Substituted pyrazolopyridine and pyrazolopyrimidine compounds and their use

Abstract

The application provides compounds of Formula (I), and their salts and solvates, wherein A1, A2, A3, A4, R1, R2, R3, R4, R5, R6, R7, R8, m, and n are defined as set forth in the specification, and their use in the treatment and / or prevention of diseases and conditions associated with the alteration of the activity of β-glucocerebrosidase.

Description

[0001]SUBSTITUTED PYRAZOLOPYRIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to European Pat Aenptplication No. EP24382380.4 filed on April 11, 2024, the entirety of which is incorpaoted by reference herein. FIELD OF THE DISCLOSURE The present disclosure provides compounds and u tshei irn the treatment and / or preventionof diseases, conditions, or disorders associatetdh w thie alteration of the activity o βf -glucocerebrosidase (GBA), specially associated w thiteh alteration of the activity of β- glucocerebrosidase in a patient, such as, for elxea,m lpysosomal storage disease αs-, synucleinopathies, and tauopathies (such as aacuuotepa tthies or chronic tauopathies). The present disclosure is also related to the use of the pylorapzyoridine and pyrazolopyrimidine compounds described herein in the treatment and / or preven otfio mnedical disorders in a patient, such as, forexample, Gaucher's disease, Parkinson's diseamse, n dtiae with Lewy bodies, diffuse Lewy bodydisease, multiple system atrophy (MSA), epilepsiyp,ol bar disorder, schizophrenia, an anxiety disorder, major depression, polycystic kidney dsisee,a type 2 diabetes, open angle glaucoma, multiple sclerosis (MS), multiple myeloma, Alzheirm'se disease, non-Alzheimer’s tauopathies (Pick’s complex), amyotrophic lateral sclerosis (SA)L, corticobasal degeneration, frontotemporal lobe dementia, GBA1 Parkinson, neuronopathic Garu'sch deisease, neuroaxonal dystrophy, neurodegenerative diseases with parkinsonism, e psrosgivre supranuclear palsy, pure autonomic failure, sporadic Creutzfeldt-Jakob disease, omr upnaiired aging. BACKGROUND OF THE DISCLOSURE Gaucher's disease, suggested to arise β fr-ogmlucocerebrosidase enzyme deficiency, is a very rare lysosomal storage disease. The cond aitsiosnociated with β-glucocerebrosidase is known to be caused by a deficiency of the enzy βm-gelucocerebrosidase due to mutations in the gene. β-Glucocerebrosidase cleave βs-glucocerebroside from different substrates, and deficiencies in its activity cause the substrati.ees., ( gangliosides, and oligosaccharides carrying terminal β-linked glucocerebroside) to accumulate in patie snutfsfering from conditions associated with β-glucocerebrosidase activity, such as Gauchere'sas deis. Beutle ert al. (Mol Med.1(1):82-92(1994)) reported that deficiency of glucocerebraos eid leads to accumulation of insolubleglucocerebrosides in the tissues, resulting in cl tihneical manifestations of Gaucher's disease. In many lysosomal disorders, like Gaucher's dis,e tahsee mutant enzymes often retain catalytic activity but fold improperly in the endloapsmic reticulum ("ER"). This triggers ER accumulation of the mutant protein, which is eveanllytu tagged for proteasome degradation by ubiquitination, avoiding the transport of the enzeym to the lysosome S.ee, e.g. P, atniak et al., Journal of Medicinal Chemistr 5y5(12):5734-5748 (2012). Gaucher's (or Gaucher) disease is a heterogenosuosrde dri having three subtypes. The majority of patients, those without neurologic mfeasntiations of the disease, are classified as type I. In type I, clinical manifestations include englaerd spleen and liver, platelet deficiency, anemia, and bone disease. Types II and III are neuronocpa fothrmi s, classified with respect to severity and to the time of onset of neurologic disease. Typ ise m IIost severe with symptoms at or near the timeof birth. Patients with type II have a median l sifpean of 9 months. Type III has a later on Sset e.,e.g., Patniak et al., Journal of Medicinal Chemistry 55(12):5734-5748 (2012). Patients with Gaucher's disease exhibit hematological manifeosntsa,ti such as anemia and thrombocytopenia, as well as hepatosplenomegaly, skeletal deformitiensd, i an some cases, neurological impairment. See, e.g., Boyd et al., Journal of Medicinal Chemistr 5y6 (7):2705–2725 (2013). Enzyme replacement therapy ("ERT") and substrahteibi itnion therapy ("SRT") are two current therapies for type I Gaucher's disease.i EnRvoTlves long term treatment via injection of a recombinant enzyme (imiglucerase) into patients.ile W EhRT may be effective in reducing and reversing the clinical symptoms of the diseas ies, v itery costly. SRT is generally indicated for the treatment of adult patients with mild to moderaytpee t I Gaucher's disease for whom ERT is not a therapeutic option. The prescribed drug, an imingoasr,u miglustat inhibits glucosylceramide synthetase, reducing the production of glucocerseidberos in the lysosome. While SRT may be effective for some patients, it is associated w siitdhe effects, including weight loss, diarrhea, tremors, and peripheral nerve damage. Neither ERoTr S nRT are effective against theneuronopathic types II and III of Gaucher's dise. Sasee , e.g. P, atniak et al., Journal of MedicinalChemistry 55(12):5734-5748 (2012). Mutations in the gene encoding glucocerebrosidarsee a also a risk factor for α- synucleinopathies, such as Parkinson's disease d aifnfduse Lewy Body disease. β- Glucocerebrosidase activity is also reduced in i Pnsaorkn’s disease patients without GBA1 mutations. The association of lower glucocerebraosseid activity in both GBA mutation carriers and Parkinson’s patients without GBA mutations sugg tehsatt loss of glucocerebrosidase function contributes to the pathogenesis of Parkinson’sa dsies.e Parkinson's disease is a degenerative disorder of the central nervous system associatiethd d weath of dopamine-containing cells in aregion of the midbrain. Diffuse Lewy Body disea isse a dementia that is sometimes confused withAlzheimer's disease. Small molecules capable odfin bgin allosterically or competitively to wild type (WT) or mutated β-glucocerebrosidase enzyme, thereby stabilizing e tnhzeyme against degradation (chaperones), constitute an imporhtaenrtap t eutic target in conditions associated with the alteration of the activity o βf-glucocerebrosidase. By binding and stabilizinga mnutt proteins,these chemical chaperones facilitate protein fogld ain d eventually increase their transport to thelysosome. Improved trafficking of the mutant pronte friom the ER to the lysosome results in the reduction of lysosome size and correction of thoera sgte. These chaperones may also increase the stability of mutant enzymes toward degradationh ien l tysosome S. ee, e.g. P, atniak et al., Journal of Medicinal Chemistry 55(12):5734-5748 (2012). Additionally, these chaperones may preserve lysoaslo hmealth. As it is described in the literature (see, Choi S e.t al., PLoS One. 10(12):e0143854 (2015); Piras, et A. al., Acta Neuropathol. Commun. (4): 22 (2016)), in Alzheim deisrease and other tauopathies, lysosomal function is compromised and consequently, the psrsoc oef autophagy and the proper elimination of toxic forms of tau would be affected. Small mcoullees improving lysosomal function and enhancing autophagy may reduce the progressioinse oafs des such as tauopathies. It has been surprisingly found that pyrazolopyreidi annd pyrazolopyrimidine compounds described herein are capable of binding β- tgolucocerebrosidase thereby stabilizing the enzyme against denaturation. There is a need for the development of compounadts e txhhibit improved properties in thetreatment or prevention of conditions associatetdh w thie altered activity o βf-glucocerebrosidase,and specifically Parkinson's disease. BRIEF SUMMARY OF THE DISCLOSURE The present disclosure is related to the discove thrayt pyrazolopyridine and pyrazolopyrimidine compounds represented by any o ofn Feormulae (I)-(X) are capable of binding to β-glucocerebrosidase (mutated or not) and are thsuesful u in the treatment or prevention of diseases, conditions, or disorders, e.g., a lysoasl o stmorage disease, such as Gaucher's disease; an α-synucleinopathy, such as Parkinson's disease;uo apa tathy, such as Alzheimer’s; or other conditions associated with the alteration of thteiv aityc of β-glucocerebrosidase. In one aspect, the present disclosure provides o coumndps represented by any one of Formulae (I)-(X), below, and pharmaceutically actcaebple salts and solvates thereof, collectively referred to herein as "Compounds of the Disclosu (erea"ch is individually referred to hereinafter as a "Compound of the Disclosure"). In another aspect, the present disclosure prov aid pehsarmaceutical composition comprising a Compound of the Disclosure and at least one pahcaerumtically acceptable excipient. In another aspect, the present disclosure prov aide msethod of treating or preventing a condition associated with the alteration of theiv aitcyt of β-glucocerebrosidase in a patient in need thereof. The method comprises administering to p tahteient in need thereof an effective amount of a Compound of the Disclosure. In another aspect, the present disclosure prov aide msethod of treating or preventing a lysosomal storage disease, such as Gaucher'se d,is ineas patient in need thereof by administering an effective amount of a Compound of the Disclo.sure In another aspect, the present disclosure prov aid mesethod of treating or preventing α a-n synucleinopathy, such as Parkinson's disease, p iantie ant in need thereof by administering an effective amount of a Compound of the Disclosure. In another aspect, the present disclosure prov aide msethod of treating or preventing a taupathy, such as Alzheimer’s disease, in a pa itnien eted thereof by administering an effective amount of a Compound of the Disclosure. In another aspect, the present disclosure is deidre tcot a method of treating or preventing adisease or disorder selected from the group coin gsis otf: Gaucher's disease, Parkinson's disease,dementia with Lewy bodies, diffuse Lewy body disee,a msultiple system atrophy (MSA), epilepsy, bipolar disorder, schizophrenia, an anxiety disro,r mdeajor depression, polycystic kidney disease, type 2 diabetes, open angle glaucoma, multiplero sscilse (MS), multiple myeloma, Alzheimer's disease, non-Alzheimer’s tauopathies (Pick’s comx)p,le amyotrophic lateral sclerosis (ALS), corticobasal degeneration, frontotemporal lobe dnetima,e GBA1 Parkinson, neuronopathic Gaucher's disease, neuroaxonal dystrophy, neurnoedreagteive diseases with parkinsonism, progressive supranuclear palsy, pure autonomiucre fa,il sporadic Creutzfeldt-Jakob disease, and unimpaired aging. In another aspect, the methods described heretihne frur comprise administering to the patient at least one other therapeutic agent.no Inth aer aspect, the therapeutic agent is an effeectiv amount of an enzyme for enzyme replacement thera Ipny. another aspect, the enzyme β- is glucocerebrosidase or an analog thereof. In anro atshpeect, the enzyme is imiglucerase. In another aspect, the therapeutic agent is an effective amt o fu an small molecule chaperone. In another aspect, the small molecule chaperone binds comivpeelytit to an enzyme. In another aspect, the small molecule chaperone is selected from the gr coounpsisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidasefa,t sausle, glycosyl transferase, phosphatase, andpeptidase inhibitors. In another aspect, the smaoll ecule chaperone is selected from the groupconsisting of isofagomine, N-nonyl-1-deoxynojiriminyc (NN-DNJ), ambroxol, and miglustat. In another aspect, the small molecule chaperonee isct seedl from the group consisting of isofagomine, N-nonyl-1-deoxynojirimycin (NN-DNJ), and ambroxol I.n another aspect, the small molecule chaperone is miglustat. In another aspect, the therapeutic agent is anct eivfefe amount of substrate reduction agent for substrate reduction therapy. In another as,p theect substrate reduction agent is miglustat. In another aspect, the present disclosure prov aide Csompound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of a condition associated with the alterationof the activity of β-glucocerebrosidase in a patient in need thereof. In another aspect, the present disclosure prov aide Csompound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of a lysosomal storage disease, such asGaucher's disease. In another aspect, the present disclosure prov aid Ceosmpound of the Disclosure for use in the prevention or treatment of α a-nsynucleinopathy, such as Parkinson's disease. In another aspect, the present disclosure prov aid Ceosmpound of the Disclosure for use in the prevention or treatment of a tauopathy, s ausch Alzheimer’s disease. In another aspect, the present disclosure prov aid Ceosmpound of the Disclosure for use inthe prevention or treatment of a disease or disro sredle cted from the group consisting of: Gaucher'sdisease, Parkinson's disease, dementia with Lewdyies b,o diffuse Lewy body disease, multiple system atrophy (MSA), epilepsy, bipolar disordecrh,iz sophrenia, an anxiety disorder, major depression, polycystic kidney disease, type 2 dteiasb,e open angle glaucoma, multiple sclerosis (MS), multiple myeloma, Alzheimer's disease, nonz-hAelimer’s tauopathies (Pick’s complex), amyotrophic lateral sclerosis (ALS), corticobasaelge dneration, frontotemporal lobe dementia, GBA1 Parkinson, neuronopathic Gaucher's diseasuer,oa nxeonal dystrophy, neurodegenerative diseases with parkinsonism, progressive supranruc plaelasy, pure autonomic failure, sporadic Creutzfeldt-Jakob disease, and unimpaired aging. In another aspect, the present disclosure is airlseocte dd to the use of a Compound of the Disclosure for the treatment or prevention of ad citoionn associated with the alteration of the activity of β-glucocerebrosidase in a patient in need thereuocfh, s as lysosomal storage diseases, α-synucleinopathies, and tauopathies describedn h.erei In another aspect, the present disclosure prov aid pehsarmaceutical composition comprising a Compound of the Disclosure and at least one pahcaerumtically acceptable excipient. In another aspect, the present disclosure prov aid Ceosmpound of the Disclosure for use as a medicament. In another aspect, the present disclosure prov uidses of a Compound of the Disclosure inthe preparation of a medicament for the preven otiro tnreatment of a condition associated with the alteration of the activity o βf-glucocerebrosidase in a patient in need thereuocfh, s as lysosomal storage disease αs-,synucleinopathies, and tauopathies describedn h.erei In another aspect, the present disclosure prov aid pehsarmaceutical composition comprising a Compound of the Disclosure and at least one pahcaerumtically acceptable excipient, for use in the treatment or prevention of a condition assoecdia wtith the alteration of the activity o βf- glucocerebrosidase in a patient in need thereocf,h s aus lysosomal storage disease α-s, synucleinopathies, and tauopathies described h.erein Other aspects and advantages of the disclosure be w rileladily apparent from the following detailed description of the disclosure. The emboednitms and advantages of the disclosure will be realized and attained by means of the elements co amndbinations particularly pointed out in the appended claims. It is to be understood that both the foregoing suamrym and the following detailed description are exemplary and explanatory only a arned not restrictive of the disclosure as claimed. DETAILED DESCRIPTION OF THE DISCLOSURE Compounds of the Disclosure are capable of bind toin βg-glucocerebrosidase. In view of this property, Compounds of the Disclosure are c etxepde to be useful for treating or preventing, e.g., Gaucher's disease, and other diseases,i coonnsd, i otr disorders described herein. I. Compounds of the Disclosure In one embodiment, Compounds of the Disclosure co amrepounds having Formula (I): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein: A1is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no more than one ofA2, A3, and A4 is N; R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R2 is selected from the group consisting of hydrog -Cen1-,6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and –ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4alkyl, and -C3-6cycloalkyl, wherein said -1C-4alkyl and -C3-6cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydrog aennd -C1-4 alkyl, wherein said -C1-4alkyl is optionally substituted with 1 or 2 subusetitnts each independently selected from the group consisting of halogen, -CN, and -ORa; or R2and R3together with the nitrogen atom to which they a trteached form an optionally substituted spirocyclic heterocyclic ring; R4 is selected from the group consisting of hydrog heanlo,gen, and -1C-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms; and each R5is independently selected from the group consis otifn hgalogen, -CN, -ORa, -1C-4alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl, wherein said -1C-4 alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substitutedh w 1it, 2 or 3 substituents each independently selected f trhoem group consisting of halogen, hydroxy, -N(Rb)2, -C1-4alkyl , -C1-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -1C-4alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl groups are optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of -C1-4alkyl, -C1-4alkoxy, and halogen, e.g., fluorine; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ring, wherein or 12 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom independe snetllyected from the group consisting of O, N, and S, and wherein said heterocyclic ring is opatliloyn substituted with 1 or 2 substituents each independently selected from the group consistin hga olofgen and -1C-4 alkyl; R7is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, e.g., fluorine, and –C3-6cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4 alkyl, and -C1- 4 alkyl, wherein said alkyl is optionally substitut beyd 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R6, R7, and R8 each take the place of a hydrogen atom that wo tuhledrwise be present inany position on the rings of Formula (I) to which6, R 7 and R8 are attached.In another embodiment, Compounds of the Disclo asurere compounds having Formula (I): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein: R2is selected from the group consisting of hydrog -Cen1-,6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5heterocyclyl, wherein said -1C-6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6- membered)-C2-5heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and –ORa; R3 is selected from the group consisting of hydrog aennd -C1-4 alkyl, wherein said -C1-4alkyl is optionally substituted with 1 or 2 subusetitnts each independently selected from the group consisting of halogen, -CN, and -ORa; and R1, R4, R5, R6, R7, R8, Ra, Rb, A1, A2, A3, A4, m, and n are as defined above. In another embodiment, Compounds of the Disclo asurere compounds having Formula (I), and the pharmaceutically acceptable salts and t seoslv tahereof, wherein the compound of Formula (I) is not: 2-((6-(benzod[][1,3]dioxol-5-ylamino)-1-(p- tolyl)-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6- (methyl(phenyl)amino)-H1-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol In another embodiment, Compounds of the Disclo asurere compounds having Formula (I), and the pharmaceutically acceptable salts and t seoslv tahereof, wherein the compound of Formula (I) is not: 2-((1-(4-fluorophenyl)-6-(indolin-1-yl)- 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6-(indolin-1-yl)- 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-(indolin-1-yl)-1-(p-tolyl)-1H- pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-(2,3-dihydro-4H- benzo[b][1,4]oxazin-4-yl)-1-(4- fluorophenyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6-(2,3-dihydro- 4H-benzo[b][1,4]oxazin-4-yl)-1H- pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-(2,3-dihydro-4H- benzo[b][1,4]oxazin-4-yl)-1-(p-tolyl)- 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-(3,4-dihydroquinolin-1(H2)-yl)-1- (4-fluorophenyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6-(3,4- dihydroquinolin-1(2H)-yl)-1H- pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-(3,4-dihydroquinolin-1(H2)-yl)-1- (p-tolyl)-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol In another embodiment, Compounds of the Disclo asurere compounds having Formula (I), and the pharmaceutically acceptable salts and t seoslv tahereof, wherein the compound of Formula (I) is not: 2-((6-(benzod[][1,3]dioxol-5-ylamino)-1-(p- tolyl)-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6- (methyl(phenyl)amino)-H1-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol 2-((1-(4-fluorophenyl)-6-(indolin-1-yl)-H1- pyrazolo[3,4d-]pyrimidin-4-yl)amino)ethan-1- ol 2-((1-(4-chlorophenyl)-6-(indolin-1-yl)-H1- pyrazolo[3,4d-]pyrimidin-4-yl)amino)ethan-1- ol 2-((6-(indolin-1-yl)-1-(p-tolyl)-1H- pyrazolo[3,4d-]pyrimidin-4-yl)amino)ethan-1- ol 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4- yl)-1-(4-fluorophenyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6-(2,3-dihydroH-4- benzo[b][1,4]oxazin-4-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4- yl)-1-(p-tolyl)-1H-pyrazolo[3,4d-]pyrimidin- 4-yl)amino)ethan-1-ol 2-((6-(3,4-dihydroquinolin-1(H2)-yl)-1-(4- fluorophenyl)-1H-pyrazolo[3,4d-]pyrimidin- 4-yl)amino)ethan-1-ol 2-((1-(4-chlorophenyl)-6-(3,4- dihydroquinolin-1(2H)-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol 2-((6-(3,4-dihydroquinolin-1(H2)-yl)-1-(p- tolyl)-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol In another embodiment, Compounds of the Disclo asurere compounds having Formula (I), and the pharmaceutically acceptable salts and t seoslv tahereof, wherein the compound of Formula (I) is not: N4-ethyl-N6,1-diphenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6,1-diphenyl-N4-propyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-cyclohexyl-N6,1-diphenyl-1H- pyrazolo[3,4-d]pyrimidine-4,6-diamine In another embodiment, Compounds of the Disclo asurere compounds having Formula (I), and the pharmaceutically acceptable salts andt seoslv thaereof, wherein when1 A is N, and A2, A3, and A4 are each CH, then at least one o6,f R 7, and R8 is other than hydrogen. In another embodiment, Compounds of the Disclo asurere compounds having Formula (I), and the pharmaceutically acceptable salts andt seoslv thaereof, wherein when1A is N, A2, A3, and A4 are each CH,1 R is hydrogen, R4 is hydrogen, and n is 0, then at least one6 o,f R R7, and R8 is other than hydrogen. In another embodiment, Compounds of the Disclo asruere compounds having Formula (II): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein1 R, R2, R3, R4, R5, R6, R7, R8, A2, A3, A4, m, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclosu are compounds havingFormula (III): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein1 R, R2, R3, R4, R5, R6, R7, R8, A2, A3, A4, m, and n are as defined above for Formula (I). In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(III), and the pharmaceutically accaebplet salts and solvates thereof, where1in is R selected from the group consisting of hydrogen1,-4 - aClkyl, -C3-6 cycloalkyl, and -C1-4 alkyl-C3-6 cycloalkyl. In another embodiment,1 R is selected from the group consisting of hydro agnedn -C1-4alkyl. In another embodiment,1R is hydrogen. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(III), and the pharmaceutically accaebplet salts and solvates thereof, where1in an Rd R6together with the nitrogen and carbon atoms toch wh thi ey are attached form an optionally substituted heterocyclic ring, wherein 1 or 2 canrb aotoms of said heterocyclic ring are optionallyreplaced with a heteroatom independently selecrtoemd fthe group consisting of O, N, and S, andwherein said heterocyclic ring is optionally sutbustteid with 1 or 2 substituents each independently selected form the group consisting of halogen aCn1d-4a -lkyl. In some embodiments, Compounds of the Disclosuere co amr pounds having any one of Formulae (I)-(III), and the pharmaceutically accaebplet salts and solvates thereof, where1in an Rd R6together with the nitrogen and carbon atoms toch wh thi ey are attached form an optionally substituted heterocyclic ring as defined abov2e i,s R as defined form Formula (I) with the proviso that R2 is not –CH2CH2OH, and R3, R4, R5, R8, A2, A3, A4, m, and n are as defined above for Formula (I). In some embodiments, Compounds of the Disclosuere co amr pounds having any one of Formulae (I)-(III), and the pharmaceutically accaebplet salts and solvates thereof, where1in an Rd R6 together with the nitrogen and carbon atoms toch wh thi ey are attached form an optionally substituted heterocyclic ring as defined above2, is R selected from the group consisting of hydrogen, methyl, -C3-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)-2C-5heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3- 6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)-2C-5heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl groups are optionally substituted b, 2y 1 or 3 substituents each independently selectedfrom the group consisting of halogen, -N(R2,a) nd –ORa, and3 R, R4, R5, R8, A2, A3, A4, m, and n are as defined above for Formula (I). In anothebro edmiment, Compounds of the Disclosure are compounds having Formula (IV): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein2R, R3, R4, R5, R7, R8, A1, A2, A3, A4, m, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclo asruere compounds having Formula (V): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein2 R, R3, R4, R5, R7, R8, A1, A2, A3, A4, m, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclosu are compounds havingFormula (VI): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein2R, R3, R4, R5, R7, R8, A1, A2, A3, A4, m, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclosu are compounds havingFormula (VII): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein2 R, R3, R4, R5, R7, R8, Rb, A1, A2, A3, A4, m, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (IV)-(VII), and the pharmaceutically actcaebple salts and solvates thereof, where1in is A N. