogenic counterparts. [0003] Provided herein are compounds with clinically relevant therapeutic efficacy that have improved physicochemical properties, and possess reduced hallucinogenic (e.g., non- hallucinogenic) properties as compared to their hallucinogenic counterparts. BRIEF SUMMARY OF THE INVENTION [0004] In one embodiment, provided herein is a compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I), (II), (III), (IV), or (V): UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO , , , or wherein:

R¹¹ is C_1-6 alkyl; R¹², R¹³ and R¹⁴ are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^12a, -C(O)OR^12a, - OC(O)R^12a, -C(O)N(R^12a)(R^12b), -N(R^12a)C(O)R^12b, - N(R^12a)C(O)N(R^12b)(R^12c), -S(O)R^12a, -S(O)2R^12a, -S(O)2OR^12a, -OS(O)2R^12a, - S(O)2N(R^12a)(R^12b), -N(R^12a)S(O)2R^12b, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl; each R^12a, R^12b and R^12c is independently is hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocycloalkyl, C6-10 aryl, or heteroaryl; R^15a, R^15b, R^15c, R^15d and R^15e are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 1₀ aryl, heteroaryl, or C_1-6 alkyl-heteroaryl, wherein at least one of R^15a, R^15b, R^15c, R^15d and R^15e is C1-6 alkyl, C2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl, such that when R^15a is alkoxy, R^15a is C_2-6 alkoxy; R²¹ C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, C_1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C_1-6 alkyl- heteroaryl, wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3 or 4 R^21a groups; each R^21a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^21b, -C(O)OR^21b, -OC(O)R^21b, -C(O)N(R^21b)(R^21c), - N(R^21b)C(O)R^21c, -N(R^21b)C(O)N(R^21c)(R^21d), -S(O)R^21b, -S(O)₂R^21b, - S(O)₂OR^21b, -OS(O)₂R^21b, -S(O)₂N(R^21b)(R^21c), or -N(R^21b)S(O)₂R^21c; R^21b, R^21c and R^21d are independently is hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, or C_1-6 haloalkyl; R²² and R²³ are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_{1- 6} alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^22a, -C(O)OR^22a, -OC(O)R^22a, - C(O)N(R^22a)(R^22b), -N(R^22a)C(O)R^22b, -N(R^22a)C(O)N(R^22b)(R^22c), -S(O)R^22a, - S(O)₂R^22a, -S(O)₂OR^22a, -OS(O)₂R^22a, -S(O)₂N(R^22a)(R^22b), -N(R^22a)S(O)₂R^22b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl- heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C1-6 alkyl- heteroaryl; R^22a, R^22b and R^22c are each independently is hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R²⁶ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^26a groups; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO each R^26a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^26b, -C(O)OR^26b, -OC(O)R^26b, -C(O)N(R^26b)(R^26c), - N(R^26b)C(O)R^26c, -N(R^26b)C(O)N(R^26c)(R^26d), -S(O)R^26b, --S(O)2R^26b, - S(O)₂OR^26b, -OS(O)₂R^26b, -S(O)₂N(R^26b)(R^26c), or -N(R^26b)S(O)₂R^26c; R^26b, R^26c and R^26d are each independently hydrogen or C1-6 alkyl; L³ is C2-6 alkylene; R³¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, -CN, -C(O)R^31b, -C(O)OR^31b, -OC(O)R^31b, -C(O)N(R^31b)(R^31c), - N(R^31b)C(O)R^31c, -N(R^31b)C(O)N(R^31c)(R^31d), -S(O)R^31b, --S(O)₂R^31b, - S(O)2OR^31b, -OS(O)2R^31b, -S(O)2N(R^31b)(R^31c), or -N(R^31b)S(O)2R^31c; R^31b, R^31c and R^31d are each independently hydrogen or C_1-6 alkyl; R³², R³³, R³⁴ and R³⁵ are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^32a, -C(O)OR^32a, - OC(O)R^32a, -C(O)N(R^32a)(R^32b), -N(R^32a)C(O)R^32b, - N(R^32a)C(O)N(R^32b)(R^32c), -S(O)R^32a, -S(O)₂R^32a, -S(O)₂OR^32a, -OS(O)₂R^32a, - S(O)₂N(R^32a)(R^32b), -N(R^32a)S(O)₂R^32b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_{6- 10} aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^32a, R^32b and R^32c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R⁴¹ is C_1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, -OR^42a, -OC(O)R^42a, - OC(O)OR^42a; each R^42a is independently C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R⁴⁴ is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO -C(O)R^44a, -C(O)OR^44a, -OC(O)R^44a, -C(O)N(R^44a)(R^44b), -N(R^44a)C(O)R^44b, - N(R^44a)C(O)N(R^44b)(R^44c), -S(O)R^44a, -S(O)2R^44a, -S(O)2OR^44a, -OS(O)2R^44a, - S(O)₂N(R^44a)(R^44b), -N(R^44a)S(O)₂R^44b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 1₀ aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^44a, R^44b, and R^44c are each independently is hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH, -OR^42a, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^51a groups; each R^51a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^51b, -C(O)OR^51b, -OC(O)R^51b, -C(O)N(R^51b)(R^51c), - N(R^51b)C(O)R^51c, -N(R^51b)C(O)N(R^51c)(R^51d), -S(O)R^51b, --S(O)₂R^51b, - S(O)₂OR^51b, -OS(O)₂R^51b, -S(O)₂N(R^51b)(R^51c), or -N(R^51b)S(O)₂R^51c; R^51b, R^51c and R^51d are each independently hydrogen or C_1-6 alkyl; R⁵⁴ is C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^54a, -C(O)OR^54a, -OC(O)R^54a, -C(O)N(R^54a)(R^54b), -N(R^54a)C(O)R^54b, - N(R^54a)C(O)N(R^54b)(R^54c), -S(O)R^54a, --S(O)₂R^54a, -S(O)₂OR^54a, -OS(O)₂R^54a, -S(O)₂N(R^54a)(R^54b), -N(R^54a)S(O)₂R^54b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6- 10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl; R^54a, R^54b, and R^54c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl,

10 aryl, or heteroaryl; and R^55a is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S. [0005] In another embodiment, provided herein is a pharmaceutical composition, comprising a therapeutically effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof. [0006] In another embodiment, provided herein is a method of treating a disease, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof, thereby treating the disease. [0007] In another embodiment, provided herein is a method for increasing neural plasticity, the method comprising contacting a neuronal cell with a compound of the present invention, or a pharmaceutically acceptable salt thereof, in an amount sufficient to increase neural plasticity of the neuronal cell. [0008] In another embodiment, provided herein is a method for increasing neural plasticity and increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound of the present invention, or a pharmaceutically acceptable salt thereof, in an amount sufficient to increase neural plasticity and increase dendritic spine density of the neuronal cell. BRIEF DESCRIPTION OF THE DRAWINGS [0009] FIG.1 shows neurite outgrowth data examining the average number of branchpoints per neuron. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, as compared to the vehicle control following a oneway ANOVA with Dunnett’s post hoc test. DON = donepezil. [0010] FIG.2 shows neurite outgrowth data examining the average total neurite length per neuron. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, as compared to the vehicle control following a oneway ANOVA with Dunnett’s post hoc test. DON = donepezil. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0011] FIG.3 shows neurite outgrowth data examining the average number of neurites per neuron. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, as compared to the vehicle control following a oneway ANOVA with Dunnett’s post hoc test. DON = donepezil. DETAILED DESCRIPTION OF THE INVENTION I. GENERAL [0012] Provided herein are tropane compounds. The compounds of the present invention are useful for treatment of diseases, such as brain disorders, neuropsychiatric diseases, and other neurological diseases. The compounds of the present invention are also useful for increasing neural plasticity, increasing dendritic spine density, or both. II. DEFINITIONS [0013] Unless specifically indicated otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this invention belongs. In addition, any method or material similar or equivalent to a method or material described herein can be used in the practice of the present invention. For purposes of the present invention, the following terms are defined. [0014] “A,” “an,” or “the” not only include aspects with one member, but also include aspects with more than one member. For instance, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and reference to “the agent” includes reference to one or more agents known to those skilled in the art, and so forth. [0015] “Alkyl” refers to a straight or branched, saturated, aliphatic radical having the number of carbon atoms indicated. Disclosures provided herein of an “alkyl” are intended to include independent recitations of a saturated alkyl, unless otherwise stated. Alkyl groups described herein are generally monovalent, but may also be divalent which may also be described herein as “alkylene” or “alkylenyl” groups. Alkyl can include any number of carbons, such as C1-2, C1-3, C1-4, C1-5, C1-6, C1-7, C1-8, C1-9, C1-10, C2-3, C2-4, C2-5, C2-6, C3-4, C_3-5, C_3-6, C_4-5, C_4-6 and C_5-6. For example, C_1-6 alkyl includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, etc. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO Alkyl can also refer to alkyl groups having up to 20 carbons atoms, such as, but not limited to heptyl, octyl, nonyl, decyl, etc. Alkyl groups can be substituted or unsubstituted. [0016] “Alkenyl” refers to a straight chain or branched hydrocarbon having at least 2 carbon atoms and at least one double bond. Alkenyl can include any number of carbons, such as C2, C2-3, C2-4, C2-5, C2-6, C2-7, C2-8, C2-9, C2-10, C3, C3-4, C3-5, C3-6, C4, C4-5, C4-6, C5, C5-6, and C₆. Alkenyl groups can have any suitable number of double bonds, including, but not limited to, 1, 2, 3, 4, 5 or more. Examples of alkenyl groups include, but are not limited to, vinyl (ethenyl), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hexatrienyl. Alkenyl groups can be substituted or unsubstituted. [0017] “Alkynyl” refers to either a straight chain or branched hydrocarbon having at least 2 carbon atoms and at least one triple bond. Alkynyl can include any number of carbons, such as C2, C2-3, C2-4, C2-5, C2-6, C2-7, C2-8, C2-9, C2-10, C3, C3-4, C3-5, C3-6, C4, C4-5, C4-6, C5, C5-6, and C₆. Examples of alkynyl groups include, but are not limited to, acetylenyl, propynyl, 1-butynyl, 2-butynyl, butadiynyl, 1-pentynyl, 2-pentynyl, isopentynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hexatriynyl. Alkynyl groups can be substituted or unsubstituted. [0018] “Alkoxy” refers to an alkyl group having an oxygen atom that connects the alkyl group to the point of attachment: alkyl-O-. As for alkyl group, alkoxy groups can have any suitable number of carbon atoms, such as C_1-6. Alkoxy groups include, for example, methoxy, ethoxy, propoxy, iso-propoxy, butoxy, 2-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, pentoxy, hexoxy, etc. The alkoxy groups can be further substituted with a variety of substituents described within. Alkoxy groups can be substituted or unsubstituted. [0019] “Alkoxyalkyl” refers to a radical having an alkyl component and an alkoxy component, where the alkyl component links the alkoxy component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent, an alkylene, to link to the alkoxy component and to the point of attachment. The alkyl component can include any number of carbons, such as C0-6, C1-2, C1-3, C1-4, C1-5, C_1-6, C_2-3, C_2-4, C_2-5, C_2-6, C_3-4, C_3-5, C_3-6, C_4-5, C_4-6 and C_5-6. In some instances, the alkyl UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO component can be absent. The alkoxy component is as defined above. Examples of the alkoxyalkyl group include, but are not limited to, 2-ethoxy-ethyl and methoxymethyl. [0020] “Alkylhydroxy” or “hydroxyalkyl” refers to an alkyl group, as defined above, where at least one of the hydrogen atoms is replaced with a hydroxy group. As for the alkyl group, alkylhydroxy groups can have any suitable number of carbon atoms, such as C1-6. Exemplary alkylhydroxy groups include, but are not limited to, hydroxy-methyl, hydroxyethyl (where the hydroxy is in the 1- or 2-position), hydroxypropyl (where the hydroxy is in the 1-, 2- or 3-position), hydroxybutyl (where the hydroxy is in the 1-, 2-, 3- or 4-position), hydroxypentyl (where the hydroxy is in the 1-, 2-, 3-, 4- or 5-position), hydroxyhexyl (where the hydroxy is in the 1-, 2-, 3-, 4-, 5- or 6-position), 1,2-dihydroxyethyl, and the like. [0021] “Halogen” refers to fluorine, chlorine, bromine and iodine. [0022] “Haloalkyl” refers to alkyl, as defined above, where some or all of the hydrogen atoms are replaced with halogen atoms. As for alkyl group, haloalkyl groups can have any suitable number of carbon atoms, such as C_1-6. For example, haloalkyl includes trifluoromethyl, flouromethyl, etc. In some instances, the term “perfluoro” can be used to define a compound or radical where all the hydrogens are replaced with fluorine. For example, perfluoromethyl refers to 1,1,1-trifluoromethyl. [0023] “Haloalkoxy” refers to an alkoxy group where some or all of the hydrogen atoms are substituted with halogen atoms. As for an alkyl group, haloalkoxy groups can have any suitable number of carbon atoms, such as C1-6. The alkoxy groups can be substituted with 1, 2, 3, or more halogens. When all the hydrogens are replaced with a halogen, for example by fluorine, the compounds are per-substituted, for example, perfluorinated. Haloalkoxy includes, but is not limited to, trifluoromethoxy, 2,2,2,-trifluoroethoxy, perfluoroethoxy, etc. [0024] “Cycloalkyl” refers to a saturated or partially unsaturated, monocyclic, fused bicyclic or bridged polycyclic ring assembly containing from 3 to 12 ring atoms, or the number of atoms indicated. Cycloalkyl can include any number of carbons, such as C_3-6, C4-6, C5-6, C3-8, C4-8, C5-8, C6-8, C3-9, C3-10, C3-11, and C3-12. In some embodiments, cycloalkyls are spirocyclic or bridged compounds. In some embodiments, cycloalkyls are optionally fused with an aromatic ring, and the point of attachment is at a carbon that is not an aromatic ring carbon atom. Saturated monocyclic cycloalkyl rings include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cyclooctyl. Saturated bicyclic and polycyclic cycloalkyl rings include, for example, norbornane, [2.2.2] bicyclooctane, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO decahydronaphthalene and adamantane. Cycloalkyl groups can also be partially unsaturated, having one or more double or triple bonds in the ring. Representative cycloalkyl groups that are partially unsaturated include, but are not limited to, cyclobutene, cyclopentene, cyclohexene, cyclohexadiene (1,3- and 1,4-isomers), cycloheptene, cycloheptadiene, cyclooctene, cyclooctadiene (1,3-, 1,4- and 1,5-isomers), norbornene, and norbornadiene. When cycloalkyl is a saturated monocyclic C3-8 cycloalkyl, exemplary groups include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. When cycloalkyl is a saturated monocyclic C3-6 cycloalkyl, exemplary groups include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Cycloalkyl groups can be substituted or unsubstituted. Cycloalkyl groups can contain one or more double bonds in the ring. [0025] “Alkyl-cycloalkyl” refers to a radical having an alkyl component and a cycloalkyl component, where the alkyl component links the cycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent, an alkylene, to link to the cycloalkyl component and to the point of attachment. In some instances, the alkyl component can be absent. The alkyl component can include any number of carbons, such as C1-6, C1-2, C1-3, C1-4, C1-5, C2-3, C2-4, C2-5, C2-6, C3-4, C3-5, C3-6, C_4-5, C_4-6 and C_5-6. The cycloalkyl component is as defined within. Exemplary alkyl- cycloalkyl groups include, but are not limited to, methyl-cyclopropyl, methyl-cyclobutyl, methyl-cyclopentyl and methyl-cyclohexyl. [0026] “Heterocycloalkyl” refers to a saturated ring system having from 3 to 12 ring members and from 1 to 4 heteroatoms of N, O and S. The heteroatoms can also be oxidized, such as, but not limited to, -S(O)- and -S(O)₂-. Heterocycloalkyl groups can include any number of ring atoms, such as, 3 to 6, 4 to 6, 5 to 6, 3 to 8, 4 to 8, 5 to 8, 6 to 8, 3 to 9, 3 to 10, 3 to 11, or 3 to 12 ring members. Any suitable number of heteroatoms can be included in the heterocycloalkyl groups, such as 1, 2, 3, or 4, or 1 to 2, 1 to 3, 1 to 4, 2 to 3, 2 to 4, or 3 to 4. In some embodiments, heterocycloalkyls are spirocyclic or bridged compounds. In some embodiments, heterocycloalkyls are optionally fused with an aromatic ring, and the point of attachment is at a carbon or heteroatom (e.g., nitrogen atom) that is not an aromatic ring carbon atom. The heterocycloalkyl group can include groups such as aziridine, azetidine, pyrrolidine, piperidine, azepane, azocane, quinuclidine, pyrazolidine, imidazolidine, piperazine (1,2-, 1,3- and 1,4-isomers), oxirane, oxetane, tetrahydrofuran, oxane (tetrahydropyran), oxepane, thiirane, thietane, thiolane (tetrahydrothiophene), thiane UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO (tetrahydrothiopyran), oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, dioxolane, dithiolane, morpholine, thiomorpholine, dioxane, or dithiane. The heterocycloalkyl groups can also be fused to aromatic or non-aromatic ring systems to form members including, but not limited to, indoline. Heterocycloalkyl groups can be unsubstituted or substituted. For example, heterocycloalkyl groups can be substituted with C_1-6 alkyl or oxo (=O), among many others. [0027] The heterocycloalkyl groups can be linked via any position on the ring. For example, aziridine can be 1- or 2-aziridine, azetidine can be 1- or 2- azetidine, pyrrolidine can be 1-, 2- or 3-pyrrolidine, piperidine can be 1-, 2-, 3- or 4-piperidine, pyrazolidine can be 1-, 2-, 3-, or 4-pyrazolidine, imidazolidine can be 1-, 2-, 3- or 4-imidazolidine, piperazine can be 1-, 2-, 3- or 4-piperazine, tetrahydrofuran can be 1- or 2-tetrahydrofuran, oxazolidine can be 2-, 3-, 4- or 5-oxazolidine, isoxazolidine can be 2-, 3-, 4- or 5-isoxazolidine, thiazolidine can be 2-, 3-, 4- or 5-thiazolidine, isothiazolidine can be 2-, 3-, 4- or 5- isothiazolidine, and morpholine can be 2-, 3- or 4-morpholine. [0028] When heterocycloalkyl includes 3 to 8 ring members and 1 to 3 heteroatoms, representative members include, but are not limited to, pyrrolidine, piperidine, tetrahydrofuran, oxane, tetrahydrothiophene, thiane, pyrazolidine, imidazolidine, piperazine, oxazolidine, isoxzoalidine, thiazolidine, isothiazolidine, morpholine, thiomorpholine, dioxane and dithiane. Heterocycloalkyl can also form a ring having 5 to 6 ring members and 1 to 2 heteroatoms, with representative members including, but not limited to, pyrrolidine, piperidine, tetrahydrofuran, tetrahydrothiophene, pyrazolidine, imidazolidine, piperazine, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, and morpholine. [0029] “Heterocycle” or “heterocyclic” refers to heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings (also known as heteroalicyclic groups) containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 3 to 10 atoms in its ring system, and with the proviso that any ring does not contain two adjacent O or S atoms. Unless stated otherwise specifically in the specification, the heterocyclyl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which optionally includes fused or bridged ring systems. The heteroatoms in the heterocyclyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocyclyl radical is partially or fully saturated. The heterocyclyl is attached to the rest of the molecule through any atom of the ring(s). Non- UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO aromatic heterocyclic groups (also known as heterocycloalkyls) include rings having 3 to 10 atoms in its ring system and aromatic heterocyclic groups include rings having 5 to 10 atoms in its ring system. The heterocyclic groups include benzo-fused ring systems. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolin-2-yl, pyrrolin-3-yl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3- azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, 3H-indolyl, indolin-2-onyl, isoindolin-1-onyl, isoindoline-1,3-dionyl, 3,4-dihydroisoquinolin-1(2H)-onyl, 3,4- dihydroquinolin-2(1H)-onyl, isoindoline-1,3-dithionyl, benzo[d]oxazol-2(3H)-onyl, 1H- benzo[d]imidazol-2(3H)-onyl, benzo[d]thiazol-2(3H)-onyl, and quinolizinyl. Examples of aromatic heterocyclic groups are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. The foregoing groups are either C-attached (or C-linked) or N-attached where such is possible. For instance, a group derived from pyrrole includes both pyrrol-1-yl (N-attached) or pyrrol-3-yl (C-attached). Further, a group derived from imidazole includes imidazol-1-yl or imidazol-3-yl (both N- attached) or imidazol-2-yl, imidazol-4-yl or imidazol-5-yl (all C-attached). The heterocyclic groups include benzo-fused ring systems. Non-aromatic heterocycles are optionally substituted with one or two oxo (=O) moieties, such as pyrrolidin-2-one. In some embodiments, at least one of the two rings of a bicyclic heterocycle is aromatic. In some embodiments, both rings of a bicyclic heterocycle are aromatic. Unless stated otherwise specifically in the specification, the term “heterocyclyl” is meant to include heterocyclyl radicals as defined above that are optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R^y-OR^x, -R^y-OC(O)- R^x, -R^y-OC(O)-OR^x, -R^y-OC(O)-N(R^x)2, -R^y-N(R^x)2, -R^y-C(O)R^x, -R^y-C(O)OR^x, -R^y- C(O)N(R^x)₂, -R^y-O-R^z-C(O)N(R^x)₂, -R^y-N(R^x)C(O)OR^x, -R^y-N(R^x)C(O)R^x, -R^y- N(R^x)S(O)tR^x (where t is 1 or 2), -R^y-S(O)tR^x (where t is 1 or 2), -R^y-S(O)tOR^x (where t is 1 or 2) and -R^y-S(O)_tN(R^x)₂ (where t is 1 or 2), where each R^x is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R^y is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R^z is a straight or branched alkylene or alkenylene chain, and where each of the above substituents is unsubstituted unless otherwise indicated. [0030] “Alkyl-heterocycloalkyl” refers to a radical having an alkyl component and a heterocycloalkyl component, where the alkyl component links the heterocycloalkyl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent, an alkylene, to link to the heterocycloalkyl component and to the point of attachment. The alkyl component can include any number of carbons, such as C_0-6, C_1-2, C_1-3, C_1-4, C_1-5, C_1-6, C_2-3, C_2-4, C_2-5, C_2-6, C_3-4, C_3-5, C_3-6, C_4-5, C_4-6 and C_5-6. In some instances, the alkyl component can be absent. The heterocycloalkyl component is as defined above. Alkyl-heterocycloalkyl groups can be substituted or unsubstituted. [0031] “Aryl” refers to an aromatic ring system having any suitable number of ring atoms and any suitable number of rings. Aryl groups can include any suitable number of ring atoms, such as, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 ring atoms, as well as from 6 to 10, 6 to 12, or 6 to 14 ring members. Aryl groups can be monocyclic, fused to form bicyclic or tricyclic groups, or linked by a bond to form a biaryl group. Representative aryl groups include phenyl, naphthyl and biphenyl. Other aryl groups include benzyl, having a methylene linking group. Some aryl groups have from 6 to 12 ring members, such as phenyl, naphthyl UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO or biphenyl. Other aryl groups have from 6 to 10 ring members, such as phenyl or naphthyl. Some other aryl groups have 6 ring members, such as phenyl. Aryl groups can be substituted or unsubstituted. [0032] “Alkyl-aryl” refers to a radical having an alkyl component and an aryl component, where the alkyl component links the aryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent, an alkylene, to link to the aryl component and to the point of attachment. The alkyl component can include any number of carbons, such as C_0-6, C_1-2, C_1-3, C_1-4, C_1-5, C_1-6, C_2-3, C_2-4, C_2-5, C2-6, C3-4, C3-5, C3-6, C4-5, C4-6 and C5-6. In some instances, the alkyl component can be absent. The aryl component is as defined above. Examples of alkyl-aryl groups include, but are not limited to, benzyl and ethyl-benzene. Alkyl-aryl groups can be substituted or unsubstituted. [0033] “Heteroaryl” refers to a monocyclic or fused bicyclic or tricyclic aromatic ring assembly containing 5 to 16 ring atoms, where from 1 to 5 of the ring atoms are a heteroatom such as N, O or S. Additional heteroatoms can also be useful, including, but not limited to, B, Al, Si and P. The heteroatoms can also be oxidized, such as, but not limited to, -S(O)- and -S(O)₂-. Heteroaryl groups can include any number of ring atoms, such as, 5 to 6, 5 to 8, 6 to 8, 5 to 9, 5 to 10, 5 to 11, or 5 to 12 ring members. Any suitable number of heteroatoms can be included in the heteroaryl groups, such as 1, 2, 3, 4, or 5, or 1 to 2, 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, 2 to 5, 3 to 4, or 3 to 5. Heteroaryl groups can have from 5 to 8 ring members and from 1 to 4 heteroatoms, or from 5 to 8 ring members and from 1 to 3 heteroatoms, or from 5 to 6 ring members and from 1 to 4 heteroatoms, or from 5 to 6 ring members and from 1 to 3 heteroatoms. The heteroaryl group can include groups such as pyrrole, pyridine, imidazole, pyrazole, triazole, tetrazole, pyrazine, pyrimidine, pyridazine, triazine (1,2,3-, 1,2,4- and 1,3,5-isomers), thiophene, furan, thiazole, isothiazole, oxazole, and isoxazole. The heteroaryl groups can also be fused to aromatic ring systems, such as a phenyl ring, to form members including, but not limited to, benzopyrroles such as indole and isoindole, benzopyridines such as quinoline and isoquinoline, benzopyrazine (quinoxaline), benzopyrimidine (quinazoline), benzopyridazines such as phthalazine and cinnoline, benzothiophene, and benzofuran. Other heteroaryl groups include heteroaryl rings linked by a bond, such as bipyridine. Heteroaryl groups can be substituted or unsubstituted. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0034] The heteroaryl groups can be linked via any position on the ring. For example, pyrrole includes 1-, 2- and 3-pyrrole, pyridine includes 2-, 3- and 4-pyridine, imidazole includes 1-, 2-, 4- and 5-imidazole, pyrazole includes 1-, 3-, 4- and 5-pyrazole, triazole includes 1-, 4- and 5-triazole, tetrazole includes 1- and 5-tetrazole, pyrimidine includes 2-, 4-, 5- and 6- pyrimidine, pyridazine includes 3- and 4-pyridazine, 1,2,3-triazine includes 4- and 5-triazine, 1,2,4-triazine includes 3-, 5- and 6-triazine, 1,3,5-triazine includes 2-triazine, thiophene includes 2- and 3-thiophene, furan includes 2- and 3-furan, thiazole includes 2-, 4- and 5-thiazole, isothiazole includes 3-, 4- and 5-isothiazole, oxazole includes 2-, 4- and 5- oxazole, isoxazole includes 3-, 4- and 5-isoxazole, indole includes 1-, 2- and 3-indole, isoindole includes 1- and 2-isoindole, quinoline includes 2-, 3- and 4-quinoline, isoquinoline includes 1-, 3- and 4-isoquinoline, quinazoline includes 2- and 4-quinoazoline, cinnoline includes 3- and 4-cinnoline, benzothiophene includes 2- and 3-benzothiophene, and benzofuran includes 2- and 3-benzofuran. [0035] Some heteroaryl groups include those having from 5 to 10 ring members and from 1 to 3 ring atoms including N, O or S, such as pyrrole, pyridine, imidazole, pyrazole, triazole, pyrazine, pyrimidine, pyridazine, triazine (1,2,3-, 1,2,4- and 1,3,5-isomers), thiophene, furan, thiazole, isothiazole, oxazole, isoxazole, indole, isoindole, quinoline, isoquinoline, quinoxaline, quinazoline, phthalazine, cinnoline, benzothiophene, and benzofuran. Other heteroaryl groups include those having from 5 to 8 ring members and from 1 to 3 heteroatoms, such as pyrrole, pyridine, imidazole, pyrazole, triazole, pyrazine, pyrimidine, pyridazine, triazine (1,2,3-, 1,2,4- and 1,3,5-isomers), thiophene, furan, thiazole, isothiazole, oxazole, and isoxazole. Some other heteroaryl groups include those having from 9 to 12 ring members and from 1 to 3 heteroatoms, such as indole, isoindole, quinoline, isoquinoline, quinoxaline, quinazoline, phthalazine, cinnoline, benzothiophene, benzofuran and bipyridine. Still other heteroaryl groups include those having from 5 to 6 ring members and from 1 to 2 ring atoms including N, O or S, such as pyrrole, pyridine, imidazole, pyrazole, pyrazine, pyrimidine, pyridazine, thiophene, furan, thiazole, isothiazole, oxazole, and isoxazole. [0036] Some heteroaryl groups include from 5 to 10 ring members and only nitrogen heteroatoms, such as pyrrole, pyridine, imidazole, pyrazole, triazole, pyrazine, pyrimidine, pyridazine, triazine (1,2,3-, 1,2,4- and 1,3,5-isomers), indole, isoindole, quinoline, isoquinoline, quinoxaline, quinazoline, phthalazine, and cinnoline. Other heteroaryl groups include from 5 to 10 ring members and only oxygen heteroatoms, such as furan and benzofuran. Some other heteroaryl groups include from 5 to 10 ring members and only sulfur UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO heteroatoms, such as thiophene and benzothiophene. Still other heteroaryl groups include from 5 to 10 ring members and at least two heteroatoms, such as imidazole, pyrazole, triazole, pyrazine, pyrimidine, pyridazine, triazine (1,2,3-, 1,2,4- and 1,3,5-isomers), thiazole, isothiazole, oxazole, isoxazole, quinoxaline, quinazoline, phthalazine, and cinnoline. [0037] “Alkyl-heteroaryl” refers to a radical having an alkyl component and a heteroaryl component, where the alkyl component links the heteroaryl component to the point of attachment. The alkyl component is as defined above, except that the alkyl component is at least divalent, an alkylene, to link to the heteroaryl component and to the point of attachment. The alkyl component can include any number of carbons, such as C0-6, C1-2, C1-3, C1-4, C1-5, C_1-6, C_2-3, C_2-4, C_2-5, C_2-6, C_3-4, C_3-5, C_3-6, C_4-5, C_4-6 and C_5-6. In some instances, the alkyl component can be absent. The heteroaryl component is as defined within. Alkyl-heteroaryl groups can be substituted or unsubstituted. [0038] “Salt” refers to acid or base salts of the compounds used in the methods of the present invention. Illustrative examples of pharmaceutically acceptable salts are mineral acid (hydrochloric acid, hydrobromic acid, phosphoric acid, and the like) salts, organic acid (acetic acid, propionic acid, glutamic acid, citric acid and the like) salts, quaternary ammonium (methyl iodide, ethyl iodide, and the like) salts. It is understood that the pharmaceutically acceptable salts are non-toxic. Additional information on suitable pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, which is incorporated herein by reference. [0039] Pharmaceutically acceptable salts of the acidic compounds of the present invention are salts formed with bases, namely cationic salts such as alkali and alkaline earth metal salts, such as sodium, lithium, potassium, calcium, magnesium, as well as ammonium salts, such as ammonium, trimethyl-ammonium, diethylammonium, and tris-(hydroxymethyl)-methyl-ammonium salts. [0040] Similarly acid addition salts, such as of mineral acids, organic carboxylic and organic sulfonic acids, e.g., hydrochloric acid, methanesulfonic acid, maleic acid, are also possible provided a basic group, such as pyridyl, constitutes part of the structure. [0041] The neutral forms of the compounds may be regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO as solubility in polar solvents, but otherwise the salts are equivalent to the parent form of the compound for the purposes of the present invention. [0042] “Therapeutically effective amount or dose” or “therapeutically sufficient amount or dose” or “effective or sufficient amount or dose” refer to a dose that produces therapeutic effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). In sensitized cells, the therapeutically effective dose can often be lower than the conventional therapeutically effective dose for non-sensitized cells. [0043] “Treat”, “treating” and “treatment” refers to any indicia of success in the treatment or amelioration of an injury, pathology, condition, or symptom (e.g., pain), including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the symptom, injury, pathology or condition more tolerable to the patient; decreasing the frequency or duration of the symptom or condition; or, in some situations, preventing the onset of the symptom. The treatment or amelioration of symptoms can be based on any objective or subjective parameter; including, e.g., the result of a physical examination. [0044] “Disease” refers abnormal cellular function in an organism, which is not due to a direct result of a physical or external injury. Diseases can refer to any condition that causes distress, dysfunction, disabilities, disorders, infections, pain, or even death. Diseases include, but are not limited to hereditary diseases such as genetic and non-genetic diseases, infectious diseases, non-infectious diseases such as cancer, deficiency diseases, neurological diseases, and physiological diseases. [0045] “Administering” refers to oral administration, administration as a suppository, topical contact, parenteral, intravenous, intraperitoneal, intramuscular, intralesional, intranasal or subcutaneous administration, intrathecal administration, or the implantation of a slow-release device e.g., a mini-osmotic pump, to the subject. [0046] “Subject” refers to animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In certain embodiments, the subject is a human. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0047] “Neural plasticity” refers to the ability of the brain to change its structure and/or function continuously throughout a subject’s life. Examples of the changes to the brain include, but are not limited to, the ability to adapt or respond to internal and/or external stimuli, such as due to an injury, and the ability to produce new neurites, dendritic spines, and synapses. [0048] “Dendritic crossing” refers to dendritic branches which overlap each other or form a cluster. Dendritic crossing can be measured by Sholl Analysis. [0049] “Dendritic spine” refers to the small membrane protruding from a dendrite which can receive electric signal from an axon at the synapse. Dendritic spines are useful for transmitting electric signals to the neuron’s cell body. Dendrites of a single neuron can comprise hundreds to thousands of spines. Dendritic spine density refers to the number of spines within the length of a dendrite. As an illustrative example, a dendritic spine density of 5µm^-1 indicates 5 spines per 1 µm stretch of a dendrite. [0050] “Modulate” or “modulating” or “modulation” refers to an increase or decrease in the amount, quality, or effect of a particular activity, function or molecule. By way of illustration and not limitation, agonists, partial agonists, antagonists, and allosteric modulators (e.g., a positive allosteric modulator) of a G protein-coupled receptor (e.g., 5HT2A or 5HT2C) are modulators of the receptor. [0051] “Agonism” refers to the activation of a receptor or enzyme by a modulator, or agonist, to produce a biological response. [0052] “Agonist” refers to a modulator that binds to a receptor or enzyme and activates the receptor to produce a biological response. By way of example only, “5HT_2A agonist” can be used to refer to a compound that exhibits an EC50 with respect to 5HT2A activity of no more than about 100 μM. In some embodiments, the term “agonist” includes full agonists or partial agonists. “Full agonist” refers to a modulator that binds to and activates a receptor with the maximum response that an agonist can elicit at the receptor. “Partial agonist” refers to a modulator that binds to and activates a given receptor, but has partial efficacy, that is, less than the maximal response, at the receptor relative to a full agonist. “Functionally selective agonist” refers to a modulator that produces one or a subset of biological responses that are possible from activation of a receptor. For example, activation of 5HT_2A receptors is known to cause many downstream effects including increased neural plasticity, increased intracellular calcium concentrations, and hallucinations, among many other biological UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO responses. A functionally selective agonist would produce only a subset of the biological responses possible from activation of the 5HT2A receptor. [0053] “Positive allosteric modulator” refers to a modulator that binds to a site distinct from the orthosteric binding site and enhances or amplifies the effect of an agonist. [0054] “Antagonism” refers to the inactivation of a receptor or enzyme by a modulator, or antagonist. Antagonism of a receptor, for example, is when a molecule binds to the receptor and does not allow activity to occur. “Functionally selective antagonists” block one signaling pathway while leaving others in tact. [0055] “Antagonist” or “neutral antagonist” refers to a modulator that binds to a receptor or enzyme and blocks a biological response. An antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either, causing no change in the biological response. III. COMPOUNDS [0056] The present invention provides tropane compounds of Formula I, Ia, II, IIa, III, IIIa, IV, IVa, V, and Va, useful for the treatment of a variety of neurological diseases and disorders as well as increasing neuronal plasticity. [0057] In some embodiments, the compounds provided herein have improved physiochemical properties as a result of the loss of a hydrogen bond donor, decreasing total polar surface area and improving central nervous system multiparameter optimization (MPO) scores. Described herein in some embodiments are non-hallucinogenic compounds that demonstrate similar therapeutic potential as hallucinogenic 5-HT modulators (e.g., 5HT2A and/or 5HT_2C modulators). In some embodiments, the non-hallucinogenic compounds described herein provide better therapeutic potential than hallucinogenic 5-HT modulators (e.g., 5HT_2A and/or 5HT_2C modulators) for neurological diseases. [0058] Provided herein are tropane compounds useful for the treatment of a variety of diseases such as brain disorders and other conditions. In some embodiments, the tropane compounds provided herein are 5-HT₂ modulators and promote neural plasticity (e.g., cortical structural plasticity). [0059] In some embodiments, provided herein is a compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I), (II), (III), (IV), or (V): UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO , , , or wherein:

