Compounds and methods for treating neurological disorders

Abstract

This disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that modulate GCase activity. These compounds are useful, e.g., for treating a disease in which Gcase activity contributes to the disease.

Description

[0001] COMPOUNDS AND METHODS FOR TREATING NEUROLOGICAL DISORDERS RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Appl. No.63 / 673,113, filed on July 18, 2024, which is hereby incorporated by reference in its entirety. FIELD This disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that modulate glucocerebrosidase (GCase) activity. These compounds are useful, e.g., for treating a disease in which Gcase activity contributes to the disease. BACKGROUND Glucocerebrosidase (GCase) is a lysosomal, membrane associated enzyme involved in the metabolism of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) and is encoded by the GBA1 gene. Inside the lysosomal compartment, GCase hydrolyzes the beta-glucosidic linkage of GluCer and GlySph to release glucose, which in turn regulates ceramide signaling and glycolipid metabolism. Homozygous or compound heterozygous loss-of-function GBA1 mutations can cause Gaucher disease (GD), a rare lysosomal storage disorder characterized by accumulation of GluCer and GluSph, resulting in neural toxicity. In addition, heterozygous mutations in GBA1 are one of the most common genetic risk factors for Parkinson’s disease (PD). It is estimated that anywhere between 7-12% of all patients with Parkinson’s disease carry a GBA1 gene mutation. Several studies have found reduced GCase activity in sporadic PD cases (not carrying GBA1 gene mutations), suggesting a role for GCase activity in the pathogenesis of PD via α-synuclein accumulation. Some variants of GBA1 are also known to increase the risk of dementia with Lewy bodies (DLB)—another type of neurodegenerative disease linked to abnormal accumulation of α- synuclein. Currently several treatments options for specific types of GD are available, particularly enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Unfortunately, both types of therapies are not able to reach the central nervous system and thus fail to address the neurological symptoms caused by the disease. Moreover, there is no disease-modifying treatment available for PD with GBA1 mutations (GBA-PD). Since nigral dopamine loss observed in individuals with GBA-PD is identical to that observed in individuals with sporadic PD, patients are normally given dopaminergic therapy to alleviate motor symptomology, without addressing non-motor symptoms or other aspects influencing disease progression. SUMMARY Some embodiments provide a compound of Formula (I): ) or a pharmaceutically acceptable salt thereof, wherein: X is N or CRX; R1is C1-C6 alkyl or C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl; R2is C1-C6 haloalkyl, C1-C6 haloalkoxy, benzyloxy, -NR2AR2B, or hydroxyl; R2Aand R2Bare independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; or R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1-NR2CR2D; each R2Cand R2Dare independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 hydroxyalkyl; R3is (CR3ER3F)0-1-(6-12 membered aryl) (CR3ER3F)0-1-(6-12 membered heterocyclyl), (CR3ER3F)0-1-(6-12 membered heteroaryl), -NR3AR3B, -OR3C, -C(=O)NR3AR3B, -N(R3A)C(=O)R3D, or -C(=O)R3D, wherein each of the 6-12 membered aryl, 6-12 membered heterocyclyl, and 6-12 membered heteroaryl are optionally substituted; each of R3A, R3B, R3C, and R3Dis independently selected from: (i) hydrogen; (ii) C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano; (iii) C1-C6 haloalkyl; (iv) 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl; (v) C1-C6 alkyl(4-6 membered heterocyclyl), wherein the 4-6 membered heterocyclyl is optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy); (vi) 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy; and (vii) C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;R3Eand R3Fare each independently hydrogen, C1-C3 alkyl, cyano, hydroxyl, or halogen; and RX, R4, and R5are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cyano, halogen, or C3-C6 cycloalkyl; wherein (i) when X is CRXand R2is -NR2AR2B, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one or optionally substituted 1'H-spiro[cyclopropane-1,6'- pyrrolo[3,4-b]pyrrol]-4'(5'H)-one; or (ii) when X is CRX, R1is C1-C6 alkyl, and R2is -NR2AR2B, wherein one of R2Aand R2Bis hydrogen and the other of R2Aand R2Bis C1-C6 alkyl, then R3is not an optionally substituted 1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one or optionally substituted 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one; or (iii) when X is CRX, and R2is -OR, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one. Also provided herein is a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. Provided herein is a method for treating a GCase-associated disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. Provided herein is a method of treating a GCase-associated disorder in a subject, the method comprising administering to a subject identified or diagnosed as having a GCase-associated disorder a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as provided herein. In some embodiments, the GCase-associated disorder is a lysosomal storage disorder or a neurodegenerative disorder. Other embodiments include those described in the Detailed Description and / or in the claims. Additional Definitions To facilitate understanding of the disclosure set forth herein, a number of additional terms are defined below. Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, and pharmacology described herein are those well-known and commonly employed in the art. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Each of the patents, applications, published applications, and other publications that are mentioned throughout the specification and the attached appendices are incorporated herein by reference in their entireties. The term “about” when referring to a number or a numerical range means that the number or numerical range referred to is an approximation, for example, within experimental variability and / or statistical experimental error, and thus the number or numerical range may vary up to ±10% of the stated number or numerical range. The term “acceptable” with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated. As used herein, the “subject” refers to any animal, including mammals such as primates (e.g., humans), mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, and humans. In some embodiments, the subject is a human. In some embodiments, the subject has experienced and / or exhibited at least one symptom of the disease to be treated. As used herein, terms “treat” or “treatment” refer to therapeutic or palliative measures. Beneficial or desired clinical results include, but are not limited to, alleviation, in whole or in part, of symptoms associated with a disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. “Treatment” can also mean prolonging survival as compared to expected survival if not receiving treatment. The phrase “therapeutically effective amount” means an amount of compound that, when administered to a subject in need of such treatment, is sufficient to achieve a desired beneficial result, for example, a reduction of symptoms in a subject, prolonging the life of a subject, improving the quality of life of a subject, and the like. The term “pharmaceutically acceptable excipient” means a pharmaceutically-acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, carrier, solvent, or encapsulating material. In one embodiment, each component is “pharmaceutically acceptable” in the sense of being compatible with the other ingredients of a pharmaceutical formulation, and suitable for use in contact with the tissue or organ of humans and animals without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, commensurate with a reasonable benefit / risk ratio. See, e.g., Remington: The Science and Practice of Pharmacy, 21st ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, FL, 2009. The term “pharmaceutically acceptable salt” refers to a formulation of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In certain instances, pharmaceutically acceptable salts are obtained by reacting a compound described herein, with acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. In some instances, pharmaceutically acceptable salts are obtained by reacting a compound having acidic group described herein with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium or a potassium salt, an alkaline earth metal salt, such as a calcium or a magnesium salt, a salt of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, and salts with amino acids such as arginine, lysine, and the like, or by other methods previously determined. The pharmacologically acceptable salt s not specifically limited as far as it can be used in medicaments. Examples of a salt that the compounds described hereinform with a base include the following: salts thereof with inorganic bases such as sodium, potassium, magnesium, calcium, and aluminum; salts thereof with organic bases such as methylamine, ethylamine and ethanolamine; salts thereof with basic amino acids such as lysine and ornithine; and ammonium salt. The salts may be acid addition salts, which are specifically exemplified by acid addition salts with the following: mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid:organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; acidic amino acids such as aspartic acid and glutamic acid. Whenever a group is described as being “optionally substituted” that group may be unsubstituted or substituted with one or more of the indicated substituents. Likewise, when a group is described as being “substituted” the substituent(s) may be selected from one or more the indicated substituents. If no substituents are indicated, it is meant that the indicated “optionally substituted” or “substituted” group may be substituted with one or more individually and independently selected group(s) that are stable and chemically acceptable for the group being substituted. Non-limiting examples of optional substituents are halogen, cyano, hydroxyl, nitro, nitroso, azido, sulfhydryl, acyl, alkyl, hydroxyalkyl, aminoalkyl, alkoxyamino, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxy, hydroxyalkoxy, alkoxyalkoxy, alkenoxy, alkynoxy, haloalkoxy, haloalkenoxy, haloalkynoxy, cycloalkyl, halocycloalkyl, cycloalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, aralkyl, cycloalkylalkyl, heteroaralkyl, alkoxyalkyl, heterocyclylalkyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N- thiocarbamyl, alkoxycarbonyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, sulfenyl, halosulfenyl, sulfonyl, sulfinyl, sulfoximino, sulfonimidamido, phosphine oxide, C-carboxy, O- carboxy, arylalkoxy, cycloalkylalkoxy, carboxaldehyde, iminyl, trihalomethanesulfonyl, trihalomethanesulfonamido, phosphityl, phosphonityl, phosphinityl, phosphinyl, phosphatyl, phosphinatyl, phosphonatyl, and ureido. In some embodiments, the optional substituents listed above can be further optionally substituted with 1-5 substituents independently selected from halogen, cyano, hydroxyl, acyl, alkyl, hydroxyalkyl, aminoalkyl, alkoxyamino, haloalkyl, alkoxy, hydroxyalkoxy, alkoxyalkoxy, haloalkoxy, cycloalkyl, halocycloalkyl, cycloalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclyl, heterocyclyloxy, aralkyl, cycloalkylalkyl, heteroaralkyl, alkoxyalkyl, and heterocyclylalkyl. The term “halogen” refers to fluoro (F), chloro (Cl), bromo (Br), or iodo (I). The term “oxo” refers to a divalent doubly bonded oxygen atom (i.e., “=O”). As used herein, oxo groups are attached to carbon atoms to form carbonyls. The term “hydroxyl” refers to an -OH radical. The term “sulfhydryl” refers to a –SH radical. The term “cyano” refers to a -CN radical. The term “azido” refers to a –N3radical. The term “nitro” refers to a –NO2radical. The term “nitroso” refers to a –N=O radical. The term “alkyl” refers to a saturated acyclic hydrocarbon radical that may be a straight chain or branched chain, containing the indicated number of carbon atoms. For example, C1-C10 indicates that the group may have from 1 to 10 (inclusive) carbon atoms in it. Non-limiting examples include methyl, ethyl, iso-propyl, tert-butyl, n-hexyl. The term “saturated” as used in this context means only single bonds present between constituent carbon atoms and other available valences occupied by hydrogen and / or other substituents as defined herein. The term “acyl” refers to a –C(=O)alkyl radical (e.g., acetyl), or a –C(=O)alkenyl radical (e.g., -C(=O)-CH=CH2), or –C(=O)alkynyl radical (e.g., ). Acyl groups can be substituted with cyano or with 1-3 independently selected halogens. As used herein, “alkenyl” refers to an alkyl group that contains in the straight or branched hydrocarbon chain one or more double bonds. As used herein, “alkynyl” refers to an alkyl group that contains in the straight or branched hydrocarbon chain one or more triple bonds. The term “heteroalkyl” refers to an alkyl group as defined herein, wherein one or more carbon atoms in the alkyl group are replaced by a heteroatom (e.g., N, O, S, P, or Si). The term “aryl” refers to a 6-20 carbon mono-, bi-, tri- or polycyclic group wherein at least one ring in the system is aromatic (e.g., 6-carbon monocyclic, 10-carbon bicyclic, or 14-carbon tricyclic aromatic ring system); and wherein 0, 1, 2, 3, or 4 atoms of each ring may be substituted by a substituent. Examples of aryl groups include phenyl, naphthyl, tetrahydronaphthyl, and the like. The term “cycloalkyl” as used herein refers to cyclic saturated or partially unsaturated hydrocarbon groups having, e.g., 3 to 20 ring carbons, preferably 3 to 16 ring carbons, and more preferably 3 to 12 ring carbons or 3-10 ring carbons or 3-6 ring carbons, wherein the cycloalkyl group may be optionally substituted. Examples of cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. Cycloalkyl may include multiple fused and / or bridged rings. Non-limiting examples of fused / bridged cycloalkyl includes: bicyclo[1.1.0]butane, bicyclo[2.1.0]pentane, bicyclo[1.1.1]pentane, bicyclo[3.1.0]hexane, bicyclo[2.1.1]hexane, bicyclo[3.2.0]heptane, bicyclo[4.1.0]heptane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[4.2.0]octane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, and the like. Cycloalkyl also includes spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic cycloalkyls include spiro[2.2]pentane, spiro[2.5]octane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[3.5]nonane, spiro[4.4]nonane, spiro[2.6]nonane, spiro[4.5]decane, spiro[3.6]decane, spiro[5.5]undecane, and the like. The term “saturated” as used in this context means only single bonds present between constituent carbon atoms. The term “heteroaryl,” as used herein, means a mono-, bi-, tri- or polycyclic group having 5 to 20 ring atoms, alternatively 5, 6, 9, 10, or 14 ring atoms; wherein at least one ring in the system contains one or more heteroatoms independently selected from the group consisting of N, O, S, P, B, and Si and at least one ring in the system is aromatic (but does not have to be a ring which contains a heteroatom, e.g., tetrahydroisoquinolinyl, e.g., tetrahydroquinolinyl). Examples of heteroaryl include thienyl, pyridinyl, furyl, oxazolyl, oxadiazolyl, pyrrolyl, imidazolyl, triazolyl, thiodiazolyl, pyrazolyl, isoxazolyl, thiadiazolyl, pyranyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl benzothienyl, benzoxadiazolyl, benzofuranyl, benzimidazolyl, benzotriazolyl, cinnolinyl, indazolyl, indolyl, isoquinolinyl, isothiazolyl, naphthyridinyl, purinyl, thienopyridinyl, pyrido[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyridinyl, quinazolinyl, quinolinyl, thieno[2,3- c]pyridinyl, pyrazolo[3,4-b]pyridinyl, pyrazolo[3,4-c]pyridinyl, pyrazolo[4,3-c]pyridine, pyrazolo[4,3-b]pyridinyl, tetrazolyl, chromane, 2,3-dihydrobenzo[b][1,4]dioxine, benzo[d][1,3]dioxole, 2,3-dihydrobenzofuran, tetrahydroquinoline, 2,3- dihydrobenzo[b][1,4]oxathiine, isoindoline, and others. In some embodiments, the heteroaryl is selected from thienyl, pyridinyl, furyl, pyrazolyl, imidazolyl, isoindolinyl, pyranyl, pyrazinyl, and pyrimidinyl. Heteroaryl groups can also include oxidized atoms, such as C or S (e.g., as C=O). For purposes of clarification, heteroaryl also includes aromatic lactams, aromatic cyclic ureas, or vinylogous analogs thereof, in which each ring nitrogen adjacent to a carbonyl is tertiary (i.e., all three valences are occupied by non-hydrogen substituents), such as one or more of pyridone (e.g., imidazolone (e.g., ), wherein each ring nitrogen adjacent to a carbonyl is tertiary (i.e., the oxo group (i.e., “=O”) herein is a constituent part of the heteroaryl ring). The term “heterocyclyl” refers to a mono-, bi-, tri-, or polycyclic saturated or partially unsaturated ring system with 3-16 ring atoms (e.g., 5-8 membered monocyclic, 8-12 membered bicyclic, or 11-14 membered tricyclic ring system) having 1-3 heteroatoms if monocyclic, 1-6 heteroatoms if bicyclic, or 1-9 heteroatoms if tricyclic or polycyclic, said heteroatoms selected from O, N, P, S, B, or Si (e.g., carbon atoms and 1-3, 1-6, or 1-9 heteroatoms of N, O, P, S, B, or Si if monocyclic, bicyclic, or tricyclic, respectively), wherein one or more ring atoms may be oxidized (forming, e.g., a carbonyl, a lactam, or a phosphinane oxide) and one or more N or S atoms may be oxidized (forming, e.g., an N-oxide, an S-oxide, or an S,S-dioxide),valence permitting. Examples of heterocyclyl groups include piperazinyl, pyrrolidinyl, dioxanyl, morpholinyl, tetrahydrofuranyl, tetrahydropyridyl, dihydropyrazinyl, dihydropyridyl, dihydropyrrolyl, dihydrofuranyl, dihydrothiophenyl, oxaphosphinanyl oxide, azaphosphinanyl oxide, and the like. Heterocyclyl may include multiple fused and bridged rings. Non-limiting examples of fused / bridged heteorocyclyl include: 2-azabicyclo[1.1.0]butane, 2- azabicyclo[2.1.0]pentane, 2-azabicyclo[1.1.1]pentane, 3-azabicyclo[3.1.0]hexane, 5- azabicyclo[2.1.1]hexane, 3-azabicyclo[3.2.0]heptane, octahydrocyclopenta[c]pyrrole, 3- azabicyclo[4.1.0]heptane, 7-azabicyclo[2.2.1]heptane, 6-azabicyclo[3.1.1]heptane, 7- azabicyclo[4.2.0]octane, 2-azabicyclo[2.2.2]octane, 3-azabicyclo[3.2.1]octane, 2- oxabicyclo[1.1.0]butane, 2-oxabicyclo[2.1.0]pentane, 2-oxabicyclo[1.1.1]pentane, 3- oxabicyclo[3.1.0]hexane, 5-oxabicyclo[2.1.1]hexane, 3-oxabicyclo[3.2.0]heptane, 3- oxabicyclo[4.1.0]heptane, 7-oxabicyclo[2.2.1]heptane, 6-oxabicyclo[3.1.1]heptane, 7- oxabicyclo[4.2.0]octane, 2-oxabicyclo[2.2.2]octane, 3-oxabicyclo[3.2.1]octane, and the like. Heterocyclyl also includes spirocyclic rings (e.g., spirocyclic bicycle wherein two rings are connected through just one atom). Non-limiting examples of spirocyclic heterocyclyls include 2- azaspiro[2.2]pentane, 4-azaspiro[2.5]octane, 1-azaspiro[3.5]nonane, 2-azaspiro[3.5]nonane, 7- azaspiro[3.5]nonane, 2-azaspiro[4.4]nonane, 6-azaspiro[2.6]nonane, 1,7-diazaspiro[4.5]decane, 7-azaspiro[4.5]decane 2,5-diazaspiro[3.6]decane, 3-azaspiro[5.5]undecane, 2- oxaspiro[2.2]pentane, 4-oxaspiro[2.5]octane, 1-oxaspiro[3.5]nonane, 2-oxaspiro[3.5]nonane, 7- oxaspiro[3.5]nonane, 2-oxaspiro[4.4]nonane, 6-oxaspiro[2.6]nonane, 1,7-dioxaspiro[4.5]decane, 2,5-dioxaspiro[3.6]decane, 1-oxaspiro[5.5]undecane, 3-oxaspiro[5.5]undecane, 3-oxa-9- azaspiro[5.5]undecane, and the like. As used herein, examples of aromatic rings include: benzene, pyridine, pyrimidine, pyrazine, pyridazine, pyridone, pyrrole, pyrazole, oxazole, thioazole, isoxazole, isothiazole, and the like. The term “haloalkyl” refers to an alkyl, in which one or more hydrogen atoms is / are replaced with an independently selected halogen. The term “halocycloalkyl” refers to a cycloalkyl, in which one or more hydrogen atoms is / are replaced with an independently selected halogen. The term “hydroxyalkyl” refers to an alkyl, in which one or more hydrogen atoms is / are replaced with hydroxyl. The term “haloalkenyl” refers to an alkenyl, in which one or more hydrogen atoms is / are replaced with an independently selected halogen. The term “haloalkynyl” refers to an alkynyl, in which one or more hydrogen atoms is / are replaced with an independently selected halogen. The term “alkoxy” refers to an -O-alkyl radical (e.g., -OCH3). The term “alkoxyalkyl” refers to an alkyl, in which one or two hydrogen atoms is / are replaced with an independently selected alkoxy (e.g., methoxyethyl). The term “hydroxyalkoxy” refers to an alkoxy group, in which one or two hydrogen atoms is / are replaced with hydroxy. The term “cyanoalkyl” refers to an alkyl group, in which one or two hydrogen atoms is / are replaced with cyano. The term “alkoxyalkoxy” refers to an alkoxy group, in which one or two hydrogen atoms is / are replaced with an independently selected alkoxy. The term “alkoxyamino” refers to an –O-amino radical (e.g., -OCH2CH2N(CH3)2). The term “haloalkoxy” refers to an -O-haloalkyl radical (e.g., -OCF3). The term “alkenoxy” refers to an -O-alkenyl radical (e.g., -O-allyl). The term “haloalkenoxy” refers to an -O-haloalkenyl radical. The term “alkynoxy” refers to an -O-alkynyl radical (e.g., -O-propargyl). The term “haloalkynoxy” refers to an -O-haloalkynyl radical. The term “cycloalkoxy” refers to an -O-cycloalkyl radical (e.g., -O-cyclopropyl). The term “aryloxy” refers to an -O-aryl radical (e.g., phenoxy). The term “heteroaryloxy” refers to an -O-heteroaryl radical (e.g., pyridinoxy). The term “heterocyclyloxy” refers to an -O-heterocyclyl radical (e.g., -O-pyrrolidinyl or –O-oxetanyl). The term “aralkyl” refer to an aryl group connected, as a substituent, via an alkyl group (e.g., benzyl). The term “cycloalkylalkyl” refers to a cycloalkyl group connected, as a substituent, via an alkyl group (e.g., ethylcyclobutyl). The term “heteroaralkyl” refers to a heteroaryl group connected, as a substituent, via an alkyl group (e.g., methylpyrimidinyl). The term “heterocyclylalkyl” refers to a heterocyclyl group connected, as a substituent, via an alkyl group (e.g., methyloxetanyl). The term “aralkoxy” refers to an aryl group connected, as a substituent, via an alkoxy group (e.g., benzyloxy). The term “cycloalkylalkoxy” refers to a cycloalkyl connected, as a substituent, via an alkoxy group (e.g., methoxycyclopropyl). The term “aminoalkyl” refers to an amino group connected, as a substituent, via an alkyl group (e.g., methyl(dimethylamino)). A “sulfenyl” group refers to an -SR group in which R can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. A “halosulfenyl” group refers to a sulfenyl, in which one or more hydrogen atoms is / are replaced with an independently selected halogen (e.g., -S(CF3) or –S(CHF2)). A “sulfinyl” group refers to an -S(=O)R group in which R can be the same as defined with respect to sulfenyl. A “sulfonyl” group refers to an -SO2R group in which R can be the same as defined with respect to sulfenyl. A “sulfoximine” group refers to an –S(=O)(=NR)R’, where R is hydrogen, alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl; and where R’ alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. A “sulfonimidamido” group refers to an –S(=O)(=NR)NR’R” where R, R’, and R” are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl; and where R’ alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “O-carboxy” group refers to a RC(=O)O- group in which R can be hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. The terms “ester” and “C-carboxy” refer to a -C(=O)OR group in which R can be the same as defined with respect to O-carboxy. A “thiocarbonyl” group refers to a -C(=S)R group in which R can be the same as defined with respect to O-carboxy. A “trihalomethanesulfonyl” group refers to an X3CSO2- group wherein each X is a halogen. A “trihalomethanesulfonamido” group refers to an X3CS(=O)2N(R’)- group wherein each X is a halogen, and R’ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “S-sulfonamido” group refers to a -SO2N(RR’) group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “N-sulfonamido” group