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (IV)-(VII), and the pharmaceutically actcaebple salts and solvates thereof, where1in is A CH. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (IV)-(VII), and the pharmaceutically actcaebple salts and solvates thereof, where2in is R not -CH2CH2OH. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in is R hydrogen. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in is R selected from the group consisting of1- -5C alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl (e.g., cyclopropyl), -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl (e.g., 2- cyclohexylethyl), -C1-2alkyl-C3-6cycloalkenyl (e.g., (cyclohex-1-en-1-yl)ethyl),1--2C alkyl-C3-6cycloalkynyl, -(3- to 6-membered)-2C-5 heterocyclyl, and -C1-2 alkyl-(3- to 6-membered)-2C-5 heterocyclyl (e.g., 2-morpholinoethyl), wherein d sa -iC1-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-2 alkyl- (3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted 1 b oyr 2 substituents each independently selected from the group consisting ha olof gen and –ORa, wherein Ra is selected from the group consisting of hydrogen, methyl, a enthdyl, wherein said methyl and ethyl groups are optionally substituted with 1, 2, or 3 fluori anteoms. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in is R selected from the group consisting of hydrogen,h myl,et ethyl, isopropyl, isobutyl, isopentyl, cyclopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,22-,trifluoroethyl, 2-methoxyethyl, 2- hydroxyethyl, 2-hydroxy-2-methyl-propyl, 2-cyclohyelexthyl, (cyclohex-1-en-1-yl)ethyl, and 2- morpholinoethyl. In some embodiments2, i Rs hydrogen. In some embodiments2, is R methyl. In some embodiments,2R is 2,2-difluoroethyl. In some embodiments2, is R 2,2,2-trifluoroethyl. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where3in is R hydrogen. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where3in is R -C1-4alkyl (e.g., methyl). In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in an Rd R3 together with the nitrogen atom to which they a trteached form an optionally substituted spirocyclic heterocyclic ring. In some embodimen Rt2s, and R3together with the nitrogen atom to which they are attached form: . In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where4in is R hydrogen. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein n is 0. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein n is 1. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein n is 2. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where5in is R halogen or –C1-4 alkyl optionally substituted with 1, 2 or 3 subtusetints each independently selected from the group consisting of halogen, hydroxy, -Nb)(2R, -C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. In some embodiments5, R is halogen or unsubstituted1--C2alkyl. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(III), and the pharmaceutically accaebplet salts and solvates thereof, where6in is R selected from the group consisting of hydrogeno,g heanl, -CN, -ORa, -N(Rb2,) and -C1-4alkyl optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of halogen, -CN, hydroxy,1 --C4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where7in is R selected from the group consisting of hydrogen,og heanl, -ORa, and -1C-4 alkyl optionallysubstituted with 1, 2, or 3 halogen atoms. In so eme bodiments, 7 R is selected from the groupconsisting of hydrogen, halogen, -OH,1--4C alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(R2,b) -C1-4 alkyl optionally substituted with 1, 2, or 3 fluinoer atoms, and –3C-6 cycloalkyl. In some embodiments, each8 R is independently selected from the group consgis otifn hydrogen, halogen, -OH, -C1-4alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, -CN, -NH2, -N(H)C1-2 alkyl, -N(C1-2 alkyl)2, -C3-5 cycloalkyl, -C1-4 alkyl, monohalo(C1-4)alkyl-, dihalo(C1- 4)alkyl-, and trihalo(C1-4)alkyl-. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein m is 1. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein m is 2. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, wherein m is 3. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(III), and the pharmaceutically accaebplet salts and solvates thereof, wherein: R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1- 4alkyl-C3-6 cycloalkyl; each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; m is 1, 2, or 3; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4 alkyl, and -C1- 4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1--4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. In another embodiment, Compounds of the Disclosu are compounds havingFormula (VIII): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein: R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, form a 5- or6-membered ring having at least one heteroatomr,e winhe the ring is optionally substituted by oneor more substituents selected from the group ctoin gsis of halogen, -CN, -C(=O)-1C-4 alkyl, and-C1-4 alkyl, wherein said alkyl, is optionally substitudt bey 1, 2 or 3 fluorine atoms; or R6 and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 7-,8-, 9-, or 10-membered spiroheterocyclyl group t ihsat saturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1--4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R2, R3, R4, R5, m, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclosu are compounds havingFormula (IX): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein: R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6cycloalkyl; R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, form a 5- or6-membered ring having at least one heteroatomr,e winhe the ring is optionally substituted by oneor more substituents selected from the group ctoin gsis of halogen, -CN, -C(=O)-1C-4 alkyl, and-C1-4alkyl, wherein said alkyl, is optionally substitudt bey 1, 2 or 3 fluorine atoms; or R6 and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 7-,8-, 9-, or 10-membered spiroheterocyclyl group t ihsat saturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R2, R3, R4, R5, m and n are as defined for Formula (I). In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(III), (VIII), or (IX), and the pharmcaeutically acceptable salts and solvates thereof,wherein R6 and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 5-or 6-membered ring having at least one heteroa wtohme,rein the ring is optionally substituted by one or more substituents selected from the grounpsis ctoing of halogen, -CN, -C(=O)1-C-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. In some embodiments, Compounds of the Disclosuere co amr pounds having any one of Formulae (I)-(III), (VIII), or (IX), and the pharmcaeutically acceptable salts and solvates thereof,wherein R6 and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 5-membered ring having at least one nitrogen atome,re winh the ring is optionally substituted by oneor more substituents selected from the group ctoin gsis of halogen, -CN, -C(=O)-1C-4 alkyl, and-C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. In some embodiments, the 5-membered ring has one nitrotgoemn. a In some embosiments, the 5-membered ring has two nitrogen atoms. In some embodiments, Compounds of the Disclosuere co amr pounds having any one of Formulae (I)-(III), (VIII), or (IX), and the pharmcaeutically acceptable salts and solvates thereof,wherein R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, form a ringselected from the group consisting of: wherein is a single bond or a double bond, and wherexin a Rnd Ryare each independently selected from the group consistin hgy odfrogen, halogen, -CN, -C(=O)1--C4 alkyl, and -C1-4alkyl, wherein said alkyl is optionally substitut beyd 1, 2 or 3 fluorine atoms, and wherein Rxand Ryeach take the place of a hydrogen atom that wotuhledrw oise be present in any position on the ring to which Rxand Ryare attached. In some embodiments, Compounds of the Disclosuere co amr pounds having any one of Formulae (I)-(III), (VIII), or (IX), and the pharmcaeutically acceptable salts and solvates thereof,wherein R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, form a ringselected from the group consisting of: wherein is a single bond or a double bond. In another embodiment, Compounds of the Disclo asruere compounds having Formula (X): and the pharmaceutically acceptable salts andt seoslv thaereof, wherein: R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1--4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; m is 1, 2, or 3; and R2, R3, R4, R5, and n are as defined for Formula (I). In another embodiment, Compounds of the Disclo asruere compounds having Formula (X),and the pharmaceutically acceptable salts andt seoslv thaereof, wherein at least one o6,f R 7, andR8is other than hydrogen. In another embodiment, Compounds of the Disclo asruere compounds having Formula (X), and the pharmaceutically acceptable salts andt seoslv thaereof, wherein when1 R is hydrogen, R4 is hydrogen, and n is 0, then at least one6o,f R R7, and R8is other than hydrogen. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (VIII)-(X), and the pharmaceutically actcaebple salts and solvates thereof, where2in is R selected from the group consisting of hydrogen1,-5-C alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl (e.g., cyclopropyl), -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-2 alkyl-C3-6 cycloalkyl (e.g., 2- cyclohexylethyl), -C1-2 alkyl-C3-6 cycloalkenyl (e.g., (cyclohex-1-en-1-yl)ethyl),1 --2C alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)-2C-5heterocyclyl, and -C1-2alkyl-(3- to 6-membered)-2C-5heterocyclyl (e.g., 2-morpholinoethyl), wherein d sa -iC1-5alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-2 alkyl-C3-6 cycloalkyl, -C1-2 alkyl-C3-6 cycloalkenyl, -C1-2 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-2 alkyl- (3- to 6-membered)-2C-5heterocyclyl groups are optionally substituted 1 b oyr 2 substituents each independently selected from the group consisting ha olof gen and –ORa, wherein Ra is selected from the group consisting of hydrogen, methyl, a enthdyl, wherein said methyl and ethyl groups are optionally substituted with 1, 2, or 3 fluori anteoms. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (VIII)-(X), and the pharmaceutically actcaebple salts and solvates thereof, where2in is R selected from the group consisting of hydrogen,h myl,et ethyl, isopropyl, isobutyl, isopentyl, cyclopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,22-,trifluoroethyl, 2-methoxyethyl, 2- hydroxyethyl, 2-hydroxy-2-methyl-propyl, 2-cyclohyelexthyl, (cyclohex-1-en-1-yl)ethyl), and 2- morpholinoethyl. In some embodiments2, i Rs hydrogen. In some embodiments2, is R methyl. In some embodiments,2R is 2,2-difluoroethyl. In some embodiments2, is R 2,2,2-trifluoroethyl. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (VIII)-(X), and the pharmaceutically actcaebple salts and solvates thereof, where2in R and R3 together with the nitrogen atom to which they a trteached form an optionally substituted spirocyclic heterocyclic ring. In some embodimen Rt2s, and R3 together with the nitrogen atom to which they are attached form: . In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in is A N; and A3 and A4 are CH. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in an Ad A4 are CH; and A3 is N. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2in an Ad A3are CH; and A4is N. In another embodiment, Compounds of the Disclos aurere compounds having any one of Formulae (I)-(VII), and the pharmaceutically accaebplet salts and solvates thereof, where2i,n A A3, and A4are CH. In some embodiments, Compounds of the Disclosuere c aormpounds of any one of Formulae (I)-(VII) and (X), and the pharmaceutiycal clceptable salts and solvates thereof, wherein R7is hydrogen, m is 1 or 2, each8R is independently selected from the group consgis otinf hydrogen, halogen, -OH, -CN, -NH(Rb), -N(R2,b -)C1-4 alkyl, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-, and R6is selected from the group consisting of hydrog heanlo,gen, -OH, -CN, -NH(Rb), -N(Rb)2, -C1-4alkyl, -C1-4alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-, wherein each Rb is independently selected from the group consisting hy odfrogen, -C1-4 alkyl, and -(5- to 6- membered)-C2-5heterocyclyl (e.g., piperidinyl and tetrahydropnyyrla), wherein said –C1-4alkyl and -(5- to 6-membered)2-C-5 heterocyclyl are optionally substituted with 12 o srubstituents each independently selected from the group consistin hga olofgen, -C1-4 alkyl, and –C1-4 alkoxy. In some embodiments, Compounds of the Disclosuere c aormpounds of any one of Formulae (I)-(X), and the pharmaceutically accelpeta sbalts and solvates thereof, wherein ea8ch R is independently selected from the group consis otifn hgydrogen, halogen, -OH, -CN,1 --C4 alkoxy, -C1-4 alkyl, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy. In some embodiments, each8i Rs independently selected from the group consisting of hydrogeno,g heanl, and unsubstituted1 --C2 alkyl. In another embodiment, Compounds of the Disclos aurere compounds selected from any one or more of the compounds of Table 1, or a pahcaermutically acceptable salt or solvate thereof. Table 1 Example # StructureName1-phenyl-N6-(3- (trifluoromethyl)phenyl)-1H- 1 pyrazolo[3,4d-]pyrimidine-4,6-diamine 2 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)phenol 3 N6-(3,5-difluorophenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 4 N6-(3-fluorophenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 5 3-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)phenol 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- 6 d]pyrimidin-6-yl)amino)-6- methylphenolExample # StructureName7 N6-(3-chlorophenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 8 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-5-fluorophenol 9 N6-(2-isopropoxyphenyl)-1-phenylH-1- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(benzo[d][1,3]dioxol-4-yl)-1-phenyl- 10 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine 11 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-5-chlorophenol 12 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-6-fluorophenol 13 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-3-fluorophenol 14 N6-(1H-indol-7-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamineExample # StructureName2-((4-amino-1-phenyl-H1-pyrazolo[3,4- 15 d]pyrimidin-6-yl)amino)-5- methylphenol N6-(2,3-dihydrobenzofuran-7-yl)-1- 16 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- 17 d]pyrimidin-6-yl)amino)-4- methoxyphenol 18 N6-(2-methoxyphenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 19 N6-(3-methoxyphenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(4-(dimethylamino)-2- 20 methoxyphenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(1H-benzo[d]imidazol-7-yl)-1- 21 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 4-((4-amino-1-phenyl-H1-pyrazolo[3,4- 22 d]pyrimidin-6-yl)amino)-3- hydroxybenzonitrileExample # StructureName23 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-4-fluorophenol 24 N6-(2-fluorophenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 25 N6-(1H-indol-4-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- 26 d]pyrimidin-6-yl)amino)-5- (trifluoromethyl)phenol 1-phenyl-N6-(3- 27 (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 28 N6-(3-isopropoxyphenyl)-1-phenylH-1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 29 N6-(1H-indol-6-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((4-(methylamino)-1-phenyl-H1- 30 pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenolExample # StructureNameN6-(2-methoxyphenyl)N-4-methyl-1- 31 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(3-chlorophenyl)N-4-methyl-1- 32 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(3-methoxyphenyl)N-4-methyl-1- 33 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-1-phenylN-6-(3- 34 (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(3-isopropoxyphenyl)N-4-methyl-1- 35 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(1H-indol-7-yl)-N4-methyl-1-phenyl- 36 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N6-(1H-indol-6-yl)-N4-methyl-1- 37 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 38 2-((4-(methylamino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6-yl)amino)- 6-(trifluoromethyl)phenolExample # StructureName2-methoxy-6-((4-(methylamino)-1- 39 phenyl-1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol 40 N4-methyl-N6,1-diphenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(1H-indazol-7-yl)-N4-methyl-1- 41 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 4-methoxy-2-((4-(methylamino)-1- 42 phenyl-1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol 2-(methyl(4-(methylamino)-1-phenyl- 43 1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol 5-chloro-2-((4-(methylamino)-1-phenyl- 44 1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol 4-chloro-2-((4-(methylamino)-1-phenyl- 45 1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol N6-(5-chloro-1H-indol-7-yl)-N4-methyl- 46 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamineExample # StructureNameN6-(4-chloro-1H-indol-7-yl)-N4-methyl- 47 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(1-methyl-1H-indol-7-yl)- 48 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(1H-benzo[d]imidazol-6-yl)-N4- 49 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(1-methyl-1H- 50 benzo[d]imidazol-5-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N4-methyl-N6-(1-methylindolin-5-yl)-1- 51 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(3,3-dimethylindolin-7-yl)N-4- 52 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-cyclopropyl-N6-(1H-indol-7-yl)-1- 53 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamineExample # StructureNameN6-(1H-indol-7-yl)-N4-(2- 54 methoxyethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((4-(dimethylamino)-1-phenyl-H1- 55 pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol N6-(2-methoxyphenyl)N-4,N4-dimethyl- 56 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(3-methoxyphenyl)N-4,N4-dimethyl- 57 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(3-chlorophenyl)N-4,N4-dimethyl-1- 58 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(1H-indol-7-yl)-N4,N4-dimethyl-1- 59 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 2-((4-((2-morpholinoethyl)amino)-1- 60 phenyl-1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenolExample # StructureNameN6-(2-methoxyphenyl)N-4-(2- 61 morpholinoethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((6-((2-methoxyphenyl)amino)-1- 62 phenyl-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-((1H-indol-7-yl)amino)-1-phenyl- 63 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((4-((2-(cyclohex-1-en-1- 64 yl)ethyl)amino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol N4-(2-(cyclohex-1-en-1-yl)ethyl)N-6- 65 (1H-indol-7-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((4-((2-(cyclohex-1-en-1- 66 yl)ethyl)amino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6-yl)amino)- 4-methoxyphenol 5-chloro-2-((4-((2-(cyclohex-1-en-1- 67 yl)ethyl)amino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenolExample # StructureNameN4-(2-cyclohexylethyl)N-6-(1H-indol-7- 68 yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(1H-indol-7-yl)-N4-isopentyl-1- 69 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(3-bromophenyl)N-4-methyl-1- 70 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 2-((6-((3-bromophenyl)amino)-1- 71 phenyl-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((4-((2-hydroxyethyl)amino)-1- 72 phenyl-1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol N6-(3-bromophenyl)N-4-(2-(cyclohex-1- 73 en-1-yl)ethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- 74 d]pyrimidin-6-yl)amino)-5- (dimethylamino)phenolExample # StructureNameN6-(benzo[d]oxazol-4-yl)-N4-methyl-1- 75 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 76 N6-(2-(difluoromethyl)phenyl)N-4- methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(2-methoxy-6-methylphenylN)-4- 77 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(2-(methylamino)phenyl)- 78 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine 79 N6-(benzo[d]oxazol-7-yl)-N4-methyl-1- phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(benzo[d]oxazol-5-yl)-N4-methyl-1- 80 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(1H-indol-5-yl)-N4-methyl-1-phenyl- 81 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N4-methyl-N6-(2-methylbenzod[]oxazol- 82 6-yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamineExample # StructureNameHN N N N6-(benzo[d]oxazol-6-4N yl)-N -methyl-1- 83 O N N N H phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(1-methyl-1H- 84 benzo[d]imidazol-6-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N4-methyl-N6-(2-methylbenzod[]oxazol- 85 5-yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(3-(methylamino)phenyl)- 86 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(1-methylindolin-7-yl)-1- 87 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(1-methyl-1H-indol-5-yl)- 88 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine 1-((6-((1H-indol-7-yl)amino)-1-phenyl- 89 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)-2-methylpropan-2-ol 2-((6-((1H-indol-6-yl)amino)-1-phenyl- 90 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-olExample # StructureName2-((6-(benzo[d]oxazol-7-ylamino)-1- 91 phenyl-1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol N6-(2-fluoro-3-methylphenyl)N-4- 92 methyl-1-phenyl-1H-pyrazolo[3,4- b]pyridine-4,6-diamine N6-(2-fluorophenyl)-N4-methyl-1- 93 phenyl-1H-pyrazolo[3,4b-]pyridine-4,6- diamine N4-methyl-N6-(1-methyl-1H-indol-7-yl)- 94 1-phenyl-1H-pyrazolo[3,4b-]pyridine- 4,6-diamine (3-((4-(methylamino)-1-phenyl-H1- 95 pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenyl)methanol (2-((4-(methylamino)-1-phenyl-H1- 96 pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenyl)methanol N6-(indolin-7-yl)-N4-methyl-1-phenyl- 97 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamineExample # StructureNameN6-(indolin-6-yl)-N4-methyl-1-phenyl- 98 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N6-(indolin-4-yl)-N4-methyl-1-phenyl- 99 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N6-(indolin-5-yl)-N4-methyl-1-phenyl- 100 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N4-cyclopropyl-N6-(indolin-6-yl)-1- 101 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-cyclopropyl-N6-(indolin-7-yl)-1- 102 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 1-((6-(indolin-7-ylamino)-1-phenyl-H1- 103 pyrazolo[3,4d-]pyrimidin-4-yl)amino)- 2-methylpropan-2-ol 1-((6-(indolin-6-ylamino)-1-phenyl-H1- 104 pyrazolo[3,4d-]pyrimidin-4-yl)amino)- 2-methylpropan-2-ol N6-(indolin-7-yl)-N4-(2-methoxyethyl)- 1-phenyl-1H-pyrazolo[3,4- 105 d]pyrimidine-4,6-diamineExample # StructureNameN6-(indolin-6-yl)-N4-(2-methoxyethyl)- 106 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine 2-((6-(indolin-7-ylamino)-1-phenyl-H1- 107 pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-(indolin-6-ylamino)-1-phenyl-H1- 108 pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol N6-(indolin-7-yl)-N4-isobutyl-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidine-4,6- 109 diamine N6-(indolin-6-yl)-N4-isobutyl-1-phenyl- 110 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine 111 N4-ethyl-N6-(indolin-7-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 112 N4-ethyl-N6-(indolin-6-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(indolin-6-yl)-1-phenyl-N4-(2,2,2- 113 trifluoroethyl)-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamineExample # StructureNameN6-(indolin-7-yl)-1-phenyl-N4-(2,2,2- 114 trifluoroethyl)-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(indolin-7-yl)-N4-isopropyl-1- 115 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(indolin-6-yl)-N4-isopropyl-1- 116 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine HN N 117 N N N N6-(indolin-7-yl)-N4-methyl-1-phenyl- NH H 1H-pyrazolo[3,4b-]pyridine-4,6-diamine 118 N6-(indolin-6-yl)-N4-methyl-1-phenyl- 1H-pyrazolo[3,4b-]pyridine-4,6-diamine 119 N4-(2,2-difluoroethyl)-N6-(indolin-7-yl)- 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine 120 N4-(2-fluoroethyl)-N6-(indolin-7-yl)-1- phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 121 N6-(indolin-7-yl)-N4,N6-dimethyl-1- phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamineExample # StructureName122 N6-(2-fluorophenyl)-1-phenyl-H1- pyrazolo[3,4b-]pyridine-4,6-diamine N6-(3,3-Dimethylindolin-6-yl)-N4- 123 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-fluoroindolin-7-yl)-N4-methyl-1- 124 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(5-methylindolin-7-yl)-1- 125 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(4-fluoroindolin-7-yl)-N4-methyl-1- 126 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(4-methylindolin-7-yl)-1- 127 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(1-methylindolin-6-yl)-1- 128 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(3-methylindolin-7-yl)-1- 129 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamineExample # StructureNameN4-methyl-N6-(2-methylindolin-7-yl)-1- 130 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-1-phenylN-6- 131 (spiro[cyclopropane-1,3'-indolin]-7'-yl)- 