R¹¹ is C_1-6 alkyl; R¹², R¹³ and R¹⁴ are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^12a, -C(O)OR^12a, - OC(O)R^12a, -C(O)N(R^12a)(R^12b), -N(R^12a)C(O)R^12b, - N(R^12a)C(O)N(R^12b)(R^12c), -S(O)R^12a, -S(O)2R^12a, -S(O)2OR^12a, -OS(O)2R^12a, - S(O)2N(R^12a)(R^12b), -N(R^12a)S(O)2R^12b, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl; each R^12a, R^12b and R^12c is independently is hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocycloalkyl, C6-10 aryl, or heteroaryl; R^15a, R^15b, R^15c, R^15d and R^15e are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 1₀ aryl, heteroaryl, or C_1-6 alkyl-heteroaryl, wherein at least one of R^15a, R^15b, R^15c, R^15d and R^15e is C1-6 alkyl, C2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl, such that when R^15a is alkoxy, R^15a is C_2-6 alkoxy; R²¹ C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, C_1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C_1-6 alkyl- heteroaryl, wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3 or 4 R^21a groups; each R^21a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^21b, -C(O)OR^21b, -OC(O)R^21b, -C(O)N(R^21b)(R^21c), - N(R^21b)C(O)R^21c, -N(R^21b)C(O)N(R^21c)(R^21d), -S(O)R^21b, -S(O)₂R^21b, - S(O)₂OR^21b, -OS(O)₂R^21b, -S(O)₂N(R^21b)(R^21c), or -N(R^21b)S(O)₂R^21c; R^21b, R^21c and R^21d are independently is hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, or C_1-6 haloalkyl; R²² and R²³ are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_{1- 6} alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^22a, -C(O)OR^22a, -OC(O)R^22a, - C(O)N(R^22a)(R^22b), -N(R^22a)C(O)R^22b, -N(R^22a)C(O)N(R^22b)(R^22c), -S(O)R^22a, - S(O)₂R^22a, -S(O)₂OR^22a, -OS(O)₂R^22a, -S(O)₂N(R^22a)(R^22b), -N(R^22a)S(O)₂R^22b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl- heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C1-6 alkyl- heteroaryl; R^22a, R^22b and R^22c are each independently is hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R²⁶ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^26a groups; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO each R^26a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^26b, -C(O)OR^26b, -OC(O)R^26b, -C(O)N(R^26b)(R^26c), - N(R^26b)C(O)R^26c, -N(R^26b)C(O)N(R^26c)(R^26d), -S(O)R^26b, --S(O)2R^26b, - S(O)₂OR^26b, -OS(O)₂R^26b, -S(O)₂N(R^26b)(R^26c), or -N(R^26b)S(O)₂R^26c; R^26b, R^26c and R^26d are each independently hydrogen or C1-6 alkyl; L³ is C2-6 alkylene; R³¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, -CN, -C(O)R^31b, -C(O)OR^31b, -OC(O)R^31b, -C(O)N(R^31b)(R^31c), - N(R^31b)C(O)R^31c, -N(R^31b)C(O)N(R^31c)(R^31d), -S(O)R^31b, --S(O)₂R^31b, - S(O)2OR^31b, -OS(O)2R^31b, -S(O)2N(R^31b)(R^31c), or -N(R^31b)S(O)2R^31c; R^31b, R^31c and R^31d are each independently hydrogen or C_1-6 alkyl; R³², R³³, R³⁴ and R³⁵ are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^32a, -C(O)OR^32a, - OC(O)R^32a, -C(O)N(R^32a)(R^32b), -N(R^32a)C(O)R^32b, - N(R^32a)C(O)N(R^32b)(R^32c), -S(O)R^32a, -S(O)₂R^32a, -S(O)₂OR^32a, -OS(O)₂R^32a, - S(O)₂N(R^32a)(R^32b), -N(R^32a)S(O)₂R^32b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_{6- 10} aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^32a, R^32b and R^32c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R⁴¹ is C_1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, -OR^42a, -OC(O)R^42a, - OC(O)OR^42a; each R^42a is independently C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R⁴⁴ is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO -C(O)R^44a, -C(O)OR^44a, -OC(O)R^44a, -C(O)N(R^44a)(R^44b), -N(R^44a)C(O)R^44b, - N(R^44a)C(O)N(R^44b)(R^44c), -S(O)R^44a, -S(O)2R^44a, -S(O)2OR^44a, -OS(O)2R^44a, - S(O)₂N(R^44a)(R^44b), -N(R^44a)S(O)₂R^44b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 1₀ aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^44a, R^44b, and R^44c are each independently is hydrogen, C1-6 alkyl, C3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH, -OR^42a, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^51a groups; each R^51a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^51b, -C(O)OR^51b, -OC(O)R^51b, -C(O)N(R^51b)(R^51c), - N(R^51b)C(O)R^51c, -N(R^51b)C(O)N(R^51c)(R^51d), -S(O)R^51b, --S(O)₂R^51b, - S(O)₂OR^51b, -OS(O)₂R^51b, -S(O)₂N(R^51b)(R^51c), or -N(R^51b)S(O)₂R^51c; R^51b, R^51c and R^51d are each independently hydrogen or C_1-6 alkyl; R⁵⁴ is C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^54a, -C(O)OR^54a, -OC(O)R^54a, -C(O)N(R^54a)(R^54b), -N(R^54a)C(O)R^54b, - N(R^54a)C(O)N(R^54b)(R^54c), -S(O)R^54a, --S(O)₂R^54a, -S(O)₂OR^54a, -OS(O)₂R^54a, -S(O)₂N(R^54a)(R^54b), -N(R^54a)S(O)₂R^54b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6- 10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl; R^54a, R^54b, and R^54c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl,

10 aryl, or heteroaryl; and R^55a is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S. [0060] In some embodiments, the present invention provides a compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I): . [0061] In some a compound, or a

pharmaceutically acceptable salt thereof, having a structure of Formula (II): . [0062] In some

provides a compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (III): . [0063] In some

provides a compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (IV): . [0064] In some

a compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (V): UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO . [0065] In some embodiments, a compound of Formula I, II, III, IV, or V, or a

having a structure of Formula (Ia), (IIa), (IIIa), (IVa), or (Va): , or wherein:

R¹¹ is C1-6 alkyl; R^15a, R^15b, and R^15c are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C_1-6 haloalkoxy, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO wherein at least one of R^15a, R^15b, R^15c, R^15d and R^15e is C_1-6 alkyl, C_2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C_1-6 haloalkoxy, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl, such that when R^15a is alkoxy, R^15a is C2-6 alkoxy; R²¹ C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C1-6 alkyl- heteroaryl, wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3 or 4 R^21a groups; each R^21a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^21b, -C(O)OR^21b, -OC(O)R^21b, -C(O)N(R^21b)(R^21c), - N(R^21b)C(O)R^21c, -N(R^21b)C(O)N(R^21c)(R^21d), -S(O)R^21b, -S(O)2R^21b, - S(O)₂OR^21b, -OS(O)₂R^21b, -S(O)₂N(R^21b)(R^21c), or -N(R^21b)S(O)₂R^21c; R^21b, R^21c and R^21d are independently is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, or C_1-6 haloalkyl; R²⁶ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^26a groups; each R^26a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^26b, -C(O)OR^26b, -OC(O)R^26b, -C(O)N(R^26b)(R^26c), - N(R^26b)C(O)R^26c, -N(R^26b)C(O)N(R^26c)(R^26d), -S(O)R^26b, --S(O)₂R^26b, - -OS(O)₂R^26b, -S(O)₂N(R^26b)(R^26c), or -N(R^26b)S(O)₂R^26c; are each independently hydrogen or C_1-6 alkyl;

L³ is C_2-6 alkylene; R³¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^31b, -C(O)OR^31b, -OC(O)R^31b, -C(O)N(R^31b)(R^31c), - N(R^31b)C(O)R^31c, -N(R^31b)C(O)N(R^31c)(R^31d), -S(O)R^31b, --S(O)2R^31b, - S(O)₂OR^31b, -OS(O)₂R^31b, -S(O)₂N(R^31b)(R^31c), or -N(R^31b)S(O)₂R^31c; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R^31b, R^31c and R^31d are each independently hydrogen or C_1-6 alkyl; R⁴¹ is C_1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; each R^42a is independently C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^51a groups; each R^51a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^51b, -C(O)OR^51b, -OC(O)R^51b, -C(O)N(R^51b)(R^51c), - N(R^51b)C(O)R^51c, -N(R^51b)C(O)N(R^51c)(R^51d), -S(O)R^51b, --S(O)₂R^51b, - S(O)₂OR^51b, -OS(O)₂R^51b, -S(O)₂N(R^51b)(R^51c), or -N(R^51b)S(O)₂R^51c; and R^51b, R^51c and R^51d are each independently hydrogen or C_1-6 alkyl; wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S. [0066] In some embodiments, the present invention provides a compound of Formula I, Ia, II, IIa, III, IIIa, IV, IVa, V, or Va, or a pharmaceutically acceptable salt thereof, wherein R¹¹ is C1-6 alkyl; R^15a, R^15b, and R^15c are each independently hydrogen, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy, wherein at least one of R^15a, R^15b, and R^15c is C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1- UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 6 hydroxyalkyl, halogen, C_1-6 haloalkyl, or C_1-6 haloalkoxy, such that when R^15a is alkoxy, R^15a is C2-6 alkoxy; R²¹ C1-6 alkyl; R²⁶ is C_6-12 aryl or heteroaryl; L³ is C_2-6 alkylene; R³¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy; R⁴¹ is C1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; each R^42a is independently C6-10 aryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is –OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^51a groups; and each R^51a is independently C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, or C_1-6 haloalkoxy; wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S. [0067] In some embodiments, the present invention provides a compound of Formula I, Ia, II, IIa, III, IIIa, IV, IVa, V, or Va, or a pharmaceutically acceptable salt thereof, wherein R¹¹ is C_1-6 alkyl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R^15a, R^15b, and R^15c are each independently hydrogen, C_1-6 alkoxy, C_1-6 alkoxyalkyl, halogen, or C1-6 haloalkoxy, wherein at least one of R^15a, R^15b, and R^15c is C_1-6 alkoxy, C_1-6 alkoxyalkyl, halogen, or C1-6 haloalkoxy, such that when R^15a is alkoxy, R^15a is C_2-6 alkoxy; R²¹ C_1-6 alkyl; R²⁶ is C6-12 aryl or heteroaryl having 6 to 9 ring members and 1 to 2 heteroatoms each independently N, O, or S; L³ is C_2-6 alkylene; R³¹ is C6-12 aryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C_1-6 alkoxy, C_1-6 alkoxyalkyl, halogen, or C_1-6 haloalkoxy; R⁴¹ is C_1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; R^42a is C_6-10 aryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is –OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C_6-12 aryl or heteroaryl having 6 to 10 ring members and 1 to 3 heteroatoms each independently N, O, or S, each substituted with 0, 1, or 2 R^51a groups; and each R^51a is independently C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, or C_1-6 haloalkoxy. [0068] In some embodiments, the present invention provides a compound of Formula I, Ia, II, IIa, III, IIIa, IV, IVa, V, or Va, or a pharmaceutically acceptable salt thereof, wherein R¹¹ is C_1-3 alkyl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R^15a, R^15b, and R^15c are each independently hydrogen, C_1-3 alkoxy, or halogen, wherein at least one of R^15a, R^15b, and R^15c is C1-3 alkoxy, or halogen, such that when R^15a is alkoxy, R^15a is C_2-3 alkoxy; R²¹ C_1-3 alkyl; R²⁶ is C6-12 aryl, or heteroaryl having 6 to 9 ring members and 1 heteroatom of N; L³ is C2-3 alkylene; R³¹ is phenyl, substituted with 0, 1, or 2 R^31a groups; each R^31a is independently C1-3 alkoxy, or halogen; R⁴¹ is C1-3 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; R^42a is phenyl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-3 alkylene; R⁵¹ is phenyl or heteroaryl having 8 to 10 ring members and 1 or 2 heteroatoms of N, each substituted with 0, 1, or 2 R^51a groups; and each R^51a is independently C_1-3 alkoxy, or C_1-3 alkoxyalkyl. [0069] In some embodiments, the present invention provides a compound of Formula I, Ia, II, IIa, III, IIIa, IV, IVa, V, or Va, or a pharmaceutically acceptable salt thereof, wherein R¹¹ is methyl; R^15a is hydrogen or fluoro; R^15b and R^15c are each independently hydrogen, methoxy, or fluoro, wherein at least one of R^15a, R^15b, and R^15c is methoxy or fluoro; R²¹ is methyl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R²⁶ is phenyl, pyridyl, or indolyl; L³ is -CH₂CH₂-; R³¹ is phenyl, substituted with 0 or 1 methoxy or fluoro; R⁴¹ is methyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; R^42a is phenyl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is –OH or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 membered heterocycloalkyl; L⁵ is –CH₂- or –CH₂CH₂-; and R⁵¹ is phenyl or indolyl, each substituted with 0 or 1 methoxy. [0070] In some embodiments, the present invention provides a compound of Formula I, or a pharmaceutically acceptable salt thereof, having a structure of Formula (Ia): . [0071] In some

a compound of Formula II, or a pharmaceutically acceptable salt thereof, having a structure of Formula (IIa): . [0072] In some

provides a compound of Formula III, or a pharmaceutically acceptable salt thereof, having a structure of Formula (IIIa): UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO . [0073] In some embodiments, provides a compound of Formula IV, or a pharmaceutically acceptable

structure of Formula (IVa): . [0074] In some a compound of Formula V, or

a pharmaceutically acceptable a structure of Formula (Va): . [0075] In some provides a compound of Formula I, Ia,