refers to a RSO2N(R’)- group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “O-carbamyl” group refers to a -OC(=O)N(RR’) group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “N-carbamyl” group refers to an ROC(=O)N(R’)- group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “O-thiocarbamyl” group refers to a -OC(=S)N(RR’) group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “N-thiocarbamyl” group refers to an ROC(=S)N(R’)— group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. A “C-amido” group refers to a -C(=O)N(RR’) group in which R and R’ are independently hydrogen, alkyl, alkoxy, alkoxyalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. An “N-amido” group refers to a RC(=O)N(R’) group in which R and R’ are independently hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. The terms “ureido” or “urea” refer to an –NR(C=O)NR’R’’ group, in which R, R’, and R” are independently hydrogen, hydroxyl, alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. The term “carboxaldehyde” refers to a –C(=O)H radical. The term “imine” or “imino” refers to a –N=R radical, in which R is hydrogen, hydroxyl, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. The term “amino” refers to a –NRR’ radical, where R and R’ are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. In some instances, an amino group is –NH2, a mono-alkyl amine (R is hydrogen and R’ is alkyl) or a dialkylamine (R and R’ are independently selected alkyl). The term “phosphine oxide” refers to a –P(=O)RR’ radical, where R and R’ are independently alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aralkyl heteroaralkyl, heterocyclylalkyl, or cycloalkylalkyl. As used herein, when a ring is described as being “partially unsaturated”, it means said ring has one or more additional degrees of unsaturation (in addition to the degree of unsaturation attributed to the ring itself; e.g., one or more double or triple bonds between constituent ring atoms), provided that the ring is not aromatic. Examples of such rings include: cyclopentene, cyclohexene, cycloheptene, dihydropyridine, tetrahydropyridine, dihydropyrrole, dihydrofuran, dihydrothiophene, and the like. In some embodiments, such as the 1,4- azaphosphinane-4-oxide of Ring B described herein, there is a phospine oxide in a ring, where R and “-” are the points of connection of the phosphorus atom to the ring and R’ is as described above. For the avoidance of doubt, and unless otherwise specified, for rings and cyclic groups (e.g., aryl, heteroaryl, heterocyclyl, cycloalkyl, and the like described herein) containing a sufficient number of ring atoms to form bicyclic or higher order ring systems (e.g., tricyclic, polycyclic ring systems), it is understood that such rings and cyclic groups encompass those having fused rings, including those in which the points of fusion are located (i) on adjacent ring atoms (e.g., [x.x.0] ring systems, in which 0 represents a zero atom bridge (e.g., )); (ii) a single ring atom (spiro-fused ring systems) (e.g., ), or (iii) a contiguous array of ring atoms (bridged ring systems having all bridge lengths > 0) (e.g., . In addition, atoms making up the compounds of the present embodiments are intended to include all isotopic forms of such atoms. Isotopes, as used herein, include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include13C and14C. In addition, the compounds generically or specifically disclosed herein are intended to include all tautomeric forms. Thus, by way of example, a compound containing the moiety: encompasses the tautomeric form containing the moiety: . Similarly, a pyr d ny or pyrimidinyl moiety that is described to be optionally s ubstituted with hydroxyl encompasses pyridone or pyrimidone tautomeric forms. The compounds provided herein may encompass various stereochemical forms. The compounds also encompass enantiomers (e.g., R and S isomers), diastereomers, as well as mixtures of enantiomers (e.g., R and S isomers) including racemic mixtures and mixtures of diastereomers, as well as individual enantiomers and diastereomers, which arise as a consequence of structural asymmetry in certain compounds. Unless otherwise indicated, when a disclosed compound is named or depicted by a structure without specifying the stereochemistry (e.g., a “flat” structure) and has one or more chiral centers, it is understood to represent all possible stereoisomers of the compound. Likewise, unless otherwise indicated, when a disclosed compound is named or depicted by a structure that specifies the stereochemistry (e.g., a structure with “wedge” and / or “dashed” bonds) and has one or more chiral centers, it is understood to represent the indicated stereoisomer of the compound. The details of one or more embodiments of this disclosure are set forth in the accompanying drawings and the description below. Other features and advantages of the present disclosure will be apparent from the description and drawings, and from the claims. DETAILED DESCRIPTION This disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that modulate GCase function. Formula (I) Compounds Some embodiments provide a compound of Formula (I): ) or a pharmaceutically acceptable salt ther eo , w ere n: X is N or CRX; R1is C1-C6 alkyl or C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl; R2is C1-C6 haloalkyl, C1-C6 haloalkoxy, benzyloxy, -NR2AR2B, or hydroxyl; R2Aand R2Bare independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; or R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1-NR2CR2D; each R2Cand R2Dare independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 hydroxyalkyl; R3is (CR3ER3F)0-1-(6-12 membered aryl) (CR3ER3F)0-1-(6-12 membered heterocyclyl), (CR3ER3F)0-1-(6-12 membered heteroaryl), -NR3AR3B, -OR3C, -C(=O)NR3AR3B, -N(R3A)C(=O)R3D, or -C(=O)R3D, wherein each of the 6-12 membered aryl, 6-12 membered heterocyclyl, and 6-12 membered heteroaryl are optionally substituted; each of R3A, R3B, R3C, and R3Dis independently selected from: (i) hydrogen; (ii) C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano; (iii) C1-C6 haloalkyl; (iv) 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl; (v) C1-C6 alkyl(4-6 membered heterocyclyl), wherein the 4-6 membered heterocyclyl is optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy); (vi) 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy; and (vii) C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;R3Eand R3Fare each independently hydrogen, C1-C3 alkyl, cyano, hydroxyl, or halogen; and RX, R4, and R5are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cyano, halogen, or C3-C6 cycloalkyl; wherein (i) when X is CRXand R2is -NR2AR2B, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one or optionally substituted 1'H-spiro[cyclopropane-1,6'- pyrrolo[3,4-b]pyrrol]-4'(5'H)-one; or (ii) when X is CRX, R1is C1-C6 alkyl, and R2is -NR2AR2B, wherein one of R2Aand R2Bis hydrogen and the other of R2Aand R2Bis C1-C6 alkyl, then R3is not an optionally substituted 1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one or optionally substituted 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one; or (iii) when X is CRX, and R2is -OR, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one. Some embodiments provide a compound of Formula (I-IA): or a pharmaceutically acceptable salt thereof, wherein: R1is C1-C6 alkyl or C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl; R2is C1-C6 haloalkyl, C1-C6 haloalkoxy, benzyloxy, -NR2AR2B, or hydroxyl; R2Aand R2Bare independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; or R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; R3is an optionally substituted 6-12 membered aryl, an optionally substituted 6-12 membered heterocyclyl, an optionally substituted 6-12 membered heteroaryl, -NR3AR3B, -OR3C, or -C(=O)R3D; X is N or CRX; R3A, R3B, R3C, and R3Dare each independently hydrogen, C1-C6 alkyl, 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl, C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl), or 5- 6 membered heteroaryl optionally substituted with 1-2 substituents independently selected from halogen, cyano, and C1-C6 alkyl; and RX, R4, and R5are each independently hydrogen, C1-C6 alkyl, or halogen; wherein when R2is -NR2AR2Band one of R2Aand R2Bis hydrogen, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one. In some embodiments, R1is C1-C6 alkyl. In some embodiments, R1is methyl or isopropyl. In some embodiments, R1is C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl. In some embodiments, R1is C3-C10 cycloalkyl substituted with C1-C6 alkyl. In some embodiments, R1is C3-C10 cycloalkyl. In some embodiments, R1is cyclopentyl. In some embodiments, R2is C1-C6 haloalkyl. In some embodiments, R2is -CF3. In some embodiments, R2is C1-C6 haloalkoxy. In some embodiments, R2is C1-C3 haloalkoxy. In some embodiments, R2is . In some embodiments, R2is benzyloxy. In some embodiments, R2is -NR2AR2B. In some embodiments, R2Aand R2Bare each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl. In some embodiments, R2Aand R2Bare each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)-NR2CR2D. In some embodiments, each R2Cand R2Dare independently selected from hydrogen, C1- C6 alkyl, C1-C6 haloalkyl, and C1-C6 hydroxyalkyl. In some embodiments, R2Cand R2Dare both hydrogen. In some embodiments, one of R2Cand R2Dis hydrogen and the other one of R2Cand R2Dis C1-C6 alkyl. In some embodiments, one of R2Cand R2Dis hydrogen and the other one of R2Cand R2Dis C1-C6 haloalkyl. In some embodiments, one of R2Cand R2Dis hydrogen and the other one of R2Cand R2Dis C1-C6 hydroxyalkyl. In some embodiments, R2Aand R2Bare both hydrogen. In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2Aand R2Bis C1-C6 alkyl. In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2Aand . In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2Aand R2Bis C1-C6 haloalkyl. In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2A. In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2Aand R2Bis a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl. In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2Aand R2Bis a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl. In some embodiments, one of R2Aand R2Bis hydrogen and the other one of R2Aand R2Bis In some embodiments, each R2Aand R2Bis independently C1-C6 alkyl. In some embodiments, both of R2Aand R2Bare methyl or both of R2Aand R2Bare ethyl. In some embodiments, R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1- C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1-NR2CR2D. In some embodiments, R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1- C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1-NR2CR2D. In some embodiments, R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl. In some embodiments, R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1- C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1- NR2CR2D. In some embodiments, R2Aand R2Btogether with the nitrogen atom to which they are attached form an optionally substituted heterocyclyl selected from the group consisting of In some embodiments, each R2Cand R2Dare independently selected from hydrogen, C1- C6 alkyl, C1-C6 haloalkyl, and C1-C6 hydroxyalkyl. In some embodiments, both R2Cand R2Dare hydrogen. In some embodiments, one of R2Cand R2Dis hydrogen and the other one of R2Cand R2Dis C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 hydroxyalkyl. In some embodiments, both R2Cand R2Dare independently selected from C1-C6 alkyl, C1- C6 haloalkyl, and C1-C6 hydroxyalkyl. In some embodiments, R2is hydroxyl. In some embodiments, R3is an optionally substituted 6-12 membered aryl. In some embodiments, R3is an optionally substituted phenyl. In some embodiments, R3is (CR3ER3F)0-1-(optionally substituted 6-12 membered aryl). In some embodiments, R3is (CR3ER3F)0-1-(optionally substituted phenyl). In some embodiments, R3is (CR3ER3F)-(optionally substituted phenyl). In some embodiments, R3is optionally substituted 6-12 membered heteroaryl. In some embodiments, R3is selected from the group consisting of , wherein “*” indicates hydrogen or an optional substituent. In some embodiments, R3is anoptionally substituted 6-12 membered heteroaryl. In some embodiments, R3is an optionallysubstituted 6-membered heteroaryl. In some embodiments, R3is selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,4- triazinyl, and 1,3,5-triazinyl, each of which is optionally substituted. In some embodiments, R3is an optionally substituted pyridinyl. In some embodiments, R3is (CR3ER3F)0-1-(optionally substituted 6-12 membered heteroaryl). In some embodiments, the heteroaryl of R3is selected from the group consisting of ,wherein “*” indicates hydrogen or an optional substituent. In some embodiments, R3is (CR3ER3F)0-1-(optionally substituted 6-12 membered heteroaryl). In some embodiments, R3is (CR3ER3F)0-1-(optionally substituted 6-membered heteroaryl). In some embodiments, R3is selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, and 1,3,5-triazinyl, each of which is optionally substituted. In some embodiments, R3is an optionally substituted pyridinyl. In some embodiments, R3is an optionally substituted 9-10 membered heteroaryl. In some embodiments, R3is an optionally substituted 9 membered heteroaryl selected from thegroup consisting of , wherein “*” indicates hydrogen or an optional substituent. In some embodiments, R3is an optionally substituted 10 membered heteroaryl selected from the group consisting of , and wherein “*” indicates hydrogen or an optional substituent. In some embodiments, R3is an optionally substituted (CR3ER3F)0-1-(6-12 membered heterocyclyl). In some embodiments, R3is an optionally substituted 6-12 membered heterocyclyl. In some embodiments, R3is -NR3AR3B. In some embodiments, one of R3Aand R3Bis hydrogen, and the other one of of R3Aand R3Bis 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl. In some embodiments, one of R3Aand R3Bis hydrogen, and the other one of of R3Aand R3Bis selected from the group consisting of , , wherein “*” indicates hydrogen or an optional subst tue t. so e e bod e ts, o e o3Aand R3Bis C1-C6 alkyl, and the other one of R3Aand R3Bis 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1- C6 alkyl. In some embodiments, one of R3Aand R3Bis methyl, and the other one of R3Aand R3Bis selected from the group consisting of . In some embodiments, one of R3Aand R3Bis hydrogen or C1-C6 alkyl, and the other one of R3Aand R3Bis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl). In some embodiments, one of R3Aand R3Bis hydrogen, and the other one of R3Aand R3Bis C1-C6 alkyl. In some embodiments, -NR3AR3Bis -NHAc. In some embodiments, one of R3Aand R3Bis hydrogen, and the other one of R3Aand R3Bis selected from the group consisting of . In some embodiments, one of R3Aand R3Bis hydrogen or C1-C6 alkyl, and the other one of R3Aand R3Bis 5-6 membered heteroaryl optionally substituted with 1-2 substituents independently selected from halogen, cyano, and C1-C6 alkyl. In some embodiments, one of R3Aand R3Bis hydrogen, and the other one of R3Aand R3Bis selected from the group consisting , wherein wherein “*” indicates hydrogen or an optional substituent. In some embodiments, one of R3Aand R3Bis methyl, and the other one of R3Aand R3Bis 4-pyridyl. In some embodiments, R3is -OR3C. In some embodiments, R3Cis . bodiments, R3is -C(=O)NR3AR3B In some em . In some embodiments, R3is -C(=O)NHR3B. In some embodiments, R3is -C(=O)NH2. In some embodiments, R3is -C(=O)NH(C1-C6 alkyl). In some embodiments, R3is -N(R3A)C(=O)R3D. In some embodiments, R3is - NHC(=O)R3D. In some embodiments, R3is -NHC(=O)(C1-C6 alkyl). In some embodiments, R3is C(=O)R3D, in which R3Dis 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl. In some embodiments, R3Dis In some embodiments, R3Ais hydrogen. In some embodiments, R3Ais C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Ais C1-C6 alkyl. In some embodiments, R3Ais C1-C6 alkyl substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Ais C1-C6 haloalkyl. In some embodiments, R3Ais trifluoromethyl. In some embodiments, R3Ais 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Ais 5-12 membered heterocyclyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Ais 5-12 membered heterocyclyl. In some embodiments, R3Ais C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Ais C1-C6 alkyl(4-6 membered heterocyclyl substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Ais C1-C6 alkyl(4-6 membered heterocyclyl). In some embodiments, R3Ais 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Ais 5-6 membered heteroaryl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Ais 5-6 membered heteroaryl. In some embodiments, R3Ais C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Ais C3-C10 cycloalkyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Ais C3-C10 cycloalkyl. In some embodiments, R3Bis hydrogen. In some embodiments, R3Bis C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Bis C1-C6 alkyl. In some embodiments, R3Bis C1-C6 alkyl substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Bis C1-C6 haloalkyl. In some embodiments, R3Bis trifluoromethyl. In some embodiments, R3Bis 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Bis 5-12 membered heterocyclyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Bis 5-12 membered heterocyclyl. In some embodiments, R3Bis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Bis C1-C6 alkyl(4-6 membered heterocyclyl substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Bis C1-C6 alkyl(4-6 membered heterocyclyl). In some embodiments, R3Bis 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Bis 5-6 membered heteroaryl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Bis 5-6 membered heteroaryl. In some embodiments, R3Bis C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Bis C3-C10 cycloalkyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Bis C3-C10 cycloalkyl. In some embodiments, R3Cis hydrogen. In some embodiments, R3Cis C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Cis C1-C6 alkyl. In some embodiments, R3Cis C1-C6 alkyl substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Cis C1-C6 haloalkyl. In some embodiments, R3Cis trifluoromethyl. In some embodiments, R3Cis 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Cis 5-12 membered heterocyclyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Cis 5-12 membered heterocyclyl. In some embodiments, R3Cis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Cis C1-C6 alkyl(4-6 membered heterocyclyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Cis C1-C6 alkyl(4-6 membered heterocyclyl). In some embodiments, R3Cis 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Cis 5-6 membered heteroaryl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Cis 5-6 membered heteroaryl. In some embodiments, R3Cis C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Cis C3-C10 cycloalkyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Cis C3-C10 cycloalkyl. In some embodiments, R3Dis hydrogen. In some embodiments, R3Dis C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Dis C1-C6 alkyl. In some embodiments, R3Dis C1-C6 alkyl substituted with 1-3 substituents independently selected from hydroxyl and cyano. In some embodiments, R3Dis C1-C6 haloalkyl. In some embodiments, R3Dis trifluoromethyl. In some embodiments, R3Dis 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Dis 5-12 membered heterocyclyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl. In some embodiments, R3Dis 5-12 membered heterocyclyl. In some embodiments, R3Dis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Dis C1-C6 alkyl(4-6 membered heterocyclyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy). In some embodiments, R3Dis C1-C6 alkyl(4-6 membered heterocyclyl). In some embodiments, R3Dis 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Dis 5-6 membered heteroaryl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Dis 5-6 membered heteroaryl. In some embodiments, R3Dis C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Dis C3-C10 cycloalkyl substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, R3Dis C3-C10 cycloalkyl. In some embodiments, both R3Eand R3Fare hydrogen. In some embodiments, one of R3Eand R3Fis hydrogen and the other one of R3Eand R3Fis C1-C3 alkyl, cyano, hydroxyl, or halogen. In some embodiments, both R3Eand R3Fare independently selected from C1-C3 alkyl, cyano, hydroxyl, and halogen. In some embodiments, X is CRX. In some embodiments, RXis hydrogen. In some embodiments, RXis C1-C6 alkyl. In some embodiments, RXis methyl. In some embodiments, RXis halogen. In some embodiments, RXis fluoro or chloro. In some embodiments, RXis C1-C6 haloalkyl. In some embodiments, RXis trifluoromethyl. In some embodiments, RXis C1-C6 alkoxy. In some embodiments, RXis methoxy. In some embodiments, RXis cyano. In some embodiments, RXis C3-C6 cycloalkyl. In some embodiments, RXis cyclopropyl. In some embodiments, R4is hydrogen. In some embodiments, R4is C1-C6 alkyl. In some embodiments, R4is methyl. In some embodiments, R4is halogen. In some embodiments, R4is fluoro or chloro. In some embodiments, R4is C1-C6 haloalkyl. In some embodiments, R4is trifluoromethyl. In some embodiments, R4is C1-C6 alkoxy. In some embodiments, R4is methoxy. In some embodiments, R4is cyano. In some embodiments, R4is C3-C6 cycloalkyl. In some embodiments, R4is cyclopropyl In some embodiments, R5is hydrogen. In some embodiments, R5is C1-C6 alkyl. In some embodiments, R5is methyl. In some embodiments, R5is halogen. In some embodiments, R5is fluoro or chloro. In some embodiments, R5is C1-C6 haloalkyl. In some embodiments, R5is trifluoromethyl. In some embodiments, R5is C1-C6 alkoxy. In some embodiments, R5is methoxy. In some embodiments, R5is cyano. In some embodiments, R5is C3-C6 cycloalkyl. In some embodiments, R5is cyclopropyl. In some embodiments, X is N. In some embodiments, R3is unsubstituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one. In some embodiments, when X is CRXand R2is -NR2AR2B, then R3is not optionally substituted 5,6- dihydropyrrolo[3,4-b]pyrrol-4(1H)-one or optionally substituted 1'H-spiro[cyclopropane-1,6'- pyrrolo[3,4-b]pyrrol]-4'(5'H)-one. In some embodiments, when X is CRX, R1is C1-C6 alkyl, and R2is -NR2AR2B, wherein one of R2Aand R2Bis hydrogen and the other of R2Aand R2Bis C1-C6 alkyl, then R3is not optionally substituted 1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one or optionally substituted 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one. In some embodiments, when X is CRX, and R2is -OR, then R3is not optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol- 4(1H)-one. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-A): (I-A) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, and R4are as defined in Formula (I) (or R1, R2, R3, and R4are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-B): or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, and R4are as defined in Formula (I) (or R1, R2, R3, and R4are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-C): or a pharmaceutically acceptable salt thereof, wherein R2, R3, and R4are as defined in Formula (I) (or R2, R3, and R4are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-D): or a pharmaceutically acceptable salt thereof, wherein R2, R3, and R4are as defined in Formula (I) (or R2, R3, and R4are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-E): or a pharmaceutically acceptable salt thereof, wherein R1, R2B, R3, and R4are as defined in Formula (I) (or R1, R2B, R3, and R4are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-F): or a pharmaceutically acceptable salt thereof, wherein R1, R2B, R3, and R4are as defined in Formula (I) (or R1, R2B, R3, and R4are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-G): ) or a pharmaceutically acceptable salt thereof, wherein R , R , and R3are as defined in Formula (I) (or R1, R2, and R3are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-H): or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3are as defined in Formula (I) (or R1, R2, and R3are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-I):