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N4-methyl-N6-(3-(methylamino)pyridin- 132 4-yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(3-((2-methoxyethyl)amino)phenyl)- 133 N4-methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(3-((1-methylpiperidin-4- 134 yl)amino)phenyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine N4-methyl-1-phenylN-6-(1,2,3,4- 135 tetrahydroquinolin-8-yl)-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N4-methyl-1-phenylN-6-(3-((tetrahydro- 136 2H-pyran-4-yl)amino)phenyl)-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(4-methoxyphenyl)N-4-methyl-1- 137 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamineExample # StructureNameN4-methyl-N6-(1-methyl-1H-indol-6-yl)- 138 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(4-(dimethylamino)phenyl)N-4- 139 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(4-(methylamino)phenyl)- 140 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(2,3-dihydrobenzofuran-5-ylN)-4- 141 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-1-phenylN-6-(1H- 142 pyrrolo[3,2-b]pyridin-7-yl)-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 1-((6-((3,3-dimethylindolin-7- 143 yl)amino)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)-2- methylpropan-2-ol 1-((6-((3,3-dimethylindolin-6- 144 yl)amino)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)-2- methylpropan-2-ol N6-(3,3-dimethylindolin-7-yl)N-4-(2- 145 methoxyethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamineExample # StructureNameN6-(3,3-dimethylindolin-6-yl)N-4-(2- 146 methoxyethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine 2-((6-((1H-indol-5-yl)amino)-1-phenyl- 147 1H-pyrazolo[3,4d-]pyrimidin-4- yl)amino)ethan-1-ol 2-((6-((1-methyl-1H-indol-7-yl)amino)- 148 1-phenyl-1H-pyrazolo[3,4d-]pyrimidin- 4-yl)amino)ethan-1-ol N6-(1H-indol-5-yl)-1-phenyl-N4-(2,2,2- 149 trifluoroethyl)-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(1-methyl-1H-indol-7-yl)-1-phenyl- 150 N4-(2,2,2-trifluoroethyl)-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 151 N6-(1H-indol-5-yl)-N4-methyl-1-phenyl- 1H-pyrazolo[3,4b-]pyridine-4,6-diamine 152 N6-(1H-indol-7-yl)-N4-methyl-1-phenyl- 1H-pyrazolo[3,4b-]pyridine-4,6-diamine 153 N6-(1H-indol-6-yl)-N4-methyl-1-phenyl- 1H-pyrazolo[3,4b-]pyridine-4,6-diamineExample # StructureNameN6-(1H-Indol-7-yl)-N4-methyl-1-(o- 154 tolyl)-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N4-methyl-N6-(3-methyl-1H-indol-7-yl)- 155 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(1H-indol-4-yl)-N4-methyl-1-phenyl- 156 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine 7-((4-(methylamino)-1-phenyl-H1- 157 pyrazolo[3,4d-]pyrimidin-6-yl)amino)- 1H-indole-3-carbonitrile N6-(2-fluoro-3-methylphenyl)N-4- 158 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-(2,2-difluoroethyl)-N6-(1H-indol-5- 159 yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(1H-indol-7-yl)-1-(4- 160 methoxyphenyl)N-4-methyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine 161 2-((4-amino-1-phenyl-H1-pyrazolo[3,4- b]pyridin-6-yl)amino)phenol In another embodiment, Compounds of the Disclos aurere compounds selected from any one or more of the compounds of Table 2, or a pahcaermutically acceptable salt or solvate thereof. Table 2 Example # StructureNameN6-(4-fluoro-1-methyl-1H-indol-7-yl)- 162 N4-methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-fluoro-1-methyl-1H-indol-7-yl)- 163 N4-methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(1-methylindolin-4-yl)-1- 164 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(4-fluoro-1-methylindolin-6-yl)N-4- 165 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-fluoro-1-methylindolin-7-yl)N-4- 166 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-(2,2-difluoroethyl)-N6-(1-methyl-1H- 167 indol-7-yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(1-methyl-1H-indol-5-yl)- 168 1-phenyl-1H-pyrazolo[3,4b-]pyridine- 4,6-diamineExample # StructureNameN6-(5-fluoro-1-methylindolin-7-yl)N-4- 169 methyl-1-phenyl-1H-pyrazolo[3,4- b]pyridine-4,6-diamine N6-(4-fluoro-1-methylindolin-7-yl)N-4- 170 methyl-1-phenyl-1H-pyrazolo[3,4- b]pyridine-4,6-diamine N4-methyl-N6-(2-methylisoindolin-4-yl)- 171 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(2,3-dihydrobenzofuran-7-ylN)-4- 172 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(4-fluoro-1,5-dimethyl-1H-indol-7- 173 yl)-N4-methyl-1-phenyl-1H- pyrazolo[3,4-d]pyrimidine-4,6-diamine N4-cyclopropyl-N6-(5-fluoro-1-methyl- 174 1H-indol-7-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(5-chloroindolin-7-yl)-N4-methyl-1- 175 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 7-((4-(methylamino)-1-phenyl-H1- 176 pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-5-carbonitrileExample # StructureNameN6-(5-cyclopropylindolin-7-yl)-N4- 177 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(4-fluoro-5-methylindolin-7-yl)N-4- 178 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-chloroindolin-7-yl)-1-phenylN-4- 179 (2,2,2-trifluoroethyl)-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine (R)-N6-(indolin-7-yl)-1-phenyl-N4- 180 (1,1,1-trifluoropropan-2-yl)-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine (S)-N6-(indolin-7-yl)-1-phenyl-N4- 181 (1,1,1-trifluoropropan-2-yl)-H1- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(4-fluoroindolin-7-yl)-1-phenylN-4- 182 (3,3,3-trifluoropropyl)-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-(2-fluoro-2-methylpropyl)N-6-(4- 183 fluoroindolin-7-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamineExample # StructureNameN6-(indolin-6-yl)-N4,N6-dimethyl-1- 184 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(indolin-7-yl)-1-(4-methoxyphenyl)- 185 N4-methyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-(2,2-difluoroethyl)-N6-(indolin-7-yl)- 186 1-phenyl-1H-pyrazolo[3,4b-]pyridine- 4,6-diamine N6-(indolin-7-yl)-N4,3-dimethyl-1- 187 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 1-(3-fluorophenyl)N-6-(indolin-7-yl)-N4- 188 methyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 1-(2-fluorophenyl)N-6-(indolin-7-yl)-N4- 189 methyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine 1-(4-fluorophenyl)N-6-(indolin-7-yl)-N4- 190 methyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(4-fluoro-5-methyl-1H-indol-7-yl)- 191 N4-methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamineExample # StructureNameN6-(4-fluoro-5-methylindolin-7-yl)N-4- 192 methyl-1-phenyl-1H-pyrazolo[3,4- b]pyridine-4,6-diamine N6-(4-fluoro-1H-indol-6-yl)-N4-methyl- 193 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(indolin-7-yl)-1-(3-methoxyphenyl)- 194 N4-methyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-cyclopropyl-N6-(5-fluoro-1H-indol- 195 7-yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-fluoro-4-methylindolin-7-yl)N-4- 196 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-cyclopropyl-N6-(5-fluoro-4-methyl- 197 1H-indol-7-yl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(5-fluoro-4-methyl-1H-indol-7-yl)-1- 198 (4-fluorophenyl)-N4-methyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(4-fluoro-1H-indol-7-yl)-N4-methyl- 199 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamineExample # StructureNameN6-(5-fluoro-1H-indol-7-yl)-N4-methyl- 200 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-1-phenylN-6-(1H- 201 pyrrolo[3,2-c]pyridin-7-yl)-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine N6-(5-chloro-1-methylindolin-7-yl)N-4- 202 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(6-fluoro-1H-indol-4-yl)-N4-methyl- 203 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N4-methyl-N6-(5-methyl-1H-indol-7-yl)- 204 1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(4-fluoro-1-methylindolin-7-yl)N-4- 205 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine 1-(7-((4-(methylamino)-1-phenyl-H1- 206 pyrazolo[3,4d-]pyrimidin-6- yl)amino)indolin-1-yl)ethan-1-one N4-(2-fluoroethyl)-N6-(1H-indol-5-yl)-1- 207 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamineExample # StructureNameN6-(4-fluoroindolin-7-yl)-N4-methyl-1- 208 phenyl-1H-pyrazolo[3,4b-]pyridine-4,6- diamine N6-(5-fluoroindolin-7-yl)-N4-methyl-1- 209 phenyl-1H-pyrazolo[3,4b-]pyridine-4,6- diamine N4-methyl-N6-(1-methylindolin-6-yl)-1- 210 phenyl-1H-pyrazolo[3,4b-]pyridine-4,6- diamine N6-(1H-indol-5-yl)-1-phenyl-N4-(2,2,2- 211 trifluoroethyl)-1H-pyrazolo[3,4- b]pyridine-4,6-diamine N4-cyclopropyl-N6-(3- 212 (methylamino)pyridin-4-yl)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidine-4,6- diamine N6-(indolin-5-yl)-N4,N6-dimethyl-1- 213 phenyl-1H-pyrazolo[3,4d-]pyrimidine- 4,6-diamine N6-(indolin-7-yl)- N6-isopropyl-N4- 214 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(indolin-7-yl)-N4,N6-dimethyl-1- 215 phenyl-1H-pyrazolo[3,4b-]pyridine-4,6- diamineExample # StructureNameN6-(6-fluoro-1-methylindolin-7-yl)N-4- 216 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(4-fluoroindolin-7-yl)-N4,N6- 217 dimethyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(4-fluoro-1-methyl-1H-indol-6-yl)- 218 N4-methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine F HN N N N6-(5-fluoro-1,4-dimethyl-1H-indol-7- 219 NN NH yl)-N4-methyl-1-phenyl-1H- N pyrazolo[3,4d-]pyrimidine-4,6-diamine F HN N N N6-(5-fluoro-4-methyl-1H-indol-7-yl)- 220 NN NN4-methyl-1-phenyl-1H-pyrazolo[3,4- NH H d]pyrimidine-4,6-diamine N6-(4,5-difluoro-1H-indol-7-yl)-N4- 221 methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-fluoro-1,4-dimethylindolin-7-yl)- 222 N4-methyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine 223 6-(indolin-1-yl)-N-methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amineExample # StructureNameN4,N6-dimethyl-N6-(1-methylindolin-7- 224 yl)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine N6-(5-fluoro-1H-indol-7-yl)-1-(4- 225 fluorophenyl)-N4-methyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine hydrochloride N-(5-fluoro-4-methyl-1H-indol-7-yl)-1- 226 phenyl-4-(2-oxa-6-azaspiro[3.3]heptan- 6-yl)-1H-pyrazolo[3,4d-]pyrimidin-6- amine N6-(5-fluoro-1H-indol-7-yl)-1-(4- 227 fluorophenyl)-N4-methyl-1H- pyrazolo[3,4d-]pyrimidine-4,6-diamine In some embodiments, Compounds of the Disclosuere pr aorvided as a pharmaceutically acceptable salt. In some embodiments, the pharmticaaclelyu acceptable salt of a Compound of the Disclosure is a hydrochloride salt (a HCl salt). II. Definitions Optional substituents attached to aryl, e.g., phl,e annyd heteroaryl, e.g., pyridyl, rings eachtake the place of a hydrogen atom that would othiserw be present in any position on the aryl orheteroaryl rings. As used herein, the terms "halogen" or "halo" bsyelf it or as part of another group refer to fluorine (-F), chlorine (-Cl), bromine (-Br), ord ioine (-I). As used herein, the term "hydroxyl" or "hydroxyly" b itself or as part of another grouprefers to the group –OH. The term "cyano" as used herein by itself or ats o pfa arnother group refers to the group -CN. As used herein, the term "alkyl" by itself or asrt p oaf another group refers to a linear or branched hydrocarbon chain radical consisting orbf o cna and hydrogen atoms, containing no unsaturation, which is attached to the rest of m thoelecule by a single bond and, unless otherwise specified, an alkyl radical typically has from 14 to carbon atoms, i.e., 1 -C-4 alkyl. Exemplary -C1-4alkyl groups can be methyl, ethyl, n-propyl, i-pyrol, n-butyl, tert-butyl, i-butyl and sec-butyl. In another embodiment, the alkyl is1 --2C alkyl (methyl or ethyl). The term "alkoxy" as used herein by itself or arst p oaf another group refers to an alkylgroup attached to a terminal oxygen atom. In omnebo ediment, the alkyl is a -1C-C6alkyl.In another embodiment, the alkyl is a1- -C 4 alkyl group. In another embodiment, the alky al is-C1-C2 alkyl group. Non-limiting exemplary alkoxy group insclude methoxy, ethoxy, an tdert- butoxy. As used herein, the term1"-C4alkoxy" as used herein by itself or as part ofth aenro group refers to oxygen substituted by one of the1-4 -C alkyl groups mentioned above (e.g., methoxy, ethoxy, propoxy, iso-propoxy, butoxy, tert-butox isyo,-butoxy, and sec-butoxy), for example by one of the -C1-2alkyl groups. The term "haloalkyl" as used herein by itself or p as rt of another group refers to an alkylgroup substituted by one or more fluorine, chlo,rin beromine, and / or iodine atoms. In one embodiment, the alkyl is substituted by one, twro, th oree fluorine and / or chlorine atoms. In another embodiment, the alkyl is substituted by, o twneo, or three fluorine atoms. In anotherembodiment, the alkyl is a -1C-C6 alkyl. In another embodiment, the alkyl is a1- -C 4 alkyl.In another embodiment, the alkyl group is1 a o Cr C2 alkyl. In some embodiments, the haloalkyl is monohalo(C1-4)alkyl- (i.e., -C1-4alkyl group substituted by one halogen atom),l doi(hCa1-4)alkyl- (i.e., -C1-4 alkyl group substituted by two halogen atoms), tri ohralo(C1-4)alkyl (i.e., -C1-4 alkylgroup substituted by three halogen atoms). In s eom beodiments, the haloalkyl is monohalo1-(C2)alkyl-, dihalo(C1-2)alkyl-, or trihalo(C1-2)alkyl. Non-limiting exemplary haloalkyl groups ilnucde fluoromethyl, difluoromethyl, trifluoromethyl, peanftluoroethyl, 1,1-difluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluorpropyl, 4,4,4-trifluorobutyl, and trichloromethyl groups. The term "haloalkoxy" as used herein by itself s or p a rt of another group refers to anhaloalkyl group attached to a terminal oxygen ato Inm o. ne embodiment, the haloalkyl is 1 a- C 4haloalkyl group. In some embodiments, the haloxaylk ios monohalo(C1-4)alkoxy- (i.e., -C1-4 alkoxy group substituted by one halogen atom),lo d(ihCa1-4)alkoxy- (i.e., -C1-4alkoxy group substituted by two halogen atoms), or trihal1o-4()Calkoxy (i.e., -C1-4 alkoxy group substituted by three halogen atoms). In some embodiments, thoeal hkaolxy is monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, or trihalo(C1-2)alkoxy. A non-limiting exemplary haloalkoxy grou isp -OCF3. As used herein, the term "cycloalkyl" as used hne breyi itself or as part of another group embraces saturated carbocyclic radicals and, un oltehsesrwise specified, a cycloalkyl radical typically has from 3 to 6 carbon atoms. Examples cy ocfloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclohep.t Iytl is, for example, cyclopropyl, cyclopentyl and cyclohexyl. In another embodiment, the cyclyola glkroup is -C3-10 cycloalkyl. As used herein, the term "alkylcycloalkyl" when elomyped in the definition of a substituent refers to a cycloalkyl group as defined above wh isic lhinked through an alkylene radical, such as -C1-4 alkylene, with the core structure which it subustetits. As an example, a cyclopentylethyl substituent is a substituent consisting of a cyecnlotypl group linked through an ethylene group to the core structure which it substitutes. In anot ehmerbodiment, the alkylcycloalkyl group is1--C4alkyl-C3-10 cycloalkyl. In another embodiment, the alkylcyclkloyal group is -C1-2 alkyl-C3-6 cycloalkyl. As used herein, the terms "heterocyclyl" or "hecteycrolic group" as used herein by itself or as part of another group embrace typically a mocnloiccy or polycyclic, non-aromatic, saturated or unsaturated2 C-10 carbocyclic ring, such as a 5- to 10-memberedc raal,d iin which one or more, for example 1, 2, 3 or 4 of the carbon atoms, for exlea,m 1p or 2 of the carbon atoms are replaced bya heteroatom selected from N, O and S. In one eimb eondt, the heterocyclyl is a3 C-7 heterocyclyl,i.e., a heterocycle having 3-7 carbon atoms an leda ast one heteroatom. In another embodiment, aheterocyclyl is a (5- to 10-membered2)--9C heterocyclyl, i.e., a heterocycle having 5- to 10- members, of which 2-9 members are carbon. In anro etmhebodiment, the heteroatom is N. In another embodiment, when a hydrogen atom is atdta tcohe the heteroatom N, the hydrogen atom can be replaced with a1 --C4 alkyl group, such as e.g., C3.H In another embodiment, the heteroatom is O. In some embodiments, the heterocyclyl i(s5- a t -o 6-membered)-2C-5heterocyclyl. In some embodiments, the -(5- to 6-membered2)-5-C heterocyclyl is tetrahyropyranyl (e.g., tetrahydropyran-4-yl) or piperidinyl (e.g., pipeirnid-4-yl). In another embodiment, the heterocyclyl radicaels s ar turated. In another embodiment, theheterocyclyl radicals are unsaturated. A heteroicy rcaldical can be a single ring or two or morefused rings wherein at least one ring containste aro haetom. When a heterocyclyl radical carries one or more substituents, the substituents cahne b sea tme or different. A said optionally substituted heterocyclyl is tyaplilcy unsubstituted or substituted with 1, 2 or 3 substituents which can be the same or diffte. r Eexnamples of heterocyclic radicals include piperidyl, pyrrolidyl, pyrrolinyl, piperazinyl, moprholinyl, thiomorpholinyl, pyrazolinyl, pyrazolidinyl, quinuclidinyl, cromanyl, isocroman,y ilmidazolidinyl, oxiranyl, azaridinyl, 4,5- dihydro-oxazolyl and 3-aza-tetrahydrofuranyl. Thuebs stituents are, for example, selected from halogen atoms, for example, fluorine or chlorinoem ast, hydroxy groups, alkoxycarbonyl groups in which the alkyl moiety has from 1 to 4 carbonom ast, hydroxycarbonyl groups, carbamoyl groups, nitro groups, cyano groups,1- -4C alkyl groups optionally substituted by one or more halogen atoms, -1C-4 alkoxy groups, optionally substituted by one orre m hoalogen atoms and1- C4 hydroxyalkyl groups. In another embodiment, the heterocyclyl is -(5- 1 t0o-membered)-C3-7heterocyclyl optionally substituted with 1, 2 or 3 substituen etasch independently selected from the group consisting of halogen, hydroxy,1 --C4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. The term "5- or 6-membered ring having at least h oente roatom" used herein by itself orpart of another group refers to an optionally siutubtsetd heterocyclic group, which is a saturated,unsaturated, aromatic or non-aromatic group, cnoint gai five or six ring members, wherein theheterocyclic group contains 1, 2, or 3 heteroato emacsh independently selected from the group consisting of N, O, and S. Non-limiting exempla 5r-y or 6-membered rings having at least one heteroatom include: wherein is a single bond or a double bond. The term "spirocyclic heterocyclic ring" or "spiryocclic heterocyclyl" as used herein by itself or as part of another group refers to ar hoectyeclyl containing seven to twelve ring members, wherein: (i) a first and second ring are connected through ate qrnuaary carbon atom, i.e., a spirocarbon; (ii) the first ring is an optionally substituted monolcicyc heterocyclyl containing anitrogen atom; and (iii) the second ring is either:a) an optionally substituted monocyclic cycloalkyl; or b) an optionally substituted monocyclic heterocycloynl t caining a nitrogen atom or an oxygen atom. In one embodiment, the first ring is an optiona slulybstituted monocyclic 4- to 6-membered heterocyclyl containing a nitrogen atom. In anot ehmerbodiment, the second ring is an optionally substituted monocyclic3 C-8 cycloalkyl. In another embodiment, the second rising an optionally substituted monocyclic 4- to 8-membered heterocly ccolyntaining an oxygen atom. In another embodiment, the second ring is a monocycl3ic-8 C cycloalkyl substituted with a hydroxy group. Non-limiting exemplary spiroheterocyclo groups u indcel: As used herein, the term "aryl" as used hereints beylf i or as part of another group refers to an aromatic ring system having six to fourteen o cnarb atoms, i.e.,6C-C14aryl. Non-limiting exemplary aryl group is typically a6- C10 monocyclic or polycyclic aryl radical such as pyhle annd naphthyl. In another embodiment, the aryl is ph.e Any slaid optionally substituted aryl radical is typically unsubstituted or substituted with 1, 23 o srubstituents which can be the same or different. The substituents are, for example, selected frolmog hean atoms, for example, fluorine or chlorine atoms, hydroxy groups, alkoxycarbonyl groups inc whh tihe alkyl moiety has from 1 to 4 carbon atoms, hydroxycarbonyl groups, carbamoyl grouptsro, n giroups, cyano groups,1--C4alkyl groups optionally substituted by one or more halogen at,o -mC1s-4 alkoxy groups, optionally substituted by one or more halogen atoms an1d-4 C hydroxyalkyl groups. When an aryl radical carr 2ies or more substituents, the substituents can be the soarm diefferent. Unless otherwise specified, the substituents on an aryl group are typically themvessel unsubstituted. As used herein, the term "heteroaryl" as used n he bryei itself or as part of another group refers to monocyclic and bicyclic aromatic ringt seymss having 5 to 14 ring members, i.e., a 5- to 14-membered heteroaryl, comprising one, two, th orere fo,ur heteroatoms. In some embodiments,the heteroaryl is a 5- to 10-membered ring sys cteom, prising at least one heteroaromatic ring andcontaining at least one heteroatom selected from S a On,d N, typically 1, 2, 3, or 4 heteroatoms. Insome embodiments, the heteroaryl is a 5- or 6-meremdb heeteroaryl having 1, 2, or 3 heteroatoms selected from O, S, and N. Aheteroaryl group can comprise a single ring oor o twr more fused rings wherein at leastone ring contains a heteroatom. A said optionaullybs stituted heteroaryl group is typicallyunsubstituted or substituted with 1, 2 or 3 suubesntit s which can be the same or different. Thesubstituents are, for example, selected from hanlo agteoms, for example, fluorine, chlorine or bromine atoms, alkoxycarbonyl groups in which thlkeyl a moiety has from 1 to 4 carbon atoms, carbamoyl groups, nitro groups, hydroxy groups1,-4- aClkyl groups, optionally substituted by one or more halogen atoms and1 --4C alkoxy groups, optionally substituted by one orre m hoalogen atoms. When a heteroaryl radical carries 2 or m sourbestituents, the substituents can be the same or different. Unless otherwise specified, the siutubesntts on a heteroaryl radical are typically themselves unsubstituted. Examples of heteroaryl groups include pyridyl, pzyinrayl, pyrimidinyl, pyridazinyl, furyl, tetrazolyl, benzofuranyl, oxadiazolyl, oxazolyl, ox isazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, thiadiazolyl, thienyl,yr prolyl, pyridinyl, benzothiazolyl, indolyl, indazolyl, purinyl, quinolyl, isoquinolyl, phthalainzyl, naphthyridinyl, quinoxalinyl, quinazolinyl, quinolizinyl, cinnolinyl, triazolyl, indolizinyl,n idolinyl, isoindolinyl, isoindolyl, imidazolidinyl, pteridinyl, thianthrenyl, pyrazolyl, 2H-pyrazolo4[3-,d]pyrimidinyl, 1H-pyrazolo[3,4- d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, and the vriaous pyrrolopyridyl radicals. The mention of optionally substituted heteroarydl ic ra ls or rests within the presentdisclosure is intended to cover the N-oxides obatbalien from these radicals when they comprise N- atoms. The term "triflate" refers to a trifluoromethanefsounlate group, which is a functional group represented with the formula -OS(=2OCF)3. Xantphos is an organophosphorus compound derivoemd t fhre heterocycle xanthene.XPhos is a phosphine ligand derived from biphe Inty ils. especially efficient and generalwhen employed as a (2-aminobiphenyl)-cyclometala ptaeldladium mesylate precatalyst complex (Buchwald's third generation precatalyst systemP)h,o Xs-G3-Pd, which is commercially available and stable to bench storage. The term "7-, 8-, 9- or 10-membered spiroheteroycly gcrloup" used herein by itself or partof another group refers to an optionally substditu hte terocyclyl group containing seven to ten ringmembers, wherein: (i) a first and second ring aornen cected through a quaternary carbon atom,i.e., a spirocarbon; (ii) the first ring is an i op ntally substituted monoheterocyclyl containing anitrogen, sulfur, or oxgen atom; and (iii) the snedco ring is an optionally substituted monocycloalkyl. Non-limiting exemplary spirohetecyroclyl groups include: wherein is a single bond or a double bond. The term "pharmaceutically acceptable" refers tmop co sitions and molecular entities thatare physiologically tolerable and do not typica pllyroduce an allergic reaction or a similar unfavorable reaction, such as gastric disorderzsz,in deiss and suchlike, when administered to a human or animal. For example, the term "pharmacaelulyti acceptable" means it is approved by aregulatory agency of a state or federal governm oern ist included in the U.S. Pharmacopoeia orother generally recognized pharmacopoeia for us aeni imnals, and more particularly in humans. The term "treatment" or "treating" refers to admstienriing a therapy in an amount, manner or mode effective to improve a condition, symptom r p,arameter associated with a condition or to prevent progression of a condition, to either atis stticaally significant degree or to a degree detectable to one skilled in the art. An effect aivmeount, manner, or mode can vary depending on the subject and can be tailored to the patient. By an "effective" amount or a "therapeutically ecftfieve amount" of a drug or pharmacologically active agent is meant a nonto bxuitc sufficient amount of the drug or agent to provide the desired effect. The amount that ise "cetfivfe" will vary from subject to subject, depending on the age and general condition ofn tdhievi idual, the particular active agent or agents, and the like. Thus, it is not always possible teoc sifpy an exact "effective amount." However, an appropriate "effective" amount in any individualse ca may be determined by one of ordinary skill in the art using routine experimentation. The term "prevention" or "to prevent" refers to trheeduction in the risk of acquiring or developing a given disease or disorder, or thec rteiodnu or inhibition of the recurrence or a disease or disorder. The term "about", as used herein in connection w ait mheasured quantity, refers to the normal variations in that measured quantity, asec etxepd by the skilled artisan making the measurement and exercising a level of care commraetnes wuith the