II, IIa, III, IIIa, IV, IVa, V, or Va, or a pharmaceutically acceptable salt thereof, having the structure: ,

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO MeO , , [0076]

acid or base salts of the compounds of the present invention. Illustrative examples of pharmaceutically acceptable salts are mineral acid (hydrochloric acid, hydrobromic acid, phosphoric acid, and the like) salts, organic acid (fumaric acid, acetic acid, propionic acid, glutamic acid, citric acid and the like) salts, quaternary ammonium (methyl iodide, ethyl iodide, and the like) salts. It is understood that the pharmaceutically acceptable salts are non- toxic. Additional information on suitable pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, which is incorporated herein by reference. [0077] The present invention also includes isotopically-labeled compounds of the present invention, wherein one or more atoms are replaced by one or more atoms having specific atomic mass or mass numbers. Examples of isotopes that can be incorporated into compounds of the invention include, but are not limited to, isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, sulfur, and chlorine (such as ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ¹⁷O, ¹⁸F, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO ³⁵S and ³⁶Cl). Isotopically-labeled compounds of the present invention are useful in assays of the tissue distribution of the compounds and their prodrugs and metabolites; preferred isotopes for such assays include ³H and ¹⁴C. In addition, in certain circumstances substitution with heavier isotopes, such as deuterium (²H), can provide increased metabolic stability, which offers therapeutic advantages such as increased in vivo half-life or reduced dosage requirements. Isotopically-labeled compounds of this invention can generally be prepared according to the methods known by one of skill in the art by substituting an isotopically- labeled reagent for a non-isotopically labeled reagent. Compounds of the present invention can be isotopically labeled at positions adjacent to the basic amine, in aromatic rings, and the methyl groups of methoxy substituents. [0078] The present invention includes all tautomers and stereoisomers of compounds of the present invention, either in admixture or in pure or substantially pure form. The compounds of the present invention can have asymmetric centers at the carbon atoms, and therefore the compounds of the present invention can exist in diastereomeric or enantiomeric forms or mixtures thereof. All conformational isomers (e.g., cis and trans isomers) and all optical isomers (e.g., enantiomers and diastereomers), racemic, diastereomeric and other mixtures of such isomers, as well as solvates, hydrates, isomorphs, polymorphs and tautomers are within the scope of the present invention. Compounds according to the present invention can be prepared using diastereomers, enantiomers or racemic mixtures as starting materials. Furthermore, diastereomer and enantiomer products can be separated by chromatography, fractional crystallization or other methods known to those of skill in the art. [0079] In some embodiments, a compound provided herein, including pharmaceutically acceptable salts and solvates thereof, is a non-hallucinogenic psychoplastogen. In some embodiments, the non-hallucinogenic psychoplastogen promotes neuronal growth, improves neuronal structure, or a combination thereof. IV. PHARMACEUTICAL COMPOSITIONS AND FORMULATIONS [0080] In some embodiments, provided herein is a pharmaceutical composition, comprising a therapeutically effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof. [0081] The compositions of the present invention can be prepared in a wide variety of oral, parenteral and topical dosage forms. Oral preparations include tablets, pills, powder, dragees, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO capsules, liquids, lozenges, cachets, gels, syrups, slurries, suspensions, etc., suitable for ingestion by the patient. The compositions of the present invention can also be administered by injection, that is, intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Also, the compositions described herein can be administered by inhalation, for example, intranasally. Additionally, the compositions of the present invention can be administered transdermally. The compositions of this invention can also be administered by intraocular, intravaginal, and intrarectal routes including suppositories, insufflation, powders and aerosol formulations (for examples of steroid inhalants, see Rohatagi, J. Clin. Pharmacol.35:1187-1193, 1995; Tjwa, Ann. Allergy Asthma Immunol.75:107-111, 1995). Accordingly, the present invention also provides pharmaceutical compositions including a pharmaceutically acceptable carrier or excipient and the compound of the present invention. [0082] For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances, which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material. Details on techniques for formulation and administration are well described in the scientific and patent literature, see, e.g., the latest edition of Remington's Pharmaceutical Sciences, Maack Publishing Co, Easton PA ("Remington's"). [0083] In powders, the carrier is a finely divided solid, which is in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain from 5% or 10% to 70% of the compound the present invention. [0084] Suitable solid excipients include, but are not limited to, magnesium carbonate; magnesium stearate; talc; pectin; dextrin; starch; tragacanth; a low melting wax; cocoa butter; carbohydrates; sugars including, but not limited to, lactose, sucrose, mannitol, or sorbitol, starch from corn, wheat, rice, potato, or other plants; cellulose such as methyl cellulose, hydroxypropylmethyl-cellulose, or sodium carboxymethylcellulose; and gums including arabic and tragacanth; as well as proteins including, but not limited to, gelatin and collagen. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO If desired, disintegrating or solubilizing agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, alginic acid, or a salt thereof, such as sodium alginate. [0085] Dragee cores are provided with suitable coatings such as concentrated sugar solutions, which may also contain gum arabic, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for product identification or to characterize the quantity of active compound (i.e., dosage). Pharmaceutical preparations of the invention can also be used orally using, for example, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a coating such as glycerol or sorbitol. Push-fit capsules can contain the compound of the present invention mixed with a filler or binders such as lactose or starches, lubricants such as talc or magnesium stearate, and, optionally, stabilizers. In soft capsules, the compound of the present invention may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycol with or without stabilizers. [0086] For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the compound of the present invention is dispersed homogeneously therein, as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify. [0087] Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water/propylene glycol solutions. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution. [0088] Aqueous solutions suitable for oral use can be prepared by dissolving the compound of the present invention in water and adding suitable colorants, flavors, stabilizers, and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia, and dispersing or wetting agents such as a naturally occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethylene oxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol (e.g., polyoxyethylene sorbitol mono-oleate), or a UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO condensation product of ethylene oxide with a partial ester derived from fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan mono-oleate). The aqueous suspension can also contain one or more preservatives such as ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, aspartame or saccharin. Formulations can be adjusted for osmolarity. [0089] Also included are solid form preparations, which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. [0090] Oil suspensions can be formulated by suspending the compound of the present invention in a vegetable oil, such as arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin; or a mixture of these. The oil suspensions can contain a thickening agent, such as beeswax, hard paraffin or cetyl alcohol. Sweetening agents can be added to provide a palatable oral preparation, such as glycerol, sorbitol or sucrose. These formulations can be preserved by the addition of an antioxidant such as ascorbic acid. As an example of an injectable oil vehicle, see Minto, J. Pharmacol. Exp. Ther.281:93-102, 1997. The pharmaceutical formulations of the invention can also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil, described above, or a mixture of these. Suitable emulsifying agents include naturally-occurring gums, such as gum acacia and gum tragacanth, naturally occurring phosphatides, such as soybean lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan mono- oleate, and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan mono-oleate. The emulsion can also contain sweetening agents and flavoring agents, as in the formulation of syrups and elixirs. Such formulations can also contain a demulcent, a preservative, or a coloring agent. [0091] The compositions of the present invention can also be delivered as microspheres for slow release in the body. For example, microspheres can be formulated for administration via intradermal injection of drug-containing microspheres, which slowly release subcutaneously (see Rao, J. Biomater Sci. Polym. Ed.7:623-645, 1995; as biodegradable and injectable gel formulations (see, e.g., Gao Pharm. Res.12:857-863, 1995); or, as microspheres for oral administration (see, e.g., Eyles, J. Pharm. Pharmacol.49:669-674, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 1997). Both transdermal and intradermal routes afford constant delivery for weeks or months. [0092] In another embodiment, the compositions of the present invention can be formulated for parenteral administration, such as intravenous (IV) administration or administration into a body cavity or lumen of an organ. The formulations for administration will commonly comprise a solution of the compositions of the present invention dissolved in a pharmaceutically acceptable carrier. Among the acceptable vehicles and solvents that can be employed are water and Ringer's solution, an isotonic sodium chloride. In addition, sterile fixed oils can conventionally be employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid can likewise be used in the preparation of injectables. These solutions are sterile and generally free of undesirable matter. These formulations may be sterilized by conventional, well known sterilization techniques. The formulations may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of the compositions of the present invention in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight, and the like, in accordance with the particular mode of administration selected and the patient's needs. For IV administration, the formulation can be a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a nontoxic parenterally-acceptable diluent or solvent, such as a solution of 1,3-butanediol. [0093] In another embodiment, the formulations of the compositions of the present invention can be delivered by the use of liposomes which fuse with the cellular membrane or are endocytosed, i.e., by employing ligands attached to the liposome, or attached directly to the oligonucleotide, that bind to surface membrane protein receptors of the cell resulting in endocytosis. By using liposomes, particularly where the liposome surface carries ligands specific for target cells, or are otherwise preferentially directed to a specific organ, one can focus the delivery of the compositions of the present invention into the target cells in vivo. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO (See, e.g., Al-Muhammed, J. Microencapsul.13:293-306, 1996; Chonn, Curr. Opin. Biotechnol.6:698-708, 1995; Ostro, Am. J. Hosp. Pharm.46:1576-1587, 1989). [0094] The compositions of the present invention can be delivered by any suitable means, including oral, parenteral and topical methods. Transdermal administration methods, by a topical route, can be formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols. [0095] The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the compounds of the present invention. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form. [0096] The compound of the present invention can be present in any suitable amount, and can depend on various factors including, but not limited to, weight and age of the subject, state of the disease, etc. Suitable dosage ranges for the compound of the present invention include from about 0.1 mg to about 10,000 mg, or about 1 mg to about 1000 mg, or about 10 mg to about 750 mg, or about 25 mg to about 500 mg, or about 50 mg to about 250 mg. Suitable dosages for the compound of the present invention include about 1 mg, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900 or 1000 mg. [0097] The compounds of the present invention can be administered at any suitable frequency, interval and duration. For example, the compound of the present invention can be administered once an hour, or two, three or more times an hour, once a day, or two, three, or more times per day, or once every 2, 3, 4, 5, 6, or 7 days, so as to provide the preferred dosage level. When the compound of the present invention is administered more than once a day, representative intervals include 5, 10, 15, 20, 30, 45 and 60 minutes, as well as 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 hours. The compound of the present invention can be administered once, twice, or three or more times, for an hour, for 1 to 6 hours, for 1 to 12 hours, for 1 to 24 hours, for 6 to 12 hours, for 12 to 24 hours, for a single day, for 1 to 7 days, for a single week, for 1 to 4 weeks, for a month, for 1 to 12 months, for a year or more, or even indefinitely. [0098] The composition can also contain other compatible therapeutic agents. The compounds described herein can be used in combination with one another, with other active UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO agents known to be useful in modulating a glucocorticoid receptor, or with adjunctive agents that may not be effective alone, but may contribute to the efficacy of the active agent. [0099] The compounds of the present invention can be co-administered with another active agent. Co-administration includes administering the compound of the present invention and active agent within 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, or 24 hours of each other. Co- administration also includes administering the compound of the present invention and active agent simultaneously, approximately simultaneously (e.g., within about 1, 5, 10, 15, 20, or 30 minutes of each other), or sequentially in any order. Moreover, the compound of the present invention and the active agent can each be administered once a day, or two, three, or more times per day so as to provide the preferred dosage level per day. [0100] In some embodiments, co-administration can be accomplished by co-formulation, i.e., preparing a single pharmaceutical composition including both the compound of the present invention and the active agent. In other embodiments, the compound of the present invention and the active agent can be formulated separately. [0101] The compound of the present invention and the active agent can be present in the compositions of the present invention in any suitable weight ratio, such as from about 1:100 to about 100:1 (w/w), or about 1:50 to about 50:1, or about 1:25 to about 25:1, or about 1:10 to about 10:1, or about 1:5 to about 5:1 (w/w). The compound of the present invention and the other active agent can be present in any suitable weight ratio, such as about 1:100 (w/w), 1:50, 1:25, 1:10, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 10:1, 25:1, 50:1 or 100:1 (w/w). Other dosages and dosage ratios of the compound of the present invention and the active agent are suitable in the compositions and methods of the present invention. V. METHODS OF TREATMENT [0102] In some embodiments, provided herein is a method of treating a disease or disorder, such as, but not limited to a nuerological disease or disorder, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of the present invention, or a pharmaceutically acceptable salt thereof, thereby treating the disease or disorder. [0103] In some embodiments, provided herein is a method of treating a disease, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO of the present invention, or a pharmaceutically acceptable salt thereof, thereby treating the disease. Neurological Disorders [0104] Neuronal plasticity, and changes thereof, have been attributed to many neurological diseases and disorders. For example, during development and in adulthood, changes in dendritic spine number and morphology (e.g., lengths, crossings, density) accompany synapse formation, maintenance and elimination; these changes are thought to establish and remodel connectivity within neuronal circuits. Furthermore, dendritic spine structural plasticity is coordinated with synaptic function and plasticity. For example, spine enlargement is coordinated with long-term potentiation in neuronal circuits, whereas long- term depression is associated with spine shrinkage. [0105] In addition, dendritic spines undergo experience-dependent morphological changes in live animals, and even subtle changes in dendritic spines can affect synaptic function, synaptic plasticity, and patterns of connectivity in neuronal circuits. For example, disease- specific disruptions in dendritic spine shape, size, and/or number accompany neurological diseases and disorders, such as, for example, neurodegenerative (e.g., Alzheimer’s disease or Parkinson’s disease) and neuropsychiatric (e.g., depression or schizophrenia) diseases and disorders, suggesting that dendritic spines may serve as a common substrate in diseases that involve deficits in information processing. [0106] Unless indicated otherwise, a neurological disease or disorder generally refers to a disease or disorder of the central nervous system (CNS) (e.g., brain, spine, and/or nerves) of an individual. [0107] In some embodiments, provided herein is a method of treating a neurological disease or disorder with a compound provided herein (e.g., a compound of Formula (K), Formula (J), Formula (I), Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), or a pharmaceutically acceptable salt or solvate thereof). [0108] In some embodiments, a compound provided herein, or a pharmaceutically acceptable salt or solvate thereof) improves dendritic spine number and dendritic spine morphology that is lost in a neurological disease or disorder. [0109] In some embodiments, a compound of the present invention is used to treat neurological diseases. In some embodiments, the compounds have, for example, anti- UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO addictive properties, antidepressant properties, anxiolytic properties, or a combination thereof. In some embodiments, the neurological disease is a neuropsychiatric disease. In some embodiments, the neuropsychiatric disease is a mood or anxiety disorder. In some embodiments, the neurological disease is a migraine, headaches (e.g., cluster headache), post- traumatic stress disorder (PTSD), anxiety, depression, neurodegenerative disorder, Alzheimer’s disease, Parkinson’s disease, psychological disorder, treatment resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, stroke, traumatic brain injury, and addiction (e.g., substance use disorder). In some embodiments, the disesase is headache disorders. In some embodiments, the neurological disease is a migraine or cluster headache. In some embodiments, the disease is migraines. In some embodiments, the disease is cluster headaches. In some embodiments, the disease is addiction. In some embodiments, the disease is substance use disorder. In some embodiments, the disease is alcohol use disorder. In some embodiments, the disease is alcohol use disorder. [0110] In some embodiments, the neurological disease is a neurodegenerative disorder, Alzheimer’s disease, or Parkinson’s disease. In some embodiments, the neurological disease is a psychological disorder, treatment resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), addiction (e.g., substance use disorder), depression, or anxiety. In some embodiments, the neuropsychiatric disease is a psychological disorder, treatment resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), addiction (e.g., substance use disorder), depression, or anxiety. In some embodiments, the neuropsychiatric disease or neurological disease is post-traumatic stress disorder (PTSD), addiction (e.g., substance use disorder), schizophrenia, depression, or anxiety. In some embodiments, the neuropsychiatric disease or neurological disease is addiction (e.g., substance use disorder). In some embodiments, the neuropsychiatric disease or neurological disease is depression. In some embodiments, the neuropsychiatric disease or neurological disease is anxiety. In some embodiments, the neuropsychiatric disease or neurological disease is post-traumatic stress disorder (PTSD). In some embodiments, the neurological disease is stroke or traumatic brain injury. In some embodiments, the neuropsychiatric disease or neurological disease is schizophrenia. [0111] In some embodiments, the disease is a neuropsychiatric disease. In some embodiments, the diseases is a neurodegenerative disease. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0112] In some embodiments, a compound of the present invention is used to treat brain disorders. In some embodiments, the compounds have, for example, anti-addictive properties, antidepressant properties, anxiolytic properties, or a combination thereof. In some embodiments, the brain disorder is a neuropsychiatric disease. In some embodiments, the neuropsychiatric disease is a mood or anxiety disorder. In some embodiments, brain disorders include, for example, migraine, cluster headache, post-traumatic stress disorder (PTSD), anxiety, depression, schizophrenia, and addiction (e.g., substance abuse disorder). In some embodiments, brain disorders include, for example, migraines, addiction (e.g., substance use disorder), depression, and anxiety. [0113] In some embodiments, provided herein is a method for increasing neural plasticity, the method comprising contacting a neuronal cell with a compound of the present invention, or a pharmaceutically acceptable salt thereof, in an amount sufficient to increase neural plasticity of the neuronal cell. [0114] The neuronal plasticity can be measured by a variety of methods, including but not limited to, the average number of branch points per neuron, the average total neurite length per neuron, and the average number of neurites per neuron. For example, the average number of branch points per neuron can be at least 1.0, 1.05, 1.1, 1.15, 1.2, or at least 1.25. Alternatively, the branch points per neuron can be at least 1.05 fold above the vehicle control, or at least 1.1, 1.15, 1.2, or at least 1.25 fold above the vehicle control. The average total neurite length per neuron can be at least 100 µm, or at least 105, 110, 115, 120, 125, 130, 135, 140, 145, or at least 150 µm. Alternatively, the neurite length per neuron can be at least 1.05 fold above the vehicle control, or at least 1.1, 1.15, 1.2, or at least 1.25 fold above the vehicle control. The average number of neurites per neuron of can be at least 2.8, or at least 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, or at least 3.5. Alternatively, the neurites per neuron can be at least 1.05 fold above the vehicle control, or at least 1.1, 1.15, 1.2, or at least 1.25 fold above the vehicle control. [0115] Neural plasticity refers to the ability of the brain to change structure and/or function throughout a subject’s life. New neurons can be produced and integrated into the central nervous system throughout the subject’s life. Increasing neural plasticity includes, but is not limited to, promoting neuronal growth, promoting neuritogenesis, promoting synaptogenesis, promoting dendritogenesis, increasing dendritic arbor complexity, increasing dendritic spine density, and increasing excitatory synapsis in the brain. In some embodiments, increasing UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO neural plasticity comprises promoting neuronal growth, promoting neuritogenesis, promoting synaptogenesis, promoting dendritogenesis, increasing dendritic arbor complexity, and increasing dendritic spine density. [0116] In some embodiments, increasing neural plasticity can treat neurodegenerative disorder, Alzheimer’s, Parkinson’s disease, psychological disorder, depression, addiction, anxiety, post-traumatic stress disorder, treatment resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, stroke, traumatic brain injury, or substance use disorder. In some embodiments, the neuropsychiatric disease is bipolar disorder. In some embodiments, the disease is depression. In some embodiments,the disease is a neurodegenerative disease. In some embodiments, the disease is Alzheimer’s disease or Parkinson’s disease. In some embodiments, the disease is Alzheimer’s disease. In some embodiments, the disease is Parkinson’s disease. [0117] In some embodiments, a compound of the present invention is used to increase neural plasticity. In some embodiments, the compounds used to increase neural plasticity have, for example, anti-addictive properties, antidepressant properties, anxiolytic properties, or a combination thereof. In some embodiments, decreased neural plasticity is associated with a neuropsychiatric disease. In some embodiments, the neuropsychiatric disease is a mood or anxiety disorder. In some embodiments, the neuropsychiatric disease includes, for example, migraine, cluster headache, post-traumatic stress disorder (PTSD), schizophrenia, anxiety, depression, and addiction (e.g., substance abuse disorder). In some embodiments, brain disorders include, for example, migraines, addiction (e.g., substance use disorder), depression, and anxiety. In some embodiments, the disease is a neuropsychiatric disease. [0118] In some embodiments, the experiment or assay to determine increased neural plasticity of any compound of the present invention is a phenotypic assay, a dendritogenesis assay, a spinogenesis assay, a synaptogenesis assay, a Sholl analysis, or a concentration- response experiment. In some embodiments, the experiment or assay to determine the hallucinogenic potential of any compounds of the present invention is a mouse head-twitch response (HTR) assay. [0119] In some embodiments, provided herein is a method for increasing neural plasticity and increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound of the present invention, or a pharmaceutically acceptable salt thereof, in an UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO amount sufficient to increase neural plasticity and increase dendritic spine density of the neuronal cell. [0120] Dendritic spines are dynamic and can have significant changes in density, shape, and volume over time. The growth or loss of dendritic spines, which contribute to the dendritic spine density, can be important for reinforcing neural pathways for learning, memory, and general cognitive function. Increasing dendritic spine density can be useful for treatment of neurological diseases, such as, but not limited to, neurodegenerative diseases and neuropsychiatric diseases. [0121] Increasing dendritic spine density can be measured by staining and immunocytochemical methods known by one of skill in the art. Staining methods include, but are not limited to electron microscopy, Golgi staining, crystal violet staining, DAPI staining, and eosin staining. For example, Golgi staining can be used to measure dendritic spine density. [0122] In some embodiments, a compound provided herein, or pharmaceutically acceptable salts thereof, is useful for promoting neuronal growth and/or improving neuronal structure. [0123] In some embodiments, a compound provided herein, or pharmaceutically acceptable salts thereof, is a non-hallucinogenic psychoplastogens useful for treating one or more diseases or disorders associated with loss of synaptic connectivity and/or plasticity. [0124] In some embodiments, an individual administered a compound provided herein does not have a hallucinogenic event (e.g., at any point after the compound has been administered to the individual). [0125] In some embodiments, provided herein is a method for treating a disease or disorder in an individual in need thereof, wherein the disease or disorder is a neurological diseases and disorder. [0126] In some embodiments, a compound provided herein, or a pharmaceutically acceptable salt thereof, is used in the preparation of medicaments for the treatment of diseases or conditions in a mammal that would benefit from promoting neuronal growth and/or improving neuronal structure. [0127] Methods for treating any of the diseases or conditions described herein in a mammal in need of such treatment, involves administration of pharmaceutical compositions that UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO include at least one compound described herein or a pharmaceutically acceptable salt, active metabolite, prodrug, or pharmaceutically acceptable solvate thereof, in therapeutically effective amounts to said mammal. [0128] In certain embodiments, the compositions containing the compound(s) described herein are administered for prophylactic and/or therapeutic treatments. In certain therapeutic applications, the compositions are administered to a mammal already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the mammal’s health status, weight, and response to the drugs, and the judgment of a healthcare practitioner. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose escalation and/or dose ranging clinical trial. [0129] In prophylactic applications, compositions containing the compounds described herein are administered to a mammal susceptible to or otherwise at risk of a particular disease, disorder or condition. Such an amount is defined to be a “prophylactically effective amount or dose.” In this use, the precise amounts also depend on the mammal’s state of health, weight, and the like. When used in mammals, effective amounts for this use will depend on the severity and course of the disease, disorder or condition, previous therapy, the mammal’s health status and response to the drugs, and the judgment of a healthcare professional. In some embodiments, prophylactic treatments include administering to a mammal, who previously experienced at least one symptom of the disease being treated and is currently in remission, a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt thereof, in order to prevent a return of the symptoms of the disease or condition. [0130] In some embodiments wherein the mammal’s condition does not improve, upon the discretion of a healthcare professional the administration of the compounds are administered chronically, that is, for an extended period of time, including throughout the duration of the mammal’s life in order to ameliorate or otherwise control or limit the symptoms of the mammal’s disease or condition. [0131] In some embodiments wherein a mammal’s status does improve, the dose of drug being administered is temporarily reduced or temporarily suspended for a certain length of time (i.e., a “drug holiday”). In some embodiments, the length of the drug holiday is between UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 2 days and 1 year, including by way of example only, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 10 days, 12 days, 15 days, 20 days, 28 days, or more than 28 days. The dose reduction during a drug holiday is, by way of example only, by 10%-100%, including by way of example only 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, and 100%. [0132] Once improvement of the patient's conditions has occurred, a maintenance dose is administered if necessary. Subsequently, in specific embodiments, the dosage or the frequency of administration, or both, is reduced, as a function of the symptoms, to a level at which the improved disease, disorder or condition is retained. In some embodiments, however, the mammal requires intermittent treatment on a long-term basis upon any recurrence of symptoms. [0133] The amount of a given agent that corresponds to such an amount varies depending upon factors such as the particular compound, disease condition and its severity, the identity (e.g., weight, sex) of the subject or host in need of treatment, but nevertheless is determined according to the particular circumstances surrounding the case, including, e.g., the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated. [0134] In general, however, doses employed for adult human treatment are typically in the range of 0.01 mg-5000 mg per day. In some embodiments, doses employed for adult human treatment are from about 1 mg to about 1000 mg per day. In some embodiments, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously or at appropriate intervals, for example as two, three, four or more sub-doses per day. [0135] In some embodiments, the daily dosages appropriate for the compound described herein, or a pharmaceutically acceptable salt thereof, are from about 0.01 to about 50 mg/kg per body weight. In some embodiments, the daily dosage or the amount of active in the dosage form are lower or higher than the ranges indicated herein, based on a number of variables in regard to an individual treatment regime. In some embodiments, the daily and unit dosages are altered depending on a number of variables including, but not limited to, the activity of the compound used, the disease or condition to be treated, the mode of administration, the requirements of the individual subject, the severity of the disease or condition being treated, and the judgment of the practitioner. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0136] Toxicity and therapeutic efficacy of such therapeutic regimens are determined by standard pharmaceutical procedures in cell cultures or experimental animals, including, but not limited to, the determination of the LD₅₀ and the ED₅₀. The dose ratio between the toxic and therapeutic effects is the therapeutic index and it is expressed as the ratio between LD50 and ED₅₀. In some embodiments, the data obtained from cell culture assays and animal studies are used in formulating the therapeutically effective daily dosage range and/or the therapeutically effective unit dosage amount for use in mammals, including humans. In some embodiments, the daily dosage amount of the compounds described herein lies within a range of circulating concentrations that include the ED₅₀ with minimal toxicity. In some embodiments, the daily dosage range and/or the unit dosage amount varies within this range depending upon the dosage form employed and the route of administration utilized. [0137] In any of the aforementioned aspects are further embodiments in which the effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by injection to the mammal; and/or (e) administered topically to the mammal; and/or (f) administered non- systemically or locally to the mammal. [0138] In any of the aforementioned aspects are further embodiments comprising single administrations of the effective amount of the compound, including further embodiments in which (i) the compound is administered once a day; or (ii) the compound is administered to the mammal multiple times over the span of one day. [0139] In any of the aforementioned aspects are further embodiments comprising multiple administrations of the effective amount of the compound, including further embodiments in which (i) the compound is administered continuously or intermittently: as in a single dose; (ii) the time between multiple administrations is every 6 hours; (iii) the compound is administered to the mammal every 8 hours; (iv) the compound is administered to the mammal every 12 hours; (v) the compound is administered to the mammal every 24 hours. In further or alternative embodiments, the method comprises a drug holiday, wherein the administration of the compound is temporarily suspended or the dose of the compound being administered is temporarily reduced; at the end of the drug holiday, dosing of the compound is resumed. In one embodiment, the length of the drug holiday varies from 2 days to 1 year. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0140] In some embodiments, the therapeutic effectiveness of one of the compounds described herein is enhanced by administration of an adjuvant (i.e., by itself the adjuvant has minimal therapeutic benefit, but in combination with another therapeutic agent, the overall therapeutic benefit to the patient is enhanced). Or, in some embodiments, the benefit experienced by a patient is increased by administering one of the compounds described herein with another agent (which also includes a therapeutic regimen) that also has therapeutic benefit. [0141] In some embodiments, different therapeutically-effective dosages of the compounds disclosed herein will be utilized in formulating pharmaceutical composition and/or in treatment regimens when the compounds disclosed herein are administered in combination with one or more additional agent, such as an additional therapeutically effective drug, an adjuvant or the like. Therapeutically-effective dosages of drugs and other agents for use in combination treatment regimens is optionally determined by means similar to those set forth hereinabove for the actives themselves. Furthermore, the methods of prevention/treatment described herein encompasses the use of metronomic dosing, i.e., providing more frequent, lower doses in order to minimize toxic side effects. In some embodiments, a combination treatment regimen encompasses treatment regimens in which administration of a compound described herein, or a pharmaceutically acceptable salt thereof, is initiated prior to, during, or after treatment with a second agent described herein, and continues until any time during treatment with the second agent or after termination of treatment with the second agent. It also includes treatments in which a compound described herein, or a pharmaceutically acceptable salt thereof, and the second agent being used in combination are administered simultaneously or at different times and/or at decreasing or increasing intervals during the treatment period. Combination treatment further includes periodic treatments that start and stop at various times to assist with the clinical management of the patient. [0142] It is understood that the dosage regimen to treat, prevent, or ameliorate the disease(s) for which relief is sought, is modified in accordance with a variety of factors (e.g. the disease or disorder from which the subject suffers; the age, weight, sex, diet, and medical condition of the subject). Thus, in some instances, the dosage regimen actually employed varies and, in some embodiments, deviates from the dosage regimens set forth herein. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO VI. EXAMPLES Detailed Methods [0143] Data Analysis and Statistics. Treatments were randomized, and data were analyzed by experimenters blinded to treatment conditions. Statistical analyses were performed using GraphPad Prism (version 9.1.3) unless noted otherwise. All comparisons were planned prior to performing each experiment. Data are represented as mean ± SEM, unless noted otherwise, with asterisks indicating *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. Materials and Methods [0144] All reagents were obtained from commercial sources and reactions were performed using oven-dried glassware (120 ^C) under an inert N2 atmosphere unless otherwise noted. Air- and moisture-sensitive liquids and solutions were transferred via syringe or stainless- steel cannula. Organic solutions were concentrated under reduced pressure (∼5 Torr) by rotary evaporation. Solvents were purified by passage under 12 psi N2 through activated alumina columns. Chromatography was performed using Fisher Chemical™ Silica Gel Sorbent (230–400 Mesh, Grade 60). Compounds purified by chromatography were typically applied to the adsorbent bed using the indicated solvent conditions with a minimum amount of added dichloromethane as needed for solubility. Thin layer chromatography (TLC) was performed on Merck silica gel 60 F254 plates (250 μm). Visualization of the developed chromatogram was accomplished by fluorescence quenching or by staining with aqueous potassium permanganate or Ehrlich’s reagent. [0145] Nuclear magnetic resonance (NMR) spectra were acquired on a Bruker 400 operating at 400 and 100 MHz for ¹H and ¹³C, respectively, and are referenced internally according to residual solvent signals. Data for ¹H NMR are recorded as follows: chemical shift (δ, ppm), multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; quint, quintet; m, multiplet), coupling constant (Hz), and integration. Data for ¹³C NMR are reported in terms of chemical shift (δ, ppm). Liquid chromatography-mass spectrometry (LC-MS) was performed using a Waters LC-MS with an ACQUITY Arc QDa detector or Waters Alliance 2695 HPLC with a Waters Micromass ZQ Detector. High-resolution mass spectra were obtained using a Thermo Fisher Scientific Q-Exactive HF Orbitrap. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO A. General Methods General procedure 1 for C6/C7 Heck coupling [0146] To a , Pd(dba)₂ (0.10