[0002] ) or a pharmaceutically acceptable salt thereof, wherein: R1, R2, and R4are as defined in Formula (I) (or R1, R2, and R4are as defined in Formula (I-IA)); each R3Eis independently halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, 5-6 membered heteroaryl, phenyl, C3-C8 cycloalkyl, -C(=O)C1-C6 alkyl, -C(=O)OC1-C6 alkyl, -C(=O)NH(C1- C6 alkyl), -C(=O)N(C1-C6 alkyl)2, -NH(5-6 membered heterocyclyl), or C1-C6 alkoxy; n is 0, 1, 2, or 3; and Ring A is an optionally substituted 5-6 membered heterocyclyl, an optionally substituted 5-6 membered heteroaryl, or an optionally substituted C5-C6 cycloalkyl. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-J): or a pharmaceutically acceptable salt thereof, wherein: R1, R2, and R4are as defined in Formula (I) (or R1, R2, and R4are as defined in Formula (I-IA)); each R3Eis independently halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, 5-6 membered heteroaryl, phenyl, C3-C8 cycloalkyl, -C(=O)C1-C6 alkyl, -C(=O)OC1-C6 alkyl, -C(=O)NH(C1- C6 alkyl), -C(=O)N(C1-C6 alkyl)2, -NH(5-6 membered heterocyclyl), or C1-C6 alkoxy; n is 0, 1, 2, or 3; and Ring A is an optionally substituted 5-6 membered heterocyclyl, an optionally substituted 5-6 membered heteroaryl, or an optionally substituted C5-C6 cycloalkyl. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-K): or a pharmaceutically acceptable salt thereof, wherein: R1and R2are as defined in Formula (I) (or R1and R2are as defined in Formula (I-IA)); each R3Eis independently halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, 5-6 membered heteroaryl, phenyl, C3-C8 cycloalkyl, -C(=O)C1-C6 alkyl, -C(=O)OC1-C6 alkyl, -C(=O)NH(C1- C6 alkyl), -C(=O)N(C1-C6 alkyl)2, -NH(5-6 membered heterocyclyl), or C1-C6 alkoxy; n is 0, 1, 2, or 3; Ring A is an optionally substituted 5-6 membered heterocyclyl, an optionally substituted 5-6 membered heteroaryl, or an optionally substituted C5-C6 cycloalkyl; and R4is C1-C6 alkyl or halogen. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-L): or a pharmaceutically acceptable salt thereof, wherein: R1and R2are as defined in Formula (I) (or R1and R2are as defined in Formula (I-IA)); each R3Eis independently halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, 5-6 membered heteroaryl, phenyl, C3-C8 cycloalkyl, -C(=O)C1-C6 alkyl, -C(=O)OC1-C6 alkyl, -C(=O)NH(C1- C6 alkyl), -C(=O)N(C1-C6 alkyl)2, -NH(5-6 membered heterocyclyl), or C1-C6 alkoxy; n is 0, 1, 2, or 3; Ring A is an optionally substituted 5-6 membered heterocyclyl, an optionally substituted 5-6 membered heteroaryl, or an optionally substituted C5-C6 cycloalkyl; R4is selected from C1-C6 alkyl and halogen; and Rxis halogen or hydrogen. In some embodiments, R4is C1-C6 alkyl. In some embodiments, R4is methyl. In some embodiments, R4is halogen. In some embodiments, R4is fluoro or chloro. In some embodiments, R4is fluoro. In some embodiments, R4is chloro. In some embodiments, Rxis hydrogen. In some embodiments, Rxis fluoro. In some embodiments, R4is fluoro and Rxis fluoro. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-M): or a pharmaceutically acceptable salt thereof, wherein: each R3Eis independently halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, 5-6 membered heteroaryl, phenyl, C3-C8 cycloalkyl, -C(=O)C1-C6 alkyl, -C(=O)OC1-C6 alkyl, -C(=O)NH(C1- C6 alkyl), -C(=O)N(C1-C6 alkyl)2, -NH(5-6 membered heterocyclyl), or C1-C6 alkoxy; n is 0, 1, 2, or 3; and R1and R2are as defined in Formula (I) (or R1and R2are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-N):