objective of measurement and precision of the measuring equipment. Typicallye, t tehrm "about" includes the recited number ± 10%. Thus, "about 10" means 9 to 11. As used herein, the term "optionally substituteedfe" r s to a group that can be unsubstitutedor substituted. The term "patient" as used herein refers to a hu.m Inan some embodiments, the patient isan adult. In some embodiments, the patient isri a t griec patient. In some embodiments, the patientis a child. In some embodiments, the patient is in afannt. In some embodiments, the patient is atoddler. In some embodiments, the patient is ad porle scent. In some embodiments, the patientis an adolescent. As used herein, the term "child" is a human beientgw been the stages of birth and puberty. The term "puberty" is the process of physical cheasn tghrough which a child's body maturesinto an adult body capable of sexual reproductio Onn. average, girls begin puberty around ages10–11 and end puberty around 15–17; boys beginn adroauges 11–12 and end around 16–17. As used herein, the term "infant" is the synonymr "b foaby," the very young offspring of a human. The term "infant" is typically applied tou ynog children under one year of age. As used herein, the term "toddler" refers to ad ch oifl 12 to 36 months old. As used herein, the term "preadolescent" refe ars p teorson of 10–13 years old. As used herein, the term "adolescent" refers teors ao pn between ages 10 and.19 The term "solvate" means any form of the active p co umnd of the disclosure which hasanother molecule (for example a polar solvent s ausch water or ethanol, a cyclodextrin or a dendrimer) attached to it through noncovalent bo. n Mdesthods of solvation are known within the art. The disclosure also provides salts of the Compou onfd tshe Disclosure. Non-limiting examples are sulphates; hydrohalide salts; phoessp;h laotwer alkane sulphonates; arylsulphonates; salts of C1-20 aliphatic mono-, di- or tribasic acids which caonnt cain one or more double bonds, an aryl nucleus or other functional groups such asro hxyyd, amino, or keto; salts of aromatic acids in which the aromatic nuclei may or may not be suubtsetdit with groups such as hydroxyl, lower alkoxyl, amino, mono- or di- lower alkylamino suolpnhamido. Also included within the scope of the disclosure are quaternary salts of the tert niaitrryogen atom with lower alkyl halides or sulphates, and oxygenated derivatives of the r teyrt niaitrogen atom, such as the N-oxides. In preparing dosage formulations, those skilled in a trhte will select the pharmaceutically acceptable salts. Solvates and salts can be prepared by methods k ino twhne state of the art. Note that thenon-pharmaceutically acceptable solvates also w fiathllin the scope of the disclosure because they can be useful in preparing pharmaceutically accbelept saalts and solvates. The Compounds of the Disclosure also seek to inec cluodmpounds that differ only in the presence of one or more isotopically enriched a.to Fmors example, compounds having the present structures except for the replacement of a hydro bgye an deuterium or tritium, or the replacement of a carbon by a carbon enriched11inC,13C or14C or the replacement of a nitrogen by15N a enriched nitrogen are within the scope of thisl doissucre. Some of the compounds disclosed herein can co onntaein or more asymmetric centers and can thus give rise to enantiomers, diastereomnedrs o,t aher stereoisomeric forms, such as epimers. The present disclosure is meant to encompass e thse o ufs all such possible forms, as well as theirracemic and resolved forms and mixtures thereoef. i Tnhdividual enantiomers can be separatedaccording to methods known to those of ordinaryll s inki the art in view of the present disclosure.When the compounds described herein contain ocle dfionuible bonds or other centers of geometric asymmetry, and unless specified otherwise, itt iesn idned that they include both E and Z geometric isomers. All tautomers are intended to be encomepda bsys the present disclosure as well. As used herein, the term "stereoisomers" is a gael n ter m for all isomers of individualmolecules that differ only in the orientation oef i trh atoms in space. It includes enantiomers and isomers of compounds with more than one chirale cre tnhtat are not mirror images of one another (diastereomers). The term "chiral center" refers to a carbon atom wh toich four different groups are attached. The term "epimer" refers to diastereomers that h oapvpeosite configuration at only one of two or more tetrahedral streogenic centers pre inse tnhte respective molecular entities. The term "stereogenic center" is an atom, bearrinougp gs such that an interchanging of any two groups leads to a stereoisomer. The terms "enantiomer" and "enantiomeric" refer a to molecule that cannot be superimposed on its mirror image and hence isa olplytic active wherein the enantiomer rotates the plane of polarized light in one direction and itsirr mor image compound rotates the plane of polarized light in the opposite direction. The term "racemic" refers to a mixture of equalts pa orf enantiomers and which mixture is optically inactive. The term "resolution" refers to the separationo onrc centration or depletion of one of the two enantiomeric forms of a molecule. The terms "a" and "an" refer to one or more. The term "one or more" as used herein is intenode mde tan that at least one component in a relevant category of components, e.g. one or m sourbestituents, is present and, in some embodiments, more than one component is presenn sto. m Ie embodiments, one or more means 1to 6. In some embodiments, one or more means 4.1 I tno some embodiments, one or more means1 to 3. In some embodiments, one or more meanrs 21. o In some embodiments, one or more means 1. As used herein, the term "enzyme replacement thy"er oarp "ERT" refers to administering an exogenously-produced natural or recombinantm enez oyr analog thereof to a patient in need thereof. In the case of a lyosomal storage dis,e foarse xample, the patient accumulates harmful levels of a substrate (i.e., material stored)s inos lyomes due to a deficiency or defect in an enzyme responsible for metabolizing the substrate, or t dou ae deficiency in an enzymatic activator required for proper enzymatic function. Enzyme replacemehnetra tpy is provided to the patient to reduce the levels of (i.e., debulk) accumulated subst irna ateffected tissues. Enzyme replacement therapies for treating lysosomal storage diseases are knonw tnhe i art. In accordance with a combinationtherapy of the disclosure, a lysosomal enzyme,, β e-.g l.ucocerebrosidase, can be used for enzymereplacement therapy to reduce the levels of coorrnedsipng substrate, e.g β.-,glucocerebroside, in a patient having a lysosomal storage disease su Gchau acsher's disease. As used herein, the term "substrate reductionp thye"r oar "SRT" is a therapeutic approach used to treat certain metabolic disorders, e.sgo.,s loymal storage disorders, in which substrate,, e.g. glycolipid, accumulation is counteracted not byla recping the deficient enzyme but by reducing the substrate level to better balance residual acti ovfit tyhe deficient enzyme S. ee, e.g,. Coutinho et al., Int. J. Mol. Sci. 17:1065 (2016). Substrate reduction therapy andm enez ryeplacement therapy (see above) can have unique, independent, andti paolltyen complementary mechanisms of action in the treatment of lyosomal storage disease ahnedr o dtiseases. The general principle of SRT is that a substradteuc retion agent is administered to a patient to partially inhibit the biosynthesis of the subastetr, which accumulates in the absence of a specific lysosomal enzyme. As used herein, the term "sutbes rteraduction agent" is a small molecule that reduces the number of substrate molecules requi criantgabolism within the lysosome, thuscontributing to balance the rate of synthesis w thiteh impaired rate of catabolism. Substratereduction agents are known in the art. As used herein, an "effective amount" of an enzy wmhee,n administered to a subject in acombination therapy of the disclosure, is an amo sun ffticient to improve the clinical course of alysosomal storage disease, where clinical improvnetm ise measured by any of the variety of defined parameters well known to the skilled artisan. As used herein the term "small molecule chapero renfee"rs to a compound, other than a Compound of the Disclosure, that is capable ofi bnignd allosterically or competitively to a mutated enzyme, e.g., β-galactosidase, thereby stabilizing the enzymen asgta diegradation. In some embodiments, the small molecule chaperone faceilsita ptroper folding and transport of an enzyme to its site of action. Small molecule chaperonoers th fe treatment of lysosomal storage diseases are known in the art. See, e.g,. US 2016 / 0207933 A1 and WO 2011 / 049737 A1. α-Synucleinopathies are neurodegenerative diseahseasrac cterized by the abnormal accumulation of aggregates α o-fsynuclein protein in neurons, nerve fibres, oarl g cliells. There is a well-established clinical association betw meeuntations in the glucocerebrosidase gene and the development of more prevalent multifactorial diseorrsd including Parkinson's disease and other synucleinopathies. See, Siebert, M., et al., Brain 137:1304-1322 (2014). According to Siebe trt al., there is a reciprocal relationship between gluecreobcrosidase activity (wild-type and mutant) and α-synuclein in synucleinopathies such as Parkins doisne'sase and dementia with Lewy bodies. This reciprocal relationship suggests that thersap foier Gaucher's disease, which are targeted towards augmenting glucocerebrosidase activitye ocrre dasing glucocerebrosides storage could prove to be providing strategies for modulati αn-gsynuclein proteostasis and its subsequent aggregation and oligomerization. Tauopathies are a class of neurodegenerative deisse raes ulting from the pathologicalaggregation of tau protein into neurofibrillary g olriofibrillary tangles in the human brain. Some examples of tauopathies include frontotemporal dnetimae (FTD), Alzheimer's disease, progressivesupranuclear palsy, corticobasal degeneration, fr aond totemporal lobar degeneration. The non-Alzheimer's tauopathies are sometimes grouped h toerge ats "Pick's complex" due to their association with frontotemporal dementia, or frotenmtoporal lobar degeneration. The term “acute tauopathy,” as used herein, re tfoer as disease, disorder, or conditionassociated with sudden onset of abnormally elev taatued (e.g., elevated compared to a normal, control level of tau) in extracellular fluid (e.g c.e,rebrospinal fluid (CSF), interstitial fluid (IS),F blood, or a blood fraction (e.g., a blood fract siounch as serum or plasma) of a subject, e.g., eldevat tau in extracellular fluid following an insult ascsiaoted with physical disturbance to a subject's brain and / or associated tissues of the centralo nuesrv system. Such insult is generally followed by elevation of tau in extracellular fluid (e.g., CS ISFF, , blood, and / or blood fractions (e.g., plasma)) within a relatively short period of time, e.g., h wiint weeks or months (or a shorter time period). Examples of such insults include, but are not nseacreilsy limited to, physical trauma (e.g., head injury) and stroke. Non-limiting examples of acu tateuopathies are stroke, chronic traumatic encephalopathy, traumatic brain injury, concussi soeniz,ures, epilepsy (e.g., Dravet Syndrome (also known as Severe Myoclonic Epilepsy of Infan (ScMy EI)), and acute lead encephalopathy. The phrase “traumatic brain injury” (also known “ aTsBI”) is a form of acquired brain injury, which occurs when a trauma causes dama tghee t borain (e.g., an injury to the brain caused by an external force). For example, TBI can re wsuhletn the head suddenly and violently hits an object (e.g., during a fall, car accident, sport einvgent, or any number of different ways) or when an object pierces the skull and enters brain ti.s Bsuoeth types of TBI can result in bruised brain tissue, bleeding inside the brain, large or smaaclelr lations in the brain, and / or nerve damage due to shearing forces. The brain can also experien ncuem aber of secondary types of damage, such as swelling, fever, seizures, or an imbalance of nleougriocal chemicals. Symptoms of TBI can be mild, moderate, or severe, depending on the ex otfe tnhte damage to the brain. A person with a mild TBI may remain conscious or may experienceos as l of consciousness for a few seconds or minutes. Other symptoms of mild TBI include headea,c chonfusion, lightheadedness, dizziness, blurred vision or tired eyes, ringing in the ea brasd, taste in the mouth, fatigue or lethargy, ag chean in sleep patterns, behavioral or mood changes, tr aonudble with memory, concentration, attention, or thinking. A person with a moderate or severe TmBaIy show these same symptoms, but may also have a headache that gets worse or does naowta gyo, repeated vomiting or nausea, convulsions or seizures, an inability to awaken from sleepa,t dioiln of one or both pupils of the eyes, slurred speech, weakness or numbness in the extremitisess, o lfo coordination, and increased confusion, restlessness, or agitation. Examples of TBI inc,lu bduet are not limited to, diffuse axonal injury, concussion, contusion, Coup-Contrecoup injury, Sndec Iompact Syndrome, penetrating injury, Shaken Baby Syndrome, and Locked In Syndrome. The term “chronic tauopathy” as used herein genlye rreaflers to a condition associated with a gradual onset of elevated. Tau in extracellulluaird f of a subject, e.g., accumulation of tau in extracellular fluid (e.g., CSF, ISF, blood, and b / olorod fractions (e.g., plasma)) over a relatively longer period of time, e.g., multiple years, e d.ge.c,ades. Chronic tauopathies include, but are not necessarily limited to, Alzheimer's disease, amoypohtric lateral sclerosis / parkinsonism-dementia complex, argyrophilic grain dementia, British typ aemyloid angiopathy, cerebral amyloid angiopathy, corticobasal degeneration, CreutzfJealdkto-b disease, dementia pugilistica, diffuse neurofibrillary tangles with calcification, Down' ssyndrome, frontotemporal dementia (FTD), frontotemporal dementia with parkinsonism linked c thoromosome 17, frontotemporal lobar degeneration, Gerstmann-Straussler-Scheinker dei,se Haasllervorden-Spatz disease, inclusion body myositis, multiple system atrophy, myotonicst droyphy, Niemann-Pick disease type C, non-Guamanian motor neuron disease with neurofibrill tar nygles, Pick's disease, postencephaliticparkinsonism, prion protein cerebral amyloid angaitohpy, progressive subcortical gliosis,progressive supranuclear palsy, subacute sclero psaing encephalitis, Tang only dementia, andmulti-infarct dementia. Some reactions for preparing Compounds of thelo Dsisucre involve employing amino protecting groups. As used herein, an "amine ptriontgec group" or "amino protecting group" refers to a group that blocks (i.e., protects) the amuinnect fionality while reactions are carried out one orth functional groups or parts of the molecule. Thoksielle sd in the art will be familiar with the selection, attachment, and cleavage of amine ptrinogtec groups and will appreciate that manydifferent protective groups are known in the ahret, s tuitability of one protective group or anotherbeing dependent on the particular synthetic sch pelmanened. Treatises on the subject are available for consultation, such as Wuts, P. G. M. & Gree Tn.e W, ., Greene's Protective Groups in Organic Synthesi,s 4th Ed. (J. Wiley & Sons, 2007), herein incorpteodra by reference in its entirety. Suitable amine protecting groups include methyl carbam taetret-,butyloxycarbonyl (tert-butyl carbamate; BOC), 9-fluorenylmethyl carbamate, benzyl carbam, a 2te-(trimethylsilyl)ethyl carbamate, trifluoroacetamide, benzylamine, allylamine, traitmyline, trichloroacetyl, trifluoroacetyl, p- toluenesulfonyl, and allyl carbamate. In anotherbo edmiment, the protected amino group can be a phthalimide-protected amino group (NPhth). As used herein, an "effective amount" of anothera thpeutic agent, when administered to a subject in a combination therapy of the discleo,s iusr an amount sufficient to improve the clinical course of a disease or condition associated weith al ttheration of the activity of GBA, where clinical improvement is measured by any of the variety ofifn deed parameters well known to the skilled artisan. III. Synthesis of Compounds of the Disclosure Compounds of the Disclosure can be prepared useinthgo mds known to those skilled in the art in view of this disclosure, or by illustrativ meethods shown in the schemes below. For example, methods described in Schemes 1-10 below can be fo urs perdeparing Compounds of the Disclosure having Formula (I). Additional methods of synthe asries described and illustrated in the working examples set forth below. Scheme 1 Method 1 Step 1 (Reaction A) In a first method, according to the disclosureo, m ap cound of Formula (XI) wherein1 A is as defined above is reacted with a hydrazine comndpou f Formula (XII) where each of5R and n are as defined above, to yield a hydrazone compou f n Fdormula (XIII) as illustrated in reaction A of the scheme above (Scheme 1). Reaction A is used to prepare compounds of Formula (XIII) re bayction of compound of Formula (XI) with a compound of Formula (XII). Sa riedaction can be performed under standardconditions in the presence or absence of a sui btaabsle (e.g., triethylamine, diisopropylethylamine,or potassium carbonate), and an appropriate solv (e .ngt. ethanol, methanol, acetonitrile,dimethylformamide, toluene, tetrahydrofuran, dioexa onr mixture thereof). Compounds of Formula (XI) and (XII) are commercyia allvailable or can be obtained by procedures described in the literature as is kn boyw tnhe person skilled in the art. The reaction mixture is stirred at a low temperea,tu rorom temperature, or heated until the starting materials have been consumed. The reac ationn be carried out with protecting groupspresent and those protecting groups can be rem aofvte rd reaction. Suitable protecting groups areknown to the person skilled in the art (see T. Wre.e Gne, "Protective Groups in Organic Synthesis," 3rdEdition, New York, 1999). Step 2 (Reaction B) Subsequently, a hydrazone compound of Formula ) (X wIIhIerein A1, R5and n are asdefined above, is reacted to yield a compound ormf Fuola (XIV) as illustrated in reactio Bn of thescheme above (Scheme 1). Reaction B can be performed under standard condensationt cioonnsd,i for example in the absence or presence of a suitable base (e.g.,m so bdiciuarbonate, triethylamine, cesium carbonate, potassium carbonate or sodium hydroxide), andp apnro apriate solvent (e.g. ethanol, methanol,acetonitrile, dimethylformamide, toluene, tetrahoyfdur an, dioxane or mixture thereof) and, forexample, at around room temperature or at reflumxp teerature or in a sealed tube or under microwave irradiation. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Compound of Formula (XI) may be directly convert ined only one step to compound of Formula (XIV) by treatment with an appropriated r hayzdine compound of Formula (XII) in the presence or absence of a suitable base, and aonp aripapter solvent. Method 2 Step 1 (Reaction C) In another method, a compound of Formula (XIV) wehiner A1, R5 and n are as defined above, is reacted with an amine compound of Form (XuVla) wherein Y can be R3 or PG, where PG is a protecting group and each o2f a Rnd R3are as defined above, to yield a compound of Formula (XVI) as illustrated in reactio Cn of the scheme above (Scheme 2). Reaction C can be performed under standard nucleophilic situb tiostn conditions, forexample in the presence of a suitable base (eri.egt.h,y tlamine, pyridine, potassium carbonate or N,N-diisopropylethylamine or sodium hydride) or aceid.g (. sulfuric acid, hydrogen chloride or acetic acid) or absence of base or acid, option inal tlhye presence of a suitable catalyst, ligand andbase (e.g. Pd(db2a,) Xantphos and cesium carbonate) and an approp sroialvte nt (e.g., ethanol,acetonitrile, propanol, butanol, toluene, tetrahoyfudrran, dioxane or mixture thereof) and, for example, at around room temperature or reflux teramtupree or under microwave irradiation. Compound of Formula (XV) is commercially availab olre can be obtained by procedures described in the literature as is known by theo pner sskilled in the art. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Scheme 3 Method 3 Step 1 (Reaction D) In another method, according to the disclosureo,m ap cound of Formula (XVI) wherein Y can be R3 or PG, where PG is a protecting group and eac Ah1, o Rf 2, R3, R5, and n are as defined above, is reacted with a halogenating agent, tlod y aie compound of Formula (XVII) as illustrated in reaction D of the scheme above (Scheme 3). Reaction D can be performed with a suitable halogenatingt a (gee.ng. bromine, chlorine, bromosuccinimide, among others) in the appropria stoelvent (e.g., water, chloroform, dichloromethane, dioxane or mixture thereof) anodr, e fxample, at around room temperature or low temperature. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Step 2 (Reaction E) Subsequently, a compound of Formula (XVII) wher Zei cnan be -Cl or -Br, Y can be3R or PG, where PG is a protecting group and each1 o,f R A2, R3, R5, and n are as defined above, is reacted with a compound of formula Q4- wRherein Q represents a suitable group such aisg ana Grdr reagent (e.g MgX), -B(OH2,) -B(OR)2or -Sn(R)3, wherein each of R independently represents an alkyl group, or, in the case of -B(O2R, ) the representative R groups may be linked togre toth feorm a 4- to 6- membered cyclic group, to yield a comnpdo ouf Formula (XVIII) as illustrated in reaction E of the scheme above (Scheme 3). Reaction E can be performed, for example in the presence su oift a ble catalyst system, e.g.a metal (or a salt or complex thereof) such as C Pud,, Pd / C, PdC2,l Pd(OAc)2, Pd(Ph3P)4, Pd(Ph3P)2Cl2 (e.g. palladium tetrakistriphenylphosphine),2( Pddba)3 or NiCl2 and a suitable ligand such as 1,′1-ferrocenediyl-bis(diphenylphosphine), XantPhos X oPrhos or a mixture thereof,together with a suitable base such as, sodium n car teb,o cesium carbonate, triethylamin Ne,N, -diisopropylethylamine, or sodium tert-butoxide in the appropriate solvent (e.g., tetrdarhoyfuran, dimethylformamide, water, toluene, dioxane or mriext tuhereof) and, for example, at around room temperature or above. Alternative reactions incl mudicerowave irradiation conditions. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Compounds of Formula (I) where1 R and R6 together do not form a heterocyclic ring can be prepared according to Scheme 4A and compound Fsor omfula (I) where R1 and R6 together form a heterocyclic ring can be prepared accord toin Sgcheme 4B. Scheme 4A Scheme 4B Method 4 Step 1 (Reaction F) In another method, a compound of Formula (XVIII)e wrehin Y can be R3or PG, where PG is a protecting group and each o1f, A R2, R3, R4, R5and n are as defined above, is reacted with an aniline compound of Formula (XIX) or (XX) where eha ocf A2, A3, A4, R1, R6, R7, R8, and m areas defined above, to yield a compound of Formu)la s (I illustrated in reactio Fn of the schemeabove (Scheme 4). Reaction F can be performed under standard conditions in p trheesence of a suitablepalladium catalyst, such as Pd(d2b,a p)alladium acetate or P2(d ba)3, the appropriate base (e.g.cesium carbonate or potassium phosphate tribas tircie othrylamine, among others) and a suitable ligand such as 1′,-1ferrocenediyl-bis(diphenylphosphine), BINAP, Xahnotps, tBuXPhos Pd G3 or XPhos in the appropriate solvent (e.g., butanolul,e tnoe, dioxane or mixture thereof) and, for example, at around room temperature or reflux teramtupree. Alternative reactions include microwave irradiation conditions. Alternatively, the transformation can be carriedt i onu the presence of a suitable base (e.g. triethylamine, pyridine, potassium carbonate N o,Nr-diisopropylethylamine) or acid (e.g. sulfuricacid, hydrogen chloride or acetic acid) and an o ap rpiarte solvent (e.g., ethanol, acetonitrile,propanol, butanol, toluene, tetrahydrofuran, dioex oarn mixture thereof). Compounds of Formula (XIX) and (XX) are commercyia allvailable or can be obtained by procedures described in the literature as is kn boyw tnhe person skilled in the art. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Scheme 5 Method 5 Step 1 (Reaction G) In another method, according to the disclosureo,m ap cound of Formula (XIV) wherein1 A,R5 and n are as defined above, is reacted with alin e an ciompound of formula (XIX) where eachof A2, A3, A4, R1, R6, R7, R8, and m are as defined above, to yield a compoufn Fdor omula (XXI) as illustrated in reactio Gn of the scheme above (Scheme 5). Reaction G can be performed under standard nucleophilic situb tiostn conditions such asthose explained for step 1 of method 4 describeodve a.b Step 2 (Reaction H) Subsequently, a compound of formula (XXI) wherei1n, A2, A3, A4, R1, R5, R6, R7, R8, m, and n are as defined above, is reacted with ane a cmoimnpound of formula (XV) wherein Y can be R3 or PG, where PG is a protecting group and eac Rh2 o afnd R3 are as defined above, to yield a compound of formula (I) as illustrated in reacti Hon of the scheme above (Scheme 5). Reaction H can be performed under standard nucleophilic situb tiostn conditions such asthose explained for step 1 of method 2 describeodve a.b Scheme 6 Method 6 Step 1 (Reaction I) In another method, according to the disclosureo,m ap cound of Formula (XIII) wherein1 A,R5, and n are as defined above, is reacted with ain e a cmompound of Formula (XV) wherein Ycan be R3or PG, where PG is a protecting group and eac Rh2o afnd R3are as defined above, to yield a compound of Formula (XXII) as illustratend r ieaction I of the scheme above (Scheme 6). Reaction I can be performed under standard nucleophilic situb tiostn conditions such asthose explained for step 1 of method 2 describeodve a.b Step 2 (Reaction J) Subsequently, a hydrazone compound of Formula ()X wXIhIerein Y can be 3 R or PG, where PG is a protecting group and each1o,f R A2, R3, R5, and n are as defined above, is reacted to yield a compound of Formula (XVI) as illustrat iend reaction J of the scheme above (Scheme 6). Reaction J can be performed under standard condensation t cioonnsdi such as those explained for step 2 of method 1 described above. Scheme 7 Method 7 Step 1 (Reaction K) In another method, according to the disclosureo,m ap cound of Formula (XXIII) wherein A1, R4, and n are as defined above and1 P isG a protecting group, is reacted with an amine compound of formula (XV) wherein Y can be3 o Rr PG2, where PG2 is a protecting group and each of R2and R3are as defined above, to yield a compound of Folarm (XuXIV) as illustrated in reaction K of the scheme above (Scheme 7). Reaction K can be performed under standard nucleophilic situb tiostn conditions such asthose explained for step 1 of method 2 describeodve a.b Compounds of Formulae (XV) and (XXIII) are commearllcyi available or can be obtained by procedures described in the literature as isw knn boy the person skilled in the art. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitablee pctriontg groups are known to the person skilled in the art (see T. W. Greene, "Protective Group Osr ignanic Synthesis,"rd3 Edition, New York, 1999). Step 2 (Reaction L) Subsequently, a compound of Formula (XXIV) wher Yei cnan be R3or PG2, where PG2is a protecting group and each o2f, R 3 and R4 are as defined above, is reacted with an aniline compound of formula (XIX) where each of2, A A3, A4, R1, R6, R7, R8, and m are as defined above, to yield a compound of formula (XXV) as illustrate ind reaction L of the scheme above (Scheme 7). Reaction L can be performed under standard nucleophilic situb tiostn conditions such asthose explained for step 1 of method 4 describeodve a.b The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Step 3 (Reaction M) Subsequently, a compound of Formula (XXV) wherein ca Yn be R3 or PG2, where PG2 is a protecting group and each o1f, A A2, A3, A4, R1, R2, R3, R4, R6, R7, R8, and m are as defined above, is reacted with a compound of Formula (XX wVhI)erein Z represents a suitable leaving group such as halogen, -B(O2H, o)r -B(OR)2 wherein the representative R groups may be linkedtogether to form a 4- to 6- membered cyclic gro aunpd, each of R5 and n are as defined above, toyield a compound of Formula (I) as illustratede inac rtion M of the scheme above (Scheme 7). Reaction M can be performed, for example in the presence s oufit a ble catalyst system,such as Pd, Cu(OA2c,) CuI, and a suitable base such as pyridine, sod ciaurmbonate, cesium carbonate, triethylamine, or diisopropylethylamine in, the appropriate solvent (e.g., tetrahydrofuran, dimethylformamide, dichlorometh,an deioxane or mixture thereof) and, for example, at around room temperature or above, f olurx re temperature or under microwave irradiation. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rdEdition, New York, 1999). Scheme 8 Method 8 Reaction N In another method, according to the disclosureo,m ap cound of Formula (XXVII) wherein Y can be R3 or PG, where PG is a protecting group and eac Ah1, o Af 2, A3, A4, R2, R4, R6, R7, R8, and m are as defined above, is reacted with a cuonmdpo f Formula (XXVIII) wherein Z representsa suitable leaving group, such as a halogen, l a te tr,if a tosylate or a mesylate group, to yield acompound of Formula (I) as illustrated in react Nion of the scheme above (Scheme 8). Reaction N can be performed under standard nucleophilic situb tiostn conditions, forexample in the presence of a suitable base (suc shod aisum hydride, pyridine, triethylamine, dimethylaminopyridine, N,N-diisopropylethylamine, sodium hydroxide, potassi cuamrbonate or sodium acetate), and an appropriate solvent (susch py aridine, dichloromethane, chloroform, tetrahydrofuran, toluene, dimethylformamide, dimyelstuhlphoxide, water or mixtures thereof) and, for example, at around room temperature or low teermatpure or heated until the starting materials have been consumed. Compounds of Formula (XXVIII) are commercially alvaabile or can be obtained by procedures described in the literature as is kn boyw tnhe person skilled in the art. Scheme 9 Method 9 Reaction O In another method, according to the disclosureo,m ap cound of Formula (I) can be preparedfrom a compound of Formula (XXVII), wherein Y caen R b3 or PG, where PG is a protecting groupand each of A1, A2, A3, A4, R2, R4, R6, R7, R8, and m are as defined above in Scheme 9, byn regacti with an appropriate aldehyde of Formula (XXIX) wehe Rr1is as defined above in Scheme 9 via reductive amination to yield a compound of Form (uI)la as illustrated in reactio On of the scheme above (Scheme 9). Reaction O is carried out under standard reductive aminat fio rn e,xample in the presenceof a reducing agent (e.g s.,odium triacetoxyborohydride s,odium cyanoborohydride or sodium borohydride), alternatively in the presence ofi ata sbule acid such as acetic acid and an appropriate solvent (e.g., acetonitrile, dichloromethane, mneothl,a ethanol, ethyl acetate, chloroform, dimethylformamide, toluene or mixtures thereof).e Th reaction mixture is stirred at roomtemperature or heated until the starting mate hria vlse been consumed.Compounds of Formula (XXIX) are commercially avablilea or can be obtained by procedures described in the literature as is kn boyw tnhe person skilled in the art. Scheme 10 Method 10 Reaction P In another method, according to the disclosureo,m ap cound of Formula (XXX) wherein Y can be R3 or PG, where PG is a protecting group and eac Ah1, o Rf 1, R2, R3, R4, R5, and n are as defined above, is reacted with a compound of Foarm (XulXXI) where Z represents a suitable leaving group, such as a halogen, a triflate,y ala totes or a mesylate group, and each o2,f A 3, A4, R6, R7, R8, and m are as defined above, to yield a compouf Fndor omula (I) as illustrated in reaction P of the scheme above (Scheme 10). Reaction P can be performed under standard conditions inr tehsee pnce of an appropriatebase (e.g. cesium carbonate or potassium phos tprihbat seic or triethylamine, among others) and asuitable ligand such as 1′-,f1errocenediyl-bis(diphenylphosphine), BINAP, XahnotPs, tBuBrettPhos Pd G3 tB, uXPhos Pd G3 or XPhos in the appropriate solve.ngt., ( butanol, toluene, dioxane or mixture thereof) and, for example, aotu anrd room temperature or reflux temperature. Alternatively, the transformation can be carriedt o inu the presence of a suitable base(e.g.triethylamine, pyridine, potassium carbonarte N o,N-diisopropylethylamine) or acid (e.g. sulfuric acid, hydrogen chloride or acetic acid)d a ann appropriate solvent (e.g., ethanol, acetonitrile, propanol, butanol, toluene, tetrahoyfudrran, dioxane or mixture thereof). Compounds of Formula (XXXI) are commercially avaabille or can be obtained by procedures described in the literature as is kn boyw tnhe person skilled in the art. The reaction can be carried out with protectingu gprso present and those protecting groups can be removed after reaction. Suitable protec gtrinogups are known to the person skilled in the art (see T. W. Greene, "Protective Groups in Organincth Seysis," 3rd Edition, New York, 1999). The compound of Formula (I) can be delivered as fre ites base or transformed into its salt form (for example HCl salt) by standard salt forimonat procedures. The starting materials and reactants can be puercdh oars synthetized as shown in the working examples below. The synthesis of amino indoline and amino indoalege rents can be synthesized as shown in the working examples below and / or according to fo thlleowing publications: 1) Lin CK, Wang YF, Cheng YC, Yang JS, "Multisite cotrnasined model of trans-4-(N,N- dimethylamino)-4'-nitrostilbene for structural eilduaction of radiative and nonradiative excited states," J. Phys. Chem. A. 117(15):31584-3 (126013). 2) Gao J, Chen Y, Zhou T, Liu G, An D, Zhuo M, Zha Gng, Zhang S, "Asymmetric Synthesis of Indoline–Benzodiazepine Scaffold Cyazteadl by Chiral Imidodiphosphoric Acids," Asian J. Org. Chem. 7(4):697-701 (2018). 3) Gale PA, Hiscock JR, Lalaoui N, Light ME, Wells N WJ,enzel M., "Benzimidazole-based anion receptors: tautomeric switching and seletcyt,i"v Oi rg. Biomol. Chem. 10(30):5909- 5915 (2012). 4) Tolnai GL, Ganss S, Brand JP, Waser J., "C2-sevleec dti rect alkynylation of indoles,"Org. Lett. 15(1):112-115 (2013). 5) Ahmed S, Ayscough A, Barker GR, Canning HE, Davertn Rpo, Downham R, Harrison D, Jenkins K, Kinsella N, Livermore DG, Wright S, Ivaect AD, Skene R, Wilkens SJ, Webster NA, Hendrick AG, "1,2,4-Triazolo-[1,5-a]pyridine HFI Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Bindin Ingteraction," J. Med. Chem. 60(13):5663-5672 (2017). The synthesis of bromo indoline and bromo indoalege rents was conducted analogously to procedures known in the ar St.ee, e.g., Lin CK, Wang YF, Cheng YC, Yang JS., "Msuilttei constrained model of trans-4-(N,N-dimethylamino-)n-i4tr'ostilbene for structural elucidation of radiative and nonradiative excited states," J.. P Chhysem. A.117(15), 315381-64 (2013); and Tolnai GL, Ganss S, Brand JP, Waser J. "C2-selectivet d airlekcynylation of indoles," Org Lett. 15(1): 112-115 (2013). IV. Use of the Compounds of the Disclosure The utility of Compounds of the Disclosure, inclnugdi pharmaceutically acceptable salts or solvates, in the present methods can be demondst irnat aeppropriate in vitro or in vivo assays. Compounds of the Disclosure have the ability tore inacse β-glucocerebrosidase. Therefore, Compounds of the Disclosure can be used / admindiste tore treat and / or prevent conditions associated with alteration of the activity β o-fglucocerebrosidase in a patient, such as for exleamp lysosomal storage disease αs-s,ynucleinopathies, and tauopathies. In one a,sp theect lysosomalstorage disease is Gaucher's disease. In anosthper ct, a the α-synucleinopathy is Parkinson'sdisease. In another aspect, the tauopathy is Aimlzehre’s disease. In another aspect, a condition associated with alteration of the activity β o-fglucocerebrosidase is a disease or disorder seedlect from the group consisting of: Gaucher's diseasrek,in Psaon's disease, dementia with Lewy bodies, diffuse Lewy body disease, multiple system atrop (hMySA), epilepsy, bipolar disorder,schizophrenia, an anxiety disorder, major deprens,s pio lycystic kidney disease, type 2 diabetes, open angle glaucoma, multiple sclerosis (MS), mpulelti myeloma, Alzheimer's disease, non- Alzheimer’s tauopathies (Pick’s complex), amyotriocph lateral sclerosis (ALS), corticobasal degeneration, frontotemporal lobe dementia, GBAr1ki Pnsaon, neuronopathic Gaucher's disease, neuroaxonal dystrophy, neurodegenerative diseaisthes p warkinsonism, progressive supranuclearpalsy, pure autonomic failure, sporadic Creutzf-eJladktob disease, and unimpaired ag Sinege,. e.g.,Maegawa G. H. B e.t al., The Journal of Biological Chemistry 284(3:253)502-23516 (2009); Jung O. et al., Expert Rev. Proteomics. 13:(457)1-479 (2016); Mazzulli J. R e.t al., The Journal ofNeuroscience 36(2:97)693-7706 (2016); Khanna R et. al., FEBS Journal 27:71618-1638 (2010);Parenti G. et al., Molecular Therapy 23(7:1)138-1148 (2015); and Sun Y et. al., The Journal ofBiological Chemistry 287(6:4)275-4287 (2012). In another aspect, the present disclosure is deidre tcot a method of treating or preventing a condition associated with the alteration of theiv aitcyt of β-glucocerebrosidase in a patient in need thereof, comprising administering to the patien nte ined thereof an effective amount of a Compound of the Disclosure. In another aspect, the present disclosure is deidre tcot a method of treating or preventing a lysosomal storage disease, such as Gaucher'se d,is inea as patient in need thereof, comprising administering an effective amount of a Compound the of Disclosure. In another aspect, the present disclosure is deidre tcot a method of treating or preventing an α-synucleinopathy, such as Parkinson's disease, p inati aent in need thereof, comprising administering an effective amount of a Compound the of Disclosure. In another aspect, the present disclosure is deidre tcot a method of treating or preventing a tauopathy, such as Alzheimer’s disease, in a pta itnie nneed thereof, comprising administering an effective amount of a Compound of the Disclosure. In another aspect, the present disclosure is deidre tcot method of treating or preventing a disease or disorder in a patient selected from g trhoeup consisting of: Gaucher's disease, Parkinson's disease, dementia with Lewy bodiesfu,s deif Lewy body disease, multiple system atrophy (MSA), epilepsy, bipolar disorder, schizroepnhia, an anxiety disorder, major depression, polycystic kidney disease, type 2 diabetes, opegnle a gnlaucoma, multiple sclerosis (MS), multiple myeloma, Alzheimer's disease, non-Alzheimer’s tauthoipes (Pick’s complex), amyotrophic lateral sclerosis (ALS), corticobasal degeneratio frno,ntotemporal lobe dementia, GBA1 Parkinson, neuronopathic Gaucher's disease, neounraola dxystrophy, neurodegenerative diseases with parkinsonism, progressive supranuclear pa plsuyre, autonomic failure, sporadic Creutzfeldt- Jakob disease, and unimpaired aging, comprisingin aisdtmering an effective amount of a Compound of the Disclosure to a patient in needre tohfe. In another aspect, any method described herein fu crtahner comprise administering to the patient at least one other therapeutic agent.no Inth aer aspect, the therapeutic agent is an effeectiv amount of an enzyme for enzyme replacement thera Ipny. another aspect, the enzyme β- is glucocerebrosidase or an analog thereof. In anro atshpeect, the enzyme is imiglucerase. In another aspect, the therapeutic agent is an effective amt o fu an small molecule chaperone. In another aspect, the small molecule chaperone binds comivpeelytit to an enzyme. In another aspect, the small molecule chaperone is selected from the gr coounpsisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidasefa,t sausle, glycosyl transferase, phosphatase, andpeptidase inhibitors. In another aspect, the smaoll ecule chaperone is selected from the groupconsisting of isofagomine, N-nonyl-1-deoxynojiriminyc (NN-DNJ), ambroxol, and miglustat. In another aspect, the small molecule chaperonee isct seedl from the group consisting of isofagomine, N-nonyl-1-deoxynojirimycin (NN-DNJ), and ambroxol I.n another aspect, the small molecule chaperone is miglustat. In another aspect, the therapeutic agent is anct eivfefe amount of substrate reduction agent for substrate reduction therapy. In another as,p theect substrate reduction agent is miglustat. In another aspect, the present disclosure is deidre tcot a Compound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of a condition associated with the alterationof the activity of β-glucocerebrosidase in a patient in need thereof. In another aspect, the present disclosure is deidre tcot a Compound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of a lysosomal storage disease, such asGaucher's disease. In another aspect, the present disclosure is deidre tcot a Compound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of an α-synucleinopathy, such asParkinson's disease. In another aspect, the present disclosure is deidre tcot a Compound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of a tauopathy, such as Alzheimer’s disease.In another aspect, the present disclosure is deidre tcot a Compound of the Disclosure, asdescribed herein, for use in the prevention ortm trea nt of a disease or disorder selected from thegroup consisting of: Gaucher's disease, Parkins doisne'sase, dementia with Lewy bodies, diffuse Lewy body disease, multiple system atrophy (MSAp)il,e epsy, bipolar disorder, schizophrenia, an anxiety disorder, major depression, polycystic keiydn disease, type 2 diabetes, open angle glaucoma, multiple sclerosis (MS), multiple myelo,m Aalzheimer's disease, non-Azheimer’s tauopathies (Pick’s complex), amyotrophic late srcallerosis (ALS), corticobasal degeneration, frontotemporal lobe dementia, GBA1 Parkinson, nneouproathic Gaucher's disease, neuroaxonaldystrophy, neurodegenerative diseases with parnki snmso, progressive supranuclear palsy, pureautonomic failure, sporadic Creutzfeldt-Jakob dsisee,a nd unimpaired aging. In another aspect, the present disclosure is airlseocte dd to the use of a Compound of the Disclosure, as described herein, for the treatm oren ptrevention of a condition associated with the alteration of the activity of β-glucocerebrosidase in a patient in need thereuocfh, s as those described herein. In another aspect, the present disclosure is deidre tcot a Compound of the Disclosure, as described herein, for use as a medicament. In another aspect, the present disclosure is deidre tcot use of a Compound of the Disclosure, as described herein, in the preparation of a memdeicnat for the prevention or treatment of a condition associated with the alteration of theiv aitcyt of β-glucocerebrosidase in a patient in need thereof, such as lysosomal storage disea αs-seysn,ucleinopathies, and tauopathies describedn h.erei In another aspect, the present disclosure is deidrec tot a pharmaceutical composition comprising a Compound of the Disclosure, as deesdcr hiberein, and at least one pharmaceutically acceptable excipient, for use in the treatmentr oerve pntion of a condition associated with the alteration of the activity o βf-glucocerebrosidase in a patient in need thereuocfh, s as lysosomal storage diseases α,-synucleinopathies, and tauopathies describedn h.erei V. Pharmaceutical Compositions The present disclosure also provides pharmaceu ctoicmapl ositions comprising an effective amount of a Compound of the Disclosure and at loenaest pharmaceutically acceptable excipient. Due to their activity, Compounds of the Disclosu caren be used in human medicine. As described above, Compounds of the Disclosure aerfeul u,s e.g., for treating or preventing lysosomal storage diseases, such as Gaucher's dis αe-assyen,ucleinopathies, such as Parkinson's diseadse, an tauopathies, such as Alzheimer’s disease. Compo oufn tdhse Disclosure can be administered to any patient suffering any of said conditions. The te "prmatient" as used herein refers to any human that can experience the beneficial effects of a Compo oufn thde Disclosure. When administered to a patient, a Compound of tihseclo Dsure can be administered as a component of a composition that comprises a phaermutaiccally acceptable excipient or carrier. Compounds of the Disclosure can be administere cdom inbination with at least one othertherapeutic agent. Administration of Compounds th oef Disclosure with at least one othertherapeutic agent can be sequential or concurre Int. another aspect, the Compound of theInvention and the at least one other therapeuteicnt a agre administered in separate dosage forms. In another aspect, the Compound of the Inventiodn th aen at least one other therapeutic agent are administered concurrently in the same dosage form. The term "excipient" refers to a vehicle, dilue onrt, adjuvant that is administered with the active ingredient. Such pharmaceutical excipienatns b ce sterile liquids, such as water and oils, including those of petroleum, animal, vegetable s,y onrthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and similar. Water s oarline aqueous solutions and aqueous dextrose and glycerol solutions, for example, for injectab sloelutions, can be used as vehicles. Suitable pharmaceutical vehicles are described in "Remin'sgt Pohnarmaceutical Sciences" by E.W. Martin, 21stEdition, 2005; or "Handbook of Pharmaceutical Epxiecnits," Rowe C.R.; Paul J.S.; MarianE.Q., sixth Edition, incorporated herein by refecre .nExamples of pharmaceutical compositions include s aonlyid composition (tablets, pills, capsules, granules, etc.) or liquid compositionoslu (tsions, suspensions, or emulsions) for oral, topical, or parenteral administration. In another embodiment, the pharmaceutical compoonsiti are in an oral delivery form.Pharmaceutical forms suitable for oral adminisotrnat cian be tablets and capsules, and can contain conventional excipients known in the art, suchi ansde brs, for example syrup, gum Arabic, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; e filrls, for example lactose, sugar, cornstarch, calcium phosphate, sorbitol, or glycine; lubrican fotsr the preparation of tablets, for example magnesium stearate; disintegrants, for examplech s,ta prolyvinylpyrrolidone, sodium starch glycolate, or microcrystalline cellulose; or pharcmeuatically acceptable wetting agents, such as sodium lauryl sulphate. Solid oral compositions can be prepared by conovennatli methods of blending, filling, orpreparation of tablets. Repeated blending opersat cioan be used to distribute the active ingredientin all the compositions that use large amountsill oefrs f. Such operations are conventional in the art. The tablets can be prepared, for example,r byy or d wet granulation and optionally can be coated by well-known methods in normal pharmaceaul pticractice, in particular enteric coating. Pharmaceutical compositions can also be adapted pa froernteral administration, such as sterile solutions, suspensions, or lyophilized purcotsd in the appropriate unit dosage form. Suitable excipients, such as fillers, buffering agents,u orrfa sctants can be used. The mentioned formulations can be prepared usinagnd satrd methods, such as those described or referred to in the Spanish and U.Sar.m Pahcopoeias and similar reference texts. In general, the effective amount of a Compoundh oef D t isclosure to be administered depends on the relative efficacy of the compounodse cnh, the severity of the condition or disorder being treated, and the patient's weight. The ac ctoivmepound can be administered one or more times a day, for example 1, 2, 3, or 4 times da wiliyth, typical total daily doses in the range from about 0.01 mg / kg of body weight / day to about 100g0 / k mg of body weight / day. In another embodiment, the effective dosage amount of a Comndpou f the Disclosure is about 500 mg / kg ofbody weight / day or less. In another embodiment, e tfhf e ctive dosage amount of a Compound ofthe Disclosure is about 100 mg / kg of body weighyt / odra less. In another embodiment, the effective dosage amount ranges from about 0.01 mg / kg of b woedigyht / day to about 100 mg / kg of body weight / day of a Compound of the Disclosure; in ahneort embodiment, from about 0.02 mg / kg of body weight / day to about 50 mg / kg of body weighyt / d oaf a Compound of the Disclosure; and in another embodiment, from about 0.025 mg / kg of b wodeyight / day to about 20 mg / kg of body weight / day of a Compound of the Disclosure. A composition of the disclosure can be prepared a b myethod comprising admixing a Compound of the Disclosure with a pharmaceutica cllcyeptable excipient or carrier. Admixing can be accomplished using methods known for admgix ain compound and a pharmaceutically acceptable excipient or carrier. In another emboednitm, the Compound of the Disclosure is present in the composition in an effective amount. VI. Particular Embodiments The disclosure provides the following particularb eomdiments. Embodiment 1. A compound having Formula (I): or a pharmaceutically acceptable salt or solvaetere tohf, wherein: A1 is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no more than one ofA2, A3, and A4 is N; R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R2 is selected from the group consisting of hydrog -Cen1-,6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and -ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4alkyl, and -C3-6 cycloalkyl, wherein said -1C-4 alkyl and -C3-6 cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydrog aennd -C1-4 alkyl, wherein said -C1-4alkyl is optionally substituted with 1 or 2 subusetitnts each independently selected from the group consisting of halogen, -CN, and -ORa; R4is selected from the group consisting of hydrog heanlo,gen, and -1C-4alkyl optionally substituted by 1, 2 or 3 halogen atoms; and each R5 is independently selected from the group consis otinf g halogen, -CN, -ORa, -C1-4alkyl, -C3-6cycloalkyl, and –(3- to 6-membered)1--5C heterocyclyl, wherein said -1C-4alkyl, -C3-6cycloalkyl, and -(3- to 6-membered)1--C5heterocyclyl groups are optionally substitutedh wit 1, 2 or 3 substituents each independently sele frcotemd the group consisting of halogen, hydroxy, -N(Rb)2, -C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl, wherein said -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl groups are optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of -C1-4 alkyl, -C1-4 alkoxy, and halogen; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1and R6together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ring, wherein or 12 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom independe snetllyected from the group consisting of O, N, and S, and wherein said heterocyclic ring is opatliloyn substituted with 1 or 2 substituents each independently selected form the group consistin hga olofgen and -1C-4 alkyl; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R6, R7, and R8each take the place of a hydrogen atom that wo tuhledrwise be present in any position on the ring of Formula (I) to which6, R 7 and R8 are attached; with the proviso the compound having Formula (I n)o ist: 2-((6-(benzo[d][1,3]dioxol-5-ylamino)-1-(p-tolyl)-H1-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(methyl(phenyl)amino)-1Hy-rpazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-fluorophenyl)-6-(indolin-1-yl)-1H-pyrazo[l3o,4-d]pyrimidin-4-yl)amino)ethan- 