equiv), and . was DMSO (0.5M), aryl halide (2.0 equiv), and triethylamine (3.5 equiv) were added sequentially. The reaction was stirred at 80 ^C overnight. Once complete, the reaction was poured into a separatory funnel with H2O and extracted with three times EtOAc. The organic extracts were combined, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to afford the Heck-coupled protected tropane compounds. General Procedure 2 for the deprotection-reduction-reductive amination sequence

[0147] To a scintillation vial containing the protected tropane (1.0 equiv) was added MeOH (0.1 M) and hydrazine monohydrate (2.0 equiv). The mixture was stirred for 15 min before adding Raney Nickel (5.0 equiv). The vial was sealed with a septum and equipped with a hydrogen balloon. The mixture was continuously sparged and stirred for 1 h at 45 ^C. Next, the aldehyde (1.1 equiv) was added, and the mixture was further sparged and stirred at 45 ^C for 1 h. The reaction mixture was diluted with DCM and filtered over a pad of celite. The filtrate was then concentrated under reduced pressure and the residue was purified by chromatography on silica gel. General Procedure 3 for the synthesis of aryl azides

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0148] To a solution of the aniline (1.0 equiv) in H₂O (0.4M) at 0°C was added conc. HCl (4M) and stirred for 10 min at 0°C. NaNO2 (1.1 equiv) was dissolved in H2O (4M) and added dropwise to the solution at 0°C. The solution was stirred for 10 min at 0°C before adding NaN3 (1.3 equiv) in three portions. Next, the solution was warmed to room temperature and stirred for 1 hour before extracting with EtOAc (3x). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure to afford essentially pure azides that were used as is in subsequent reactions. General Procedure 4 for the synthesis of triazolines [0149] To an oven tropane (1.0 equiv), the

aryl azide (4.4–10.0 equiv) and anhydrous toluene (0.1M). The vial was purged with N2 and stirred at 100°C for 48 hours. The solution was then cooled to RT, concentrated under reduced pressure, and purified by chromatography on silica gel to afford the triazolines. General Procedure 5 for the synthesis of C6/C7 aziridines [0150] Tropane

(0.05M) and placed in a Rayonet photochemical UV reactor. The solution was irradiated with UV light at room temperature and monitored by TLC until starting material was completely consumed (2–5 hours). The solution was concentrated under reduced pressure to afford essentially pure aziridines. General Procedure 6 for Boc-indole deprotection

[0151] To a vial containing the Boc protected indole (1.0 equiv) was added MeOH (0.2M), THF (0.2M), and 2M LiOH_(aq) (0.2M). The solution was stirred at room temperature until all starting material was consumed (monitored by TLC). DCM (10 mL) was added, and the UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO resulting solution was washed once with 2M NaOH_(aq) (20 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was then purified by chromatography on silica gel to afford the deprotected products. General Procedure 7 for the oxidation of 2-phenylethanols [0152] To a (0.15M) was added

IBX (1.4 equiv). The mixture was stirred at 80°C for 2 h before being cooled to 0°C and filtered. The solid was washed twice with ice cold EtOAc and the filtrate concentrated under reduced pressure. The residue was used as is in subsequent reactions. General Procedure 8 for the synthesis of 3-hydroxy tropanes [0153] To a

was added THF (0.2M), MeOH (0.1M), and 1M LiOH_(aq) (0.2 M) sequentially. The reaction mixture was stirred at room temperature overnight. Upon completion, the reaction was poured into a separatory funnel containing 1M NaOH solution and extracted with DCM (4x). The organic extracts were combined, dried over Na2SO4, and concentrated under reduced pressure to afford the 3-hydroxy-6-phenyltropanes. General Procedure 9 for the Robinson-Schöpf reaction

[0154] 2,5-dimethoxy-2,5-dihydrofuran (mixture of cis/trans) (1.0 equiv) was added to 3M HCl(aq) (0.55M) and stirred for 18 h at room temperature. The solution was cooled to 0°C, neutralized by the addition of 6M NaOH_(aq), and added dropwise to a solution of 3- oxoglutaric acid (1.2 equiv), NaOAc (4.5 equiv), and the alkylamine (1.1 equiv) in H2O (0.3M). The resulting mixture was stirred at 40°C for 16 h before the pH was adjusted to ~11 UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO using 6M NaOH_(aq). The mixture was extracted three times with EtOAc, and the combined organic extracts were dried over Na2SO4 before being concentrated under reduced pressure. The residue was then purified by column chromatography on silica gel to afford the desired tropanes. B. Intermediates (1R,3R,7S)-8-(1,3-dioxoisoindolin-2-yl)-8-azabicyclo[5.1.0]oct-5-en-3-yl benzoate (S3) and (1R,3S,7S)-8-(1,3-dioxoisoindolin-2-yl)-8-azabicyclo[5.1.0]oct-5-en-3-yl benzoate (S4) [0155] Cyclohepta-3-5-dien- of tropone (10.0 g, 94.2 mmol) in

MeOH (235.0 mL, 0.4 M) and water (33.7 mL, 2.8 M) was added NaBH₄ (7.38 g, 195.1 mmol, 2.07 mmol) portion-wise at 0 ^C. The solution was stirred for 5 minutes at 0 ^C, then 3 h at room temperature. Glacial acetic acid (195.1 mmol) was then added, followed by saturated aqueous NaHCO3 (97.5 mmol). The mixture was transferred to a separatory funnel and extracted with DCM (3 x 150 mL). The combined organic extracts were dried over Na2SO4, concentrated under reduced pressure, and purified by chromatography on silica gel with hexanes/EtOAc (3:1) to afford S1 (9.69 g, 93%) as a clear oil.¹H NMR (300 MHz, CDCl3) δ 5.97–5.82 (m, 2H), 5.74–5.59 (m, 2H), 4.28–4.14 (m, 1H), 2.65–2.43 (m, 4H), 1.87 (dd, J = 16.8, 7.9 Hz, 1H).¹³C NMR (76 MHz, CDCl3) δ 128.29, 126.51, 68.45, 39.51; HRMS (ES⁺) calcd for C7H11O [M+H] 111.0810 found 111.0806. [0156] Cyclohepta-3,5-

of benzoic acid (12.2 g, 108.9 mmol, 1.1 equiv) and DMAP (2.04 g, 18.2 mmol, 0.2 equiv) in DCM (227.0 mL) was added S1 (10.0 g, 90.8 mmol, 1.0 equiv). The mixture was stirred vigorously while DCC (20.6 g, 99.9 mmol, 1.1 equiv) was added in portions. The mixture was stirred for 5 h at room UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO temperature. Once complete, the mixture was filtered through a pad of celite. The resulting filtrate was washed with 1 N HCl (2 x 200 mL) and saturated aqueous NaHCO3 (200 mL). The organic layer was dried with Na₂SO₄ and concentrated under reduced pressure. The crude mixture was purified by chromatography on silica gel with Hexanes/EtOAc (95:5) to afford S2 (18.52 g, 95%) as a clear oil.¹H NMR (400 MHz, CDCl₃) δ 8.07–8.00 (m, 2H), 7.59–7.51 (m, 1H), 7.48–7.39 (m, 3H), 5.96–5.88 (m, 2H), 5.79–5.69 (m, 2H), 5.38 (tt, J = 8.1, 4.0 Hz, 1H), 2.78 – 2.59 (m, 4H); ¹³C NMR (101 MHz, CDCl₃) δ 165.87, 132.99, 130.79, 129.73, 128.45, 127.42, 126.86, 73.37, 36.39; HRMS (ES⁺) calcd for C14H15O2 [M+H] 215.1072 found 215.1065. [0157]

5-en-3-yl benzoate (S3) and (1R,3S,7S)-8-(1,3-dioxoisoindolin-2-yl)-8-azabicyclo[5.1.0]oct-5-en-3- yl benzoate (S4). To a suspension of N-amino-phthalimide (0.530 g, 3.27 mmol, 1.4 equiv), K₂CO₃ (0.903 g, 6.53 mmol, 2.8 equiv) and MgO (0.282 g, 7.00 mmol, 3.0 equiv) in DCM (11.7 mL, 0.2 M) was added S2 (0.500 g, 2.33 mmol, 1.0 equiv). The mixture was cooled to 0 °C and stirred vigorously before PhI(OAc)₂ (1.13 g, 3.50 mmol, 1.5 equiv) was added portion wise over 1 h. The reaction mixture was allowed to warm up to room temperature before stirring for 24 h. Once completed, the reaction was filtered over filter paper and rinsed with additional DCM. The organic filtrate was concentrated under reduced pressure and then purified by chromatography on silica gel with DCM/EtOAc (75:1) to afford first S3 (0.343g, 39%) and then S4 (0.377, 43%) as yellow solids. [0158] Compound S3: ¹H NMR (300 MHz, CDCl3) δ 8.10–8.03 (m, 2H), 7.81 (dd, J = 5.5, 3.0 Hz, 2H), 7.71 (dd, J = 5.4, 3.1 Hz, 2H), 7.64–7.56 (m, 1H), 7.52–7.43 (m, 2H), 6.26 (d, J = 9.2 Hz, 1H), 5.75 (dt, J = 10.8, 5.0 Hz, 1H), 5.41–5.30 (m, 1H), 3.18–2.85 (m, 4H), 2.58–2.44 (m, 1H), 2.14–2.00 (m, 1H); ¹³C NMR (76 MHz, CDCl₃) δ 165.91, 165.04, 134.22, 133.20, 130.55, 130.38, 129.77, 128.93, 128.53, 124.19, 123.24, 69.17, 45.39, 44.69, 36.57, 33.77; HRMS (ES⁺) calcd for C₂₂H₁₉N₂O₄ [M+H] 375.1345 found 375.1337. [0159] Compound S4: ¹H NMR (300 MHz, CDCl₃) δ 8.08 – 8.00 (m, 2H), 7.78 (dd, J = 5.5, 3.0 Hz, 2H), 7.68 (dd, J = 5.4, 3.1 Hz, 2H), 7.60–7.52 (m, 1H), 7.48–7.39 (m, 2H), 6.33– UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 6.23 (m, 1H), 5.86 (ddd, J = 11.4, 7.6, 3.9 Hz, 1H), 5.29–5.18 (m, 1H), 3.11–2.98 (m, 2H), 2.88–2.75 (m, 1H), 2.73–2.44 (m, 3H); ¹³C NMR (76 MHz, CDCl3) δ 165.56, 165.11, 134.20, 133.06, 130.60, 130.19, 129.74, 128.48, 125.44, 123.21, 70.53, 47.05, 46.00, 34.07; HRMS (ES⁺) calcd for C22H19N2O4 [M+H] 375.1345 found 375.1328. (1R,3r,5S)-8-(1,3-dioxoisoindolin-2-yl)-8-azabicyclo[3.2.1]oct-6-en-3-yl benzoate (S5)

[0160] (1R,3r,5S)- oct-6-en-3-yl benzoate

(S5). To a 10 mL round bottom flask containing anhydrous sodium bromide (0.110 g, 1.07 mmol, 2.0 equiv), anhydrous copper triflate (0.019 g, 0.053 mmol, 0.1 equiv), and S3 (0.200 g, 0.534 mmol, 1.0 equiv) was added DMF (2.67 mL, 0.2 M). The mixture was heated to 65 °C and stirred vigorously for 24 h. The solvent level was made sure to be lower than the oil bath level. The reaction was monitored by TLC. Once complete, the reaction mixture was cooled to rt and poured into a separatory funnel containing water (100 mL). The aqueous solution was extracted EtOAc (5 x 25 mL). The combined organic extracts were dried over Na2SO4, concentrated under reduced pressure, and then purified by chromatography on silica gel with hexanes/EtOAC (3:1) to afford S5 (0.145, 73%) as a light yellow solid.¹H NMR (400 MHz, CDCl3) δ 8.06–8.00 (m, 2H), 7.76 (dd, J = 5.4, 3.1 Hz, 2H), 7.68 (dd, J = 5.4, 3.1 Hz, 2H), 7.58–7.52 (m, 1H), 7.47–7.40 (m, 2H), 6.26 (s, 2H), 5.18 (p, J = 8.2 Hz, 1H), 4.44 (s, 2H), 2.27 (dd, J = 8.4, 3.0 Hz, 4H).¹³C NMR (101 MHz, CDCl3) δ 166.08, 166.01, 134.09, 133.03, 130.78, 130.50, 130.40, 129.73, 128.45, 123.05, 68.20, 66.61, 32.49. HRMS (ES⁺) m/z [M + H]⁺ Calcd for C22H19N2O4⁺ 375.1345; Found 375.1331. (1R,3s,5S)-8-(1,3-dioxoisoindolin-2-yl)-8-azabicyclo[3.2.1]oct-6-en-3-yl benzoate (S6)

[0161] (1R,3s,5S)-8-

oct-6-en-3-yl benzoate (S6). To a 10 mL round bottom flask containing anhydrous sodium bromide (0.110 g, 1.07 UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO mmol, 2.0 equiv), anhydrous copper triflate (0.039 g, 0.107 mmol, 0.2 equiv), and S4 (0.200 g, 0.534 mmol, 1.0 equiv) was added DMF (2.67 mL, 0.2 M). The mixture was heated to 90 °C and stirred vigorously for 24 h. The solvent level was made sure to be lower than the oil bath level. The reaction was monitored by TLC. Once complete, the reaction mixture was cooled to rt and poured into a separatory funnel containing water (100 mL). The aqueous solution was extracted EtOAc (4 x 25 mL). The combined organic extracts were dried over Na₂SO₄, concentrated under reduced pressure, and then purified by chromatography on neutral alumina with hexanes/EtOAC (3:1) to afford S6 (0.060 g, 30%) as a light yellow solid.¹H NMR (400 MHz, CDCl₃) δ 8.05–7.98 (m, 2H), 7.77 (dd, J = 5.5, 3.0 Hz, 2H), 7.68 (dd, J = 5.4, 3.1 Hz, 2H), 7.60–7.54 (m, 1H), 7.49–7.43 (m, 2H), 6.40 (s, 2H), 5.34 (t, J = 5.9 Hz, 1H), 4.34 (s, 2H), 2.76–2.68 (m, 2H), 2.04–1.97 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 166.19, 165.66, 134.10, 133.35, 132.99, 130.44, 129.66, 128.52, 123.06, 67.18, 66.23, 34.73; HRMS (ES⁺) calcd for C₂₂H₁₉N₂O₄ [M+H] 375.1345 found 375.1331. 2-((1R,5S)-8-azabicyclo[3.2.1]oct-6-en-8-yl)isoindoline-1,3-dione (S8)

[0162] 2-(8-azabicyclo[5.1.0]oct-2-en-8-yl)isoindoline-1,3-dione (S7). Cycloheptadiene (1.15 mL, 10.2 mmol, 1.0 equiv) was added to DCM (25.5 mL, 0.4 M) in a flame dried flask at 0°C. N-aminophthalimide (2.478 g, 15.3 mmol, 1.5 equiv) and K₂CO₃ (4.225 g, 30.6 mmol, 3.0 equiv) were added, then PhI(OAc)2 (5.250 g, 16.3 mmol, 1.6 equiv). The mixture was allowed to slowly warm to room temperature and stirred overnight. Next, the mixture was vacuum filtered, and the filtrate concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel with hexanes/EtOAc (3:1) to afford S7 (1.650 g, 64%) as a yellow solid.¹H NMR (400 MHz, CDCl3) δ 7.81–7.73 (m, 2H), 7.71–7.64 (m, 2H), 6.15 (ddd, J = 11.0, 5.1, 2.8 Hz, 1H), 5.93 (ddd, J = 11.0, 7.1, 3.2 Hz, 1H), 3.07 (dt, J = 8.3, 4.1 Hz, 1H), 2.91 (dd, J = 8.3, 4.9 Hz, 1H), 2.55 (dq, J = 14.5, 4.9 Hz, 1H), 2.38–2.23 (m, 1H), 2.14–2.00 (m, 2H), 1.75–1.62 (m, 2H) ppm; ¹³C NMR (101 MHz, CDCl3) δ 165.08, 137.06, 133.95, 130.54, 123.36, 122.93, 52.10, 47.82, 31.07, 29.05, 23.75 ppm; LRMS (ES⁺) calcd for C₁₅H₁₄N₂O₂ [M+H] 255.11 found 255.25. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0163] 2-((1R,5S)-8-

1,3-dione (S8). Cu(hfacac)₂ hydrate (0.141 g, 0.295 mmol, 0.1 equiv) was dried under reduced pressure in a microwave vial for 2 h before adding S7 (0.750 g, 2.95 mmol, 1.0 equiv) in toluene (15 mL, 0.2 M). The solution was stirred under N₂ at 150°C for 6 h before being filtered through a pad of celite/neutral alumina/silica. The pad was washed with 3:1 hexane/EtOAc to elute the crude product. The filtrate was concentrated under reduced pressure and the resulting residue was purified by chromatography on silica gel with hexanes/EtOAc (3:1) to afford S8 (0.487 g, 65%) as a yellow solid.¹H NMR (400 MHz, CDCl₃) δ 7.79–7.77 (m, 2H), 7.71–7.64 (m, 2H), 6.16 (s, 2H), 4.29 (s, 2H), 2.16–2.02 (m, 2H), 1.71–1.54 (m, 2H), 1.53–1.41 (m, 3H) ppm; ¹³C NMR (101 MHz, CDCl₃) 166.21, 133.79, 130.40, 129.79, 122.78, 68.07, 26.07, 15.94 ppm; LRMS (ES⁺) calcd for C15H14N2O2 [M+H] 255.11 found 255.44. C. Examples Example 1: (1S,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octane (1)

[0164] 2-((1S,5R,6R)-6-phenyl-8-azabicyclo[3.2.1]octan-8-yl)isoindoline-1,3-dione (1a). Synthesized from S8 (0.106 g, 0.417 mmol) and iodobenzene (0.100 mL, 0.834 mmol) with Pd(dba)₂ (0.024 g, 0.042 mmol), HCO₂Na (0.086 g, 1.25 mmol), and triethylamine (0.2 mL, 1.46 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (3:1) to afford 1a (0.110 g, 81%) as a yellow solid.¹H NMR (300 MHz, CDCl3) δ 7.78–7.70 (m, 2H), 7.69–7.62 (m, 2H), 6.14 (s, 2H), 4.30–4.23 (m, 2H), 2.15–2.00 (m, 2H), 1.69–1.40 (m, 5H) ppm; LRMS (ES⁺) calcd for C21H21N2O2 [M+H] 333.16 found 333.03.