[0003] or a pharmaceutically acceptable salt thereof, wherein: each R3Eis independently halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, 5-6 membered heteroaryl, phenyl, C3-C8 cycloalkyl, -C(=O)C1-C6 alkyl, -C(=O)OC1-C6 alkyl, -C(=O)NH(C1- C6 alkyl), -C(=O)N(C1-C6 alkyl)2, -NH(5-6 membered heterocyclyl), or C1-C6 alkoxy; n is 0, 1, 2, or 3; and R1and R2are as defined in Formula (I) (or R1and R2are as defined in Formula (I-IA)). In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-O): ) or a pharmaceutically acceptable salt t ereo , w ere n: R1and R2are as defined in Formula (I) (or R1and R2are as defined in Formula (I-IA)); and Ring B is an optionally substituted 6-12 membered aryl, an optionally substituted 6-12 membered heterocyclyl, or an optionally substituted 6-12 membered heteroaryl. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-P):

[0004] or a pharmaceutically acceptable salt thereof, wherein: R1and R2are as defined in Formula (I) (or R1and R2are as defined in Formula (I-IA)); and Ring B is an optionally substituted 6-12 membered aryl, an optionally substituted 6-12 membered heterocyclyl, or an optionally substituted 6-12 membered heteroaryl. In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is a compound of Formula (I-Q): ) or a pharmaceutically acceptable sa lt thereof, wherein: R2is C1-C6 haloalkoxy, benzyloxy, or -NR2AR2B; R4is as defined in Formula (I); and Ring B is an 6 membered heteroaryl optionally substituted with 1-3 substitutents independently selected from C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy. In some embodiments, n is 0 or 1. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, each R3Eis independently halogen or C1-C6 alkyl. In some embodiments, each R3Eis independently halogen. In some embodiments, each R3Eis independently C1-C6 alkyl. In some embodiments, each R3Eis independently fluoro or methyl. In some embodiments, each R3Eis fluoro. In some embodiments, each R3Eis methyl. In some embodiments, at least one R3Eis fluoro. In some embodiments, at least one R3Eis chloro. In some embodiments, one R3Eis fluoro. In some embodiments, one R3Eis chloro. In some embodiments, at least one R3Eis cyano. In some embodiments, one R3Ais cyano. In some embodiments, at least one R3Eis C1-C6 alkyl. In some embodiments, at least one R3Ais methyl. In some embodiments, one R3Eis C1-C6 alkyl. In some embodiments, one R3Ais methyl. In some embodiments, at least one R3Eis isopropyl. In some embodiments, one R3Ais C1-C6 alkyl. In some embodiments, one R3Eis isopropyl. In some embodiments, at least one R3Eis C1-C6 haloalkyl. In some embodiments, at least one R3Ais -CF3. In some embodiments, at least one R3Eis -CH2CF3. In some embodiments, one R3Eis C1-C6 haloalkyl. In some embodiments, one R3Ais -CF3. In some embodiments, one R3Eis -CH2CF3. In some embodiments, at least one R3Eis 5 membered heteroaryl. In some embodiments, one R3Ais 5 membered heteroaryl. In some embodiments, at least one R3Ais selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, furzanyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,2,3,4-oxatriazolyl, 1,2,3,5-oxatriazolyl, 1,2,3,4- thiatriazolyl, and 1,2,3,5-thiatriazolyl. In some embodiments, one R3Ais selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, isothiazolyl, thiazolyl, furzanyl, 1,2,4-oxadiazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4- thiadiazolyl, 1,2,5-thiadiazolyl, 1,2,3,4-oxatriazolyl, 1,2,3,5-oxatriazolyl, 1,2,3,4-thiatriazolyl, and 1,2,3,5-thiatriazolyl. In some embodiments, at least one R3Eis . In some embodiments, one . so e e o ents, at least one R3Eis phenyl. In some embodiments, one R3Eis phenyl. In some embodiments, at least one R3Eis C3-C7 cycloalkyl. In some embodiments, at least one R3Eis cyclopropyl. In some embodiments, one R3Eis C3-C7 cycloalkyl. In some embodiments, one R3Eis cyclopropyl. In some embodiments, at least one R3Eis cyclobutyl. In some embodiments, one R3Eis 3-7 membered heterocyclyl. In some embodiments, one . In some embodiments, at least one R3Eis -C(=O)C1-C6 alkyl. In some embodiments, at least one R3Eis acyl. In some embodiments, one R3Eis -C(=O)C1-C6 alkyl. In some embodiments, one R3Eis acyl. In some embodiments, at least one R3Eis -C(=O)OC1-C6 alkyl. In some embodiments, at least one R3Eis . In some embodiments, one R3Eis -C(=O)OC1-C6 alkyl. In some embodiments, one . In some embodiments, at least one R3Eis -C(=O)NH(C1-C6 alkyl). In some embodiments, at least one R3Eis -C(=O)NHCH3. In some embodiments, one R3Eis -C(=O)NH(C1-C6 alkyl). In some embodiments, one R3Eis -C(=O)NHCH3. In some embodiments, at least one R3Eis -C(=O)N(C1-C6 alkyl)2. In some embodiments, at least one R3Eis -C(=O)N(CH3)2. In some embodiments, one R3Eis -C(=O)N(C1-C6 alkyl)2. In some embodiments, one R3Eis -C(=O)N(CH3)2. In some embodiments, at least one R3Eis -NH(C=O)(C1-C6 alkyl). In some embodiments, at least one R3Eis -NH(C=O)CH3. In some embodiments, one R3Eis -NH(C=O)CH3. In some embodiments, at least one R3Eis C1-C6 alkoxy optionally substituted with phenyl. In some embodiments, one R3Ais C1-C6 alkoxy. In some embodiments, one R3Ais methoxy. In some embodiments, one R3Abenzyloxy. In some embodiments, at least one R3Eis C1-C6 alkoxy substituted with C1-C6 alkoxy. In some embodiments, one R3Eis C1-C6 alkoxy substituted with C1-C6 alkoxy. In some embodiments, one R3Eis . Non-Limiting Exemplary Compounds In some embodiments, the compound is selected from the group consisting of the compounds delineated in Table A, or a pharmaceutically acceptable salt thereof. Table A In some embodiments, the compound is selected from the group consisting of the compounds delineated in Table B, or a pharmaceutically acceptable salt thereof.