1-ol; 2-((1-(4-chlorophenyl)-6-(indolin-1-yl)-1H-pyrazo[l3o,4-d]pyrimidin-4-yl)amino)ethan- 1-ol; 2-((6-(indolin-1-yl)-1-(p-tolyl)-1H-pyrazolo[3,4-dp]yrimidin-4-yl)amino)ethan-1-ol; 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-14--(fluorophenyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(2,3-dihydro-4H-benzo[b,]4[1]oxazin-4-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-1p--(tolyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((6-(3,4-dihydroquinolin-1(2H)-yl)-1-(4-fluorophneyl)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(3,4-dihydroquinolin-1(2-Hy)l)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; or 2-((6-(3,4-dihydroquinolin-1(2H)-yl)-1-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol. Embodiment 2. The compound of Embodiment 1 havionrgm Fula (II): or a pharmaceutically acceptable salt or solvaetere tohf. Embodiment 3. The compound of Embodiment 1 havionrgm Fula (III): or a pharmaceutically acceptable salt or and seol tvhaetreof. Embodiment 4. The compound of any one of Embodims en 1t-3, or a pharmaceutically acceptable salt or solvate the,re wohferein R1 is selected from the group consisting of hydrogen, -1C-4 alkyl, -C3-6 cycloalkyl, and -C1-4 alkyl-C3-6 cycloalkyl. Embodiment 5. The compound of Embodiment 4, ora arm phaceutically acceptablesalt or solvate thereof, wherein1 R is selected from the group consisting of hydrog aennd -C1-4alkyl. Embodiment 6. The compound of Embodiment 5, ora arm phaceutically acceptable salt or solvate thereof, wherein1R is hydrogen. Embodiment 7. The compound of any one of Embodims en 1t-3, or a pharmaceutically acceptable salt or solvate the,r wehoef rein R1and R6together with the nitrogen and carbon atoms to which they are attached form op atinonally substituted heterocyclic ring,wherein 1 or 2 carbon atoms of said heterocycnlicg r aire optionally replaced with a heteroatomindependently selected from the group consisting O, o Nf , and S, and wherein said heterocyclic ring is optionally substituted with 1 or 2 subsetintuts each independently selected form the group consisting of halogen and1 --C4 alkyl. Embodiment 8. The compound of Embodiment 7, ora arm phaceutically acceptable salt or solvate thereof, wherein2R is selected from the group consisting of hydrog meent,hyl, -C3-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl, wherein said methyl,3--C6alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl groups are optionally substituted by 1, 2 or 3 substituents each indeepnetnlyd selected from the group consisting of halogen, -N(Ra2), and –ORa. Embodiment 9. The compound of Embodiment 7, whe Rre2iins not -CH2CH2OH. Embodiment 10. The compound of any one of Embodtism 1en or 7-9 having Formula (IV): or a pharmaceutically acceptable salt or solvaetere tohf. Embodiment 11. The compound of any one of Embodtism 1en or 7-9 having Formula (V): or a pharmaceutically acceptable salt or solvaetere tohf. Embodiment 12. The compound of any one of Embodtism 1en or 7-9 having Formula (VI): or a pharmaceutically acceptable salt or solvaetere tohf. Embodiment 13. The compound of any one of Embodtism 1en or 7-9 having Formula (VII): or a pharmaceutically acceptable salt or solvaetere tohf. Embodiment 14. The compound of any one of Embodtisme 1n-13, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R2is hydrogen. Embodiment 15. The compound of any one of Embodtisme 1n-13, or a pharmaceutically acceptable salt or solvate the,r weohferein R2 is selected from the group consisting of -C1-5alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2 alkyl-C3-6 cycloalkyl, -C1-2 alkyl-C3-6 cycloalkenyl, -C1-2 alkyl-C3-6 cycloalkynyl, -(3- to 6- membered)-C2-5 heterocyclyl, and -C1-2 alkyl-(3- to 6-membered)-2C-5 heterocyclyl, wherein said -C1-5alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl- C3-6 cycloalkyl, -C1-2 alkyl-C3-6 cycloalkenyl, -C1-2 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)- C2-5 heterocyclyl, and -C1-2 alkyl-(3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted by 1 or 2 substituents each indepenlyd seenltected from the group consisting of halogenand –ORa, wherein Ra is selected from the groupsis ctoin g of hydrogen, methyl, and ethyl,wherein said methyl and ethyl groups are option saullbystituted with 1, 2, or 3 fluorine atoms. Embodiment 16. The compound of any one of Embodtisme 1n-13, or a pharmaceutically acceptable salt or solvate the,re wohferein R2is selected from the group consisting of hydrogen, methyl, ethyl, isopropyslo,b iutyl, isopentyl, cyclopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-methoxtyheyl, 2-hydroxyethyl, 2-hydroxy-2-methyl- propyl, cyclohexylethyl, (cyclohex-1-en-1-yl)eth,y al)nd 2-morpholinoethyl. Embodiment 17. The compound of any one of Embodtisme 1n-16, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R3 is hydrogen. Embodiment 18. The compound of any one of Embodtisme 1n-16, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R3is -C1-4alkyl. Embodiment 19. The compound of any one of Embodtisme 1n-18, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R4 is hydrogen. Embodiment 20. The compound of any one of Embodtisme 1n-19, or a pharmaceutically acceptable salt or solvate the,r wehoefrein n is 0. Embodiment 21. The compound of any one of Embodtisme 1n-19, or a pharmaceutically acceptable salt or solvate the,r wehoefrein n is 1. Embodiment 22. The compound of any one of Embodtisme 1n-19 or 21, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R5 is halogen or –C1-4 alkyl optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the group consisting of halogen, hydroxy, -N(Rb2,) -C1-4alkyl , -C1-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 23. The compound of any one of Embodtisme 1n-9 or 14-22, or a pharmaceutically acceptable salt or solvate the,re wohferein R6 is selected from the group consisting of hydrogen, halogen, -CN, -ORa, -N(2R, abn)d -C1-4alkyl optionally substituted by 1, 2 or 3 substituents each independently selectemd f trhoe group consisting of halogen, -CN, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 24. The compound of any one of Embondtisme 1-23, or a pharmaceutically acceptable salt or solvate the,re wohferein R7is selected from the group consisting of hydrogen, halogen, -ORa, an1d-4 - aClkyl optionally substituted with 1, 2, or 3 haelong atoms. Embodiment 25. The compound of any one of Embodtisme 1n-24, or a pharmaceutically acceptable salt or solvate the,re wohferein R7 is selected from the group consisting of hydrogen, halogen, -OH,1- -4C alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 26. The compound of any one of Embodtisme 1n-25, or a pharmaceutically acceptable salt or solvate the,r wehoefrein each8 R is independently selected from the group consisting of hydrogen, halogen, -ORaN,, - -CN(Rb)2, -C1-4alkyl optionally substituted with 1, 2, or 3 fluorine atoms, and 3 –-C6 cycloalkyl. Embodiment 27. The compound of any one of Embodtisme 1n-26, or a pharmaceutically acceptable salt or solvate the,r wehoefrein each8R is independently selected from the group consisting of hydrogen, halogen, -OH1,-4- aClkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, -CN, -NH2, -N(H)C1-2 alkyl, -N(C1-2 alkyl)2, -C3-5 cycloalkyl, -C1- 4 alkyl, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 28. The compound of any one of Embodtisme 1n-27, or a pharmaceutically acceptable salt or solvate the,r wehoefrein m is 1. Embodiment 29. The compound of any one of Embondtisme 1-27, or a pharmaceutically acceptable salt or solvate the,r wehoefrein m is 2. Embodiment 30. The compound of any one of Embondtisme 1-27, or a pharmaceutically acceptable salt or solvate the,r wehoefrein m is 3. Embodiment 31. The compound of any one of Embodtisme 1n-9 or 14-22, or a pharmaceutically acceptable salt or solvate the,r wehoefrein: R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1- 4alkyl-C3-6 cycloalkyl; each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; m is 1, 2, or 3; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4 alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1--4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. Embodiment 32. The compound of Embodiment 31, p ohra armaceutically acceptable salt or solvate thereof, having Formula (VIII): Embodiment 33. The compound of Embodiment 31, p ohra armaceutically acceptable salt or solvate thereof, having Formula (IX): Embodiment 34. The compound of any one of Embodtism 1e,n 2, 4-6 or 14-22, or a pharmaceutically acceptable salt or solvate the,r heaovfing Formula (X): wherein R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and m is 1, 2, or 3. Embodiment 35. The compound of any one of Embodtisme 1n-6 or 31-33, or a pharmaceutically acceptable salt or solvate the,r wehoef rein R6and R7, together with the adjacent carbon atoms to which they are attached, form a or 56--membered ring having at least one heteroatom, wherein the ring is optionally substetidtu by one or more substituents selected from the group consisting of halogen, -CN, -C(=O1)--4C alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atoms. Embodiment 36. The compound of Embodiment 35, p ohra armaceutically acceptable salt or solvate thereof, wherein6R and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 5-membered ring having att l oenaes nitrogen atom, wherein the ring is optionally substituted by one or more substitue snetlsected from the group consisting of halogen, -CN, -C(=O)-C1-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. Embodiment 37. The compound of Embodiment 36, p ohra armaceutically acceptable salt or solvate thereof, wherein the 5-memberegd h rians one nitrogen atom. Embodiment 38. The compound of Embodiment 36, p ohra armaceutically acceptable salt or solvate thereof, wherein the 5-memberegd h rians two nitrogen atoms. Embodiment 39. The compound of Embodiment 37, p ohra armaceutically acceptable salt or solvate thereof, wherein6R and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a ring selected from the groounpsi csting of: wherein is a single bond or a double bond, and wherexin a Rnd Ryare each independently selected from the group consistin hgy odfrogen, halogen, -CN, -C(=O)1--C4 alkyl, and -C1-4 alkyl, wherein said alkyl is optionally substitut beyd 1, 2 or 3 fluorine atoms, and wherein Rxand Ryeach take the place of a hydrogen atom that wotuhledrw oise be present in any position on the ring to which Rxand Ryare attached. Embodiment 40. The compound of any one of Embodtism 1e-n6, 31-33, 39, or 40, or a pharmaceutically acceptable salt or solvateo thf,e wreherein R6and R7, together with the adjacent carbon atoms to which they are attached, formg a s reinlected from the group consisting of: wherein is a single bond or a double bond. Embodiment 41. The compound of any one of Embodtisme 1n-31 and 35-40, or a pharmaceutically acceptable salt or solvate the,r wehoefrein A2 is N; and A3 and A4 are CH. Embodiment 42. The compound of any one of Embodtisme 1n-31 and 35-40, or a pharmaceutically acceptable salt or solvate the,r wehoefrein A2and A4are CH; and A3is N. Embodiment 43. The compound of any one of Embodtisme 1n-31 and 35-40, or a pharmaceutically acceptable salt or solvate the,r wehoefrein A2 and A3 are CH; and A4 is N. Embodiment 44. The compound of any one of Embodtisme 1n-31 and 35-40, or a pharmaceutically acceptable salt or solvate the,r wehoefrein A2, A3, and A4 are CH. Embodiment 45. The compound of Embodiment 1, ohra arm paceutically acceptable salt or solvate thereof, that is any one or mor tehe of compounds of Table 1. Embodiment 46. A pharmaceutical composition cominpgris the compound of any one of Embodiments 1-45, or a pharmaceutically accelept saablt or solvate thereof, and at least one pharmaceutically acceptable excipient. Embodiment 47. A method of treating or preventin dgis aease, condition, or disorder in a patient in need thereof, comprising admininsgter to the patient an effective amount of a compound having Formula (I s),ee Embodiment 1, or a pharmaceutically acceptablte o sra slolvate thereof, wherein: A1 is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no more than one ofA2, A3, and A4is N; R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1- 4alkyl-C3-6 cycloalkyl; R2is selected from the group consisting of hydrog -Cen1-,6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, –(3- to 6-membered)2--C5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and -ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4 alkyl, and -C3-6 cycloalkyl, wherein said -1C-4 alkyl and -C3-6 cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydrog aennd -C1-4 alkyl, wherein said -C1-4alkyl is optionally substituted with 1 or 2 subusetitnts each independently selected from the group consisting of halogen, -CN, and -ORa; R4is selected from the group consisting of hydrog heanlo,gen, and -1C-4alkyl optionally substituted by 1, 2 or 3 halogen atoms; and each R5 is independently selected from the group consis otinf g halogen, -CN, -ORa, -C1-4alkyl, -C3-6cycloalkyl, and –(3- to 6-membered)1--5C heterocyclyl, wherein said -1C-4alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substitutedh wit 1, 2 or 3 substituents each independently sele frcotemd the group consisting of halogen, hydroxy, -N(Rb)2, -C1-4alkyl , -C1-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl, wherein said -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl groups are optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of -C1-4 alkyl, -C1-4 alkoxy, and halogen; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1and R6together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ring, wherein or 12 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom independe snetllyected from the group consisting of O, N, and S, and wherein said heterocyclic ring is opatliloyn substituted with 1 or 2 substituents each independently selected form the group consistin hga olofgen and -1C-4 alkyl; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R6, R7, and R8 each take the place of a hydrogen atom that wo tuhledrwise be present in any position on the ring of Formula (I) to which6, R 7 and R8 are attached. Embodiment 48. The method of Embodiment 47, wher theein compound having Formula (I) is a compound having Formula (I sI)e,e Embodiment 2, or a pharmaceutically acceptable salt or solvate thereof. Embodiment 49. The method of Embodiment 47, wher theein compound having Formula (I) is a compound having Formula (II sI)e,e Embodiment 3, or a pharmaceutically acceptable salt or and solvate thereof. Embodiment 50. The method of any one of Embodime 4n7t-s49, wherein R1 is selected from the group consisting of hydrogen1,-4- aClkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl. Embodiment 51. The method of Embodiment 50, whe Rre1in is selected from the group consisting of hydrogen and1--4C alkyl. Embodiment 52. The method of Embodiment 51, whe Rre1iins hydrogen. Embodiment 53. The method of any one of Embodim 4e7n-ts49, wherein R1 and R6 together with the nitrogen and carbon atoms to h wh thicey are attached form an optionally substituted heterocyclic ring, wherein 1 or 2 canrb aotoms of said heterocyclic ring are optionallyreplaced with a heteroatom independently selecrtoemd fthe group consisting of O, N, and S, and wherein said heterocyclic ring is optionally sutbustteid with 1 or 2 substituents each independently selected form the group consisting of halogen aCn1d-4a -lkyl. Embodiment 54. The method of Embodiment 53, whe Rre2in is selected from the group consisting of hydrogen, methyl,3- -6C alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6- membered)-C2-5 heterocyclyl, wherein said methyl,2 --C6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and –ORa. Embodiment 55. The method of Embodiment 53, whe Rre2iins not -CH2CH2OH. Embodiment 56. The method of any one of Embodim 4e7nts or 53-55, wherein the compound having Formula (I) is a compound havingrm Fuola (IV), see Embodiment 10, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 57. The method of any one of Embodim 4e7nts or 53-55, wherein the compound having Formula (I) is a compound havingrm Fuola (V), see Embodiment 11, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 58. The method of any one of Embodim 4e7nts or 53-55, wherein the compound having Formula (I) is a compound havingrm Fuola (VI), see Embodiment 12, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 59. The method of any one of Embodim 4e7nts or 53-55, wherein the compound having Formula (I) is a compound havingrm Fuola (VII), see Embodiment 13, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 60. The method of any one of Embodime 4n7t-s59, wherein R2is hydrogen. Embodiment 61. The method of any one of Embodime 4n7t-s59, wherein R2 is selected from the group consisting of1--5C alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-2 alkyl-(3- to 6- membered)-C2-5 heterocyclyl, wherein said -1C-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-2 alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 by or 2 substituents each independently selected from the group consisting ha olof gen and –ORa, wherein Ra is selected from the group consisting of hydrogen, methyl, a enthdyl, wherein said methyl and ethyl groups are optionally substituted with 1, 2, or 3 fluori anteoms. Embodiment 62. The method of any one of Embodime 4n7t-s59, wherein R2is selected from the group consisting of hydrogen,h myl,et ethyl, isopropyl, isobutyl, isopentyl, cyclopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,22-,trifluoroethyl, 2-methoxyethyl, 2- hydroxyethyl, 2-hydroxy-2-methyl-propyl, cyclohexeythlyl, (cyclohex-1-en-1-yl)ethyl), and 2- morpholinoethyl. Embodiment 63. The method of any one of Embodime 4n7t-s62, wherein R3 is hydrogen. Embodiment 64. The method of any one of Embodim 4e7n-t6s2, wherein R3is -C1-4alkyl. Embodiment 65. The method of any one of Embodime 4n7t-s62, wherein R4 is hydrogen. Embodiment 66. The method of any one of Embodim 4e7n-t6s5, wherein n is 0. Embodiment 67. The method of any one of Embodimen 4t7s-65, or a pharmaceutically acceptable salt or solvate the,r wehoefrein n is 1. Embodiment 68. The method of any one of Embodime 4n7t-s55 or 67, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R5 is halogen or –C1-4 alkyl optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the group consisting of halogen, hydroxy, -N(Rb2,) -C1-4alkyl , -C1-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 69. The method of any one of Embodim 4e7n-t5s5 or 60-68, wherein6 R is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of halogen, -CN, hydroxy,1 --C4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 70. The method of any one of Embodims e 4n7t-69, wherein 7 R is selected from the group consisting of hydrogen,og heanl, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halogen atoms. Embodiment 71. The method of any one of Embodime 4n7t-s70, wherein R7 is selected from the group consisting of hydrogen,og heanl, -OH, -C1-4 alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 72. The method of any one of Embodimen 4t7s-71, or a pharmaceutically acceptable salt or solvate the,r wehoefrein each8R is independently selected from the group consisting of hydrogen, halogen, -ORaN,, - -CN(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 fluorine atoms, and 3 –-C6 cycloalkyl. Embodiment 73. The method of any one of Embodimen 4t7s-71, or a pharmaceutically acceptable salt or solvate the,r wehoefrein each8 R is independently selected from the group consisting of hydrogen, halogen, -OH1,-4 - aClkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, -CN, -NH2, -N(H)C1-2alkyl, -N(C1-2alkyl)2, -C3-5cycloalkyl, -C1-4alkyl, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 74. The method of any one of Embodimen 4t7s-73, or a pharmaceutically acceptable salt or solvate the,r wehoefrein m is 1. Embodiment 75. The method of any one of Embodims en 4t7-73, or a pharmaceutically acceptable salt or solvate the,r wehoefrein m is 2. Embodiment 76. The method of any one of Embodims en 4t7-73, or a pharmaceutically acceptable salt or solvate the,r wehoefrein m is 3. Embodiment 77. The method of any one of Embodim 4e7n-t4s9 or 60-68, wherein: R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; m is 1, 2, or 3; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4 alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1--4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. Embodiment 78. The method of Embodiment 77, wher theein compound having Formula (I) is a compound having Formula (VII sI)e,e Embodiment 32, or a pharmaceutically acceptable salt or solvate thereof. Embodiment 79. The method of Embodiment 77, wher theein compound having Formula (I) is a compound having Formula (IX s)e,e Embodiment 33, or a pharmaceutically acceptable salt or solvate thereof. Embodiment 80. The method of any one of Embodim 7e7n-t7s9, wherein R6 and R7,together with the adjacent carbon atoms to whicehy t ahre attached, form a 5- or 6-membered ringhaving at least one heteroatom, wherein the ring op itsionally substituted by one or more substituents selected from the group consistin hga olofgen, -CN, -C(=O)-1C-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substituted by 21 o,r 3 fluorine atoms. Embodiment 81. The method of Embodiment 80, whe Rre6in and R7, together with the adjacent carbon atoms to which they are atdta,c fohrem a 5-membered ring having at least one nitrogen atom, wherein the ring is optionally suitbustetd by one or more substituents selected from the group consisting of halogen, -CN, -C(=O1)--4C alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atoms. Embodiment 82. The method of Embodiment 81, whe trheein 5-membered ring has one nitrogen atom. Embodiment 83. The method of Embodiment 82, whe trheein 5-membered ring has two nitrogen atoms. Embodiment 84. The method of Embodiment 82, whe Rre6in and R7, together with the adjacent carbon atoms to which they are atdta,c fhoerm a ring selected from the group consisting of a double bond, and whereinx R and Ry are each independently selected from the groupsis ctoin gof hydrogen, halogen, -CN, -C(=O)1--C4 alkyl, and -C1-4 alkyl, wherein said alkyl is optionally substituted by 1, 2 or 3 fluorine atoms, and whner Rexi and Ryeach take the place of a hydrogen atom that would otherwise be present in any ponsi otino the ring to whichxR and Ryare attached. Embodiment 85. The method of any one of Embodime 8n0t-s82 or 84, wherein6 Rand R7, together with the adjacent carbon atoms to wh thicehy are attached, form a ring selectedfrom the group consisting of wherein is a single bond or a double bond. Embodiment 86. The method of Embodiment 47, 485,25,0 o-r 60-68, wherein the compound having Formula (I) is a compound havingrm Fuola (X), see Embodiment 34, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 87. The method of any one of Embodims 4e7n-t77, wherein A2is N; and A3 and A4 are CH. Embodiment 88. The method of any one of Embodim 4e7n-t7s7, wherein A2 and A4 are CH; and A3is N. Embodiment 89. The method of any one of Embodim 4e7n-t7s7, wherein A2and A3are CH; and A4 is N. Embodiment 90. The method of any one of Embodim 4e7n-t7s7, wherein A2, A3and A4are CH. Embodiment 91. The method of Embodiment 47, wher theein compound having Formula (I) is any one or more of the compound Tsa obfle 1. Embodiment 92. The method of any one of Embodim 4e7n-t9s1, wherein the disease, condition, or disorder is associated with the alttieorn of the activity of β-glucocerebrosidase (GBA). Embodiment 93. The method of any one of Embodim 4e7n-t9s1, wherein the disease, condition, or disorder is a lysosomal storage dsies.ea Embodiment 94. The method of Embodiment 93 wher tehien lysosomal storage disease is Gaucher's disease. Embodiment 95. The method of any one of Embodim 4e7n-t9s1, wherein the disease, condition, or disorder is a αn-synucleinopathy. Embodiment 96. The method of Embodiment 95, whe trheein α-synucleinopathy is Parkinson’s disease. Embodiment 97. The method of any one of Embodim 4e7n-t9s1, wherein the disease, condition, or disorder is a tauopathy. Embodiment 98. The method of Embodiment 97, wher tehine tauopathy is Alxheimer’s disease. Embodiment 99. The method of any one of Embodim 4e7n-t9s1, wherein the disease, condition, or disorder is selected from the grouopns cisting of: Gaucher's disease, Parkinson's disease, dementia with Lewy bodies, diffuse Lewdyy b doisease, multiple system atrophy (MSA), epilepsy, bipolar disorder, schizophrenia, an atnyx dieisorder, major depression, polycystic kidney disease, type 2 diabetes, open angle glaucoma,ip mleu sltclerosis (MS), multiple myeloma, Alzheimer's disease, non-Alzheimer’s tauopathieicsk (’sP complex), amyotrophic lateral sclerosis (ALS), corticobasal degeneration, frontotemporable lo dementia, GBA1 Parkinson, neuronopathic Gaucher's disease, neuroaxonal dystrophy, neurnoedreagteive diseases with parkinsonism, progressive supranuclear palsy, pure autonomiucre fa,il sporadic Creutzfeldt-Jakob disease, and unimpaired aging. Embodiment 100. The method of any one of Embodims e 4n7t-99 further comprisingadministering to the patient at least one otherra tphe utic agent.Embodiment 101. The method of Embodiment 100, winhe thre therapeutic agent is aneffective amount of an enzyme for enzyme replacetm then rapy.Embodiment 102. The method of Embodiment 101, winher tehe enzyme is β-glucocerebrosidase or an analog thereof. Embodiment 103. The method of Embodiment 101, winher tehe enzyme is imiglucerase. Embodiment 104. The method of Embodiment 100, winhe thre therapeutic agent is aneffective amount of a small molecule chaperone. Embodiment 105. The method of Embodiment 104, winher thee small