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0165] (1S,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octane (1). Synthesized from 1a (0.110 g, 0.263 mmol) with Raney Nickel (0.141 mg, 1.66 mmol), hydrazine monohydrate (0.033 g, 0.662 mmol), and 37% formaldehyde (0.030 g, 0.364 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with DCM/MeOH (98:2) plus 2% NH₃OH and 2% DMS to afford 1 (0.024 g, 37%, >99% purity by UHPLC) as a clear oil.¹H NMR (300 MHz, CDCl₃) δ 7.41–7.35 (m, 2H), 7.31–7.23 (m, 3H), 7.19–7.12 (m, 1H), 3.33–3.27 (m, 1H), 3.25–3.17 (m, 2H), 2.47 (s, 3H), 2.26–2.08 (m, 2H), 2.05–1.89 (m, 2H), 1.87–1.53 (m, 3H), 1.32–1.12 (m, 2H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 128.40, 127.01, 125.67, 66.44, 60.35, 47.58, 38.41, 35.99, 25.27, 24.60, 17.43 ppm; LRMS (ES⁺) calcd for C14H20N [M+H] 202.16 found 202.24. Example 2: (1S,5R,6R)-6-(2-methoxyphenyl)-8-methyl-8-azabicyclo[3.2.1]octane (2)

[0166] 2-((1S,5R,6R)-6-(2-methoxyphenyl)-8-azabicyclo[3.2.1]octan-8-yl)isoindoline- 1,3-dione (2a). Synthesized from S8 (0.134 g, 0.527 mmol) and 2-iodoanisole (0.247 g, 1.05 mmol) with Pd(dba)₂ (0.030 g, 0.053 mmol), HCO₂Na (0.108 g, 1.58 mmol), and triethylamine (0.187 g, 1.85 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (6:1) to afford 2a (0.117 g, 61%) as an orange solid.¹H NMR (400 MHz, CDCl3) δ 7.75– 7.69 (m, 2H), 7.67–7.62 (m, 2H), 7.60 (d, J = 7.7 Hz, 1H), 7.08 (td, J = 7.8, 1.6 Hz, 1H), 6.83–6.77 (m, 2H), 4.44–4.36 (m, 1H), 3.88 (s, 1H), 3.82 (s, 3H), 3.78 – 3.68 (m, 2H), 2.62 (dt, J = 12.8, 6.3 Hz, 1H), 2.33 – 2.21 (m, 2H), 2.20 – 2.10 (m, 1H), 2.02–1.87 (m, 1H), 1.78– 1.64 (m, 2H), 1.59–1.50 (m, 1H) ppm; ¹³C NMR (101 MHz, CDCl3) δ 167.16, 156.89, 134.59, 133.89, 130.53, 126.74, 126.17, 122.75, 120.52, 109.96, 68.37, 60.40, 55.45, 39.35, 36.40, 30.50, 30.47, 17.05 ppm; LRMS (ES⁺) calcd for C22H24N2O3 [M+H] 363.17 found 363.32. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0167] (1S,5R,6R)-6-(2- 8-azabicyclo[3.2.1]octane (2).

Synthesized from 2a (0.117 g, 0.324 Nickel (0.138 g, 1.62 mmol), hydrazine monohydrate (0.032 g, 0.647 mmol), and 37% formaldehyde (0.011 g, 0.356 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH₃OH to afford 2 (0.042 mg, 56%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 7.6, 1.3 Hz, 1H), 7.19–7.11 (m, 1H), J = 7.5

Hz, 1H), 6.83 (d, J = 8.1 Hz, 1H), 3.84 (s, 3H), 3.57 (dd, J = 8.8, 6.6 Hz, 1H), 3.31 (s, 1H), 3.19 (s, 1H), 2.46 (s, 3H), 2.21–2.08 (m, 2H), 2.01–1.77 (m, 4H), 1.63–1.55 (m, 1H), 1.43– 1.35 (m, 1H), 1.28–1.20 (m, 1H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 157.04, 126.53, 126.12, 120.71, 110.15, 66.17, 60.85, 55.51, 40.22, 17.32 ppm; LRMS (ES⁺) calcd for C₁₅H₂₂NO [M+H] 232.17 found 232.24. Example 3: (1S,5R,6R)-6-(3-methoxyphenyl)-8-methyl-8-azabicyclo[3.2.1]octane (3)

[0168] 2-((1S,5R,6R)-6-(3-methoxyphenyl)-8-azabicyclo[3.2.1]octan-8-yl)isoindoline- 1,3-dione (3a). Synthesized from S8 (0.060 g, 0.236 mmol) and 3-iodoanisole (0.110 g, 0.472 mmol) with Pd(dba)2 (0.014 g, 0.0235 mmol), HCO2Na (0.048 g, 0.738 mmol), and triethylamine (0.084 g, 0.826 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (6:1) to afford 3a (0.078 g, 91%) as an orange solid.¹H NMR (300 MHz, CDCl₃) δ 7.82 – 7.74 (m, 2H), 7.73 – 7.65 (m, 2H), 7.30–7.27 (m, 1H), 7.07–7.01 (m, 1H), 6.74–6.66 (m, 2H), 4.21–4.10 (m, 1H), 3.81 (s, 3H), 3.27 (dd, J = 9.7, 5.3 Hz, 1H), 2.52–2.18 (m, 4H), 2.04–1.72 (m, 2H), 1.55–1.41 (m, 2H). ¹³C NMR (76 MHz, CDCl3) δ 168.00, 160.01, 149.25, 134.10, 130.46, 129.14, 122.98, 119.81, 112.29, 112.11, 67.45, 60.04, 55.45, 46.95, 38.70, 28.99, 16.97. LRMS (ES⁺) calcd for C22H24N2O3 [M+H] 363.17 found 363.20. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0169] (1S,5R,6R)-6-(3- 8-azabicyclo[3.2.1]octane (3).

Synthesized from 3a (0.118 g, 0.326 Nickel (0.139 g, 1.63 mmol), hydrazine monohydrate (0.033 g, 0.651 mmol), and 37% formaldehyde (0.029 mg, 0.358 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with DCM/MeOH (30:1) plus 2% NH3OH and 2% DMS to afford 3 (0.036 g, 48%, >99% purity by UHPLC) as a clear oil.¹H NMR (300 MHz, CDCl₃) δ 7.22–7.15 (m, 1H), 7.00–6.94 (m, 2H), 6.74–6.68 (m, 1H), 3.80 (s, 3H), 3.29 (s, 1H), 3.25–3.14 (m, 2H), 2.46 (s, 3H), 2.19–2.12 (m, 2H), 2.04– 1.88 (m, 2H), 1.85–1.53 (m, 3H), 1.31–1.13 (m, 2H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 159.73, 150.43, 129.26, 119.45, 113.09, 110.66, 66.41, 60.32, 55.27, 47.58, 38.24, 36.09, 25.38, 24.70, 17.41 ppm; LRMS (ES⁺) calcd for C₁₅H₂₂NO [M+H] 232.1 found 232.24. Example 4: (1S,5R,6R)-6-(4-methoxyphenyl)-8-methyl-8-azabicyclo[3.2.1]octane (4) [0170] 2-((1S,5R,6R)-6-(4-

[3.2.1]octan-8-yl)isoindoline- 1,3-dione (4a). Synthesized from S8 (0.050 g, 0.197 mmol) and 4-iodoanisole (0.092 g, 0.393 mmol) with Pd(dba)2 (0.011 mg, 0.0197 mmol), HCO2Na (0.040 g, 0.590 mmol), and triethylamine (0.070 g, 0.688 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (4:1) to afford 4a (0.050 g, 70%) as an orange solid.¹H NMR (400 MHz, CDCl₃) δ 7.77 (dd, J = 5.5, 3.1 Hz, 2H), 7.68 (dd, J = 5.4, 3.1 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H), 6.80 (d, J = 8.7 Hz, 2H), 4.21–4.15 (m, 1H), 3.80 (s, 1H), 3.75 (s, 3H), 3.24 (dd, J = 9.8, 5.1 Hz, 1H), 2.48– 2.38 (m, 1H), 2.39–2.17 (m, 3H), 2.01–1.86 (m, 1H), 1.83–1.72 (m, 1H), 1.55 (dd, J = 13.2, 5.4 Hz, 1H), 1.46 (dd, J = 13.1, 5.5 Hz, 1H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 167.94, 157.89, 139.72, 134.07, 130.47, 128.19, 122.92, 113.76, 67.73, 60.03, 55.36, 45.92, 38.73, 29.57, 29.04, 16.98 ppm; LRMS (ES⁺) calcd for C₂₂H₂₄N₂O₃ [M+H] 363.17 found 363.32. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0171] (1S,5R,6R)-6-(4- 8-azabicyclo[3.2.1]octane (4).

Synthesized from 4a (0.104 g, Nickel (0.123 g, 1.43 mmol), hydrazine monohydrate (0.030 g, 0.573 mmol), and 37% formaldehyde (0.009 g, 0.316 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH₃OH to afford 4 (0.041 g, 61%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl3) δ 7.29 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 3.78 (s, 3H), 3.29 (s, 1H), 3.21–3.13 (m, 2H), 2.47 (s, 3H), 2.22–2.06 (m, 2H), 2.04–1.90 (m, 3H), 1.84–1.68 (m, 2H), 1.64–1.54 (m, 1H), 1.30–1.21 (m, 1H), 1.21–1.13 (m, 1H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 157.64, 140.76, 127.82, 113.71, 66.62, 60.39, 55.35, 46.63, 38.42, 36.04, 25.26, 24.61, 17.34 ppm; LRMS (ES⁺) calcd for C15H22NO [M+H] 232.17 found 232.24. Example 5: (1S,5R,6R)-6-(2-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane (5) [0172] 2-((1S,5R,6R)-6-(2-

[3.2.1]octan-8-yl)isoindoline-1,3- dione (5a). Synthesized from S8 (0.050 g, 0.197 mmol) and 2-fluoro-iodobenzene (0.087 g, 0.393 mmol) with Pd(dba)₂ (0.011 g, 0.020 mmol), HCO₂Na (0.040 g, 0.590 mmol), and triethylamine (0.070 g, 0.688 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (4:1) to afford 5a (0.040 g, 58%) as an orange solid.¹H NMR (400 MHz, CDCl3) δ 7.81 (td, J = 7.8, 1.5 Hz, 1H), 7.76 (dd, J = 5.5, 3.1 Hz, 2H), 7.68 (dd, J = 5.4, 3.1 Hz, 2H), 7.14–7.06 (m, 1H), 7.06–6.99 (m, 1H), 6.99–6.91 (m, 1H), 4.30–4.22 (m, 1H), 3.87 (s, 1H), 3.67 (dd, J = 9.9, 5.3 Hz, 1H), 2.50 (dt, J = 12.4, 6.1 Hz, 1H), 2.39–2.27 (m, 2H), 2.26–2.15 (m, 1H), 2.03–1.88 (m, 1H), 1.83–1.72 (m, 1H), 1.63 (dd, J = 13.0, 4.8 Hz, 1H), 1.51 (dd, J = 13.2, 5.0 Hz, 1H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 167.61, 134.10, 130.45, 127.89, 127.85, 127.38, 127.30, 124.30, 124.27, 122.94, 114.88, 114.65, 67.36, 60.12, 38.24, 37.11, 29.83, 29.59, 16.92 ppm; LRMS (ES⁺) calcd for C₂₁H₂₀FN₂O₂ [M+H] 351.15 found 351.23. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0173] (1S,5R,6R)-6-(2- 8-azabicyclo[3.2.1]octane (5).

Synthesized from 5a (0.050 g, 0.144 Nickel (0.062 g, 0.723 mmol), hydrazine monohydrate (0.015 g, 0.290 mmol), and 37% formaldehyde (0.005 g, 0.159 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH3OH to afford 5 (0.018 g, 57%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl₃) δ 7.54 (td, J = 7.7, 1.8 Hz, 1H), 7.16–7.04 (m, 2H),

3.53 (dd, J = 9.1, 6.0 Hz, 1H), 3.35–3.28 (m, 1H), 3.21 (s, 1H), 2.49 (s, 3H), 2.23–2.08 (m, 2H), 2.04–1.92 (m, 2H), 1.89–1.74 (m, 1H), 1.66–1.56 (m, 1H), 1.37–1.28 (m, 1H), 1.24– 1.16 (m, 1H) ppm; ¹³C NMR (101 MHz, CDCl3) δ 161.81, 159.39, 135.01, 134.86, 127.52, 127.48, 127.03, 126.95, 124.27, 124.23, 114.96, 114.73, 65.77, 60.26, 39.28, 39.25, 36.75, 36.02, 25.10, 24.68, 17.30 ppm; LRMS (ES⁺) calcd for C14H20FN [M+H] 220.15 found 220.21. Example 6: (1S,5R,6R)-6-(3-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane (6) [0174] 2-((1S,5R,6R)-6-(3-

[3.2.1]octan-8-yl)isoindoline-1,3- dione (6a). Synthesized from S8 (0.060 g, 0.236 mmol) and 3-fluoro-iodobenzene (0.105 g, 0.472 mmol) with Pd(dba)₂ (0.014 g, 0.024 mmol), HCO₂Na (0.048 g, 0.738 mmol), and triethylamine (0.084 g, 0.826 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (6:1) to afford 6a (0.078 g, 91%) as an orange solid.¹H NMR (300 MHz, CDCl3) δ 7.82– 7.75 (m, 2H), 7.74–7.66 (m, 2H), 7.48–7.38 (m, 1H), 7.30–7.26 (m, 1H), 7.24–7.13 (m, 1H), 6.83 (td, J = 8.2, 1.5 Hz, 1H), 4.19–4.10 (m, 1H), 3.80 (s, 1H), 3.27 (dd, J = 9.8, 5.1 Hz, 1H), 2.49–2.18 (m, 4H), 2.03–1.73 (m, 2H), 1.61–1.55 (m, 1H), 1.51–1.41 (m, 1H), 1.32–1.21 (m, 1H) ppm; ¹³C NMR (76 MHz, CDCl3) δ 168.03, 134.18, 130.39, 129.65, 129.55, 123.04, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 114.39, 112.74, 67.33, 59.92, 46.56, 38.51, 29.45, 28.84, 16.95 ppm; LRMS (ES⁺) calcd for C21H20FN2O2 [M+H] 351.15 found 351.23.

[0175] (1S,5R,6R)-6-(3- - 8-azabicyclo[3.2.1]octane (6). Synthesized from 6a (0.092 g, 0.263 mmol) with Raney Nickel (0.113 g, 1.31 mmol), hydrazine monohydrate (0.026 g, 0.525 mmol), and 37% formaldehyde (0.009 g, 0.289 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH3OH to afford 6 (0.034 g, 58%, 93% purity by UHPLC) as a clear oil.¹H NMR (300 MHz, CDCl₃) δ 7.25–7.09 (m, 3H), 6.84 (ddt, J = 9.7, 8.1, 1.9 Hz, 1H), 3.33–3.26 (m, 1H), 3.21–3.14 (m, 2H), 2.48 (s, 3H), 2.24–1.89 (m, 4H), 1.85–1.54 (m, 3H), 1.29–1.10 (m, 2H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 129.60, 122.72, 113.73, 112.36, 66.33, 59.99, 47.49, 38.73, 35.44, 24.66, 24.02, 17.44 ppm; LRMS (ES⁺) calcd for C14H20FN [M+H] 220.15 found 220.14. Example 7: (1S,5R,6R)-6-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane (7)

[0176] 2-((1S,5R,6R)-6-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-8-yl)isoindoline-1,3- dione (7a). Synthesized from S8 (0.050 g, 0.197 mmol) and 4-fluoro-iodobenzene (0.087 g, 0.393 mmol) with Pd(dba)2 (0.011 g, 0.0197 mmol), HCO2Na (0.040 g, 0.590 mmol), and triethylamine (0.070 g, 0.688 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (4:1) to afford 7a (0.060 g, 86%) as an orange solid.¹H NMR (400 MHz, CDCl₃) δ 7.78 (dd, J = 5.5, 3.0 Hz, 2H), 7.70 (dd, J = 5.4, 3.1 Hz, 2H), 7.59–7.50 (m, 2H), 6.98–6.89 (m, 2H), 4.17–4.11 (m, 1H), 3.76 (s, 1H), 3.25 (dd, J = 9.7, 5.1 Hz, 1H), 2.44–2.20 (m, 4H), 2.01–1.86 (m, 1H), 1.85–1.74 (m, 1H), 1.60–1.50 (m, 1H), 1.46 (dd, J = 13.3, 5.8 Hz, 1H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 168.07, 143.29, 134.19, 130.40, 128.76, 128.69, 122.99, 115.12, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 114.91, 67.50, 59.95, 46.02, 38.72, 29.37, 28.80, 16.95 ppm; LRMS (ES⁺) calcd for C21H20FN2O2 [M+H] 351.15 found 351.17. [0177] (1S,5R,6R)-6-(4-

- 8-azabicyclo[3.2.1]octane (7). Synthesized from 7a (0.104 g, 0.297 mmol) with Raney Nickel (0.123 g, 1.43 mmol), hydrazine monohydrate (0.030 g, 0.574mmol), and 37% formaldehyde (0.010 g, 0.316 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH3OH to afford 7 (0.040 g, 61%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl₃) δ 7.37–7.30 (m, 2H), 6.99–6.89 (m, 2H), 3.33–3.26 (m, 1H),

(m, 2H), 2.48 (s, 3H), 2.23–2.13 (m, 1H), 2.10–1.91 (m, 3H), 1.84–1.69 (m, 1H), 1.64–1.54 (m, 1H), 1.26–1.09 (m, 2H) ppm; ¹³C NMR (101 MHz, CDCl₃) δ 162.42, 160.00, 144.67, 144.64, 128.39, 128.32, 115.04, 114.84, 66.48, 60.01, 46.96, 39.13, 35.32, 24.48, 23.87, 17.45 ppm; LRMS (ES⁺) calcd for C₁₄H₂₀FN [M+H] 220.15 found 220.11. Example 8: (1R,2R,4S,5S)-9-methyl-3-phenyl-3,9-diazatricyclo[3.3.1.0^2,4]nonane (8) [0178] Azidobenzene (8a).

the General Procedure 3 for the synthesis of aryl azides using aniline (1.47 mL, 16.1 mmol, 1.0 equiv), H₂O (40 mL, 0.4M), conc. HCl (4 mL, 4M), NaNO2 (1.22 g, 17.7 mmol, 1.1 equiv) in H2O (4 mL, 4M), and NaN3 (1.361 g, 20.9 mmol, 1.3 equiv).¹H NMR (400 MHz, CDCl₃): δ 7.40–7.35 (m, 2H), 7.23–7.15 (m, 1H), 7.12–7.03 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 140.05, 129.80, 124.91, 119.07 ppm.

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0179] 2-((3aS,4S,8R,8aR)-1-phenyl-1,3a,4,5,6,7,8,8a-octahydro-4,8- epiminocyclohepta[d][1,2,3]triazol-9-yl)isoindoline-1,3-dione (8b). Synthesized from S8 (0.100 g, 0.393 mmol, 1.0 equiv), 8a (0.468 g, 3.93 mmol, 10.0 equiv), and toluene (3.9 mL, 0.1M) following the General Procedure 4 for the synthesis of triazolines. The product was purified using hexanes/EtOAc (2:1) to afford 8b (0.082 g, 56%) as a yellow solid.¹H NMR (400 MHz, CDCl3): δ 7.79–7.72 (m, 2H), 7.72–7.64 (m, 2H), 7.42–7.26 (m, 4H), 7.03 (t, J = 7.1 Hz, 1H), 4.95 (d, J = 10.1 Hz, 1H), 4.28 (s, 1H), 4.24 (d, J = 10.1 Hz, 1H), 4.04 (s, 1H), 2.51–2.29 (m, 2H), 2.03–1.92 (m, 1H), 1.81–1.59 (m, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 167.39, 140.10, 134.16, 130.02, 129.44, 123.02, 122.15, 114.52, 83.94, 63.67, 61.93, 59.08, 26.00, 25.46, 17.20 ppm; LRMS (ES⁺) calcd for C21H19N5O2 [M-N2+H] 346.16 found 346.16. [0180] 2-((1R,2S,4R,5S)-3-phenyl- ^2,4

[3.3.1.0 ]nonan-9-yl)isoindoline- 1,3-dione (8c). Synthesized from 8b (0.038 g, 0.102 mmol) and acetone (2.0 mL, 0.05 M) using the General Procedure 5 for the synthesis of C6/C7 aziridines to afford 8c (0.035 g, 99%) as a brown solid that was used without further purification.¹H NMR (400 MHz, CDCl3): δ 7.70–7.62 (m, 2H), 7.61–7.53 (m, 2H), 7.26–7.18 (m, 2H), 7.05–6.99 (m, 2H), 6.94–6.88 (m, 1H), 4.58–4.47 (m, 2H), 2.95 (s, 2H), 2.21–2.08 (m, 2H), 1.85–1.71 (m, 3H), 1.57–1.48 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 165.03, 152.62, 133.29, 130.63, 128.85, 122.41, 121.74, 120.78, 60.80, 43.53, 28.38, 16.72 ppm; LRMS (ES⁺) calcd for C21H19N3O2 [M+H] 346.16 found 346.19.