[0005] Table B

[0006]

[0007]

[0008] In some embodiments, the compound of Formula (I), or a pharmaceutically acceptable salt thereof, selected from the compounds described in Table A or Table B, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is selected from the group consisting of the compounds delineated in Table C, or a pharmaceutically acceptable salt thereof. Table C.

[0009] Pharmaceutical Compositions Some embodiments provide a pharmaceutical composition comprising a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. Methods of Treatment Provided herein are methods for modulating glucocerebrosidase (GCase) activity, encoded by the GBA1 gene. For example, provided herein are compounds that enhance GCase activity that are useful for treating diseases associated with dysregulation of a GBA1 gene, a GCase protein, or the activity of any of the same (i.e., a GCase-associated disease), such as Parkinson’s disease (e.g., a GCase-associated neurological disease). The ability of test compounds to act as a GCase enhancer may be demonstrated by assays known in the art. The activity of the compounds and compositions provided herein as GCase enhancers can be assayed in vitro, in vivo, or in a cell line. In vitro assays include assays that determine activation of the protein and / or a change in its conformation. Potency of a GCase enhancer as provided herein can be determined by EC50value. A compound with a lower EC50value, as determined under substantially similar conditions, is a more potent GCase enhancer relative to a compound with a higher EC50value. Indications Compounds disclosed herein (e.g., compounds of Formula (I) or compounds of Formula (I-IA)), or pharmaceutically acceptable salts thereof, are useful for treating diseases which can be treated with a GCase enhancer, such as GCase-associated diseases, e.g., lysosomal storage disorder and neurological diseases. Some embodiments provide a method of treating a subject with a GCase-asssociated disease, comprising administering to the subject a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. Some embodiments provide a method of treating a neurological disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. In some embodiments, the neurological disorder is a GCase-associated neurological disorder. Some embodiments provide a method of treating a neurological disorder in a subject that has been identified or diagnosed as having a GCase-associated neurological disorder, comprising administering to the subject a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. Some embodiments provide a method of treating a neurological disorder in a subject in need thereof, comprising (a) determing that the subject has a GCase-associated neurological disorder, and (b) administering to the subject a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. Also provided herein are methods for treating a subject identified or diagnosed as having a GCase-associated disease that include administering to the subject a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the subject that has been identified or diagnosed as having a GCase- associated disease through the use of a regulatory agency-approved, e.g., FDA-approved test or assay for identifying dysregulation of a GBA1 gene, a GCase protein, or activity of any of the same, in a subject or sample from the subject. In some embodiments, the test or assay is provided as a kit. Also provided are methods for treating a neurological disease in a subject in need thereof, the method comprising: (a) detecting a GCase-associated neurological disease in the subject; and (b) administering to the subject a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some embodiments, the GCase-associated disease is a lysosomal storage disease. In some embodiments, the GCase-associated disease is a sphingolipidosis. In some embodiments, the GCase-associated disease is Parkinson’s disease (PD), Gaucher’s disease, dementia with Lewy bodies (DLB), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), Mild Cognitive Impairment (MCI), Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick’s disease, Corticobasal degeneration, Niemann-Pick disease, Progressive supranuclear palsy (PSP), Fabry disease, Krabbe disease, Metachromatic leukodystrophy, Sandhoff disease, or Tay-Sachs disease. In some embodiments, the GCase-associated disease is PD. In some embodiments, the GCase-associated disease is Gaucher’s disease. In some embodiments, the GCase-associated disease is DLB. In some embodiments, the GCase-associated disease is AD. In some embodiments, the GCase-associated disease is ALS. In some embodiments, the GCase-associated disease is HD. In some embodiments, the GCase-associated disease is MCI. In some embodiments, the GCase-associated disease is FTDP-17. In some embodiments, the GCase-associated disease is Pick’s disease. In some embodiments, the GCase-associated disease is Corticobasal degeneration. In some embodiments, the GCase-associated disease is Niemann-Pick disease. In some embodiments, the GCase-associated disease is PSP. In some embodiments, the GCase-associated disease is Fabry disease. In some embodiments, the GCase-associated disease is Krabbe disease. In some embodiments, the GCase-associated disease is Metachromatic leukodystrophy. In some embodiments, the GCase-associated disease is Sandhoff disease. In some embodiments, the GCase-associated disease is Tay-Sachs disease. In some embodiments of any of the methods or uses described herein, the subject has a clinical record indicating that the subject has a dysregulation of a GBA1 gene, a GCase protein, or activity of any of the same. Also provided are methods of treating a subject that include administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof, to a subject having a clinical record that indicates that the subject has a dysregulation of a GBA1 gene, a GCase protein, or activity of any of the same. Some embodiments provide a method of increasing GCase activity in a cell comprising a GCase protein, the method comprising contacting the cell with a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. Some embodiments provide a method of stabilizing GCase protein conformation, the method comprising contacting the GCase protein with a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. In some embodiments, the GCase protein is misfolded prior to the contacting. In some embodiments, the GCase protein is misfolded prior to the contacting and is in its native conformation after the contacting. Some embodiments provide a method of reducing the level of GluCer and / or GluSph in a cell comprising GluCer and / or GluSph, the method comprising contacting the cell with a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof. In some embodiments, the contacting is in vitro. In some embodiments, the contacting is in vivo. In some embodiments, the contacting is in vivo, wherein the method comprises administering an effective amount of a compound disclosed herein (e.g., a compound of Formula (I) or a compound of Formula (I-IA)), or a pharmaceutically acceptable salt thereof, to a subject having a cell having aberrant GCase function. In some embodiments, the cell is a neural cell. As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” a GCase protein with a compound provided herein includes the administration of a compound provided herein to an individual or subject, such as a human, having a GCase protein, as well as, for example, introducing a compound provided herein into a sample containing a cellular or purified preparation containing the GCase protein. EMBODIMENTS 1. A compound of Formula (I)) or a pharmaceutically acceptable salt ther eof, wherein: R1is C1-C6 alkyl or C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl; R2is C1-C6 haloalkyl, C1-C6 haloalkoxy, benzyloxy, -NR2AR2B, or hydroxyl; R2Aand R2Bare independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; or R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; R3is an optionally substituted 6-12 membered aryl, an optionally substituted 6-12 membered heterocyclyl, an optionally substituted 6-12 membered heteroaryl, -NR3AR3B, -OR3C, or -C(O)R3D; X is N or CRX; R3A, R3B, R3C, and R3Dare independently hydrogen, C1-C6 alkyl, 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl, C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl), and 5-6 membered heteroaryl optionally substituted with 1-2 substituents independently selected from halogen, cyano, and C1-C6 alkyl; and RX, R4, and R5are independently hydrogen, C1-C6 alkyl, or halogen; wherein when R2is -NR2AR2Band one of R2Aand R2Bis hydrogen, then R3is not optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one. 2. The compound of embodiment 1, wherein R1is C1-C6 alkyl. 3. The compound of embodiment 1 or 2, wherein R1is methyl or isopropyl. 4. The compound of embodiment 1, wherein R1is C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl. 5. The compound of embodiment 1 or 4, wherein R1is C3-C10 cycloalkyl substituted with C1-C6 alkyl. 6. The compound of embodiment 1 or 4, wherein R1is C3-C10 cycloalkyl. 7. The compound of embodiment 1, 4, or 6, wherein R1is cyclopentyl. 8. The compound of any one of embodiments 1-7, wherein R2is C1-C6 haloalkyl. 9. The compound of any one of embodiments 1-8, wherein R2is -CF3. 10. The compound of any one of embodiments 1-7, wherein R2is C1-C6 haloalkoxy.11. The compound of any one of embodiments 1-7 and 10, wherein R2 is C1-C3haloalkoxy. 12. The compound of any one of embodiments 1-7 and 10-11, wherein R2 is 13. The compound of any one of embodiments 1-7, wherein R2 is benzyloxy.14. The compound of any one of embodiments 1-7, wherein R2 is -NR2AR2B.15. The compound of any one of embodiments 1-7 and 14, wherein R2A and R2B areindependently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl. 16. The compound of any one of embodiments 1-7 and 14-15, wherein R2A and R2B areboth hydrogen. 17. The compound of any one of embodiments 1-7 and 14-15, wherein one of R2A andR2Bis hydrogen and the other one of R2Aand R2Bis C1-C6 alkyl. 18. The compound of any one of embodiments 1-7, 14, and 17, wherein one of R2A andR2Bis hydrogen and the other one of R2Aand R2Bis 19. The compound of any one of embodiments 1-7 and 14-15, wherein one of R2A andR2Bis hydrogen and the other one of R2Aand R2Bis C1-C6 haloalkyl. 20. The compound of any one of embodiments 1-7, 14-15 and 19, wherein one R2A andR2Bis hydrogen and the other one of R2Aand R2Bis 21. The compound of any one of embodiments 1-7 and 14-15, wherein one of R2A andR2Bis hydrogen and the other one of R2Aand R2Bis a 4-10 membered heterocyclyl optionally substituted 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl. 22. The compound of any one of embodiments 1-7, 14-15, and 21, wherein one R2Aand R2Bis hydrogen and the other one of R2Aand R2Bis . 23. The compound of any one of embodiments 1-7 and 14-15, wherein each R2A andR2Bis independently selected C1-C6 alkyl. 24. The compound of any one of embodiments 1-7, 14-15, and 23, wherein one of R2Aand R2Bis methyl and the other one of R2Aand R2Bis 25. The compound of any one of embodiments 1-7, 14-15 and 23, wherein both of R2Aand R2Bis methyl or both of R2Aand R2Bis ethyl. 26. The compound of any one of embodiments 1-7 and 14, wherein R2A and R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1- C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl. 27. The compound of any one of embodiments 1-7, 14 and 26, wherein R2A and R2Btogether with the nitrogen atom to which they are attached form an optionally substituted heterocyclyl selected from the group consisting of , , 28. The compound of any one of embodiments 1-7, wherein R2 is hydroxyl.29. The compound of any one of embodiments 1-28, wherein R3 is an optionallysubstituted 6-12 membered aryl. 30. The compound of any one of embodiments 1-29, wherein R3 is an optionallysubstituted phenyl. 31. The compound of any one of embodiments 1-28, wherein R3 is an optionallysubstituted 6-12 membered heterocyclyl. 32. The compound of any one of embodiments 1-28 and 31, wherein R3 is selectedfrom the group consisting of ,and , wherein “*” indicates hydrogen or an optional substituent. 33. The compound of any one of embodiments 1-28, wherein R3 is an optionallysubstituted 6-12 membered heteroaryl.34. The compound of any one of embodiments 1-28 and 33, wherein R3 is an optionallysubstituted 6-membered heteroaryl. 35. The compound of any one of embodiments 1-28 and 33-34, wherein R3 is selectedfrom the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, and 1,3,5-triazinyl, each of which is optionally substituted. 36. The compound of any one of embodiments 1-28 and 33-35, wherein R3 is anoptionally substituted pyridinyl. 37. The compound of any one of embodiments 1-28 and 33, wherein R3 is an optionallysubstituted 9-10 membered heteroaryl. 38. The compound of any one of embodiments 1-28, 33, and 37, wherein R3 is anoptionally substituted 9 membered heteroaryl selected from the group consisting of , , wherein “*” indicates hydrogen or an optional substituent. 39. The compound of any one of embodiments 1-28, 33, and 37, wherein R3 is anoptionally substituted 10 membered heteroaryl selected from the group consisting of wherein “*” indicates hydrogen or an optional substituent. 40. The compound of any one of embodiments 1-28, wherein R3 is -NR3AR3B.41. The compound of any one of embodiments 1-28 and 40, wherein one of R3A andR3Bis hydrogen, and the other one of of R3Aand R3Bis 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl. 42. The compound of any one of embodiments 1-28 and 40-41, wherein one of R3A andR3Bis hydrogen, and the other one of of R3Aand R3Bis selected from the group consisting of , wherein “*” indicates hydrogen or an optional C1-C6 alkyl substituent. 43. The compound of any one of embodiments 1-28 and 40, wherein one of R3A andR3Bis C1-C6 alkyl, and the other one of R3Aand R3Bis 5-12 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl. 44. The compound of any one of embodiments 1-28, 40 and 43, wherein one of R3Aand R3Bis methyl, and the other one of R3Aand R3Bis selected from the group consisting of . 45. The compound of any one of embodiments 1-28, and 40, wherein one of R3A andR3Bis hydrogen or C1-C6 alkyl, and the other one of R3Aand R3Bis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-2 independently selected C1-C6 alkyl).46. The compound of any one of embodiments 1-28, 40, and 45, wherein one of R3Aand R3Bis hydrogen, and the other one of R3Aand R3Bis selected from the group consisting of . 47. The compound of any one of embodiments 1-28, and 40, wherein one of R3A andR3Bis hydrogen or C1-C6 alkyl, and the other one of R3Aand R3Bis 5-6 membered heteroaryl optionally substituted with 1-2 substitutents independently selected from halogen, cyano, and C1- C6 alkyl. 48. The compound of any one of embodiments 1-28, 40, and 47, wherein one of R3Aand R3Bis hydrogen, and the other one of R3Aand R3Bis selected from the group consisting of 4- pyridyl , wherein wherein “*” indicates hydrogen or an optional substituent. 49. The compound of any one of embodiments 1-28, 40, and 47, wherein one of R3Aand R3Bis methyl, and the other one of R3Aand R3B4-pyridyl. 50. The compound of any one of embodiments 1-28, wherein R3 is -OR3C.51. The compound of embodiment 50, wherein R3C is 5-12 membered heterocyclyloptionally substituted with 1-2 independently selected C1-C6 alkyl. 52. The compound of embodiment 50 or 51, wherein R3C is . 53. The compound of any one of embodiments 1-28, wherein R3 is -C(O)R3D.54. The compound of embodiment 53, wherein R3D is 5-12 membered heterocyclyloptionally substituted with 1-2 independently selected C1-C6 alkyl.55. The compound of embodiment 53 or 54, wherein R3D is .56. The compound of any one of embodiments 1-55, wherein X is CRX.57. The compound of any one of embodiments 1-56, wherein RX is hydrogen.58. The compound of any one of embodiments 1-56, wherein RX is C1-C6 alkyl.59. The compound of any one of embodiments 1-56 and 58, wherein RX is methyl.60. The compound of any one of embodiments 1-56, wherein RX is halogen.61. The compound of any one of embodiments 1-56 and 60, wherein RX is fluoro orchloro. 62. The compound of any one of embodiments 1-61, wherein R4is hydrogen.63. The compound of any one of embodiments 1-61, wherein R4is C1-C6 alkyl.64. The compound of any one of embodiments 1-61 and 63, wherein R4 is methyl.65. The compound of any one of embodiments 1-61, wherein R4 is halogen.66. The compound of any one of embodiments 1-61 and 65, wherein R4 is fluoro orchloro. 67. The compound of any one of embodiments 1-66, wherein R5 is hydrogen.68. The compound of any one of embodiments 1-66, wherein R5is C1-C6 alkyl. 69. The compound of any one of embodiments 1-66 and 68, wherein R5is methyl. 70. The compound of any one of embodiments 1-66, wherein R5is halogen. 71. The compound of any one of embodiments 1-66 and 70, wherein R5is fluoro or chloro. 72. The compound of any one of embodiments 1-55 and 62-71, wherein X is N. 73. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, selected from the compounds described in Table A or Table B, or a pharmaceutically acceptable salt thereof. 74. A pharmaceutical composition comprising a compound of any one of embodiments 1-73, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. 75. A method of treating a GCase-associated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of any one of embodiments 1-73, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of embodiment 74. 76. The method of embodiment 75, wherein the GCase-associated disease is a lysosomal storage disorder or a neurodegenerative disorder. EXAMPLES Compound Preparation The compounds disclosed herein can be prepared in a variety of ways using commercially available starting materials, compounds known in the literature, or from readily prepared intermediates, by employing standard synthetic methods and procedures either known to those skilled in the art, or in light of the teachings herein. The synthesis of the compounds disclosed herein can be achieved by generally following the schemes provided herein, with modification for specific desired substituents. Standard synthetic methods and procedures for the preparation of organic molecules and functional group transformations and manipulations can be obtained from the relevant scientific literature or from standard textbooks in the field. Although not limited to any one or several sources, classic texts such as R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis, John Wiley and Sons (1994); Smith, M. B., March, J., March' s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th edition, John Wiley & Sons: New York, 2001; and Greene, T.W., Wuts, P.G. M., Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons: New York, 1999, are useful and recognized reference textbooks of organic synthesis known to those in the art. The following descriptions of synthetic methods are designed to illustrate, but not to limit, general procedures for the preparation of compounds of the present disclosure. The synthetic processes disclosed herein can tolerate a wide variety of functional groups; therefore, various substituted starting materials can be used. The processes generally provide the desired final compound at or near the end of the overall process, although it may be desirable in certain instances to further convert the compound to a pharmaceutically acceptable salt thereof. The starting materials used for the synthesis were synthesized according to known literature procedures or obtained from commercial sources, such as, but not limited to, Sigma- Aldrich, Fluka, Acros Organics, Alfa Aesar, VWR Scientific, and the like. Normal phase chromatography and reverse phase chromatography were performed on a CombiFlash Companion automated flash chromatography system, using either RediSep® Silver (230-400 mesh, 40-63 μm irregular) or Silicycle, SiliaSep C18 (230-400 mesh, 40-63 μm irregular) pre-packed silica cartridges respectively. RP flash chromatography was performed using basic modifier (C18, 0 – 100% MeCN in 0.1% aq. ammonia) except where acidic modifier (C18, 0 – 100% MeCN with 0.1% HCO2H in 0.1% aq. HCO2H) was used. Analytical LC-MS and UPLC-MS experiments were carried out as described in the tables below. Method A – LCMS Acidic Method Mobile phase (A) 0.1% Formic acid in water