molecule chaperone binds competitively to an enzyme. Embodiment 106. The method of Embodiments 104 o5r, 1 w0herein the smallmolecule chaperone is selected from the group s ctoin gsi of iminoalditols, iminosugars,aminosugars, thiophenylglycosides, glycosidasefa,t sausle, glycosyl transferase, phosphatase, and peptidase inhibitors. Embodiment 107. The method of Embodiment 105, winher thee small molecule chaperone is selected from the group consisting iso offagomine, N-nonyl-1-deoxynojirimycin (NN-DNJ), ambroxol, and miglustat. Embodiment 108. A compound of Formula (I) s,ee Embodiment 1, or a pharmaceutically acceptable salt or solvate the,r wehoefrein: A1 is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no more than one ofA2, A3, and A4 is N; R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R2 is selected from the group consisting of hydrog -Cen1-,6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl- (3- to 6-membered)-2C-5heterocyclyl, wherein said -1C-6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6- membered)-C2-5heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and -ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4 alkyl, and -C3-6cycloalkyl, wherein said -1C-4alkyl and -C3-6cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydro agnedn –C1-4 alkyl, wherein said –1C-4alkyl is optionally substituted with 1 or 2 subusetitnts each independently selected from the group consisting of halogen, -CN, and -ORa; R4 is selected from the group consisting of hydrog heanlo,gen, and -1C-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms; and each R5is independently selected from the group consis otinf g halogen, -CN, -ORa, -C1-4 alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl, wherein said -1C-4 alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substitutedh wit 1, 2 or 3 substituents each independently sele frcotemd the group consisting of halogen, hydroxy, -N(Rb)2, -C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -1C-4alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl groups are optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of -C1-4alkyl, -C1-4alkoxy, and halogen; R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1and R6together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ring, wherein or 12 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom independe snetllyected from the group consisting of O, N, and S, and wherein said heterocyclic ring is opatliloyn substituted with 1 or 2 substituents each independently selected form the group consistin hga olofgen and -1C-4alkyl; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroarom, winhe thre ring is optionally substituted by oneor more substituents selected from the group ctoin gsis of halogen, -CN, -C(=O)-1C-4 alkyl, and-C1-4alkyl, wherein said alkyl is optionally substitut beyd 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R6, R7, and R8each take the place of a hydrogen atom that wo tuhledrwise be present in any position on the ring of Formula (I) to which6, R 7 and R8 are attached, or a pharmaceutical composition thereof, for use as a medicament for treating or preven atin dgisease, condition, or disorder in a patient. Embodiment 109. The compound or composition for o ufs Eembodiment 108, wherein the compound of Formula (I) is a compound havingrm Fuola (II), see Embodiment 2, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 110. The compound or composition for o ufs Eembodiment 108, wherein the compound of Formula (I) is a compound havingrm Fuola (III), see Embodiment 3, or a pharmaceutically acceptable salt or and solvatreeo thf.e Embodiment 111. The compound or composition for o ufs aeny one of Embodiments 108-110, wherein1R is selected from the group consisting of hydrog -eCn1,-4alkyl, -C3-6cycloalkyl, and -C1-4 alkyl-C3-6 cycloalkyl. Embodiment 112. The compound or composition for o ufs Eembodiment 111, wherein R1is selected from the group consisting of hydro agnedn -C1-4alkyl. Embodiment 113. The compound or composition for o ufs Eembodiment 112, wherein R1 is hydrogen. Embodiment 114. The compound or composition for o ufs aeny one of Embodiments 108-110, wherein1R and R6together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ringh,e wrein 1 or 2 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom p inednedently selected from the group consisting of O, N, and S, and wherein said heterocyclic r isin ogptionally substituted with 1 or 2 substituents each independently selected form the group consgis otfi halogen and -1C-4 alkyl. Embodiment 115. The compound or composition for o ufs Eembodiment 114, wherein R2is selected from the group consisting of hydrog meent,hyl, -C3-6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said methyl,3 --C6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consgis otfi halogen, -N(Ra2,) and –ORa. Embodiment 116. The compound or composition for o ufs Eembodiment 114, wherein R2 is not -CH2CH2OH. Embodiment 117. The compound or composition for o ufs aeny one of Embodiments 108 or 114-116, wherein the compound of Formula is (I) a compound having Formula (IV), see Embodiment 10, or a pharmaceutically acceptabltle or sa solvate thereof. Embodiment 118. The compound or composition for o ufs aeny one of Embodiments 108 or 114-116, wherein the compound of Formula is (I) a compound having Formula (V), see Embodiment 11, or a pharmaceutically acceptabltle or sa solvate thereof. Embodiment 119. The compound or composition for o ufs aeny one of Embodiments 108 or 114-116, wherein the compound of Formula is (I) a compound having Formula (VI), see Embodiment 12, or a pharmaceutically acceptabltle or sa solvate thereof. Embodiment 120. The compound or composition for o ufs aeny one of Embodiments 108 or 114-116, wherein the compound of Formula is (I a) compound having Formula (VII), see Embodiment 13, or a pharmaceutically acceptabltle or sa solvate thereof. Embodiment 121. The compound or composition for o ufs aeny one of Embodiments 108-120, wherein2R is hydrogen. Embodiment 122. The compound or composition for o ufs aeny one of Embodiments 108-120, wherein 2 R is selected from the group consisting o1f-5 -C alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-2 alkyl-C3-6 cycloalkyl, -C1-2 alkyl-C3-6 cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-2alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-2 alkyl-C3-6 cycloalkyl, -C1-2 alkyl-C3-6 cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-2alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 by or 2 substituents each independently selected from the group consisting ha olof gen and –ORa, wherein Ra is selected from the group consisting of hydrogen, methyl, a enthdyl, wherein said methyl and ethyl groups are optionally substituted with 1, 2, or 3 fluori anteoms. Embodiment 123. The compound or composition for o ufs aeny one of Embodiments 108-120, wherein 2 R is selected from the group consisting of hydrog meent,hyl, ethyl, isopropyl, isobutyl, isopentyl, cyclopropyl, 2-fluoroethyl, 22-d,ifluoroethyl, 2,2,2-trifluoroethyl, 2-methoxyethyl, 2-hydroxyethyl, 2-hydroxy-2-methylo-pr yl, cyclohexylethyl, (cyclohex-1-en-1-yl)ethyl), and 2-morpholinoethyl. Embodiment 124. The compound or composition for o ufs aeny one of Embodiments 108-123, wherein 3 R is hydrogen. Embodiment 125. The compound or composition for o ufs aeny one of Embodiments 108-123, wherein3R is -C1-4alkyl. Embodiment 126. The compound or composition for o ufs aeny one of Embodiments 108-125, wherein 4 R is hydrogen. Embodiment 127. The compound or composition for o ufs aeny one of Embodiments 108-126, wherein n is 0. Embodiment 128. The compound or composition for o ufs aeny one of Embodiments 108-126, or a pharmaceutically acceptable salotl ovra ste thereof, wherein n is 1. Embodiment 129. The compound or composition for o ufs aeny one of Embodiments 108-126 or 128, or a pharmaceutically acceptabltle or sa solvate thereof, wherein5 R is halogen or –C1-4alkyl optionally substituted with 1, 2 or 3 subtusetints each independently selected from the group consisting of halogen, hydroxy, -N(R2,b -)C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 130. The compound or composition for o ufs aeny one of Embodiments 108-116 or 121-129, wherein6R is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(Rb2), and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -C hyNd,roxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 131. The compound or composition foer o ufs any one of Embodiments 108-130, wherein 7 R is selected from the group consisting of hydrog heanlo,gen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halong aetoms. Embodiment 132. The compound or composition for o ufs aeny one of Embodiments 108-131, wherein 7 R is selected from the group consisting of hydrog heanl,ogen, -OH, -C1-4 alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 133. The compound or composition for o ufs aeny one of Embodiments 108-132, or a pharmaceutically acceptable salotl ovra ste thereof, wherein each8 i Rs independently selected from the group consisting of hydrogen,og heanl, -ORa, -CN, -N(Rb2,) -C1-4alkyl optionally substituted with 1, 2, or 3 fluorinem atso, and –C3-6 cycloalkyl. Embodiment 134. The compound or composition for o ufs aeny one of Embodiments 108-133, or a pharmaceutically acceptable salotl ovra ste thereof, wherein each8i Rs independently selected from the group consisting of hydrogen,og heanl, -OH, -C1-4 alkoxy, monohalo(C1- 4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, -CN, -NH2, -N(H)C1-2 alkyl, -N(C1-2 alkyl)2, -C3-5cycloalkyl, -C1-4alkyl, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 135. The compound or composition for o ufs aeny one of Embodiments 108-134, or a pharmaceutically acceptable salotl ovra ste thereof, wherein m is 1. Embodiment 136. The compound or composition foer o ufs any one of Embodiments 108-134, or a pharmaceutically acceptable salotl ovra ste thereof, wherein m is 2. Embodiment 137. The compound or composition foer o ufs any one of Embodiments 108-134, or a pharmaceutically acceptable salotl ovra ste thereof, wherein m is 3. Embodiment 138. The compound or composition for o ufs aeny one of Embodiments 108-110 or 121-129, wherein: R1is selected from the group consisting of hydrog -eCn1,-4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6cycloalkyl; m is 1, 2, or 3; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. Embodiment 139. The compound or composition for o ufs Eembodiment 138, wherein the compound of Formula (I) is a compound havingrm Fuola (VIII), see Embodiment 32, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 140. The compound or composition for o ufs Eembodiment 138, wherein the compound of Formula (I) is a compound havingrm Fuola (IX), see Embodiment 33, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 141. The compound or composition for o ufs aeny one of Embodiments138-140, wherein 6 R and R7, together with the adjacent carbon atoms to wh thicehy are attached,form a 5- or 6-membered ring having at least onte r hoeatom, wherein the ring is optionallysubstituted by one or more substituents selectoemd f trhe group consisting of halogen, -CN, -C(=O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substitudt bey 1, 2 or 3 fluorine atoms. Embodiment 142. The compound or composition for o ufs Eembodiment 141, whereinR6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, form a 5-memberedring having at least one nitrogen atom, wherein ri tnhge is optionally substituted by one or more substituents selected from the group consistin hga olofgen, -CN, -C(=O)-1C-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substituted by 21 o,r 3 fluorine atoms. Embodiment 143. The compound or composition for o ufs Eembodiment 142, wherein the 5-membered ring has one nitrogen atom. Embodiment 144. The compound or composition for o ufs Eembodiment 142, wherein the 5-membered ring has two nitrogen atoms. Embodiment 145. The compound or composition for o ufs Eembodiment 143, whereinR6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, form a ring selectedfrom the group consisting of: wherein is a single bond or a double bond, and wherexin a Rnd Ryare each independently selected from the group consistin hgy odfrogen, halogen, -CN, -C(=O)1--C4 alkyl, and -C1-4 alkyl, wherein said alkyl is optionally substitut beyd 1, 2 or 3 fluorine atoms, and wherein Rxand Ryeach take the place of a hydrogen atom that wotuhledrw oise be present in any position on the ring to which Rxand Ryare attached. Embodiment 146. The compound or composition for o ufs aeny one of Embodiments 138-140 or 145, wherein6R and R7, together with the adjacent carbon atoms to wh thicehy areattached, form a ring selected from the group csotins gi of:, Embodiment 147. The compound or composition for o ufs Eembodiment 138, wherein the compound of Formula (I) is a compound havingrm Fuola (X), see Embodiment 34, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 148. The compound or composition for o ufs aeny one of Embodiments 108-138, wherein A2 is N; and A3 and A4 are CH. Embodiment 149. The compound or composition for o ufs aeny one of Embodiments 108-138, wherein A2and A4are CH; and A3is N. Embodiment 150. The compound or composition for o ufs aeny one of Embodiments 108-138, wherein A2 and A3 are CH; and A4 is N. Embodiment 151. The compound or composition for o ufs aeny one of Embodiments 108-138, wherein A2, A3, and A4 are CH. Embodiment 152. The compound or composition for o ufs Eembodiment 108, wherein the compound of Formula (I) is any one or moreh oef c tompounds of Table 1. Embodiment 153. The compound or composition for o ufs aeny one of Embodiments 108-152, wherein the disease, condition, or disro irsd aessociated with the alteration of the activity of β-glucocerebrosidase (GBA). Embodiment 154. The compound or composition for o ufs aeny one of Embodiments 108-152, wherein the disease, condition, or disro irsd ae lysosomal storage disease. Embodiment 155. The compound or composition for o ufs Eembodiment 154 wherein the lysosomal storage disease is Gaucher's disease. Embodiment 156. The compound or composition for o ufs aeny one of Embodiments 108-152, wherein the disease, condition, or disro irsd aen α-synucleinopathy. Embodiment 157. The compound or composition for o ufs Eembodiment 156, wherein the α-synucleinopathy is Parkinson’s disease. Embodiment 158. The compound or composition for o ufs aeny one of Embodiments 108-152, wherein the disease, condition, or disro irsd ae tauopathy. Embodiment 159. The compound or composition for o ufs Eembodiment 158, wherein the tauopathy is Alzheimer’s disease. Embodiment 160. The compound or composition for o ufs aeny one of Embodiments 108-152, wherein the disease, condition, or disro irsde selected from the group consisting of: Gaucher's disease, Parkinson's disease, dementhtia Le wwiy bodies, diffuse Lewy body disease, multiple system atrophy (MSA), epilepsy, bipolarso drider, schizophrenia, an anxiety disorder, major depression, polycystic kidney disease, typ deia 2betes, open angle glaucoma, multiple sclerosis (MS), multiple myeloma, Alzheimer's dissee,a non-Alzheimer’s tauopathies (Pick’s complex), amyotrophic lateral sclerosis (ALS), cicoorbtasal degeneration, frontotemporal lobe dementia, GBA1 Parkinson, neuronopathic Gaucheri'ssea dse, neuroaxonal dystrophy, neurodegenerative diseases with parkinsonism, e psrosgivre supranuclear palsy, pure autonomic failure, sporadic Creutzfeldt-Jakob disease, animdp uanired aging. Embodiment 161. The compound or composition for o ufs aeny one of Embodiments 108-160 further comprising administering to theie pnatt at least one other therapeutic agent. Embodiment 162. The compound or composition for o ufs Eembodiment 161, wherein the therapeutic agent is an effective amount o efn aznyme for enzyme replacement therapy. Embodiment 163. The compound or composition for o ufs Eembodiment 162, wherein the enzyme is β-glucocerebrosidase or an analog thereof. Embodiment 164. The compound or composition for o ufs Eembodiment 162, wherein the enzyme is imiglucerase. Embodiment 165. The compound or composition for o ufs Eembodiment 161, whereinthe therapeutic agent is an effective amount omf a ll s molecule chaperone.Embodiment 166. The compound or composition for o ufs Eembodiment 165, wherein the small molecule chaperone binds competitivel ayn to enzyme. Embodiment 167. The compound or composition for o ufs Eembodiments 165 or 166, wherein the small molecule chaperone is selectoemd f trhe group consisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides,co gsliydase, sulfatase, glycosyl transferase, phosphatase, and peptidase inhibitors. Embodiment 168. The compound or composition for o ufs Eembodiment 166, wherein the small molecule chaperone is selected from r thoeup g consisting of isofagomine, N-nonyl-1- deoxynojirimycin (NN-DNJ), ambroxol, and miglustat. Embodiment 169. Use of a compound of Formula ( sIe),e Embodiment 1, or a pharmaceutically acceptable salt or solvate the,r wehoefrein: A1is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no more than one ofA2, A3, and A4 is N; R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; R2 is selected from the group consisting of hydrog -Cen1-,6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and -ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4 alkyl, and -C3-6 cycloalkyl, wherein said -1C-4 alkyl and -C3-6 cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydro agendn -C1-4 alkyl, wherein said –1C-4alkyl is optionally substituted with 1 or 2 subusetitnts each independently selected from the group consisting of halogen, -CN, and -ORa; R4is selected from the group consisting of hydrog heanlo,gen, and -1C-4alkyl optionally substituted by 1, 2 or 3 halogen atoms; and each R5 is independently selected from the group consis otinf g halogen, -CN, -ORa, -C1-4alkyl, -C3-6cycloalkyl, and -(3- to 6-membered)1--C5heterocyclyl, wherein said -1C-4alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substitutedh wit 1, 2 or 3 substituents each independently sele frcotemd the group consisting of halogen, hydroxy, -N(Rb)2, -C1-4alkyl , -C1-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -1C-4alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl groups are optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of -C1-4 alkyl, -C1-4 alkoxy, and halogen; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ring, wherein or 12 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom independe snetllyected from the group consisting of O, N, and S, and wherein said heterocyclic ring is opatliloyn substituted with 1 or 2 substituents each independently selected form the group consistin hga olofgen and -1C-4 alkyl; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6cycloalkyl; and m is 1, 2, or 3; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4 alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1--4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; and R6, R7, and R8 each take the place of a hydrogen atom that wo tuhledrwise be present in any position on the ring of Formula (I) to which6, R7and R8are attached, in the manufacture of a medicament for treating pr oerventing a disease, condition, or disorder in a patient. Embodiment 170. The use of Embodiment 169, whe trheein compound of Formula (I) is a compound having Formula (II s)e,e Embodiment 2, or a pharmaceutically acceptablte o sral solvate thereof. Embodiment 171. The use of Embodiment 169, whe trheein compound of Formula (I) is a compound having Formula (III s)e,e Embodiment 3, or a pharmaceutically acceptablte o sral and solvate thereof. Embodiment 172. The use of any one of Embodime6n9ts-1171, wherein R1 is selected from the group consisting of hydrogen,1--4C alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl. Embodiment 173. The use of Embodiment 172, whe Rre1i ins selected from the groupconsisting of hydrogen and1 --C4 alkyl. Embodiment 174. The use of Embodiment 173, whe Rre1i ins hydrogen.Embodiment 175. The use of any one of Embodime6n9ts-1171, wherein R1and R6together with the nitrogen and carbon atoms to h wh thicey are attached form an optionally substituted heterocyclic ring, wherein 1 or 2 canrb aotoms of said heterocyclic ring are optionallyreplaced with a heteroatom independently selecrtoemd fthe group consisting of O, N, and S, and wherein said heterocyclic ring is optionally sutbustteid with 1 or 2 substituents each independently selected form the group consisting of halogen aCn1d-4a -lkyl. Embodiment 176. The use of Embodiment 175, whe Rre2i ins selected from the groupconsisting of hydrogen, methyl,3 --C6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)-2C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6-membered)-2C-5 heterocyclyl, wherein said methyl, 3 --C6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consistin hga olofgen, -N(Ra2), and –ORa. Embodiment 177. The use of Embodiment 175, whe Rre2i ins not -CH2CH2OH.Embodiment 178. The use of any one of Embodime6n9ts o 1r 175-177, wherein the compound of Formula (I) is a compound having Foramu (IlV), see Embodiment 10, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 179. The use of any one of Embodime6n9ts o 1r 175-177, wherein the compound of Formula (I) is a compound having Foramu (Vl ), see Embodiment 11, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 180. The use of any one of Embodime6n9ts o 1r 175-177, wherein the compound of Formula (I) is a compound having Foramu (Vl I), see Embodiment 12, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 181. The use of any one of Embodimen9t o 1r6175-177, wherein the compound of Formula (I) is a compound having Foramu (VlII), see Embodiment 13, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 182. The use of any one of Embodimen6t9s-1181, wherein R2is hydrogen. Embodiment 183. The use of any one of Embodime6n9ts-1181, wherein R2 is selected from the group consisting of -1C-5alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6-membered)-2C-5 heterocyclyl, and -C1-2 alkyl-(3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6-membered)-2C-5 heterocyclyl, and -C1-2 alkyl-(3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted b oyr 12 substituents each independently selected from the group consisting of halogen and –ORa, weihne Rra is selected from the group consisting of hydrogen, methyl, and ethyl, wherein said met ahnydl ethyl groups are optionally substituted with 1, 2, or 3 fluorine atoms. Embodiment 184. The use of any one of Embodime6n9ts-1181, wherein R2is selected from the group consisting of hydrogen, methyl, el,th isyopropyl, isobutyl, isopentyl, cyclopropyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroheytl, 2-methoxyethyl, 2-hydroxyethyl, 2-hydroxy- 2-methyl-propyl, cyclohexylethyl, (cyclohex-1-eny-1l)-ethyl), and 2-morpholinoethyl. Embodiment 185. The use of any one of Embodimen6t9s-1184, wherein R3is hydrogen. Embodiment 186. The use of any one of Embodime6n9ts-1184, wherein R3 is -C1-4 alkyl. Embodiment 187. The use of any one of Embodimen6t9s-1186, wherein R4 is hydrogen. Embodiment 188. The use of any one of Embodime7n8ts-1187, wherein n is 0. Embodiment 189. The use of any one of Embodime7n8ts-1187, or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Embodiment 190. The use of any one of Embodimen7t8s-1187 or 189, or a pharmaceutically acceptable salt or solvate the,r wehoefrein R5is halogen or –C1-4alkyl optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the group consisting of halogen, hydroxy, -N(Rb2,) -C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 191. The use of any one of Embodime6n9ts-1174 or 182-190, wherein R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 substituentsch ea independently selected from the group consisting of halogen, -CN, hydroxy,1--C4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. Embodiment 192. The use of any one of Embodim 1e6n9ts-191, wherein7 R is selected from the group consisting of hydrogen, halogen,a -O, aRnd -C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms. Embodiment 193. The use of any one of Embodime6n9ts-1192, wherein R7is selected from the group consisting of hydrogen, halogen, , -O -CH1-4 alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 194. The use of any one of Embodime6n9ts-1193, or a pharmaceutically acceptable salt or solvate thereof, wherein ea8ch is R independently selected from the group consisting of hydrogen, halogen, -ORa, -CN, -N(2R, -bC)1-4 alkyl optionally substituted with 1, 2, or 3 fluorine atoms, and –3C-6 cycloalkyl. Embodiment 195. The use of any one of Embodime6n9ts-1194, or a pharmaceutically acceptable salt or solvate thereof, wherein ea8ch is R independently selected from the group consisting of hydrogen, halogen, -OH,1- -4C alkoxy, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, trihalo(C1-4)alkoxy-, -CN, -NH2, -N(H)C1-2alkyl, -N(C1-2alkyl)2, -C3-5cycloalkyl, -C1-4alkyl, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, and trihalo(C1-4)alkyl-. Embodiment 196. The use of any one of Embodime6n9ts-1195, or a pharmaceutically acceptable salt or solvate thereof, wherein m is 1. Embodiment 197. The use of any one of Embodim 1e6n9ts-195, or a pharmaceutically acceptable salt or solvate thereof, wherein m is 2. Embodiment 198. The use of any one of Embodim 1e6n9ts-195, or a pharmaceutically acceptable salt or solvate thereof, wherein m is 3. Embodiment 199. The use of any one of Embodime6n9ts-1174 or 182-190, wherein: R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4 alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from the group consisting of halogen and1--4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms. Embodiment 200. The use of Embodiment 199, whe