[0181] (1R,2R,4S,5S)-9-methyl-3-phenyl-3,9-diazatricyclo[3.3.1.0^2,4]nonane (8). Synthesized from 8c (0.059 g, 0.171 mmol, 1.0 equiv), hydrazine monohydrate (0.025 mL, 0.256 mmol, 1.5 equiv), Raney Ni (0.020 g, 0.342 mmol, 2.0 equiv), 37% CH₂O_(aq) (0.014 mL, 0.188 mmol, 1.1 equiv), and MeOH (1.7 mL, 0.1 M) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The product was purified by chromatography on silica gel using DCM/MeOH/NH₄OH (9:1:0.1) to afford 8 (0.026 g, 71%, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO >99% purity by UHPLC) as a tan solid.¹H NMR (400 MHz, CDCl₃): δ 7.22 (t, J = 7.7 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.93 (t, J = 7.4 Hz, 1H), 3.35 (s, 2H), 2.82 (s, 2H), 2.63 (s, 3H), 2.08–1.94 (m, 2H), 1.88–1.73 (m, 1H), 1.49 (dt, J = 13.9, 6.6 Hz, 1H), 1.37 (dd, J = 13.8, 6.8 Hz, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 153.17, 128.80, 121.73, 120.78, 57.91, 44.01, 36.29, 21.85, 16.66 ppm; LRMS (ES⁺) calcd for C₁₄H₁₈N₂ [M+H] 215.16 found 215.24. Example 9: (1R,2R,4S,5S)-9-methyl-3-(pyridin-3-yl)-3,9-diazatricyclo[3.3.1.0^2,4]nonane (9) [0182] 3-azidopyridine (9a).

the General Procedure 3 for the synthesis of aryl azides using 3-aminopyridine (1.00 g, 10.6 mmol, 1.0 equiv), H₂O (26.6 mL, 0.4M), conc. HCl (2.7 mL, 4M), NaNO2 (0.807 g, 11.7 mmol, 1.1 equiv) in H2O (2.7 mL, 4M), and NaN₃ (0.898 g, 13.8 mmol, 1.3 equiv).¹H NMR (400 MHz, CDCl₃): δ 8.41–8.31 (m, 2H), 7.36–7.30 (m, 1H), 7.30–7.23 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 146.02, 141.31, 137.06, 125.83, 124.08 ppm. [0183] 2-((3aS,4S,8R,8aR)-1-

octahydro-4,8- epiminocyclohepta[d][1,2,3]triazol-9-yl)isoindoline-1,3-dione (9b). Synthesized from S8 (0.050 g, 0.197 mmol, 1.0 equiv), 9a (0.237 g, 1.97 mmol, 10.0 equiv), and toluene (2.0 mL, 0.1M) following the General Procedure 4 for the synthesis of triazolines. The product was purified using hexanes/EtOAc (1:2) to afford 9b (0.063 g, 85%) as a yellow solid.¹H NMR (400 MHz, CDCl3): δ 8.44 (d, J = 2.8 Hz, 1H), 8.30 (d, J = 4.0 Hz, 1H), 7.90–7.84 (m, 1H), 7.79–7.73 (m, 2H), 7.73–7.65 (m, 2H), 7.31 (dd, J = 8.3, 4.0 Hz, 1H), 5.02 (d, J = 9.9 Hz, 1H), 4.31–4.20 (m, 2H), 3.98 (s, 1H), 2.55–2.42 (m, 1H), 2.43–2.31 (m, 1H), 2.07–1.95 (m, 1H), 1.82–1.62 (m, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 167.43, 143.50, 136.72, 135.46, 134.27, 129.91, 124.16, 123.11, 122.16, 85.02, 63.58, 61.67, 58.62, 26.12, 25.52, 17.17 ppm; LRMS (ES⁺) calcd for C₂₀H₁₈N₆O₂ [M-N₂+H] 347.15 found 347.33. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0184] 2-((1R,2S,4R,5S)-3-

[3.3.1.0^2,4]nonan-9- yl)isoindoline-1,3-dione (9c). Synthesized from 9b (0.100 g, 0.267 mmol) and acetone (5.3 mL, 0.05 M) using the General Procedure 5 for the synthesis of C6/C7 aziridines to afford 9c (0.091 g, 98%) as a yellow solid that was used without further purification.¹H NMR (400 MHz, CDCl₃): δ 8.33 (d, J = 2.6 Hz, 1H), 8.18 (dd, J = 4.7, 1.6 Hz, 1H), 7.71–7.64 (m, 2H), 7.63–7.55 (m, 2H), 7.32 (ddd, J = 8.2, 2.7, 1.5 Hz, 1H), 7.12 (dd, J = 8.2, 4.6 Hz, 1H), 4.58– 4.46 (m, 2H), 2.98 (s, 2H), 2.23–2.10 (m, 2H), 1.85–1.73 (m, 3H), 1.59–1.49 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 165.04, 148.44, 143.17, 143.15, 133.42, 130.54, 127.90, 123.38, 122.48, 60.77, 43.38, 28.24, 16.67 ppm; LRMS (ES⁺) calcd for C₂₀H₁₈N₄O₂ [M+H] 347.15 found 347.24. Me N

[0185] (1R,2R,4S,5S)-9-methyl-3-(pyridin-3-yl)-3,9-diazatricyclo[3.3.1.0^2,4]nonane (9). Synthesized from 9c (0.087 g, 0.251 mmol, 1.0 equiv), hydrazine monohydrate (0.040 mL, 0.377 mmol, 1.5 equiv), Raney Ni (0.029 g, 0.502 mmol, 2.0 equiv), 37% CH₂O_(aq) (0.021 mL, 0.276 mmol, 1.1 equiv), and MeOH (2.5 mL, 0.1 M) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The product was purified by chromatography on silica gel using DCM/MeOH/NH4OH (9:1:0.1) to afford 9 (0.032 g, 59%, >99% purity by UHPLC) as a tan solid.¹H NMR (400 MHz, CDCl₃): δ 8.29 (d, J = 2.7 Hz, 1H), 8.14 (dd, J = 4.7, 1.5 Hz, 1H), 7.22 (ddd, J = 8.2, 2.8, 1.5 Hz, 1H), 7.09 (dd, J = 8.1, 4.6 Hz, 1H), 3.30–3.23 (m, 2H), 2.80 (s, 2H), 2.47 (s, 3H), 1.96–1.85 (m, 2H), 1.84–1.70 (m, 1H), 1.51–1.42 (m, 1H), 1.34–1.24 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 149.25, 142.76, 142.65, 127.06, 123.21, 56.61, 43.63, 34.43, 20.70, 16.78 ppm; LRMS (ES⁺) calcd for C13H17N3 [M+H] 216.16 found 216.17. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO Example 10: (1R,2R,4S,5S)-3-(1H-indol-5-yl)-9-methyl-3,9- diazatricyclo[3.3.1.0^2,4]nonane (10)

containing 5-bromoindole (0.500 g, 1.688 mmol, 1.0 equiv), L-proline (0.039 g, 0.338 mmol, 0.2 equiv), NaN3 (0.165 g, 2.53 mmol, 1.5 equiv), Na2CO3 (0.036 g, 0.338 mmol, 0.2 equiv) was added DMF/H₂O (2:1) (0.3M). Next, sodium-L-ascorbate (0.167 g, 0.844 mmol, 0.5 equiv) and CuSO4·5H2O (0.084 g, 0.338 mmol.0.2 equiv) were added. The solution was stirred at 85°C for 17 hours before being cooled to room temperature. To the solution was added 30% NH4OH(aq) (40 mL) before being extracted with Et2O (3 x 30 mL). The combined organic extracts were washed once with saturated NH₄Cl_(aq) (40 mL), dried over Na₂SO₄, and concentrated under reduced pressure. The residue was dissolved in 2:1 hexanes/DCM (~5 mL) and loaded onto a pad of silica. The pad was washed with 2:1 hexanes/DCM (250 mL) and the filtrate concentrated under reduced pressure to afford a brown solid. [0187] The solid (0.370 g) was dissolved in DCM (23.4 mL, 0.1 M) before adding NEt3 (0.39 mL, 2.81 mmol, 1.2 equiv), DMAP (0.014 g, 0.12 mmol, 0.05 equiv), and Boc₂O (0.561 g, 2.57 mmol, 1.1 equiv). The solution was stirred for 1 h at room temperature, then washed once with sat. NaHCO_3(aq) before being dried over Na₂SO₄ and concentrated under reduced pressure. The product was purified by column chromatography on silica gel using 4:1 hexanes/DCM to afford 10a (0.455 g, 69% over two steps) as a tan solid.¹H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.8 Hz, 1H), 7.64 (d, J = 3.8 Hz, 1H), 7.24 (d, J = 2.3 Hz, 1H), 7.00 (dd, J = 8.8, 2.3 Hz, 1H), 6.54 (d, J = 3.8 Hz, 1H), 1.70 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 149.48, 134.81, 132.67, 131.63, 127.31, 116.27, 115.71, 110.62, 106.77, 84.00, 28.19 ppm.

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0188] tert-butyl 5-((3aS,4S,8R,8aR)-9-(1,3-dioxoisoindolin-2-yl)-4,5,6,7,8,8a- hexahydro-4,8-epiminocyclohepta[d][1,2,3]triazol-1(3aH)-yl)-1H-indole-1-carboxylate (10b). Synthesized from S8 (0.100 g, 0.393 mmol, 1.0 equiv), 10a (0.450 g, 1.74 mmol, 4.4 equiv), and toluene (3.9 mL, 0.1M) following the General Procedure 4 for the synthesis of triazolines. The product was purified using hexanes/EtOAc (2:1) to afford 10b (0.093 g, 46%) as a brown solid.¹H NMR (400 MHz, CDCl3): δ 8.15–8.04 (m, 1H), 7.75–7.70 (m, 2H), 7.70–7.64 (m, 2H), 7.62–7.56 (m, 1H), 7.43–7.36 (m, 2H), 6.54 (d, J = 3.8 Hz, 1H), 4.95 (d, J = 10.1 Hz, 1H), 4.36–4.25 (m, 2H), 4.09 (s, 1H), 2.49–2.27 (m, 2H), 2.03–1.92 (m, 1H), 1.85–1.63 (m, 12H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 167.37, 149.66, 135.92, 134.11, 131.30, 130.02, 126.79, 122.99, 115.98, 112.79, 107.30, 106.28, 83.72, 63.94, 61.94, 59.76, 28.21, 26.10, 25.57, 17.23 ppm; LRMS (ES⁺) calcd for C₂₈H₂₈N₆O₄ [M-N₂+H] 485.22 found 485.13. [0189] tert-butyl 5-(

2-yl)-3,9- diazatricyclo[3.3.1.0^2,4]nonan-3-yl)-1H-indole-1-carboxylate (10c). Synthesized from 10b (0.090 g, 0.176 mmol) and acetone (3.5 mL, 0.05 M) using the General Procedure 5 for the synthesis of C6/C7 aziridines to afford 10c (0.085 g, >99%) as a brown solid that was used without further purification.¹H NMR (400 MHz, CDCl₃): δ 7.95 (d, J = 7.7 Hz, 1H), 7.70– 7.62 (m, 2H), 7.59–7.51 (m, 3H), 7.13 (d, J = 2.2 Hz, 1H), 7.05 (dd, J = 8.8, 2.3 Hz, 1H), 6.45 (d, J = 3.8 Hz, 1H), 4.60–4.50 (m, 2H), 2.97 (s, 2H), 2.22–2.09 (m, 2H), 1.83–1.75 (m, 3H), 1.66 (s, 9H), 1.57–1.47 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 165.07, 149.72, 148.07, 133.26, 131.04, 130.67, 126.39, 122.38, 118.39, 115.35, 111.51, 106.97, 83.41, 60.85, 43.88, 28.41, 28.20, 16.73 ppm; LRMS (ES⁺) calcd for C28H28N4O4 [M+H] 485.22 found 485.24.

[0190] tert-butyl 5-((1R,2R,4S,5S)-9-methyl-3,9-diazatricyclo[3.3.1.0^2,4]nonan-3-yl)- 1H-indole-1-carboxylate (10d). Synthesized from 10c (0.088 g, 0.180 mmol, 1.0 equiv), hydrazine monohydrate (0.026 mL, 0.270 mmol, 1.5 equiv), Raney Ni (0.021 g, 0.360 mmol, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 2.0 equiv), 37% CH₂O_(aq) (0.015 mL, 0.198 mmol, 1.1 equiv), and MeOH (1.8 mL, 0.1 M) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The product was purified by chromatography on silica gel using EtOAc/MeOH/NH4OH (9:1:0.1) to afford 10d (0.045 g, 71%) as a tan solid.¹H NMR (400 MHz, CDCl₃): δ 7.96 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 3.8 Hz, 1H), 7.12 (d, J = 2.3 Hz, 1H), 7.02 (dd, J = 8.8, 2.3 Hz, 1H), 6.45 (d, J = 3.8 Hz, 1H), 3.31 (s, 2H), 2.81 (s, 2H), 2.60 (s, 3H), 2.00–1.89 (m, 2H), 1.87–1.77 (m, 1H), 1.66 (s, 9H), 1.51–1.41 (m, 1H), 1.32 (dd, J = 13.2, 6.6 Hz, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 149.74, 149.04, 131.00, 130.72, 126.31, 118.61, 115.22, 111.64, 106.95, 83.36, 57.53, 44.59, 35.55, 28.20, 21.43, 16.78 ppm; LRMS (ES⁺) calcd for C21H27N3O2 [M+H] 354.22 found 354.38.

[0191] (1R,2R,4S,5S)-3-(1H-indol-5-yl)-9-methyl-3,9-diazatricyclo[3.3.1.0^2,4]nonane (10). Synthesized from 10d (0.040 g, 0.113 mmol, 1.0 equiv), 2M LiOH_(aq) (0.57 mL, 0.2M), MeOH (0.57 mL, 0.2M), and THF (0.57 mL, 0.2M) following the General Procedure 6 for Boc-indole deprotection. The product was purified using chromatography on silica gel using EtOAc/MeOH/NH4OH (9:1:0.1) to afford 10 (0.021 g, 73%, >99% purity by UHPLC) as a tan solid.¹H NMR (400 MHz, CDCl₃): δ 8.69 (s, 1H), 7.22 (d, J = 8.6 Hz, 1H), 7.19–7.11 (m, 2H), 6.92–6.84 (m, 1H), 6.38 (s, 1H), 3.34 (s, 2H), 2.81 (s, 2H), 2.64 (s, 3H), 2.10–1.93 (m, 2H), 1.88–1.70 (m, 1H), 1.51–1.41 (m, 1H), 1.35 (dd, J = 13.9, 6.6 Hz, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 146.22, 132.05, 128.14, 125.02, 117.22, 111.35, 110.80, 101.74, 57.92, 44.58, 35.91, 21.69, 16.67 ppm; LRMS (ES⁺) calcd for C₁₆H₁₉N₃ [M+H] 254.17 found 254.18. Example 11: (1R,2R,4S,5S)-3-(1H-indol-4-yl)-9-methyl-3,9- diazatricyclo[3.3.1.0^2,4]nonane (11) N Boc

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0192] tert-butyl 4-azido-1H-indole-1-carboxylate (11a). To a flask containing 4-Bpin- indole (0.500 g, 2.06 mmol, 1.0 equiv) in MeOH (26 mL, 0.08M) was added Cu(OAc)2 (0.041 g, 0.206 mmol, 0.1 equiv) and NaN₃ (0.201 g, 3.09 mmol, 1.5 equiv). The solution was stirred at 50°C overnight open to air before being concentrated under reduced pressure. The resulting residue was dissolved in DCM (20 mL) and washed with sat. NH₄Cl_(aq) (50 mL). The aqueous layer was extracted twice more with DCM (20 mL), the combined organic extracts were dried over Na₂SO₄ and concentrated under reduced pressure. The residue was taken up in 2:1 hexanes/DCM and loaded onto a pad of silica. The pad was washed with 2:1 hexanes/DCM (250 mL) and the filtrate concentrated to afford a brown solid. [0193] The solid (0.268 g) was dissolved in DCM (18 mL, 0.1 M) before adding NEt₃ (0.30 mL, 2.17 mmol, 1.2 equiv), DMAP (0.011 g, 0.091 mmol, 0.05 equiv), and Boc2O (0.434 g, 1.99 mmol, 1.1 equiv). The solution was stirred for 1 h at room temperature, then washed once with sat. NaHCO3(aq) before being dried over Na2SO4 and concentrated under reduced pressure. The product was purified by column chromatography on silica gel using 4:1 hexanes/DCM to afford 11a (0.375 g, 70% over 2 steps) as a tan solid.¹H NMR (400 MHz, CDCl₃): δ 7.97 (d, J = 8.0 Hz, 1H), 7.59 (d, J = 3.8 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 3.8 Hz, 1H), 1.70 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 149.54, 136.42, 132.36, 125.85, 125.05, 123.24, 111.92, 111.66, 104.06, 84.10, 28.17 ppm. [0194] tert-butyl 4-(

2-yl)-4,5,6,7,8,8a- hexahydro-4,8-epiminocyclohepta[d][1,2,3]triazol-1(3aH)-yl)-1H-indole-1-carboxylate (11b). Synthesized from S8 (0.100 g, 0.393 mmol, 1.0 equiv), 11a (0.450 g, 1.74 mmol, 4.4 equiv), and toluene (3.9 mL, 0.1M) following the General Procedure 4 for the synthesis of triazolines. The product was purified using hexanes/EtOAc (2:1) to afford 11b (0.116 g, 58%) as a brown solid.¹H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.0 Hz, 1H), 7.76–70 (m, 2H), 7.70–7.64 (m, 2H), 7.60 (d, J = 3.9 Hz, 1H), 7.31–7.26 (m, 2H), 6.72 (d, J = 8.0 Hz, 1H), 4.94 (d, J = 10.1 Hz, 1H), 4.45 (d, J = 10.1 Hz, 1H), 4.27 (s, 1H), 3.97 (s, 1H), 2.49– 2.31 (m, 2H), 2.04–1.95 (m, 1H), 1.83–1.65 (m, 12H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 167.42, 149.74, 137.07, 134.10, 133.03, 130.00, 124.94, 124.57, 123.02, 120.52, 110.17, 108.51, 108.07, 83.65, 83.09, 63.99, 62.20, 60.04, 28.20, 26.10, 25.51, 17.29 ppm; LRMS (ES⁺) calcd for C₂₈H₂₈N₆O₄ [M-N₂+H] 485.22 found 485.19. [0195] tert-butyl 4-( 2-yl)-3,9-

diazatricyclo[3.3.1.0^2,4]nonan-3-yl)-1H-indole-1-carboxylate (11c). Synthesized from 11b (0.110 g, 0.215 mmol) and acetone (4.3 mL, 0.05 M) using the General Procedure 5 for the synthesis of C6/C7 aziridines to afford 11c (0.104 g, >99%) as a brown solid that was used without further purification.¹H NMR (400 MHz, CDCl3): δ 7.78–7.71 (m, 1H), 7.66–7.61 (m, 2H), 7.59–7.52 (m, 3H), 7.15 (t, J = 8.0 Hz, 1H), 7.04 (d, J = 3.8 Hz, 1H), 6.74 (d, J = 7.7 Hz, 1H), 4.72–4.62 (m, 2H), 3.07 (s, 2H), 2.26–2.12 (m, 2H), 1.86 – 1.78 (m, 3H), 1.68 (s, 9H), 1.59 – 1.50 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 165.04, 149.87, 145.44, 136.00, 133.27, 130.60, 124.66, 124.56, 123.97, 122.42, 112.92, 109.34, 105.70, 83.54, 60.67, 43.84, 28.51, 28.21, 16.77 ppm; LRMS (ES⁺) calcd for C₂₈H₂₈N₄O₄ [M+H] 485.22 found 485.21.

[0196] tert-butyl 4-((1R,2R,4S,5S)-9-methyl-3,9-diazatricyclo[3.3.1.0^2,4]nonan-3-yl)- 1H-indole-1-carboxylate (11d). Synthesized from 11c (0.100 g, 0.206 mmol, 1.0 equiv), hydrazine monohydrate (0.030 mL, 0.310 mmol, 1.5 equiv), Raney Ni (0.024 g, 0.412 mmol, 2.0 equiv), 37% CH₂O_(aq) (0.017 mL, 0.227 mmol, 1.1 equiv), and MeOH (2.0 mL, 0.1 M) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The product was purified by chromatography on silica gel using EtOAc/MeOH/NH4OH (9:1:0.1) to afford 11d (0.050 g, 69%) as a tan solid.¹H NMR (400 MHz, CDCl₃): δ 7.72 (d, J = 8.3 Hz, 1H), 7.51 (d, J = 3.8 Hz, 1H), 7.13 (t, J = 8.0 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 6.69 (d, J = 3.8 Hz, 1H), 3.36 (s, 2H), 2.87 (s, 2H), 2.60 (s, 3H), 1.99–1.89 (m, 2H), 1.84–1.73 (m, 1H), 1.65 (s, 9H), 1.50–1.40 (m, 1H), 1.33 (dd, J = 13.4, 6.9 Hz, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 149.87, 145.94, 135.88, 124.65, 124.46, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 124.04, 112.59, 109.17, 105.01, 83.56, 57.56, 44.30, 35.91, 28.20, 21.73, 16.82 ppm; LRMS (ES⁺) calcd for C21H27N3O2 [M+H] 354.22 found 354.38.

[0197] Synthesized from 11d g, 1.0 equiv), 2M LiOH(aq) (0.64 mL, 0.2M), MeOH (0.64 mL, 0.2M), and THF (0.64 mL, 0.2M) following the General Procedure 6 for Boc-indole deprotection. The product was purified using chromatography on silica gel using EtOAc/MeOH/NH₄OH (9:1:0.1) to afford 11 (0.025 g, 78%, >99% purity by UHPLC) as a tan solid.¹H NMR (400 MHz, CDCl3): δ 8.59 (s, 1H), 7.11–7.07 (m, 1H), 7.05–7.00 (m, 1H), 6.98–6.94 (m, 1H), 6.65–6.59 (m, 2H), 3.41–3.36 (m, 2H), 2.93 (s, 2H), 2.65 (s, 3H), 1.99–1.88 (m, 2H), 1.86–1.72 (m, 1H), 1.49–1.41 (m, 1H), 1.37 (dd, J = 12.7, 6.2 Hz, 2H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 145.60, 136.68, 123.12, 122.26, 121.82, 109.17, 105.55, 100.16, 58.19, 44.14, 37.03, 22.55, 16.75 ppm; LRMS (ES⁺) calcd for C16H19N3 [M+H] 254.17 found 254.24. Example 12: (1R,5S)-8-phenethyl-8-azabicyclo[3.2.1]octane (12)

[0198] 2-phenylacetaldehyde (12a). Synthesized from 2-phenylethanol (0.10 mL, 0.835 mmol, 1.0 equiv), IBX (0.327 g, 1.17 mmol, 1.4 equiv), and EtOAc (5.6 mL, 0.15M) using the General Procedure 7 for the oxidation of 2-phenylethanols to afford a clear liquid (0.143 g) that was used as is in subsequent reactions.

[0199] (1R,5S)-8-phenethyl-8-azabicyclo[3.2.1]octane (12). Synthesized from S8 (0.050 g, 0.197 mmol, 1.0 equiv), hydrazine monohydrate (0.029 mL, 0.295 mmol, 1.5 equiv), UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 12a (0.026 g, 0.217 mmol, 1.1 equiv), and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH4OH (9:1:0.1) to afford 12 (0.022 g, 52%, 97.7% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl₃): δ 7.33–7.27 (m, 2H), 7.27–7.18 (m, 3H), 3.44– 3.32 (m, 2H), 2.96–2.84 (m, 2H), 2.76–2.63 (m, 2H), 2.06–1.97 (m, 2H), 1.97–1.84 (m, 2H), 1.70–1.49 (m, 4H), 1.46–1.35 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 140.09, 128.76, 128.43, 126.14, 59.82, 54.32, 34.98, 30.12, 26.20, 16.41 ppm; LRMS (ES⁺) calcd for C₁₅H₂₁N [M+H] 216.18 found 216.17. Example 13: (1R,5S)-8-(2-methoxyphenethyl)-8-azabicyclo[3.2.1]octane (13)

[0200] 2-(2-methoxyphenyl)acetaldehyde (13a). Synthesized from 2-(2- methoxyphenyl)ethanol (0.114 g, 0.749 mmol, 1.0 equiv), IBX (0.294 g, 1.05 mmol, 1.4 equiv), and EtOAc (5.0 mL, 0.15M) using the General Procedure 7 for the oxidation of 2- phenylethanols to afford a clear liquid (0.079 g) that was used as is in subsequent reactions.