[0010] NMR spectra were measured at 298 K, unless indicated otherwise, and were referenced relativeto the solvent resonance. The chemical shifts are reported in parts per million ( ppm).NMR spectra were recorded using a Bruker 500 MHz Avance III HD spectrometer equipped with a Bruker 5mm SmartProbeTM. Data were acquired using Bruker TopSpin software and processed using MestreNova software. Standard abbreviations and acronyms as defined in Journal of Organic Chemistry’s Author’s Guideline, and in Hans Reich's Collection. Organic Acronyms are used herein. Other abbreviations and acronyms used herein are as follows: Ac acetate

[0011] General Synthetic Routes The compounds described herein may be prepared by direct Suzuki coupling (Route A or Route G) with a boronic acid or ester II and a Q-functionalized moiety I, where Q is a halogen or other moiety that enables oxidative addition to Pd, e.g., -OSO2CF3. The coupling is generally done at elevated temperatures in the presence of base and Pd catalyst. Route A: Route G: Alternatively, the boronic acid or ester may be prepared in-situ (Route B and Route C) by reacting a Q-functionalized moiety, e.g. I, wherein Q is a halogen or other moiety that enables oxidative addition to Pd, e.g., -OSO2CF3, in the presence of base, Pd catalyst, and a boronation source, e.g., B2(Neop)2(Route B) or B2Pin2(Route C) to give the boronic ester, which is then coupled (typically without isolation) with a second Q’-functionalized moety, I or II, wherein Q’ is a halogen or other moiety that enables oxidative addition to Pd, e.g., -OSO2CF3, in the presence of base and additional Pd catalyst.

[0012] Route B: Route C: The compounds described herein may be prepared as seen below (Route D or Route E) where W is a halogen or other moiety that enables oxidative addition to Pd, e.g., -OSO2CF3. Route D: Route E: The compounds described herein may be prepared as seen below (Route F) where W is a halogen or similar leaving group. Route F: Route H: The compounds described herein may be prepared as seen below (Route I), Route I: The compounds described herein may be prepared as seen below (Route J), Route J: The compounds described herein may be prepared as seen below (Route K), Route K: The compounds described herein may be prepared as seen below (Route L) where W is a halogen or similar leaving group, Route L: Example 1. Synthesis of 2-(tert-butylamino)-3-methyl-8-(1-methylindazol-5- yl)quinazolin-4-one (Compound 1) Prepared according to route A: To a stirred suspension of 1-methyl-5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)indazole (40 mg, 0.155 mmol), 8-bromo-2-(tert-butylamino)-3-methyl- quinazolin-4-one (53 mg, 0.17 mmol) and K2CO3(43 mg, 0.31 mmol) in MeCN (2.5 mL) and water (0.25 mL) was added Pd(dppf)Cl2.CH2Cl2(10 mg, 0.02 mmol). The reaction was heated to 60oC for 18 h, before being cooled to RT and filtered. The filtrate was concentrated in vacuo. The residue was purified by acidic prep HPLC to afford the title compound (6.0 mg, 0.02 mmol, 11% yield) as an off-white solid. LCMS (ESI) [M+H]+m / z: calc. for C21H23N5O: 362.2, found: 362.2.1H NMR (400 MHz, DMSO) δ 8.03 (s, 1H), 7.97 (dd, J = 7.9, 1.6 Hz, 1H), 7.90 (d, J = 1.3 Hz, 1H), 7.67 – 7.56 (m, 3H), 7.20 (t, J = 7.6 Hz, 1H), 5.77 (s, 1H), 4.07 (s, 3H), 3.44 (s, 3H), 1.26 (s, 9H). Example 2. Synthesis of N-(6-(2-(tert-butylamino)-3-methyl-4-oxo-3,4- dihydroquinazolin-8-yl)pyridin-2-yl)acetamide (Compound 2) Prepared by Route B: To a stirred suspension of 5,5,5',5'-tetramethyl-2,2'-bi(1,3,2- dioxaborinane) (104 mg, 0.46 mmol), 8-bromo-2-(tert-butylamino)-3-methyl-quinazolin-4-one (100 mg, 0.31 mmol), 1,4-Dioxane (5 mL) and potassium 2-ethylhexanoate solution (0.5 M in isopropyl acetate) (1.8 mL, 0.92 mmol) was added Pd(dppf)2Cl2(22 mg, 0.03 mmol). The reaction was heated to 100 °C for 2 hours then allowed to cool to RT. K2CO3(44 mg, 0.32 mmol), N-(6- bromo-2-pyridyl)acetamide (34 mg, 0.16 mmol), water (0.2 mL) and Pd(dppf)Cl2.CH2Cl2(7.0 mg, 0.01 mmol) were added and the reaction mixture heated to 80 °C for 3 h. The reaction mixture was allowed to cool to RT, diluted with EtOAc (3 mL), filtered through hydrophobic filter paper and concentrated in vacuo. The residue was purified by silica gel chromatography (0-100% EtOAc in heptane) and by reverse phase chromatography (10-40% MeCN in water (0.1% formic acid)) to afford the title compound (10 mg, 0.026 mmol, 25% yield) as a colourless solid. LCMS (ESI) [M+H]+m / z: calc. for C20H23N5O2: 366.2, found: 365.8. 1H NMR (400 MHz, DMSO) δ 10.48 (s, 1H), 8.05 – 7.98 (m, 2H), 7.85 – 7.74 (m, 2H), 7.53 (d, J = 7.5 Hz, 1H), 7.26 – 7.17 (m, 1H), 5.84 (s, 1H), 3.44 (s, 3H), 2.09 (s, 3H), 1.31 (s, 9H). Example 3. Synthesis of N-[3-[2-(tert-butylamino)-3-methyl-4-oxo-quinazolin-8-yl]-5- methyl-phenyl]acetamide (Compound 3) Prepared by Route C: To a stirred suspension of N-(3-bromo-5-methyl-phenyl)acetamide (50 mg, 0.22 mmol), KOAc (43 mg, 0.44 mmol) and bis(pinacolato)diboron (83 mg, 0.33 mmol) in 1,4-Dioxane (2.5 mL) was added Pd(dppf)2Cl2(16 mg, 0.02 mmol) and the reaction heated to 80 °C for 3 h. The reaction was cooled to RT, 8-bromo-2-(tert-butylamino)-3-methyl- quinazolin-4-one (54 mg, 0.18 mmol), water (0.25 mL), K2CO3(61 mg, 0.44 mmol) and Pd(dppf)Cl2.CH2Cl2(14 mg, 0.02 mmol) were added and the reaction mixture heated to 80 °C for 3h. The reaction mixture was filtered and concentrated in vacuo. The residue was purified by basic prep HPLC and then triturated with MTBE to afford the title compound (15 mg, 0.04 mmol, 18% yield) as an off-white solid. LCMS (ESI) [M+H]+m / z: calc. for C22H26N4O2: 379.2, found: 379.2 1H NMR (400 MHz, DMSO) δ 9.82 (s, 1H), 7.96 (dd, J = 7.9, 1.7 Hz, 1H), 7.54 (dd, J = 7.3, 1.7 Hz, 1H), 7.47 (s, 1H), 7.37 (s, 1H), 7.23 – 7.14 (m, 1H), 7.08 (s, 1H), 5.78 (s, 1H), 3.44 (s, 3H), 2.30 (s, 3H), 2.02 (s, 3H), 1.29 (s, 9H). Example 4. Synthesis of 2-(tert-butylamino)-8-[(3-hydroxycyclobutyl)amino]-3-methyl- pyrido[3,4-d]pyrimidin-4-one (Compound 270) Prepared by Route D: To a stirred suspension of 2-(tert-butylamino)-8-chloro-3-methyl- pyrido[3,4-d]pyrimidin-4-one (100 mg, 0.37 mmol), 3-aminocyclobutanol hydrochloride (65 mg, 0.53 mmol) , Cs2CO3(364 mg, 1.1 mmol), XantPhos (43 mg, 0.074 mmol) in 1,4-dioxane (4 mL) was added Pd2(dba)3(39 mg, 0.043 mmol) and the reaction heated to 100 °C for 3 h. The reaction was evaporated and the residue purified by basic prep-HPLC to afford the title compound (23 mg, 0.069 mmol, 19% yield) as an off-white solid. LCMS (ESI) [M+H]+m / z: calc. for C16H23N5O2: 318.2, found: 318.1. 1H NMR (400 MHz, DMSO) δ 7.65 (d, J = 5.5 Hz, 1H), 6.85 (d, J = 5.5 Hz, 1H), 6.10 – 6.01 (m, 2H), 5.09 (d, J = 4.5 Hz, 1H), 4.50 – 4.40 (m, 1H), 4.32 (m, 1H), 3.42 (s, 3H), 2.32 – 2.21 (m, 2H), 2.18 – 2.06 (m, 2H), 1.53 (s, 9H). Example 5. Synthesis of 2-(tert-butylamino)-3-methyl-8-[(1-methyl-6-oxo-3- piperidyl)amino]pyrido[3,4-d]pyrimidin-4-one (Compound 171) Prepared by Route E: To a stirred suspension of 2-(tert-butylamino)-8-chloro-3-methyl- pyrido[3,4-d]pyrimidin-4-one (70 mg, 0.26 mmol), 5-amino-1-methyl-piperidin-2-one (67 mg, 0.53 mmol), NaOtBu (101 mg, 1.1 mmol) in THF (2 mL) was added BrettPhos Pd G3 (24 mg, 0.026 mmol) and the reaction was heated to 70 °C for 16 h. The reaction was evaporated and the residue purified by silica gel chromatography (0-10% MeOH in EtOAc) to afford the title compound (41 mg, 0.11 mmol, 43% yield) as a beige solid. LCMS (ESI) [M+H]+m / z: calc. for C18H26N6O2: 359.2, found: 359.1 1H NMR (400 MHz, DMSO) δ 7.69 (d, J = 5.5 Hz, 1H), 6.90 (d, J = 5.5 Hz, 1H), 6.14 (d, J = 7.7 Hz, 1H), 6.08 (s, 1H), 4.45 – 4.30 (m, 1H), 3.67 (dd, J = 12.0, 4.4 Hz, 1H), 3.42 (s, 3H), 3.30 – 3.25 (m, 1H), 2.82 (s, 3H), 2.43 – 2.22 (m, 2H), 2.10 – 2.00 (m, 1H), 2.00 – 1.89 (m, 1H), 1.49 (s, 9H). Example 6. Synthesis of 2-(tert-butylamino)-3-methyl-8-(8-oxo-2,7- diazaspiro[4.4]nonan-2-yl)pyrido[3,4-d]pyrimidin-4-one (Compound 242)

[0013] Prepared by Route F: A suspension of 2-(tert-butylamino)-8-chloro-3-methyl-pyrido[3,4- d]pyrimidin-4-one (75 mg, 0.28 mmol), 2-aza-7-azoniaspiro[4.4]nonan-3-one chloride (50 mg, 0.28 mmol) and DIPEA (0.15 mL, 0.87 mmol) in MeCN (4 mL) was heated at 150 °C under microwave irradiation for 12 h. The reaction was filtered, the filtrate evaporated and the residue purified via silica gel chromatography (0-10% MeOH in DCM) to afford the title compound (60 mg, 0.16 mmol, 56% yield) as a yellow solid. LCMS (ESI) [M+H]+m / z: calc. for C19H26N6O2: 371.2, found: 371.1. 1H NMR (400 MHz, DMSO) δ 7.76 (d, J = 5.2 Hz, 1H), 7.63 (s, 1H), 7.01 (d, J = 5.2 Hz, 1H), 5.83 (s, 1H), 3.96 – 3.89 (m, 1H), 3.88 – 3.78 (m, 3H), 3.44 (s, 3H), 3.24 – 3.17 (m, 2H), 2.29 – 2.15 (m, 2H), 1.99 – 1.88 (m, 2H), 1.46 (s, 9H). Example 7. Synthesis of 2-(tert-butylamino)-8-(4-methoxypyrimidin-5-yl)-3-methyl- pyrido[3,4-d]pyrimidin-4-one (Compound 405) Prepared by Route G: To a stirred suspension of 2-(tert-butylamino)-8-chloro-3-methyl- pyrido[3,4-d]pyrimidin-4-one (70 mg, 0.26 mmol), 4-methoxy-5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)pyrimidine (74 mg, 0.32 mmol), CsF (120 mg, 0.79 mmol) in DMF (1.5 mL) was added Pd(PPh3)4(30 mg, 0.026 mmol) and CuI (10 mg, 0.053 mmol). The reaction was heated to 150 °C for 1 h under microwave irradiation, then filtered. The filtrate was diluted with EtOAc (10 mL) then washed with water (20 mL) and brine (20 mL), dried via phase separator and evaporated. The residue was purified by reverse phase chromatography (20-75% MeCN in water (0.1% formic acid)) to afford the title compound (12 mg, 0.035 mmol, 13% yield) as a tan solid. LCMS (ESI) [M+H]+m / z: calc. for C17H20N6O2: 341.2, found: 340.9 1H NMR (400 MHz, DMSO) δ 8.87 (s, 1H), 8.48 (s, 1H), 8.34 (d, J = 5.1 Hz, 1H), 7.82 (d, J = 5.2 Hz, 1H), 6.06 (s, 1H), 3.84 (s, 3H), 3.43 (s, 3H), 1.20 (s, 9H). Example 8. Synthesis of 2-(tert-butylamino)-3-methyl-8-(tetrahydropyran-4- ylamino)pyrido[3,4-d]pyrimidin-4-one (Compound 172) Prepared by Route H: A solution of 2-(tert-butylamino)-8-chloro-3-methyl-pyrido[3,4- d]pyrimidin-4-one (50 mg, 0.18 mmol), DIPEA (0.10 mL, 0.57 mmol) and tetrahydro-2H-pyran- 4-amine (0.020 mL, 0.18 mmol) in NMP (2.5 mL) was heated at 210 °C for 15 h under microwave irradiation. The reaction was purified directly by reverse phase chromatography (0-100% MeCN in water (0.1% formic acid)) to afford the title compound (27 mg, 0.077 mmol, 42% yield) as a white solid. LCMS (ESI) [M+H]+m / z: calc. for C17H25N5O2: 332.2, found: 332.0 1H NMR (400 MHz, DMSO) δ 7.66 (d, J = 5.5 Hz, 1H), 6.86 (d, J = 5.5 Hz, 1H), 6.06 (s, 1H), 5.96 (d, J = 7.8 Hz, 1H), 4.15 – 4.04 (m, 1H), 3.84 (dt, J = 11.7, 4.0 Hz, 2H), 3.53 – 3.45 (m, 2H), 3.42 (s, 3H), 2.03 – 1.95 (m, 2H), 1.52 (s, 9H), 1.50 – 1.41 (m, 2H). Example 9. Synthesis of 2-(tert-butylamino)-8-[1-hydroxy-1-(6-methoxy-3- pyridyl)ethyl]-3-methyl-pyrido[3,4-d]pyrimidin-4-one (Compound 425) Prepared by Route I: iPrMgCl.LiCl solution (1.3 M in THF, 0.68 mL, 0.88 mmol) was added dropwise to a stirred solution of 5-bromo-2-methoxypyridine (150 mg, 0.80 mmol) in THF (1 mL) at 0 °C. The reaction was stirred at RT for 16 h. This mixture was then added dropwise over 30 minutes to a stirred solution of 8-acetyl-2-(tert-butylamino)-3-methyl-pyrido[3,4- d]pyrimidin-4-one (111 mg, 0.34 mmol) in THF (1 mL) at –20 °C. The reaction was stirred at RT for 4 h. The reaction was quenched with sat. aq. NH4Cl (5 mL) and extracted with EtOAc (2 x 20 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-50% 3:1 EtOAc:EtOH in heptane) and reverse phase chromatography (20-50% MeCN in water (0.1% formic acid)) to afford the title compound (21 mg, 0.051 mmol, 15% yield) as a yellow solid. LCMS (ESI) [M+H]+m / z: calc. for C20H25N5O3: 384.2, found: 384.0 1H NMR (400 MHz, DMSO) δ 8.34 (d, J = 5.1 Hz, 1H), 7.96 (dd, J = 2.5, 0.7 Hz, 1H), 7.81 (d, J = 5.1 Hz, 1H), 7.51 (dd, J = 8.7, 2.6 Hz, 1H), 7.33 (s, 1H), 6.68 (dd, J = 8.6, 0.7 Hz, 1H), 6.07 (s, 1H), 3.76 (s, 3H), 3.42 (s, 3H), 1.85 (s, 3H), 1.24 (s, 9H). Example 10. Synthesis of N-[2-(tert-butylamino)-3-methyl-4-oxo-pyrido[3,4- d]pyrimidin-8-yl]tetrahydrofuran-3-carboxamide (Compound 317) Prepared by Route J: A solution of 8-amino-2-(tert-butylamino)-3-methyl-pyrido[3,4- d]pyrimidin-4-one (75 mg, 0.19 mmol) in DMF (0.93 mL) and Et3N (78 μL, 0.56 mmol) was stirred for 1h at RT. EDCI (70 mg, 0.19 mmol), HOAt (25 mg, 0.19 mmol), tetrahydrofuran-3- carboxylic acid (35 μL, 0.37 mmol) and Et3N (51 μL, 0.37 mmol) were added and the reaction mixture stirred at RT for 3h. The reaction was partitioned between water (10 mL) and EtOAc (15 mL), the layers separated and the aqueous layer extracted with EtOAc (2 x 10 mL). The combined organic extracts were dried via phase separator and concentrated in vacuo. The residue was purified by reverse phase chromatography (10-40% MeCN in water (0.1% NH4OH)) and silica gel chromatography (50-100% EtOAc in heptane) to afford the title compound (26 mg, 0.072 mmol, 39% yield) as an off-white solid. LCMS (ESI) [M+H]+m / z: calc. for C17H23N5O3: 346.2, found: 346.0 1H NMR (400 MHz, DMSO) δ 9.57 (s, 1H), 8.02 (d, J = 5.3 Hz, 1H), 7.56 (d, J = 5.2 Hz, 1H), 6.14 (s, 1H), 4.01 – 3.92 (m, 1H), 3.86 – 3.75 (m, 2H), 3.75 – 3.66 (m, 1H), 3.54 (s, 1H), 3.45 (s, 3H), 2.18 – 2.08 (m, 2H), 1.51 (s, 9H). Example 11. Synthesis of 2-(tert-butylamino)-3-methyl-8-(1-morpholinoethyl)pyrido[3,4- d]pyrimidin-4-one (Compound 429) Prepared by Route K: To a stirred solution of 8-acetyl-2-(tert-butylamino)-3-methyl- pyrido[3,4-d]pyrimidin-4-one (50 mg, 0.18 mmol) in DCM (2 mL) was added AcOH (0.052 mL, 0.91 mmol) and morpholine (0.031 mL, 0.37 mmol) at RT. The reaction was stirred for 1 h at RT, then NaBH(OAc)3(77 mg, 0.37 mmol) was added and the reaction stirred overnight at RT. The reaction was quenched with sat. aq. NaHCO3 (10 mL) and extracted with DCM (3 x 20 mL). The combined organic extracts were dried via phase separator and concentrated in vacuo. The residue was purified by reverse phase chromatography (10-60% MeCN in water (0.1% NH4OH)) and silica gel chromatography (0-100% EtOAc in isohexane) afford the title compound (15 mg, 0.043 mmol, 24% yield) as an off-white solid. LCMS (ESI) [M+H]+m / z: calc. for C18H27N5O2: 346.2, found: 346.1. 1H NMR (400 MHz, DMSO) δ 8.25 (d, J = 5.1 Hz, 1H), 7.65 (d, J = 5.1 Hz, 1H), 6.05 (s, 1H), 4.85 (q, J = 6.8 Hz, 1H), 3.56 – 3.45 (m, 4H), 3.44 (s, 3H), 2.66 – 2.59 (m, 2H), 2.43 – 2.35 (m, 2H), 1.53 (s, 9H), 1.32 (d, J = 6.8 Hz, 3H). Example 12. Synthesis of 2-(tert-butylamino)-3-methyl-8-(tetrahydropyran-4- ylamino)pyrido[3,4-d]pyrimidin-4-one (Compound 156) Prepared by Route L: A suspension of 2-(tert-butylamino)-8-chloro-3-methyl-pyrido[3,4- d]pyrimidin-4-one (50 mg, 0.18 mmol), 18-crown-6 (26 mg, 0.098 mmol) , tetrahydro-4-pyranol (0.090 mL, 0.94 mmol) and KOtBu (62 mg, 0.55 mmol) in PhMe (1.5 mL) was heated at 120 °C for 5 h under microwave irradiation. The reaction was diluted with water (10 mL) and EtOAc (20 mL), the layers separated and the aqueous layer extracted with EtOAc (2 x 20 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified via acidic prep-HPLC to afford the title compound (23 mg, 0.066 mmol, 37% yield) as an off-white solid. LCMS (ESI) [M+H]+m / z: calc. for C17H24N4O3: 333.2, found: 333.1 1H NMR (400 MHz, DMSO) δ 7.72 (d, J = 5.4 Hz, 1H), 7.27 (d, J = 5.4 Hz, 1H), 6.07 (s, 1H), 5.42 – 5.27 (m, 1H), 3.93 – 3.81 (m, 2H), 3.64 – 3.56 (m, 2H), 3.43 (s, 3H), 2.04 – 1.92 (m, 2H), 1.75 – 1.61 (m, 2H), 1.54 (s, 9H). Table 1. Exemplary compounds, analytical data, and synthetic route 1

[0014]

[0015]

[0016]

[0017]

[0018]

[0019]

[0020] Assays Live cell GCase activity assay Compounds were evaluated for they ability to increase GCase activation in live cells assay reporting on enzyme activation in lysosomal compartment of H4 Human Neurogliama cell line. Cells were seeded onto 96 well plates at 15,000 cells per well. One day latter, cells were treated with either compounds or DMSO and treated with PFB-FDGlu (5-(Pentafluorobenzoylamino) Fluorecein Di-B-D-Glucopyranoside) substrate at a final concertation of 50uM and incubated overnight at 37C, 5%CO2. After incubation, cells were washed twice with PBS and lysed in 1x RIPA buffer. In the endpoint mode, fluorescent signal (EX / EM: 485 / 520 nm) was measured with PheraStar reader. Data were normalized with total protein concertation. Table 2 shows the AC200(μM) potency for exemplary compounds: ++++ is ≤0.05≤0.3; +++ is ≤0.3≤1.0; ++ ≤1≤10; and + is 10≤. AC200refers to the concentration which doubles GCase activity. Table 2. Biological activity Cmpd GCase cellular activity