[0201] (1R,5S)-8-(2-methoxyphenethyl)-8-azabicyclo[3.2.1]octane (13). Synthesized from S8 (0.050 g, 0.197 mmol, 1.0 equiv), hydrazine monohydrate (0.029 mL, 0.295 mmol, 1.5 equiv), Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 13a (0.033 g, 0.217 mmol, 1.1 equiv), and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH4OH (18:1:0.1) to afford 13 (0.016 g, 33%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl₃): δ 7.19 (t, J = 7.8 Hz, 1H), 6.83–6.76 (m, 2H), 6.74 (dd, J = 8.2, 2.9 Hz, 1H), 3.79 (s, 3H), 3.36 (s, 2H), 2.91–2.80 (m, 2H), 2.73–2.61 (m, 2H), 2.03–1.84 (m, 4H), 1.68–1.48 (m, 4H), 1.43–1.33 (m, 2H) ppm; ¹³C NMR (100 MHz, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO CDCl₃): δ 159.68, 141.66, 129.40, 121.11, 114.52, 111.49, 59.88, 55.18, 54.17, 34.97, 30.10, 26.17, 16.37 ppm; LRMS (ES⁺) calcd for C16H23NO [M+H] 246.19 found 246.31. Example 14: (1R,5S)-8-(3-methoxyphenethyl)-8-azabicyclo[3.2.1]octane (14) Synthesized from 2-(3-

methoxyphenyl)ethanol (0.102 g, 0.670 mmol, 1.0 equiv), IBX (0.263 g, 0.938 mmol, 1.4 equiv), and EtOAc (4.5 mL, 0.15M) using the General Procedure 7 for the oxidation of 2- phenylethanols to afford a clear liquid (0.102 g) that was used as is in subsequent reactions. [0203] (1R,5S)-8-(3-

[3.2.1]octane (14). Synthesized from S8 (0.050 g, 0.197 mmol, 1.0 equiv), hydrazine monohydrate (0.029 mL, 0.295 mmol, 1.5 equiv), Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 14a (0.033 g, 0.217 mmol, 1.1 equiv), and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH4OH (18:1:0.1) to afford 14 (0.020 g, 41%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl₃): δ 7.22–7.15 (m, 2H), 6.87 (t, J = 7.4 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H), 3.81 (s, 3H), 3.46 (s, 2H), 3.00–2.89 (m, 2H), 2.74–2.63 (m, 2H), 2.09–1.94 (m, 4H), 1.70–1.50 (m, 4H), 1.45–1.34 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 157.43, 130.55, 127.63, 120.61, 110.28, 60.00, 55.28, 52.13, 29.74, 28.98, 26.05, 16.22 ppm; LRMS (ES⁺) calcd for C₁₆H₂₃NO [M+H] 246.19 found 246.31. Example 15: (1R,5S)-8-(4-methoxyphenethyl)-8-azabicyclo[3.2.1]octane (15)

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0204] 2-(4-methoxyphenyl)acetaldehyde (15a). Synthesized from 2-(4- methoxyphenyl)ethanol (0.100 g, 0.657 mmol, 1.0 equiv), IBX (0.258 g, 0.920 mmol, 1.4 equiv), and EtOAc (4.4 mL, 0.15M) using the General Procedure 7 for the oxidation of 2- phenylethanols to afford a clear liquid (0.113 g) that was used as is in subsequent reactions. MeO [0205] (1R,5S)-8-(4- [3.2.1]octane (15). Synthesized

from S8 (0.050 g, 0.197 mmol, 1.0 equiv), hydrazine monohydrate (0.029 mL, 0.295 mmol, 1.5 equiv), Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 15a (0.033 g, 0.217 mmol, 1.1 equiv), and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH4OH (18:1:0.1) to afford 15 (0.016 g, 33%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl3): δ 7.17–7.10 (m, 2H), 6.85–6.78 (m, 2H), 3.77 (s, 3H), 3.38 (s, 2H), 2.89–2.79 (m, 2H), 2.70–2.61 (m, 2H), 2.04–1.87 (m, 4H), 1.68–1.60 (m, 2H), 1.60–1.47 (m, 2H), 1.43–1.33 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 158.07, 131.83, 129.67, 113.90, 59.92, 55.27, 54.37, 33.71, 29.92, 26.09, 16.28 ppm; LRMS (ES⁺) calcd for C16H23NO [M+H] 246.19 found 246.21. Example 16: (1R,5S)-8-(2-fluorophenethyl)-8-azabicyclo[3.2.1]octane (16)

[0206] 2-(2-fluorophenyl)acetaldehyde (16a). Synthesized from 2-(2- fluorophenyl)ethanol (0.100 g, 0.713 mmol, 1.0 equiv), IBX (0.280 g, 0.999 mmol, 1.4 equiv), and EtOAc (4.8 mL, 0.15M) using the General Procedure 7 for the oxidation of 2- phenylethanols to afford a clear liquid (0.080 g) that was used as is in subsequent reactions. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0207] (1R,5S)-8-(2- [3.2.1]octane (16). Synthesized from

S8 (0.050 g, 0.197 mmol, 1.0 equiv), (0.029 mL, 0.295 mmol, 1.5 equiv), Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 16a (0.030 g, 0.217 mmol, 1.1 equiv), and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH4OH (18:1:0.1) to afford 16 (0.008 g, 17%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl₃): δ 7.29–7.23 (m, 1H), 7.23–7.15 (m, 1H), 7.10– 6.98 (m, 2H), 3.35 (s, 2H), 2.95–2.84 (m, 2H), 2.69–2.57 (m, 2H), 2.05–1.93 (m, 2H), 1.93– 1.78 (m, 2H), 1.67–1.47 (m, 4H), 1.44–1.33 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 161.18 (d, ¹JCF = 243.6 Hz), 131.16 (d, ³JCF = 5.1 Hz), 127.80 (d, ³JCF = 7.8 Hz), 127.18 (d, ²J_CF = 15.8 Hz), 124.00 (d, ⁴J_CF = 3.5 Hz), 115.17 (d, ²J_CF = 21.9 Hz), 59.77, 52.84, 30.35, 28.64, 26.30, 16.51 ppm; LRMS (ES⁺) calcd for C15H20FN [M+H] 234.17 found 234.21. Example 17: (1R,5S)-8-(3-fluorophenethyl)-8-azabicyclo[3.2.1]octane (17) [0208] 2-(3-fluorophenyl)

from 2-(3- fluorophenyl)ethanol (0.100 g, 0.713 mmol, 1.0 equiv), IBX (0.280 g, 0.999 mmol, 1.4 equiv), and EtOAc (4.8 mL, 0.15M) using the General Procedure 7 for the oxidation of 2- phenylethanols to afford a clear liquid (0.082 g) that was used as is in subsequent reactions. [0209] (1R,5S)-8-(3-

[3.2.1]octane (17). Synthesized from S8 (0.050 g, 0.197 mmol, 1.0 equiv), hydrazine monohydrate (0.029 mL, 0.295 mmol, 1.5 equiv), Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 17a (0.030 g, 0.217 mmol, 1.1 equiv), UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH₄OH (18:1:0.1) to afford 17 (0.020 g, 44%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl3): δ 7.25–7.18 (m, 1H), 6.99 (d, J = 7.7 Hz, 1H), 6.96–6.83 (m, 2H), 3.31 (s, 2H), 2.92–2.78 (m, 2H), 2.73–2.54 (m, 2H), 2.05–1.91 (m, 2H), 1.91–1.75 (m, 2H), 1.67–1.45 (m, 4H), 1.42–1.31 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 162.86 (d, ¹J_CF = 244.6 Hz), 142.80 (d, ³J_CF = 6.6 Hz), 129.77 (d, ³J_CF = 8.6 Hz), 124.43 (d, ⁴JCF = 2.9 Hz), 115.59 (d, ²JCF = 20.6 Hz), 112.96 (d, ²JCF = 20.9 Hz), 59.83, 53.98, 34.88, 30.22, 26.22, 16.43 ppm; LRMS (ES⁺) calcd for C15H₂₀FN [M+H] 234.17 found 234.31. Example 18: (1R,5S)-8-(4-fluorophenethyl)-8-azabicyclo[3.2.1]octane (18)

[0210] 2-(4-fluorophenyl)acetaldehyde (18a). Synthesized from 2-(4- fluorophenyl)ethanol (0.100 g, 0.713 mmol, 1.0 equiv), IBX (0.280 g, 0.999 mmol, 1.4 equiv), and EtOAc (4.8 mL, 0.15M) using the General Procedure 7 for the oxidation of 2- phenylethanols to afford a clear liquid (0.098 g) that was used as is in subsequent reactions.

[0211] (1R,5S)-8-(4-fluorophenethyl)-8-azabicyclo[3.2.1]octane (18). Synthesized from S8 (0.050 g, 0.197 mmol, 1.0 equiv), hydrazine monohydrate (0.029 mL, 0.295 mmol, 1.5 equiv), Raney Ni (0.023 g, 0.394 mmol, 2.0 equiv), 18a (0.030 g, 0.217 mmol, 1.1 equiv), and MeOH (2 mL, 0.1M) following the General Procedure 2 for the deprotection-reduction- reductive amination sequence. The product was purified using chromatography on silica gel using DCM/MeOH/NH₄OH (18:1:0.1) to afford 18 (0.011 g, 24%, >99% purity by UHPLC) as a clear oil.¹H NMR (400 MHz, CDCl3): δ 7.22–7.10 (m, 2H), 7.01–6.89 (m, 2H), 3.29 (s, 2H), 2.85–2.72 (m, 2H), 2.65–2.52 (m, 2H), 2.02–1.88 (m, 2H), 1.88–1.72 (m, 2H), 1.66– UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 1.43 (m, 4H), 1.41–1.29 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 161.45 (d, ¹J_CF = 241.5 Hz), 135.68, 130.12 (d, ³JCF = 7.6 Hz), 115.15 (d, ²JCF = 21.2 Hz), 59.85, 54.27, 34.09, 30.08, 26.16, 16.36 ppm; LRMS (ES⁺) calcd for C15H₂₀FN [M+H] 234.17 found 234.21. Example 19: (1R,3R,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octan-3-yl benzoate (19)

[0212] (1R,3R,5R,6R)-8-(1,3-dioxoisoindolin-2-yl)-6-phenyl-8-azabicyclo[3.2.1]octan- 3-yl benzoate (19a). Synthesized from S5 (0.500 g, 1.34 mmol, 1.0 equiv) and iodobenzene (0.300 mL, 2.67 mmol, 2.0 equiv) with Pd(dba)2 (0.100 g, 0.134 mmol, 0.10 equiv), HCO2Na (0.272 g, 4.01 mmol, 3.0 equiv), and triethylamine (0.651 mL, 4.67 mmol, 3.5 equiv) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (4:1) to afford 19a (0.569 g, 94%) as a yellow-orange solid.¹H NMR (400 MHz, CDCl3): δ 8.17–8.11 (m, 2H), 7.89–7.83 (m, 2H), 7.79–7.73 (m, 2H), 7.69–7.64 (m, 2H), 7.62–7.56 (m, 1H), 7.48 (dd, J = 8.3, 6.9 Hz, 2H), 7.33 (t, J = 7.7 Hz, 2H), 7.24–7.18 (m, 1H), 5.68 (tt, J = 10.7, 6.4 Hz, 1H), 4.33 (s, 1H), 4.06 (s, 1H), 3.36 (dd, J = 8.8, 6.0 Hz, 1H), 2.53 (ddd, J = 13.4, 10.6, 3.1 Hz, 1H), 2.49–2.37 (m, 3H), 2.26 (ddd, J = 13.6, 6.7, 2.8 Hz, 1H), 2.16 (ddd, J = 14.0, 6.7, 2.6 Hz, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ167.76, 166.29, 146.80, 134.22, 132.90, 130.58, 130.27, 129.72, 128.48, 128.33, 127.26, 126.31, 123.07, 67.70, 65.88, 58.86, 46.46, 38.48, 34.97, 34.28 ppm; LRMS (ES⁺) calcd for C28H24N2O4 [M+H] 453.18 found 453.20.

[0213] (1R,3R,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octan-3-yl benzoate (19). Synthesized from 19a (0.281 g, 0.621 mmol, 1.0 equiv), Raney Nickel (0.266 g, 3.12 mmol, 5.0 equiv), hydrazine monohydrate (0.09 mL, 1.24 mmol, 2.0 equiv), and 37% formaldehyde (0.05 mL, 0.683 mmol, 1.1 equiv) following the General Procedure 2 for the deprotection- reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with hexanes/acetone/NH4OH/dimethyl sulfide (9:1:0.1:0.1) to afford 19 (0.166 g, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 83%, >99% purity by UHPLC) as a light yellow oil.¹H NMR (400 MHz, CDCl₃): δ 8.11– 8.05 (m, 2H), 7.62–7.55 (m, 1H), 7.52–7.40 (m, 4H), 7.34–7.27 (m, 2H), 7.24–7.17 (m, 1H), 5.47 (tt, J = 10.9, 6.4 Hz, 1H), 3.50 (dd, J = 6.9, 3.3 Hz, 1H), 3.35 (s, 1H), 3.26 (dd, J = 9.4, 5.3 Hz, 1H), 2.61 (s, 3H), 2.34 (dd, J = 13.0, 9.4 Hz, 1H), 2.19–2.02 (m, 3H), 2.00–1.91 (m, 1H), 1.83–1.89 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 166.12, 148.18, 132.87, 130.68, 129.58, 128.38, 128.33, 126.93, 125.92, 68.46, 65.70, 59.03, 47.68, 39.68, 34.07, 29.71, 29.16 ppm; LRMS (ES⁺) calcd for C₂₁H₂₃NO₂ [M+H] 322.18 found 322.25. Example 20: (1R,3S,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octan-3-yl benzoate (20) Phth N [0214] (1R,3S,5R,6R)-8-(1,3-

6-phenyl-8-azabicyclo[3.2.1]octan-3- yl benzoate (20a). Synthesized from S6 (0.086 g, 0.230 mmol) and iodobenzene (0.051 mL, 0.459 mmol) with Pd(dba)2 (0.013 g, 0.023 mmol), HCO2Na (0.047 g, 0.689 mmol), and triethylamine (0.112 mL, 0.804 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (6:1) to afford 20a (0.068 g, 65%) as a yellow-orange solid.¹H NMR (300 MHz, CDCl₃) δ 8.15–8.09 (m, 2H), 7.86–7.79 (m, 2H), 7.77–7.71 (m, 2H), 7.71–7.65 (m, 2H), 7.65–7.57 (m, 1H), 7.55–7.47 (m, 2H), 7.35–7.27 (m, 2H), 7.22–7.14 (m, 1H), 5.67 (t, J = 5.5 Hz, 1H), 4.08 (s, 1H), 3.85–3.72 (m, 2H), 2.93–2.70 (m, 3H), 2.54–2.43 (m, 1H), 2.09–1.88 (m, 2H) ppm.

[0215] (1R,3S,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octan-3-yl benzoate (20). Synthesized from 20a (0.067 g, 0.148 mmol) with Raney Nickel (0.063 g, 0.740 mmol), hydrazine monohydrate (0.022 g, 0.296 mmol), and 37% formaldehyde (0.004 g, 0.163 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with hexanes/acetone (4:1) to afford 20 (0.017 g, 36%, >99% purity by UHPLC) as a light yellow oil.¹H NMR UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO (300 MHz, CDCl₃) δ 8.13–8.07 (m, 2H), 7.63–7.56 (m, 1H), 7.53–7.45 (m, 2H), 7.44–7.38 (m, 2H), 7.33–7.25 (m, 3H), 7.21–7.14 (m, 1H), 5.41 (t, J = 5.5 Hz, 1H), 3.75 (dd, J = 9.4, 5.3 Hz, 1H), 3.42–3.34 (m, 1H), 3.29–3.24 (m, 1H), 2.64 (dd, J = 12.8, 9.3 Hz, 1H), 2.51 (s, 3H), 2.47–2.35 (m, 2H), 2.29–2.17 (m, 1H), 1.82–1.62 (m, 3H) ppm;LRMS (ES⁺) calcd for C₂₁H₂₄NO₂ [M+H] 322.18 found 322.25. Example 21: (1R,3R,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octan-3-ol (21) [0216] Synthesized from 19 (0.100 1.0 equiv), THF (1.60 mL, 0.2M),

MeOH (3.10 mL, 0.1M), and 1M LiOH (1.60 mL, 0.2M) using the General Procedure 8 for the synthesis of 3-hydroxy tropanes to afford 21 (0.077 g, >99%, >99% purity by UHPLC) as a white solid.¹H NMR (400 MHz, CDCl₃): δ 7.40 (d, J = 7.6 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.20 (t, J = 7.3 Hz, 1H), 4.08 (tt, J = 10.5, 6.5 Hz, 1H), 3.44 (dt, J = 6.4, 3.0 Hz, 1H), 3.32 (s, 1H), 3.08 (dd, J = 9.2, 5.6 Hz, 1H), 2.57 (s, 1H), 2.52 (s, 3H), 2.19–2.06 (m, 2H), 1.92–1.78 (m, 3H), 1.78–1.69 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 148.14, 128.37, 126.88, 125.87, 65.88, 64.30, 59.32, 47.80, 39.38, 34.44, 34.11, 33.54 ppm; LRMS (ES⁺) calcd for C14H19NO [M+H] 218.16 found 218.14. Example 22: (1R,3S,5R,6R)-8-methyl-6-phenyl-8-azabicyclo[3.2.1]octan-3-ol (22) Me N

[0217] Synthesized using 20 (0.017 g, 0.053 mmol, 1.0 equiv), THF (0.264 mL, 0.2M), MeOH (0.528 mL, 0.1M), and 1M LiOH (0.264 mL, 0.2 M) using the General Procedure 8 for the synthesis of 3-hydroxy tropanes to afford 22 (0.011 g, >99%, >99% purity by UHPLC), as a light yellow oil.¹H NMR (300 MHz, CDCl₃) δ 7.44–7.35 (m, 2H), 7.32–7.22 (m, 2H), 7.20–7.10 (m, 1H), 4.18 (t, J = 5.4 Hz, 1H), 3.80 (dd, J = 9.4, 5.3 Hz, 1H), 3.28 (s, 1H), 3.20 (s, 1H), 2.60 (dd, J = 12.5, 9.3 Hz, 1H), 2.44 (s, 3H), 2.35–2.21 (m, 2H), 2.15–2.02 (m, 1H), 1.71–1.54 (m, 2H), 1.52–1.38 (m, 3H) ppm; ¹³C NMR (76 MHz, CDCl3) δ 149.17, UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 128.37, 127.00, 125.59, 65.16, 64.86, 58.57, 47.22, 39.08, 35.70, 33.21, 32.86 ppm; LRMS (ES⁺) calcd for C14H20NO [M+H] 218.15 found 218.24. Example 23: (2R,4R,5R,11R,11aR)-1,3,4,6,11,11a-hexahydro-2H-4,11- methanopyrido[1,2-b]isoquinolin-2-yl benzoate (23) Phth N O Ph [0218] (1R,3R,5R,6R)-6-(2- 8-(1,3-dioxoisoindolin-2-yl)-8-

azabicyclo[3.2.1]octan-3-yl benzoate (23a). Synthesized from S5 (0.100 g, 0.267 mmol) and 2-bromobenzyl bromide (0.134 g, 0.534 mmol) with Pd(dba)2 (0.015 g, 0.027 mmol), HCO₂Na (0.055 g, 0.801 mmol), and triethylamine (0.130 mL, 0.935 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (6:1) to afford 23a (0.015 g, 10%) as a yellow solid.¹H NMR (300 MHz, CDCl3) δ 8.08 (dd, J = 8.3, 1.3 Hz, 2H), 7.75–7.70 (m, 2H), 7.70–7.64 (m, 2H), 7.59–7.52 (m, 1H), 7.46–7.40 (m, 2H), 7.23–7.16 (m, 4H), 5.61–5.48 (m, 1H), 4.35– 4.27 (m, 1H), 4.27–4.19 (m, 1H), 3.76 (d, J = 8.5 Hz, 1H), 3.50 (dd, J = 16.7, 10.0 Hz, 1H), 3.14 (dd, J = 16.6, 4.2 Hz, 1H), 3.09–2.97 (m, 1H), 2.57–2.35 (m, 3H), 2.35–2.11 (m, 4H). CNMR LRMS (ES⁺): calcd for C29H25BrN2O4 [M+H+Na] 568.10 found 568.64.

[0219] (2R,4R,5R,11R,11aR)-1,3,4,6,11,11a-hexahydro-2H-4,11-methanopyrido[1,2- b]isoquinolin-2-yl benzoate (23). Synthesized from 23a (0.015 g, 0.0275 mmol) with Raney Nickel (0.012 g, 0.138 mmol), hydrazine monohydrate (0.039 g, 0.55 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH₃OH to afford 23 (0.003 g, 34%, >99% purity by UHPLC) as a clear oil.¹H NMR (300 MHz, CDCl3) δ 8.08–8.00 (m, 2H), 7.61–7.53 (m, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.24–7.14 (m, 4H), 5.43–5.29 (m, 1H), 3.86 (d, J = 7.9 Hz, 1H), 3.65 (d, J = 19.8 Hz, 2H), 3.45 (dd, J = 17.2, 10.2 Hz, 1H), 3.17–3.03 (m, 1H), 2.92 (dd, J = 17.0, 3.4 Hz, 1H), 2.44–2.22 (m, 2H), UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 2.12–1.93 (m, 2H), 0.95–0.78 (m, 1H); LRMS (ES⁺) calcd for C₂₁H₂₂NO₂ [M+H] 320.17 found 320.26. Example 24: (4S,5R,11R,11aR)-1,3,4,6,11,11a-hexahydro-2H-4,11-methanopyrido[1,2- b]isoquinoline (24)

[0220] 2-((1S,5R,6R)-6-(2- -8-azabicyclo[3.2.1]octan-8- yl)isoindoline-1,3-dione (24a). Synthesized from S8 (0.100 g, 0.393 mmol) and 2- bromobenzyl bromide (0.116 g, 0.471 mmol) with Pd(dba)₂ (0.023 g, 0.039 mmol), HCO₂Na (0.080 g, 1.18 mmol), and triethylamine (0.164 mL, 1.18 mmol) following the General Procedure 1 for C6/C7 Heck coupling. The residue was purified by chromatography on silica gel with hexanes/EtOAc (6:1) to afford 24a (0.012 g, 7%) as a yellow solid. LRMS (ES⁺) calcd for C22H21BrN2O2 [M+H+Na] 448.08 found 448.47. [0221] (4S,5R,11R,11aR)-

2H-4,11-methanopyrido[1,2- b]isoquinoline (24). Synthesized from 24a (0.012 g, 0.0287 mmol) with Raney Nickel (0.0123 g, 0.143 mmol) and hydrazine monohydrate (0.0387 g, 0.0574 mmol) following the General Procedure 2 for the deprotection-reduction-reductive amination sequence. The residue was purified by chromatography on silica gel with EtOH/MeOH (9:1) plus 1% NH3OH to afford 24 (0.002 g, 35%, >99% purity by UHPLC) as a clear oil. LRMS (ES⁺) calcd for C₁₄H₁₇N [M+H] 200.14 found 200.27.

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO Example 25: (1R,5R,6S)-6-hydroxy-8-(4-methoxybenzyl)-8-azabicyclo[3.2.1]octan-3- one (25)

[0222] Synthesized from 2,5-dimethoxy-2,5-dihydrofuran (1.86 mL, 15.4 mmol, 1.0 equiv), 3M HCl (28 mL), 3-oxoglutaric acid (2.703 g, 18.5 mmol, 1.2 equiv), NaOAc (5.685 g, 69.3 mmol, 4.5 equiv), 4-methoxybenzylamine (2.2 mL, 16.8 mmol, 1.1 equiv) and H2O (52 mL) following the General Procedure 9 for the Robinson-Schöpf reactions. The residue was purified by column chromatography on silica gel with 9.8:0.1:0.1 EtOAc/MeOH/NEt3 to afford 25 (1.698 g, 42%, >99% purity by UHPLC) as an orange solid.¹H NMR (400 MHz, CDCl3): δ 7.38–7.30 (m, 2H), 6.92–6.87 (m, 2H), 4.08 (dd, J = 6.4, 3.0 Hz, 1H), 4.01–3.89 (m, 2H), 3.82 (s, 3H), 3.65–3.59 (m, 1H), 3.41 (d, J = 4.9 Hz, 1H), 2.75–2.63 (m, 2H), 2.26– 2.18 (m, 1H), 2.15–2.08 (m, 1H), 2.05–2.00 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl3): δ 208.47, 158.92, 130.75, 129.57, 113.93, 75.45, 66.10, 56.73, 55.31, 51.66, 44.78, 42.25, 41.12 ppm; LRMS (ES⁺) calcd for C15H19NO3 [M+H] 262.15 found 262.24. Example 26: (1R,5R,6S)-8-(2-(1H-indol-3-yl)ethyl)-6-hydroxy-8-azabicyclo[3.2.1]octan-