Claims

WHAT IS CLAIMED IS:

1. A compound of Formula (I)or a pharmaceutically acceptable salt thereof, wherein: X is N or CRX; R1is C1-C6 alkyl or C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl; R2is C1-C6 haloalkyl, C1-C6 haloalkoxy, benzyloxy, -NR2AR2B, or hydroxyl; R2Aand R2Bare independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl; or R2Aand R2Btogether with the nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1-NR2CR2D; each R2Cand R2Dare independently selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 hydroxyalkyl; R3is (CR3ER3F)0-1-(6-12 membered aryl) (CR3ER3F)0-1-(6-12 membered heterocyclyl), (CR3ER3F)0-1-(6-12 membered heteroaryl), -NR3AR3B, -OR3C, -C(=O)NR3AR3B, -N(R3A)C(=O)R3D, or -C(=O)R3D, wherein each of the 6-12 membered aryl, 6-12 membered heterocyclyl, and 6-12 membered heteroaryl are optionally substituted; each of R3A, R3B, R3C, and R3Dis independently selected from: (i) hydrogen; (ii) C1-C6 alkyl optionally substituted with 1-3 substituents independently selected from hydroxyl and cyano; (iii) C1-C6 haloalkyl; (iv) 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and 4-6 membered heterocyclyl; (v) C1-C6 alkyl(4-6 membered heterocyclyl), wherein the 4-6 membered heterocyclyl is optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy); (vi) 5-6 membered heteroaryl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy; and (vii) C3-C10 cycloalkyl optionally substituted with 1-3 substituents independently selected from hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy;R3Eand R3Fare each independently hydrogen, C1-C3 alkyl, cyano, hydroxyl, or halogen; and RX, R4, and R5are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cyano, halogen, or C3-C6 cycloalkyl; wherein (i) when X is CRXand R2is -NR2AR2B, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one or optionally substituted 1'H-spiro[cyclopropane-1,6'- pyrrolo[3,4-b]pyrrol]-4'(5'H)-one; or (ii) when X is CRX, R1is C1-C6 alkyl, and R2is -NR2AR2B, wherein one of R2Aand R2Bis hydrogen and the other of R2Aand R2Bis C1-C6 alkyl, then R3is not an optionally substituted 1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one or optionally substituted 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one; or (iii) when X is CRX, and R2is -OR, then R3is not an optionally substituted 5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one.

2. The compound of claim 1, wherein R1is C1-C6 alkyl.

3. The compound of claim 1 or 2, wherein R1is methyl or isopropyl.

4. The compound of claim 1, wherein R1is C3-C10 cycloalkyl optionally substituted with C1-C6 alkyl.

5. The compound of claim 1 or 4, wherein R1 is C3-C10 cycloalkyl substituted withC1-C6 alkyl.

6. The compound of claim 1 or 4, wherein R1 is C3-C10 cycloalkyl.

7. The compound of claim 1, 4, or 6, wherein R1 is cyclopentyl.

8. The compound of any one of claims 1-7, wherein R2 is C1-C6 haloalkyl.

9. The compound of any one of claims 1-8, wherein R2 is -CF3.

10. The compound of any one of claims 1-7, wherein R2 is C1-C6 haloalkoxy.

11. The compound of any one of claims 1-7 and 10, wherein R2 is C1-C3 haloalkoxy.

12. The compound of any one of claims 1-7 and 10-11, wherein R2 is or13. The compound of any one of claims 1-7, wherein R2 is benzyloxy.

14. The compound of any one of claims 1-7, wherein R2 is -NR2AR2B.

15. The compound of any one of claims 1-7 and 14, wherein R2A and R2B areindependently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, or a 4-10 membered heterocyclyl optionally substituted 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl.

16. The compound of any one of claims 1-7 and 14-15, wherein R2A and R2B are bothhydrogen.

17. The compound of any one of claims 1-7 and 14-15, wherein one of R2A and R2B ishydrogen and the other one of R2Aand R2Bis C1-C6 alkyl.

18. The compound of any one of claims 1-7, 14, and 17, wherein one of R2A and R2B ishydrogen and the other one of R2Aand R2Bis19. The compound of any one of claims 1-7 and 14-15, wherein one of R2A and R2B ishydrogen and the other one of R2Aand R2Bis C1-C6 haloalkyl.

20. The compound of any one of claims 1-7, 14-15 and 19, wherein one R2A and R2B ishydrogen and the other one of R2Aand R2Bis21. The compound of any one of claims 1-7 and 14-15, wherein one of R2A and R2B ishydrogen and the other one of R2Aand R2Bis a 4-10 membered heterocyclyl optionally substituted 1-3 substituents independently selected from hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and C1-C6 aminoalkyl.

22. The compound of any one of claims 1-7, 14-15, and 21, wherein one R2A and R2Bis hydrogen and the other one of R2Aand R2Bis23. The compound of any one of claims 1-7 and 14-15, wherein each R2A and R2B isindependently selected C1-C6 alkyl.

24. The compound of any one of claims 1-7, 14-15, and 23, wherein one of R2A and R2Bis methyl and the other one of R2Aand R2Bis25. The compound of any one of claims 1-7, 14-15 and 23, wherein both of R2A andR2Bis methyl or both of R2Aand R2Bis ethyl.

26. The compound of any one of claims 1-7 and 14, wherein R2A and R2B together withthe nitrogen atom to which they are attached form a 4-10 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from halogen, hydroxyl, C1-C6 alkyl, C1- C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, and -(C1-C6 alkyl)0-1- NR2CR2D.

27. The compound of any one of claims 1-7, 14 and 26, wherein R2A and R2B togetherwith the nitrogen atom to which they are attached form an optionally substituted heterocyclyl selected from the group consisting of, ,28. The compound of any one of claims 1-7, wherein R2 is hydroxyl.

29. The compound of any one of claims 1-28, wherein R3 is (CR3ER3F)0-1-(optionallysubstituted 6-12 membered aryl).

30. The compound of any one of claims 1-29, wherein R3 is (CR3ER3F)0-1-(optionallysubstituted phenyl.

31. The compound of any one of claims 1-28, wherein R3 is an (CR3ER3F)0-1-(optionallysubstituted 6-12 membered heterocyclyl).

32. The compound of any one of claims 1-28, wherein R3 is (CR3ER3F)0-1-(optionallysubstituted 6-12 membered heteroaryl).

33. The compound of any one of claims 1-28 and 32, wherein R3 is selected from thegroup consisting of,, wherein “*” indicates hydrogenor an optional substituent 34. The compound of any one of claims 1-28 and 32, wherein R3 is (CR3ER3F)0-1-(optionally substituted 6-membered heteroaryl).

35. The compound of any one of claims 1-28 and 32, wherein R3 is selected from thegroup consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,2,4-triazinyl, and 1,3,5- triazinyl, each of which is optionally substituted.

36. The compound of any one of claims 1-28, 32, and 34-35, wherein R3is an optionallysubstituted pyridinyl.

37. The compound of any one of claims 1-28, 32, and 33, wherein R3is an optionallysubstituted 9-10 membered heteroaryl.

38. The compound of any one of claims 1-28, 32, and 37, wherein R3is an optionallysubstituted 9 membered heteroaryl selected from the group consisting of ,, wherein “*” indicates hydrogen or an optional substituent.

39. The compound of any one of claims 1-28, 32, and 37, wherein R3 is an optionallysubstituted 10 membered heteroaryl selected from the group consisting ofwherein “*” indicates hydrogen or anoptional substituent.

40. The compound of any one of claims 1-28, wherein R3 is -NR3AR3B.

41. The compound of any one of claims 1-28, wherein R3 is -C(=O)NR3AR3B.

42. The compound of any one of claims 1-28 and 40-41, wherein one of R3A and R3B ishydrogen, and the other one of of R3Aand R3Bis 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy and 4-6 membered heterocyclyl.

43. The compound of any one of claims 1-28 and 40-42, wherein one of R3Aand R3Bishydrogen, and the other one of of R3Aand R3Bis selected from the group consisting of, wherein “*” indicates hydrogen or an optional C1-C6 alkyl substituent.

44. The compound of any one of claims 1-28 and 40-41, wherein one of R3A and R3B isC1-C6 alkyl, and the other one of R3Aand R3Bis 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy and 4-6 membered heterocyclyl.

45. The compound of any one of claims 1-28 and 40-41, wherein one of R3A and R3B isC1-C6 alkyl, and the other one of R3Aand R3Bis C3-C10 cycloalkyl optionally substituted 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

46. The compound of any one of claims 1-28, and 40-41, wherein one of R3A and R3Bis hydrogen or C1-C6 alkyl, and the other one of R3Aand R3Bis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy).

47. The compound of any one of claims 1-28, 40-41, and 46, wherein one of R3A andR3Bis hydrogen, and the other one of R3Aand R3Bis selected from the group consisting of .

48. The compound of any one of claims 1-28 and 40-41, wherein one of R3A and R3B ishydrogen or C1-C6 alkyl, and the other one of R3Aand R3Bis 5-6 membered heteroaryl optionally substituted 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

49. The compound of any one of claims 1-28, 40-41, and 48, wherein one of R3A andR3Bis hydrogen, and the other one of R3Aand R3Bis selected from the group consisting of 4- pyridyl, wherein wherein “*” indicates hydrogen or an optional substituent.

50. The compound of any one of claims 1-28, 40-41, and 48, wherein one of R3A andR3Bis methyl, and the other one of R3Aand R3B4-pyridyl.

51. The compound of any one of claims 1-28 and 40-41, wherein one of R3A and R3B isC1-C6 haloalkyl.

52. The compound of any one of claims 1-28, wherein R3 is -OR3C.

53. The compound of claim 52, wherein R3C is 5-12 membered heterocyclyl optionallysubstituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy and 4-6 membered heterocyclyl.

54. The compound of claim 52, wherein R3Cis 5-6 membered heteroaryl optionallysubstituted 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

55. The compound of claim 52, wherein R3C is C3-C10 cycloalkyl optionallysubstituted 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

56. The compound of any one of claims 1-28, wherein R3is -C(=O)R3D.

57. The compound of claim 56, wherein R3Dis C1-C6 alkyl optionally substituted with1-3 substituents independently selected from hydroxyl and cyano.

58. The compound of claim 56, wherein R3D is C1-C6 haloalkyl.

59. The compound of claim 56, wherein R3Dis 5-12 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy and 4-6 membered heterocyclyl.

60. The compound of claim 56, wherein R3Dis C1-C6 alkyl(4-6 membered heterocyclyl optionally substituted with 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

61. The compound of claim 56, wherein R3Dis 5-6 membered heteroaryl optionally substituted 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

62. The compound of claim 56, wherein R3Dis C3-C10 cycloalkyl optionally substituted 1-3 substituents independently selected from: hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.

63. The compound of any one of claims 1-28, wherein R3is -N(R3A)C(=O)R3D.

64. The compound of any one of claims 1-63, wherein X is CRX.

65. The compound of any one of claims 1-63, wherein RXis hydrogen.

66. The compound of any one of claims 1-63, wherein RXis C1-C6 alkyl.

67. The compound of any one of claims 1-63 and 66, wherein RXis methyl.

68. The compound of any one of claims 1-63, wherein RXis halogen.

69. The compound of any one of claims 1-63 and 68, wherein RXis fluoro or chloro.

70. The compound of any one of claims 1-63, wherein RXis C1-C6 haloalkyl.

71. The compound of any one of claims 1-63, wherein RXis C1-C6 alkoxy.

72. The compound of any one of claims 1-63, wherein RXis cyano.

73. The compound of any one of claims 1-63, wherein RXis C3-C6 cycloalkyl.

74. The compound of any one of claims 1-73, wherein R4is hydrogen.

75. The compound of any one of claims 1-73, wherein R4is C1-C6 alkyl.

76. The compound of any one of claims 1-73 and 75, wherein R4is methyl.

77. The compound of any one of claims 1-73, wherein R4is halogen.

78. The compound of any one of claims 1-73 and 77, wherein R4is fluoro or chloro.

79. The compound of any one of claims 1-73, wherein R4is C1-C6 haloalkyl.

80. The compound of any one of claims 1-73, wherein R4is C1-C6 alkoxy.

81. The compound of any one of claims 1-73, wherein R4is cyano.

82. The compound of any one of claims 1-73, wherein R4is C3-C6 cycloalkyl.

83. The compound of any one of claims 1-82, wherein R5is hydrogen.

84. The compound of any one of claims 1-82, wherein R5is C1-C6 alkyl.

85. The compound of any one of claims 1-82 and 84, wherein R5is methyl.

86. The compound of any one of claims 1-82, wherein R5is halogen.

87. The compound of any one of claims 1-82 and 86, wherein R5is fluoro or chloro.

88. The compound of any one of claims 1-82, wherein R5is C1-C6 haloalkyl.

89. The compound of any one of claims 1-82, wherein R5is C1-C6 alkoxy.

90. The compound of any one of claims 1-82, wherein R5is cyano.

91. The compound of any one of claims 1-82, wherein R5is C3-C6 cycloalkyl.

92. The compound of any one of claims 1-63 and 74-91, wherein X is N.

93. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, selected from the compounds described in Table A or Table B, or a pharmaceutically acceptable salt thereof.

94. A pharmaceutical composition comprising a compound of any one of claims 1-93, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

95. A method of treating a GCase-associated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1-93, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 94.

96. The method of claim 95, wherein the GCase-associated disease is a lysosomal storage disorder or a neurodegenerative disorder.

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