equiv), 3M HCl (3.5 mL), 3-oxoglutaric acid (0.336 g, 2.30 mmol, 1.2 equiv), NaOAc (0.709 g, 8.64 mmol, 4.5 equiv), tryptamine (0.338 g, 2.11 mmol, 1.1 equiv) and H₂O (6.5 mL) following the General Procedure 9 for the Robinson-Schöpf reaction. The residue was purified by column chromatography on silica gel with 9.5:0.5:0.05 DCM/MeOH/NH₄OH to afford 26 (0.140 g, 26%, >99% purity by UHPLC) as an off-white solid.¹H NMR (400 MHz, CDCl₃): δ 8.11 (s, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 7.4 Hz, 1H), 7.09 (d, J = 2.6 Hz, 1H), 4.07 (d, J = 5.4 Hz, 1H), 3.81–3.72 UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO (m, 1H), 3.55 (d, J = 5.4 Hz, 1H), 3.25–3.14 (m, 2H), 3.14–3.05 (m, 2H), 2.74–2.59 (m, 2H), 2.25–2.19 (m, 1H), 2.18–2.09 (m, 1H), 2.09–1.94 (m, 2H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ 208.14, 136.30, 127.43, 122.16, 121.65, 119.43, 118.66, 114.11, 111.32, 74.98, 66.26, 56.92, 47.69, 43.92, 41.23, 41.11, 25.17 ppm; LRMS (ES⁺) calcd for C17H20N2O2 [M+H] 285.16 found 285.18. D. Biological Examples Example 1: Assays [0224] Neurite Outgrowth Assays. Female Wistar rats of 17 days gestation were killed by cervical dislocation and the fetuses were removed from the uterus. Their brains were placed in ice-cold medium of Leibovitz (L15, Gibco, Fisher bioblock, France). Cortex was dissected and meninges were carefully removed. The cortical neurons were dissociated by trypsinization for 30 min at 37°C (trypsin-EDTA, Gibco) in presence of 0.1 mg/mL DNAse I (Roche, France). The reaction was stopped by addition of Dulbecco’s Modified Eagle Medium (DMEM; Gibco) with 10% of fetal bovine serum (FBS; Gibco). The suspension was triturated with a 10-mL pipette and using a needle syringe 21G and centrifuged at 350 x g for 10 min at room temperature. The pellet of dissociated cells was resuspended in a medium consisting of Neurobasal (Gibco) supplemented with 2% B27 supplement (Gibco), 0.5 mM L-Glutamine (Gibco), an antibiotic-antimicotic mixture. Viable cells were counted in a Neubauer cytometer using the trypan blue exclusion test (Sigma). Cells were seeded at a density of 10,000 cells per well in 96-well plate (Costar) precoated with poly-L-lysine. Test compounds at different concentrations were added to the cultures. Donepezil (positive control) was tested at 250 nM. After 72 h, cultures were fixed with paraformaldehyde in PBS (4%, Sigma) for 30 min at 4°C. Then, cells were successively permeabilized with 0.1% Triton X100 for 30 min, saturated with PBS containing 3% of BSA and were incubated 1 h with anti-beta III tubulin antibody (Sigma) at 1:10000 in PBS containing 0.5% BSA. Cells were washed three times with PBS containing 0.5% BSA and incubated 1 h with goat anti- mouse antibody coupled with AF488 (Invitrogen A11001) diluted at 1:1000 in PBS containing 0.5% BSA. Finally, nuclei were stained using DAPI (1 mg/mL) at 1:1000 in PBS containing 0.5% BSA. After rinsing with PBS, the plate was filmed and neurite networks were examined and analyzed using High-Content Screening (CellInsight, Thermo Scientific). The average number of neurites per neuron, average total length of neurites per neuron, and average number of branchpoints per neuron were the main parameters analyzed. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0225] Radioligand Binding Assays (5-HT2AR, 5-HT2CR, M1-5R). The 5-HT2AR, 5- HT2CR, and M1R, M2R, M3R, M4R, and M5R competitive radioligand binding assays were performed at Epics Therapeutics S.A. (Belgium, FAST-0505B, FAST-0507B, FAST0260A, FAST-0261G, ES-212A, ES-213G, FAST-0264A) using conventional methods. Experiments were performed using the free bases of all compounds. Briefly, competition binding was performed in duplicate in the wells of a 96-well plate (Master Block, Greiner, 786201) containing binding buffer, membrane extracts, radiotracer ([³H]-DOI for 5-HT2A and 5- HT2C, [³H]-Scopolamine for M1-5) and test compound. Nonspecific binding was determined by co-incubation with 200-fold excess of cold competitor (DOI for 5-HT2A and 5-HT2C, N- Me-Scopolamine for M1-4, and atropine for M5). The samples were incubated in a final volume of 0.1 mL at a temperature and for a duration optimized for either the 5-HT2AR, 5- HT2CR, or M1-5R, and then filtered over filter plates. Filters were washed six times with 0.5 mL of ice-cold washing buffer and 50 μL of Microscint 20 (Packard) were added in each well. The plates were incubated for 15 min on an orbital shaker and then counted with a PerkinElmer TopCount™ reader for 1 min/well. [0226] IP1 Assays. The 5-HT2AR and 5-HT2CR IPOne HTRF assays were performed at Epics Therapeutics S.A. (Belgium, FAST-0505I, FAST-0507I) using conventional methods. Experiments were performed using the free bases of all compounds. Briefly, CHO-K1 cells expressing human recombinant 5-HT2AR or 5-HT2CR grown to mid-log phase in culture media without antibiotics are detached with PBS-EDTA, centrifuged, and resuspended in stimulation buffer. For agonist testing, 5 µL of test compounds or reference agonist ( ^-Me-5- HT) diluted in stimulation buffer are dispensed in the wells of a 384-well plate. Then, 5 µL of cells suspension (20,000 cells) are added and the plate is incubated 60 min at 37ºC with 5% CO₂. After addition of the lysis buffer containing IP1-d2 and anti-IP1 cryptate detection reagents (5 µL each), plates are incubated for 1 h at room temperature and fluorescence ratios are measured according to the manufacturer’s specifications using the HTRF kit. For antagonist testing, 5 µL of test compounds or reference antagonist (Ketanserin for 5-HT2AR and Methysergide for 5-HT2CR) diluted in stimulation buffer with reference agonist ( ^-Me- 5-HT for a final concentration corresponding to its EC80) are dispensed in the wells of a 384- well plate. Then, 5 µL of cells suspension (20,000 cells) are added and the plate is incubated 60 min at 37ºC with 5% CO2. After addition of the lysis buffer containing IP1-d2 and anti- IP1 cryptate detection reagents (5 µL each), plates are incubated for 1 h at room temperature UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO and fluorescence ratios are measured according to the manufacturer’s specifications using the HTRF kit. [0227] Aequorin Assays (M1R, M3R, M5R). CHO-K1 cells coexpressing mitochondrial apoaequorin and recombinant human M1R, M3R, or M5R grown to mid-log phase in culture media without antibiotics are detached with PBS-EDTA, centrifuged, and resuspended in assay buffer (DMEM/HAM’s F12 with HEPES, without phenol red + 0.1 % BSA protease free) at a concentration of 1 x 10⁶ cells/ml. Cells are incubated at room temperature for at least 4h with coelenterazine h. The reference agonist (acetylcholine) is tested to evaluate the performance of the assay on each day of the test and determine EC50. For agonist testing, 30 µL of cell suspension is mixed with 30 µL of test or reference agonist (acetylcholine) in a 384-well plate. The resulting emission of light is recorded using Hamamatsu Functional Drug Screening System 6000 (FDSS 6000) luminometer. For antagonist testing 30 µL of the reference agonist (acetylcholine) at its EC80 (final concentration) is injected on the mix of cells and test compound or reference antagonist (4-DAMP), following an incubation of 15 min after the first injection. The resulting emission of light is recorded using Hamamatsu Functional Drug Screening System 6000 (FDSS 6000) luminometer. [0228] GTPγS Scintillation Proximity Assays (M2R, M4R). For agonist testing, membranes are mixed with GDP. In parallel, GTPγ[³⁵S] is mixed with the beads just before starting the reaction. The following reagents are successively added in the wells of an Optiplate (Perkin Elmer): 50 µL of test or reference ligand (acetylcholine for M2R, oxotremorine for M4R), 25 µL of the membranes/GDP mix, and 25 µL of the GTPγ[³⁵S]/beads mix. For antagonist testing, membranes are mixed with GDP and incubated for at least 15 min on ice. In parallel, GTPγ[³⁵S] is mixed with the beads just before starting the reaction. The following reagents are successively added in the wells of an Optiplate (Perkin Elmer): 50 µL of test or reference ligand (methoctramine for M2R, 4-DAMP for M4R), 20 µL of the membranes/GDP mix, 10 µL of reference agonist (acetylcholine for M2R, oxotremorine for M4R) at historical EC₈₀ and 20 µL of the GTPγ[³⁵S]/beads mix. The plates are covered with a top seal, mixed on an orbital shaker for 2 min, and then incubated for 1 hour at room temperature. Then the plates are centrifuged for 10 min at 2000 rpm, incubated at room temperature for 1 h and counted for 30 sec/well with a PerkinElmer TopCount™ reader. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO [0229] In some embodiments, a compound of the present invention increases the pattern of neurite outgrowth. In some embodiments, a compound of the present invention increases neurite average length compared to a control. In some embodiments, a compound of the present invention increases neurite branch points compared to a control. In some embodiments, a compound of the present invention significantly increases the number of new neurites, and/or the average neurite length, and/or the total length of the dendritic arbor compared to a control. Table 1. Summary of radioligand binding Ki values for compounds 1–26 at 5-HT2A, 5- HT2C, M1, M2, M3, M4, and M5. C_ompound ^{Radio Ligand Binding Affinities ( ^M)} 5_{-HT2A 5-HT2C M1 M2 M3 M4 M5}10 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO Table 2. Summary of radioligand binding pKi ± SEM values for compounds at 5-HT2A, 5-HT2C, M1, M2, M3, M4, and M5. C^{ompound pKi ± SEM} 5_{-HT2A 5-HT2C M1 M2 M3 M4 M5} 1 4.67 ± 0.09 — 5.59 ± 0.11 4.97 ± 0.13 5.52 ± 0.09 5.41 ± 0.10 5.52 ± 0.14 06 09 09 07 12 14 16 08 08 09 07 11 18 20 39

Table 3. Summary of functional assay EC50 values for compounds 1–26 at 5-HT2A, 5- HT2C, M1, M2, M3, M4, and M5 run in agonist mode. C_ompound ^{Agonist Functional Assay EC50 ( ^M)} 5_{-HT2A 5-HT2C M1 M2 M3 M4 M5}

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 19 >30.00 >30.00 >30.00 >30.00 >30.00 >30.00 >30.00 18 >30.00 >30.00 >45.0 >30.00 >45.00 >30.0 >45.00 20 >30.00 >30.00 >30.00 >30.00 >30.00 >30.00 >30.00

, -HT2C, M1, M2, M3, M4, and M5. C^{mpd pEC50 ± SEM} 5_{-HT2A 5-HT2C M1 M2 M3 M4 M5 1} — — — — — — —

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO Table 5. Summary of functional assay IC50 values for compounds 1–26 at 5-HT2A, 5- HT2C, M1, M2, M3, M4, and M5 run in antagonist mode. C_ompound ^{Antagonist Functional Assay IC50 ( ^M)} 5_{-HT2A 5-HT2C M1 M2 M3 M4 M5} 1 >30.00 >30.00 1.53 >30.00 4.43 >30.00 4.56

Table 6. Summary of functional assay pIC50 ± SEM values for compounds at 5-HT2A, 5-HT2C, M1, M2, M3, M4, and M5. Compound pIC50 ± SEM 5-HT2A 5-HT2C M1 M2 M3 M4 M5 ± ± ± ± ± ±

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO 10 — — ^{4.51 ±} 0_.27 — — — — 1₁ ^{5.09 ±} 4.55 ± 5.13 ± ± ± ± ± ±

[0230] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference. Where a conflict exists between the instant application and a reference provided herein, the instant application shall dominate.

Claims

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO WHAT IS CLAIMED IS: 1. A compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I), (II), (III), (IV), or (V): , , , or wherein:

R¹¹ is C1-6 alkyl; R¹², R¹³ and R¹⁴ are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^12a, -C(O)OR^12a, - OC(O)R^12a, -C(O)N(R^12a)(R^12b), -N(R^12a)C(O)R^12b, - N(R^12a)C(O)N(R^12b)(R^12c), -S(O)R^12a, -S(O)₂R^12a, -S(O)₂OR^12a, -OS(O)₂R^12a, - S(O)2N(R^12a)(R^12b), -N(R^12a)S(O)2R^12b, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6- 10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO each R^12a, R^12b and R^12c is independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C6-10 aryl, or heteroaryl; R^15a, R^15b, R^15c, R^15d and R^15e are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 1₀ aryl, heteroaryl, or C_1-6 alkyl-heteroaryl, wherein at least one of R^15a, R^15b, R^15c, R^15d and R^15e is C1-6 alkyl, C2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl, such that when R^15a is alkoxy, R^15a is C_2-6 alkoxy; R²¹ C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, C_1-6 haloalkyl, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C_1-6 alkyl- heteroaryl, wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3 or 4 R^21a groups; each R^21a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^21b, -C(O)OR^21b, -OC(O)R^21b, -C(O)N(R^21b)(R^21c), - N(R^21b)C(O)R^21c, -N(R^21b)C(O)N(R^21c)(R^21d), -S(O)R^21b, -S(O)₂R^21b, - S(O)₂OR^21b, -OS(O)₂R^21b, -S(O)₂N(R^21b)(R^21c), or -N(R^21b)S(O)₂R^21c; R^21b, R^21c and R^21d are independently is hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, or C_1-6 haloalkyl; R²² and R²³ are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_{1- 6} alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, –CN, -C(O)R^22a, -C(O)OR^22a, -OC(O)R^22a, - C(O)N(R^22a)(R^22b), -N(R^22a)C(O)R^22b, -N(R^22a)C(O)N(R^22b)(R^22c), -S(O)R^22a, - S(O)2R^22a, -S(O)2OR^22a, -OS(O)2R^22a, -S(O)2N(R^22a)(R^22b), -N(R^22a)S(O)2R^22b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl- heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C1-6 alkyl- heteroaryl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R^22a, R^22b and R^22c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C6-10 aryl, or heteroaryl; R²⁶ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^26a groups; each R^26a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, -CN, -C(O)R^26b, -C(O)OR^26b, -OC(O)R^26b, -C(O)N(R^26b)(R^26c), - N(R^26b)C(O)R^26c, -N(R^26b)C(O)N(R^26c)(R^26d), -S(O)R^26b, --S(O)₂R^26b, - S(O)2OR^26b, -OS(O)2R^26b, -S(O)2N(R^26b)(R^26c), or -N(R^26b)S(O)2R^26c; R^26b, R^26c and R^26d are each independently hydrogen or C_1-6 alkyl; L³ is C_2-6 alkylene; R³¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^31b, -C(O)OR^31b, -OC(O)R^31b, -C(O)N(R^31b)(R^31c), - N(R^31b)C(O)R^31c, -N(R^31b)C(O)N(R^31c)(R^31d), -S(O)R^31b, --S(O)2R^31b, - S(O)₂OR^31b, -OS(O)₂R^31b, -S(O)₂N(R^31b)(R^31c), or -N(R^31b)S(O)₂R^31c; R^31b, R^31c and R^31d are each independently hydrogen or C1-6 alkyl; R³², R³³, R³⁴ and R³⁵ are each independently hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^32a, -C(O)OR^32a, - OC(O)R^32a, -C(O)N(R^32a)(R^32b), -N(R^32a)C(O)R^32b, - N(R^32a)C(O)N(R^32b)(R^32c), -S(O)R^32a, -S(O)₂R^32a, -S(O)₂OR^32a, -OS(O)₂R^32a, - S(O)₂N(R^32a)(R^32b), -N(R^32a)S(O)₂R^32b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_{6- 10} aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^32a, R^32b and R^32c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C_6-10 aryl, or heteroaryl; R⁴¹ is C_1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, -OR^42a, -OC(O)R^42a, - OC(O)OR^42a; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO each R^42a is independently C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R⁴⁴ is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^44a, -C(O)OR^44a, -OC(O)R^44a, -C(O)N(R^44a)(R^44b), -N(R^44a)C(O)R^44b, - N(R^44a)C(O)N(R^44b)(R^44c), -S(O)R^44a, -S(O)₂R^44a, -S(O)₂OR^44a, -OS(O)₂R^44a, - S(O)2N(R^44a)(R^44b), -N(R^44a)S(O)2R^44b, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6- 10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl; R^44a, R^44b, and R^44c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C6-10 aryl, or heteroaryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH, -OR^42a, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1,

2,

3,

4, or 5 R^51a groups; each R^51a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^51b, -C(O)OR^51b, -OC(O)R^51b, -C(O)N(R^51b)(R^51c), - N(R^51b)C(O)R^51c, -N(R^51b)C(O)N(R^51c)(R^51d), -S(O)R^51b, --S(O)₂R^51b, - S(O)₂OR^51b, -OS(O)₂R^51b, -S(O)₂N(R^51b)(R^51c), or -N(R^51b)S(O)₂R^51c; R^51b, R^51c and R^51d are each independently hydrogen or C_1-6 alkyl; R⁵⁴ is C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, -OH, oxo, -NO2, -CN, -C(O)R^54a, -C(O)OR^54a, -OC(O)R^54a, -C(O)N(R^54a)(R^54b), -N(R^54a)C(O)R^54b, - N(R^54a)C(O)N(R^54b)(R^54c), -S(O)R^54a, --S(O)2R^54a, -S(O)2OR^54a, -OS(O)2R^54a, -S(O)₂N(R^54a)(R^54b), -N(R^54a)S(O)₂R^54b, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6- 1₀ aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R^54a, R^54b, and R^54c are each independently is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, heterocycloalkyl, C6-10 aryl, or heteroaryl; and R^55a is hydrogen, C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S. 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I): . 3. The

acceptable salt thereof, having a structure of Formula (II): .

4. The or a pharmaceutically acceptable salt thereof, having a structure of Formula (III): .

5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, having a structure of Formula (IV): UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO .

6. The

acceptable salt thereof, having a structure of Formula (V): .

7. The

1 to 6, or a pharmaceutically acceptable salt thereof, having a structure of Formula (Ia), (IIa), (IIIa), (IVa), or (Va): , or wherein:

UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R¹¹ is C_1-6 alkyl; R^15a, R^15b, and R^15c are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C1-6 haloalkoxy, C3-10 cycloalkyl, C1-6 alkyl-C3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C_6-10 aryl, C_1-6 alkyl-C_6-10 aryl, heteroaryl, or C1-6 alkyl-heteroaryl, wherein at least one of R^15a, R^15b, R^15c, R^15d and R^15e is C_1-6 alkyl, C_2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, C_1-6 haloalkoxy, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl, such that when R^15a is alkoxy, R^15a is C2-6 alkoxy; R²¹ C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, C1-6 haloalkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C_1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C1-6 alkyl- heteroaryl, wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is substituted with 0, 1, 2, 3 or 4 R^21a groups; each R^21a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, –CN, -C(O)R^21b, -C(O)OR^21b, -OC(O)R^21b, -C(O)N(R^21b)(R^21c), - N(R^21b)C(O)R^21c, -N(R^21b)C(O)N(R^21c)(R^21d), -S(O)R^21b, -S(O)₂R^21b, - S(O)₂OR^21b, -OS(O)₂R^21b, -S(O)₂N(R^21b)(R^21c), or -N(R^21b)S(O)₂R^21c; R^21b, R^21c and R^21d are independently is hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, or C_1-6 haloalkyl; R²⁶ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^26a groups; each R^26a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, -CN, -C(O)R^26b, -C(O)OR^26b, -OC(O)R^26b, -C(O)N(R^26b)(R^26c), - N(R^26b)C(O)R^26c, -N(R^26b)C(O)N(R^26c)(R^26d), -S(O)R^26b, --S(O)₂R^26b, - S(O)2OR^26b, -OS(O)2R^26b, -S(O)2N(R^26b)(R^26c), or -N(R^26b)S(O)2R^26c; R^26b, R^26c and R^26d are each independently hydrogen or C_1-6 alkyl; L³ is C_2-6 alkylene; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO R³¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO2, -CN, -C(O)R^31b, -C(O)OR^31b, -OC(O)R^31b, -C(O)N(R^31b)(R^31c), - N(R^31b)C(O)R^31c, -N(R^31b)C(O)N(R^31c)(R^31d), -S(O)R^31b, --S(O)₂R^31b, - S -OS(O)2R^31b, -S(O)2N(R^31b)(R^31c), or -N(R^31b)S(O)2R^31c; are each independently hydrogen or C_1-6 alkyl;

6 R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; each R^42a is independently C_1-6 alkyl, C_3-10 cycloalkyl, C_1-6 alkyl-C_3-10 cycloalkyl, heterocycloalkyl, C1-6 alkyl-heterocyclyl, C6-10 aryl, C1-6 alkyl-C6-10 aryl, heteroaryl, or C_1-6 alkyl-heteroaryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C_1-6 alkylene; R⁵¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^51a groups; each R^51a is independently C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, C_1-6 haloalkoxy, -OH, oxo, -NO₂, -CN, -C(O)R^51b, -C(O)OR^51b, -OC(O)R^51b, -C(O)N(R^51b)(R^51c), - N(R^51b)C(O)R^51c, -N(R^51b)C(O)N(R^51c)(R^51d), -S(O)R^51b, --S(O)₂R^51b, - S(O)₂OR^51b, -OS(O)₂R^51b, -S(O)₂N(R^51b)(R^51c), or -N(R^51b)S(O)₂R^51c; and R^51b, R^51c and R^51d are each independently hydrogen or C_1-6 alkyl; wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S. UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO

8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R¹¹ is C1-6 alkyl; R^15a, R^15b, and R^15c are each independently hydrogen, C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy, wherein at least one of R^15a, R^15b, and R^15c is C1-6 alkoxy, C1-6 alkoxyalkyl, C1- 6 hydroxyalkyl, halogen, C_1-6 haloalkyl, or C_1-6 haloalkoxy, such that when R^15a is alkoxy, R^15a is C2-6 alkoxy; R²¹ C1-6 alkyl; R²⁶ is C_6-12 aryl or heteroaryl; L³ is C_2-6 alkylene; R³¹ is C6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C_1-6 alkoxy, C_1-6 alkoxyalkyl, C_1-6 hydroxyalkyl, halogen, C1-6 haloalkyl, or C1-6 haloalkoxy; R⁴¹ is C1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; each R^42a is independently C6-10 aryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is –OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C1-6 alkylene; R⁵¹ is C_6-12 aryl or heteroaryl, each substituted with 0, 1, 2, 3, 4, or 5 R^51a groups; and each R^51a is independently C1-6 alkoxy, C1-6 alkoxyalkyl, C1-6 hydroxyalkyl, halogen, C_1-6 haloalkyl, or C_1-6 haloalkoxy; UC Docket No.: UC-2023-9A2-2 Mintz Docket No.: 052564-581001WO wherein each heterocyclyl is a 3 to 10 membered heterocyclyl having 1 to 4 heteroatoms each independently N, O, or S, and wherein each heteroaryl is a 5 to 10 membered heteroaryl having 1 to 4 heteroatoms each independently N, O, or S.

9. The compound of any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein R¹¹ is C_1-6 alkyl; R^15a, R^15b, and R^15c are each independently hydrogen, C1-6 alkoxy, C1-6 alkoxyalkyl, halogen, or C_1-6 haloalkoxy, wherein at least one of R^15a, R^15b, and R^15c is C1-6 alkoxy, C1-6 alkoxyalkyl, halogen, or C_1-6 haloalkoxy, such that when R^15a is alkoxy, R^15a is C2-6 alkoxy; R²¹ C1-6 alkyl; R²⁶ is C_6-12 aryl or heteroaryl having 6 to 9 ring members and 1 to 2 heteroatoms each independently N, O, or S; L³ is C2-6 alkylene; R³¹ is C_6-12 aryl, each substituted with 0, 1, 2, 3, 4, or 5 R^31a groups; each R^31a is independently C1-6 alkoxy, C1-6 alkoxyalkyl, halogen, or C1-6 haloalkoxy; R⁴¹ is C1-6 alkyl; R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a; R^42a is C6-10 aryl; R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is –OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl; L⁵ is C1-6 alkylene; R⁵¹ is C6-12 aryl or heteroaryl having 6 to 10 ring members and 1 to 3 heteroatoms each independently N, O, or S, each substituted with 0, 1, or 2 R^51a groups; and each R^51a is independently Ci-6 alkoxy, Ci-6 alkoxyalkyl, Ci-6 hydroxyalkyl, halogen, Ci-6 haloalkyl, or Ci-6 haloalkoxy.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein

Rⁿ is Ci-₃ alkyl;

R^15a, R^15b, and R^15c are each independently hydrogen, C1-3 alkoxy, or halogen, wherein at least one of R^15a, R^15b, and R^15c is C1-3 alkoxy, or halogen, such that when R^15a is alkoxy, R^15a is C2-3 alkoxy;

R²¹ C1.3 alkyl;

R²⁶ is C6-12 aryl, or heteroaryl having 6 to 9 ring members and 1 heteroatom of N;

L³ is C2-3 alkylene;

R³¹ is phenyl, substituted with 0, 1, or 2 R^31a groups; each R^31a is independently C1-3 alkoxy, or halogen;

R⁴¹ is C1-3 alkyl;

R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a;

R^42a is phenyl;

R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 membered heterocycloalkyl; wherein one of R⁴² and R⁴' is -OH, or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 to 8 membered heterocycloalkyl;

I? is C1-3 alky lene;

R⁵¹ is phenyl or heteroaryl having 8 to 10 ring members and 1 or 2 heteroatoms of N, each substituted with 0, 1, or 2 R^51a groups; and each R^51a is independently C1-3 alkoxy, or C1-3 alkoxyalkyd.

11. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein

R¹¹ is methyl;

R^15a is hydrogen or fluoro;

R^15b and R^15c are each independently hydrogen, methoxy, or fluoro. wherein at least one of R^15a, R^15b, and R^15c is methoxy or fluoro;

R²¹ is methyl;

R²⁶ is phenyl, pyridyl, or indolyl;

L³ is -CH2CH2-;

R³¹ is phenyl, substituted with 0 or 1 methoxy or fluoro;

R⁴¹ is methyl;

R⁴² and R⁴³ are each independently hydrogen, -OH, or -OC(O)R^42a;

R^42a is phenyl;

R^45e is hydrogen; alternatively, R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 membered heterocycloalkyl; wherein one of R⁴² and R⁴³ is -OH or -OC(O)R^42a, or R⁴¹ and R^45e are combined with the atoms to which they are attached to form a 6 membered heterocycloalkyl;

1? is -CH2- or -CH2CH2-; and

R⁵¹ is phenyl or indolyl, each substituted with 0 or 1 methoxy.

12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, having a structure of Formula (la):

13. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, having a structure of Formula (Ila):

14. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, having a structure of Formula (Illa):

15. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, having a structure of Formula (IV a):

16. The compound of any one of claims 1 to 11 , or a pharmaceutically acceptable salt thereof, having a structure of Formula (Va):

17. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, having the structure:

18. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof.

19. A method of treating a disease, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, thereby treating the disease.

20. The method of claim 19, wherein the disease is a neuropsychiatric disease.

21. The method of claim 20, wherein the neuropsychiatric disease is schizophrenia.

22. The method of claim 20, wherein the neuropsychiatric disease is bipolar disorder.

23. The method of claim 19, wherein the disease is depression.

24. The method of claim 19, wherein the disease is a neurodegenerative disease.

25. The method of claim 19, wherein the disease is Alzheimer’s disease or Parkinson’s disease.

26. The method of claim 19, wherein the disease is Alzheimer’s disease.

27. The method of claim 19, wherein the disease is Parkinson’s disease.

28. The method of claim 19, wherein the disease is headache disorders.

29. The method of claim 19, wherein the disease is migraines.

30. The method of claim 19, wherein the disease is cluster headaches.

31. The method of claim 19, wherein the disease is addiction.

32. The method of claim 19, wherein the disease is substance use disorder.

33. The method of claim 19, wherein the disease is alcohol use disorder.

34. A method for increasing neural plasticity and increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound of any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, in an amount sufficient to increase neural plasticity’ and increase dendritic spine density of the neuronal cell.