trheein compound of Formula (I) is a compound having Formula (VIII s),ee Embodiment 32, or a pharmaceutically acceptabltle sa or solvate thereof. Embodiment 201. The use of Embodiment 199, whe trheein compound of Formula (I) is a compound having Formula (IX s)e,e Embodiment 33, or a pharmaceutically acceptabltle or sa solvate thereof. Embodiment 202. The use of any one of Embodime9n9ts-2101, wherein R6 and R7,together with the adjacent carbon atoms to whicehy t ahre attached, form a 5- or 6-membered ringhaving at least one heteroatom, wherein the ring op itsionally substituted by one or more substituents selected from the group consistin hga olofgen, -CN, -C(=O)-1C-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substituted by 21 o,r 3 fluorine atoms. Embodiment 203. The use of Embodiment 202, whe Rre6iannd R7, together with theadjacent carbon atoms to which they are attachoermd, a f 5-membered ring having at least onenitrogen atom, wherein the ring is optionally suitbustetd by one or more substituents selected from the group consisting of halogen, -CN, -C(=O1)--4C alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atoms. Embodiment 204. The use of Embodiment 203, whe trheein 5-membered ring has one nitrogen atom. Embodiment 205. The use of Embodiment 203, whe threein 5-membered ring has two nitrogen atoms. Embodiment 206. The use of Embodiment 203, whe Rre6iannd R7, together with theadjacent carbon atoms to which they are attachoermd, a f ring selected from the group consistingof: wherein is a single bond or a double bond, and wherexin a Rnd Ryare each independently selected from the group consistin hgy odfrogen, halogen, -CN, -C(=O)1--C4 alkyl, and -C1-4alkyl, wherein said alkyl is optionally substitut beyd 1, 2 or 3 fluorine atoms, and wherein Rxand Ryeach take the place of a hydrogen atom that wotuhledrw oise be present in any position on the ring to which Rxand Ryare attached. Embodiment 207. The use of any one of Embodime6n9ts-1174, 182-190, 199-204, or206, wherein R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, forma ring selected from the group consisting of: wherein is a single bond or a double bond. Embodiment 208. The use of any one of Embodime6n9ts, 170, or 182-190, wherein the compound of Formula (I) is a compound havingrm Fuola (X,) see Embodiment 34, or a pharmaceutically acceptable salt or solvate the.reof Embodiment 209. The use of any one of Embodime6n9ts-2107, wherein A2is N; and A3 and A4 are CH. Embodiment 210. The use of any one of Embodime6n9ts-2107, wherein A2 and A4 are CH; and A3is N. Embodiment 211. The use of any one of Embodime6n9ts-2107, wherein A2 and A3 are CH; and A4 is N. Embodiment 212. The use of any one of Embodime6n9ts-2107, wherein A2, A3, and A4 are CH. Embodiment 213. The use of Embodiment 169, whe trheein compound of Formula (I) is any one or more of the compounds of Table 1. Embodiment 214. The use of any one of Embodime6n9ts-2113, wherein the disease, condition, or disorder is associated with the alttieorn of the activity of β-glucocerebrosidase (GBA). Embodiment 215. The use of any one of Embodime6n9ts-2113, wherein the disease, condition, or disorder is a lysosomal storage dsies.ea Embodiment 216. The use of Embodiment 215 wherheein ly tsosomal storage disease is Gaucher's disease. Embodiment 217. The use of any one of Embodime6n9ts-2113, wherein the disease, condition or disorder is a αn-synucleinopathy. Embodiment 218. The use of Embodiment 217, whe trheein α-synucleinopathy is Parkinson’s disease. Embodiment 219. The use of any one of Embodime6n9ts-2113, wherein the disease, condition or disorder is a tauopathy. Embodiment 220. The use of Embodiment 219, whe trheein tauopathy is Alzheimer’s disease. Embodiment 221. The use of any one of Embodime6n9ts-2113, wherein the disease, condition, or disorder is selected from the grouopns cisting of: Gaucher's disease, Parkinson's disease, dementia with Lewy bodies, diffuse Lewdyy b doisease, multiple system atrophy (MSA), epilepsy, bipolar disorder, schizophrenia, an atnyx dieisorder, major depression, polycystic kidney disease, type 2 diabetes, open angle glaucoma,ip mleu sltclerosis (MS), multiple myeloma, Alzheimer's disease, non-Alzheimer’s tauopathieicsk (’sP complex), amyotrophic lateral sclerosis (ALS), corticobasal degeneration, frontotemporable lo dementia, GBA1 Parkinson, neuronopathic Gaucher's disease, neuroaxonal dystrophy, neurnoedreagteive diseases with parkinsonism, progressive supranuclear palsy, pure autonomiucre fa,il sporadic Creutzfeldt-Jakob disease, and unimpaired aging. Embodiment 222. The use of any one of Embodime6n9ts-2121 further comprisingadministering to the patient at least one otherra tphe utic agent.Embodiment 223. The use of Embodiment 222, whe trheein therapeutic agent is aneffective amount of an enzyme for enzyme replacetm then rapy.Embodiment 224. The use of Embodiment 223, wher tehine enzyme is β-glucocerebrosidase or an analog thereof. Embodiment 225. The use of Embodiment 223, whe threein enzyme is imiglucerase. Embodiment 226. The use of Embodiment 222, whe trheein therapeutic agent is an effective amount of a small molecule chaperone. Embodiment 227. The use of Embodiment 226, whe threein small molecule chaperone binds competitively to an enzyme. Embodiment 228. The use of Embodiments 226 or 2 w2h7e,rein the small molecule chaperone is selected from the group consisting im oinfoalditols, iminosugars, aminosugars,thiophenylglycosides, glycosidase, sulfatase, gsly lco transferase, phosphatase, and peptidaseinhibitors. Embodiment 229. The use of Embodiment 227, whe threein small molecule chaperone is selected from the group consisting of isofagoem, i Nn-nonyl-1-deoxynojirimycin (NN-DNJ), ambroxol, and miglustat. The following examples are illustrative, but nomti ltiing, of the compounds, compositions and methods of the present disclosure. Suitableifi mcaotdions and adaptations of the variety of conditions and parameters normally encountereldin iinca cl therapy, and which are obvious to those skilled in the art in view of this disclosure areith win the spirit and scope of the disclosure. EXAMPLES General experimental conditions Hereinafter, the term "h" means hours, "eq" meaqnusiv ealents, "min" means minutes, “CV” means column volume, "RT" means room temperature, "HPL mCe"ans high-performance liquid chromatography, "UPLC" mean Usltra Performance Liquid Chromatograp,h "yLC-MS" means liquid chromatography–mass spectrometry, "DMSO- md6e"ans deuterated dimethyl sulfoxide, "DCM" means dichloromethane, "ACN" means acetolnei,tri "THF" means tetrahydrofuran, "EtOAc" means ethyl acetate, "DMF" means N,N-dimyelfothrmamide, "Pd(OAc2)" means palladium(II) acetate, "BINAP" mean 2s,2′-bis(diphenylphosphino)-1′,-1binaphthyl, "XPhos" means 2-dicyclohexylphosphino′,-42′,6′-triisopropylbiphenyl, "Pd2(dba)3" means tris(dibenzylideneacetone)dipalladium,(0) "dppf" means 1,′1-ferrocenediyl- bis(diphenylphosphine), "tBuXPhos Pd G3" means d [i(-2te-rt-butylphosphino-′2,4′,6′- triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)] palladium(II) methanesulfonate, "AcOH" means acetic acid, "Xantphos" means 4,5-Bis(diplhpehnoysphino)-9,9-dimethylxanthene, "tBuBrettPhos Pd G3" means [(2-Dtei-rt-butylphosphino-3,6-dimethoxy′-,24′,6′-triisopropyl-1,1′- biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate, and "R mt"eans retention time. The compound IUPAC names given herein were gender waite h ChemBioDraw 20.11.HNMR spectra were recorded on a Bruker (400 MHz0 o0r M 5Hz) or Variant (300 MHz or 400 MHz). LC-MS analysis of the compounds was conductedr a osn pee of the following methods: Method Description Column: Acquity UPLC BEH C18 (50 mm x 2.1 mm, 1.m7) µ Mobile Phase: A: 50 mM ammonium formiate solutioHn 4 p with HCOOH, B: A water, C: ACN Gradient: A:B:C 0.3 min in 5:85:10 + from 5:85:1o05 t:10:85 in 1.7 min + 3.0 min in 5:10:85 Method Description Column Temp: 35 °C Flow rate: 0.50 mL / min Column: HPLC-MS Waters Alliance HT 2795 Luna C180 ( m5m x 2.0 mm, 5 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN B Gradient: A:B:C 0.3 min in 5:85:10 + from 5:85:1o05 t:10:85 in 1.7 min + 3.0 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Column: HPLC-MS Waters Alliance HT 2795 SunFire8 C (100 mm x 2.1 mm,3.5 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN C Gradient: A:B:C 3 min in 5:85:10 + 5:85:10 to 5:8150: in 9 min + 8 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Column: HPLC Agilent 1200 Binary Pump with Agile 1n1t00 DAD XBridge C18 (4.6 x 150 mm, 3.5 µm) Mobile Phase: A: 5 mM ammonium acetate buffer p0H w 9i.th NH4OH, B: ACN D Gradient: A:B 3 min in 90:10 + from 90:10 to 15: i8n59 min + 8 min in 15:85 Column Temp: 40 °C Flow rate: 1.2 mL / min Column: HPLC-MS Waters Alliance HT 2795 SunFire C (1080 mm x 2.1 mm,3.5 µm) Mobile Phase: A: 50 mM ammonium acetate buffer p,H B: 7 water, C: ACN E Gradient: A:B:C 3 min in 5:85:10 + 5:85:10 to 5:8150: in 9 min + 8 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Method Description Column: Agilent UHPLC 1290 Infinity ZORBAX Extend-1C8 RRHD (50 mm x 2.1 mm, 1.8 µm) Mobile Phase: A: 50 mM ammonium bicarbonate buf Bfe:r A, CN F Gradient: A:B 0.3 min in 98:2 + from 98:2 to 0:1 i0n02.65 min + 2.05 min in 0:100 Column Temp: 35 ºC Flow rate: 0.61 mL / min Column: HPLC Agilent 1200 Binary Pump with Agile 1n1t00 DAD Luna C18 (50 mm x 2.0 mm, 5 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN G Gradient: A:B:C 0.3 min in 5:85:10 + from 5:85:1o05 t:10:85 in 1.7 min + 3.0 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Column: HPLC-MS Waters Alliance HT 2795 Poroshe2l0l 1 CS-C18 (50 mm x 2.0 mm, 5 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN H Gradient: A:B:C 0.3 min in 5:85:10 + from 5:85: t1o05:10:85 in 1.7 min + 3.0 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Column: HPLC-MS Waters Alliance HT 2795 SunFire C (1080 mm x 2.1 mm,3.5 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN I Gradient: A:B:C 3 min in 5:55:40 + 5:55:40 to 5:7250: in 9 min + 8 min in 5:20:75 Column Temp: 40 ºC Flow rate: 0.50 mL / min Method Description Column: HPLC-MS Waters Alliance HT 2795 Kinetex C (1850 mm x 2.1 mm,5 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN J Gradient: A:B:C 3 min in 5:85:10 + 5:85:10 to 5:8150: in 9 min + 8 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Column: HPLC-MS Waters Alliance HT 2795 SunFire C (1080 mm x 2.1 mm,3.5 µm) Mobile Phase: A: ACN / MeOH (50:50), B: 100 mM ammuomni acetate solution, C: water K Gradient: A:B:C 5 min in 10:5:85 + from 10:5:859 to5:5:0 in 15 min + 10 min in 95:5:0 Column Temp: 35 ºC Flow rate: 0.30 mL / min Column: HPLC-MS Waters Alliance HT 2795 InfinityLa Pboroshell 120 CS- C18 (50 mm x 2.1 mm, 2.7 µm) Mobile Phase: A: 50 mM ammonium formate buffer pH wi 4th HCOOH, B: water, C: ACN L Gradient: A:B:C 0.5 min in 5:85:10 + from 5:85:1o05 t:10:85 in 4.5 min + 4.0 min in 5:10:85 Column Temp: 40 ºC Flow rate: 0.50 mL / min Column: HPLC-MS Waters Alliance HT 2795 Poroshe2l0l 1 CS-C18 (50 mm x 2.0 mm, 5 µm) Mobile Phase: A: 50 mM ammonium formate solutioHn 4 p with HCOOH, B: water, C: ACN M Gradient: A:B:C 0.3 min in 5:90:5 + from 5:90:55 t:o20:75 in 1.7 min + 3.0 min in 5:20:75 Column Temp: 40 °C Flow rate: 0.50 mL / min Method Description Column: Acquity HSS-T3 (2.1 x 100 mm, 1 μ.8m) Mobile Phase: A: 0.1% Trifluoroacetic Acid in Wra,te B: ACN Gradient: A:B 1.0 min in 90:10 + from 90:10 to 85: i1n 1.0 min + from 85:15 N to 45:55 in 2.5 min + from 45:55 to 10:90 in 1.5n m +i 2.0 min in 10:90 + from 10:90 to 90:10 in 1.0 min + 1.0 min in 10:90. Column Temp: 35 °C Flow rate: 0.30 mL / min General Procedure A To a cooled solution (0 ºC) of the appropriate ar tyrilchloride (ex: 2,4,6- trichloropyrimidine-5-carbaldehyde) (1.0 eq) in TH (4F3 mL / mmol) was added phenylhydrazine (1.05 eq). The resulting mixture was allowed toch rea RT and stirred for 1 h. Volatiles were removed under reduced pressure and the crude ptro wdausc purified by flash column chromatography (Silica gel, hexane / EtOAc to obt haein desired product (ex: 2,4,6-trichloro-5-((2- phenylhydrazineylidene)methyl)pyrimidine). The following intermediates (Int.) were preparedco arcding to the general procedure A: Characterization and Int.# Structure and name procedure Yellow solid. Yield: (1.410 g, 50%). +1LC-MS [M+H] : 302.1, Rt = 2,4,6-trichloro-5-((2- 3.68 min (Method-B). phenylhydrazineylidene)methyl)pyrimidine Yellow-orange solid. Yield: (1.910 g, 92%). 2 LC-MS [M+H]+: 300.0 / 301.9, Rt = 3.86 min (Method-B). (E)-2,4,6-trichloro-3-((2- phenylhydrazineylidene)methyl)pyridine General Procedure B A solution of aryl phenylhydrazineylidene)methyl)pyrimidine) (1.0 e inq) ACN (2 mL / mmol) was stirred in a sealed tube at 130 ºC for 16 h or under microwave irraiodniat at 150 ºC for 11 h. The solvents were removed under reduced pressure to obtain the de psirroeduct (ex: 4,6-dichloro-1-phenyHl-1- pyrazolo[3,4d-]pyrimidine), which was purified by flash columnr cohmatography (Silica gel, hexane / EtOAc) or used in the next step withouth feurrt purification. The following intermediates (Int.) were preparedco arcding to the general procedure B: Characterization and Int.# Structure and name procedure Brown solid. Yield: (1.120 g, 98%). LC-MS [M+H]+: does 3 not ionize, Rt = 3.662 min (Method-B). 4,6-dichloro-1-phenyl-H1-pyrazolo[3,4d-]pyrimidine Pale Yellow solid. Yield: (0.840 g, 28%). LC-MS+4 [M+H] : 264.0 / 265.9, Rt = 5.17 min (Method-A). 4,6-dichloro-1-phenyl-H1-pyrazolo[3,4b-]pyridine Intermediate 5: 4,6-dichloro-1-o(-tolyl)-1H-pyrazolo[3,4d-]pyrimidine To a solution of o-tolylhydrazine hydrochloride (0.247 g, 1.56 mm 1o.l1, eq) in 20 mL of THF was added triethylamine (0.217 mL, 1.56 mmo.1l, e 1q). The solution was stirred at 0 ºC for 1 h. The mixture was then filtered to remove thlets s aand the filtrate was added dropwise to an ice-cold solution of 2,4,6-trichloropyrimidine-5-rcbaaldehyde (0.300 g, 1.42 mmol, 1.0 eq) in 40 mL of THF and the solution was stirred at 0 ºC 3 fo hr. The volatiles were removed under reduced pressure and the resulting crude was purified baysh fl column chromatography (Silica, hexane / EtOAc 0-30%) afforded 4,6-dichloro-o1-t-o(lyl)-1H-pyrazolo[3,4d-]pyrimidine as a yellow solid. Yield: (0.058 g, 15%). LC-MS [M+H+]: 279.1 / 281.0, Rt = 3.14 min (Method-H). Intermediate 6: 4,6-dichloro-1-(4-methoxyphenyl)H-1-pyrazolo[3,4d-]pyrimidine A solution of 1-(4-methoxyphenyl)-1,7-dihydroH-4-pyrazolo[3,4d-]pyrimidine-4,6(5H)- dione (0.240 g, 0.93 mmol, 1.0 eq) in 1 mL of doicrholphosphoryloxybenzene was stirred at 170 °C for 16 h. The mixture was then basified until = pH 8 with a solution of NaOH 3 M, and the brown precipitate formed was filtered and washetdh wi ater. Purification of the crude product by flash columhnro cmatography (Silica gel, hexane / EtOAc, 0- 20%) afforded 4,6-dichloro-1-(4-methoxyphenyHl)--1pyrazolo[3,4d-]pyrimidine as a white solid. Yield: (0.100 g, 36%). LC-MS [M+H+]: 296.3, Rt = 3.40 min (Method-H). General Procedure C Aqueous NH3 (200 equiv) or the appropriate amin (e x. methylamine) (2.0 eq) was addedto a solution of the appropriate aryl dichloridex. (e 4,6-dichloro-1-phenyl-H1-pyrazolo[3,4- d]pyrimidine) (1.0 eq) in dioxane or THF or EtOH ( m10L / mmol). The solution was stirred at 100 °C for 3 h or RT for 16 h or under microwave irratdioin at 100 °C for 4 h. The volatiles were removed under reduced pressnudre th ae resulting crude was purified by column chromatography on silica gel (DCM / MeOH orxa hnee / EtOAc) to obtain the desired aryl chloride intermediate (ex: 6-chloro-1-phenyHl--1pyrazolo[3,4d-]pyrimidin-4-amine). The following intermediates (Int.) were preparedco arcding to the general procedure C: Characterization and Int.# Structure and name procedure Pale yellow solid. Yield: (0.556 g, quantitative 7 yield). LC-MS [M+H]+: 245.9, Rt = 6-chloro-1-phenyl-1H-pyrazolo[3,4- 3.07 min (Method-B). d]pyrimidin-4-amine Yellow solid. Yield: (0.802 g, 82%). 8 LC-MS [M+H]+: 360.1 / 261.8, Rt = 3.34 min (Method-B). 6-chloro-N-methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine White solid. Yield: (0.200 g, 93%). LC-MS [M+H]+: 286.0 / 288.0, Rt = 3.47 min (Method-B). 9 6-chloro-N-cyclopropyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine White solid. Yield: (0.097 g, 40%). 10 LC-MS [M+H]+: 318.3 / 319.9, Rt = 3.31 min (Method-B). 1-((6-chloro-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-4-yl)amino)-2-methylpropan-2-ol White solid. Yield: (0.200 g, 87%). 11 LC-MS [M+H]+: 304.2, Rt = 3.41 min (Method-B). 6-chloro-N-(2-methoxyethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-4-amine Pale brown solid. Yield: (0.133 g, quantitative 12 yield) LC-MS [M+H]+: 274, Rt = 2.24 6-chloro-N,N-dimethyl-1-phenyl-1H- min (Method-F). pyrazolo[3,4d-]pyrimidin-4-amine Characterization and Int.# Structure and name procedure White solid. Yield: (0.216 g, 60%). LC-MS [M+H]+: 359.3 / 360.9, Rt = 2.78 min (Method-B). 13 6-chloro-N-(2-morpholinoethyl)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin-4-amine Off-white solid. Yield: (0.080 g, 92%). LC-MS [M+H]+: 289.9 / 291.9, Rt = 3.07 min (Method-B). 142-((6-chloro-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol Off-white solid. Yield: (0.283 g, 85%). LC-MS [M+H]+: 354.2 / 356.0, Rt = 4.26 min (Method-B). 15 6-chloro-N-(2-(cyclohex-1-en-1-yl)ethyl)-1- phenyl-1H-pyrazolo[3,4d-]pyrimidin-4-amine Yellow solid. Yield: (0.228 g, 90%). LC-MS [M+H]+: 356.3 / 358.0, Rt = 4.55 min (Method-B). 16 6-chloro-N-(2-cyclohexylethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-4-amine Off-white solid. Yield: (0.227 g, 76%). LC-MS [M+H]+: 316.1 / 318.0, Rt = 4.00 min (Method-B). 17 6-chloro-N-isopentyl-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-4-amine Brown solid. Yield: (0.227 g, 76%). 18 LC-MS [M+H]+: 302.3 / 304.0, Rt = 3.51 min (Method-H). Characterization and Int.# Structure and name procedure 6-chloro-N-isobutyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine Pale-yellow solid. Yield: (0.275 g, 53%). 19 LC-MS [M+H]+: 274.3 / 275.9, Rt = 3.23 min (Method-H). 6-chloro-N-ethyl-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-4-amine Yellow solid. Yield: (0.550 g, 89%). 20 LC-MS [M+H]+: 328.0 / 329.9, Rt = 3.35 min (Method-H). 6-chloro-1-phenylN--(2,2,2-trifluoroethyl)- 1H-pyrazolo[3,4d-]pyrimidin-4-amine Brownish oil. Yield: (0.300 g, 55%). 21 LC-MS [M+H]+: 288.2 / 290.0, Rt = 3.38 min (Method-H). 6-chloro-N-isopropyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine White solid. Yield: (0.510 g, 80%). 22 LC-MS [M+H]+: 259.1 / 260.9, Rt = 3.22 min (Method-H). 6-chloro-N-methyl-1-phenyl-1H- pyrazolo[3,4b-]pyridin-4-amine Off-white solid. Yield: (0.050 g, 93%). 23 LC-MS [M+H]+: 274.3, Rt = 2.69 min (Method-H). 6-chloro-N-methyl-1-(o-tolyl)-1H- pyrazolo[3,4d-]pyrimidin-4-amine Yellow solid. Yield: (0.490 g, 84%). LC-MS [M+H]+: 310.0 / 312.0, 24 Rt = 3.27 min (Method-H). Characterization and Int.# Structure and name procedure 6-chloro-N-(2,2-difluoroethyl)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-4-amine Triethylamine (2.5 eq) was added to the reaction mixture. Yellow solid. 25 Yield: (0.460 g, 84%). LC-MS [M+H]+: 292.1 / 294.0, Rt = 3.19 min (Method-H). 6-chloro-N-(2-fluoroethyl)-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine White solid. Yield: (0.080 g, 81%). LC-MS [M+H]+: 290.1 / 291.9, 26 Rt = 3.07 min (Method-H). 6-chloro-1-(4-methoxyphenylN)--methyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine Triethylamine (2.5 eq) was added to the reaction mixture. Yellow wax. Yield: (0.250 g, 39%). LC-MS [M+H]+: 342.0, Rt = 533.49 min (Method-H). (R)-6-chloro-1-phenylN--(1,1,1- trifluoropropan-2-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-amine Triethylamine (2.5 eq) was added to the reaction mixture. Yellow oil. Yield: (0.250 g, 54 39%). LC-MS [M+H]+: 342.0, Rt = 3.48 min (Method-H). (S)-6-chloro-1-phenylN--(1,1,1- trifluoropropan-2-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-amine Triethylamine (2.5 eq) was added to the reaction mixture. White solid. Yield: (0.215 g, 55 67%). LC-MS [M+H]+: 342.0 / 343.9, 6-chloro-1-phenylN--(3,3,3-trifluoropropyl)- Rt = 3.48 min (Method-H). 1H-pyrazolo[3,4d-]pyrimidin-4-amine Characterization and Int.# Structure and name procedure Triethylamine (2.5 eq) was added to the reaction mixture. White solid. Yield: (0.250 g, 56 69%). LC-MS [M+H]+: 320.1 / 321.7, 6-chloro-N-(2-fluoro-2-methylpropyl)-1- Rt = 3.41 min (Method-H). phenyl-1H-pyrazolo[3,4d-]pyrimidin-4-amine Yellow solid. Yield: (0.608 g, 77%). LC-MS [M+H]+: 350.0 / 351.9, 57 Rt = 3.60 min (Method-H). N-benzyl-6-chloroN--methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidin-4-amine Pale yellow solid. Yield: (1.000 g, 70%). LC-MS [M+H]+: 380.0, Rt = 58 3.57 min (Method-H). 6-chloro-N-(4-methoxybenzyl)N--methyl-1- phenyl-1H-pyrazolo[3,4d-]pyrimidin-4-amine N,N-diisopropylethylamine (1.2 eq) was added to the reaction mixture and DMSO 59 was used as a solvent. Orange solid. Yield: (0.116 g, 24%). 6-chloro-1-phenylN--(2,2,2-trifluoroethyl)-1H- LC-MS [M+H]+: 326.9 / 328.8, pyrazolo[3,4b-]pyridin-4-amine Rt = 3.39 min (Method-H). N,N-diisopropylethylamine (1.2 eq) was added to the reaction mixture and DMSO 60 was used as a solvent. Brown oil. Yield: (0.096 g, 6-chloro-N-(2,2-difluoroethyl)-1-phenyl-1H- 47%). pyrazolo[3,4-b]pyridin-4-amine LC-MS [M+H]+: 391.2, Rt = 3.30 min (Method-H). White solid. Yield: (0.090 g, 66%). LC-MS [M+H]+: 274.0, Rt = 61 3.24 min (Method-H). 6-chloro-N,3-dimethyl-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-4-amine Characterization and Int.# Structure and name procedure O Off-white solid. Yield: (0.303 g, 82%). N LC-MS [M+H]+: 327.9 / 329.8, N N Rt = 3.18 min (Method-H). N 62 ClN6-(6-chloro-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-4-yl)-2-oxa-6- azaspiro[3.3]heptane General Procedure D To a solution of the appropriate aryl chloride (e 6x-c:hloro-1-phenyl-H1-pyrazolo[3,4- d]pyrimidin-4-amine) (1.0 eq) and the correspond ainmgine (ex: 3-aminobenzotrifluoride) (1.5 eq) in 1-butanol (4.0 mL / mmol) was added2S HO4 (conc) (4.9 eq). The solution was stirred at 1C20 ° for 4 h. The reaction mixture was quenched withe aoquus NaHCO3 solution (15 mL), the organic product was extracted with EtOAc (3 x 15 mL). Thoem cbined organic extracts were washed with water (15 mL) and brine (15 mL). The resulting onrigca layer was dried over anhydrous2NSaO4, filtered and volatiles were removed under reducreedss pure. The crude product was purified by flash column chromatography (Silica gel, hexane / AEctO or DCM / MeOH with 2% of NH3) or semi-preparative HPLC (10 mM N4H CO3(pH 7 with HCOOH) / ACN) or reverse phase flash column chromatography (C18, 10 mM aqueous4O NAHc (pH 7) / ACN) followed by a strong cation exchange (SCX) column, which was washed w3it ChVs of MeOH and the product was eluted with 3 CVs of NH3 / MeOH (3.5 N), to obtain the desired product (e-pxh:1enyl-N6-(3- (trifluoromethyl)phenyl)-1H-pyrazolo[3,4d-]pyrimidine) . The following Examples (Ex.) were prepared accogrd toin the general procedure D: Ex. # Structure and name Characterization and procedure Pale brown solid. Yield (:0.032 g, 35%). LC- MS [M+H]+: 371.0, Rt = 11.47 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.59 (s, 1H), 8.54 (s, 1H), 8.26 – 8.16 (m, 3H), 1 1-phenyl-N6-(3- 7.89 (d, J = 8.3 Hz, 1H), 7.58 – 7.45 (m, 3H), (trifluoromethyl)phenyl)-1H- 7.32 (tt, J = 7.1, 1.2 Hz, 1H), 7.25 (d, J = 7.7 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 1H). diamine Pale brown solid. Yield: (0.066 g, 42%). LC- MS [M+H]+: 319.1, Rt = 9.59 min (Method- C).1H NMR (500 MHz, DMSO-d6 δ,): 10.05 (s, 1H), 8.22 – 8.14 (m, 4H), 7.88 (s, 1H), 2 7.56 – 7.49 (m, 2H), 7.34 – 7.27 (m, 1H), 2-((4-amino-1-phenyl-H1- 6.90 – 6.78 (m, 3H). pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenol Off-white powder.Yield: (0.065 g, 47%). LC-MS [M+H]+: 339.2, Rt = 11.33 min (Method-C).1H NMR (400 MHz, DMSO-d6, 3 δ): 9.65 (d, J = 3.9 Hz, 1H), 8.22 (d, J = 4.2 6 Hz, 1H), 8.20 – 8.11 (m, 2H), 7.72 – 7.62 (m, N -(3,5-difluorophenyl)-1-phenyl- 2H), 7.58 – 7.47 (m, 2H), 7.38 – 7.29 (m, 1H-pyrazolo[3,4d-]pyrimidine- 1H), 6.74 – 6.64 (m, 1H). 4,6-diamine Off-white powder.Yield: (0.052 g, 40%). LC-MS [M+H]+: 321.4, Rt = 10.86 min (Method-C).1H NMR (400 MHz, DMSO-d6, 4 δ): 9.46 (s, 1H), 8.25 – 8.16 (m, 3H), 8.06 – N6-(3-fluorophenyl)-1-phenyl-H1- 7.98 (m, 1H), 7.57 – 7.48 (m, 3H), 7.36 – pyrazolo[3,4d-]pyrimidine-4,6- 7.23 (m, 2H), 6.76 – 6.67 (m, 1H). diamine Pale brown solid. Yield: (0.036 g, 46%). LC- MS [M+H]+: 319.2, Rt = 8.97 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.17 (s, 1H), 9.07 (s, 1H), 8.29 – 8.22 (m, 2H), 5 8.20 – 8.14 (m, 1H), 7.55 – 7.47 (m, 2H), 3-((4-amino-1-phenyl-H1- 7.35 – 7.23 (m, 3H), 7.04 (td, J = 8.1, 1.5 Hz, pyrazolo[3,4d-]pyrimidin-6- 1H), 6.40 – 6.34 (m, 1H). yl)amino)phenol Ex. # Structure and name Characterization and procedure Brown + solid. Yield: (0.026 g, 32%). LC-MS [M+H] : 333.4, Rt = 10.35 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.55 (s, 1H), 8.54 (s, 1H), 8.20 – 8.16 (m, 1H), 8.16 6 – 8.10 (m, 2H), 7.57 – 7.47 (m, 3H), 7.35 – 2-((4-amino-1-phenyl-H1- 7.27 (m, 1H), 6.88 – 6.82 (m, 1H), 6.74 (t, J pyrazolo[3,4d-]pyrimidin-6- = 7.7 Hz, 1H), 2.22 (s, 3H). yl)amino)-6-methylphenol White + solid. Yield: (0.019 g, 23%). LC-MS [M+H] : 337, Rt = 12.12 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.44 (s, 1H), 8.28 (t, J = 2.1 Hz, 1H), 8.22 – 8.16 (m, 7 N6-(3-chlorophenyl)-1-phenyl- 3H), 7.60 – 7.48 (m, 3H), 7.35 – 7.21 (m, 1H-pyrazolo[3,4d-]pyrimidine- 2H), 6.97 – 6.91 (m, 1H). 4,6-diamine Pale grey solid. Yield: (0.026 g, 32%). LC- MS [M+H]+: 337, Rt = 10.81 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 10.53 (s, 1H), 8.20 – 8.13 (m, 3H), 8.02 (dd, J = 8.8, 6.5 Hz, 1H), 7.66 (s, 1H), 7.56 – 7.48 (m, 8 2-((4-amino-1-phenyl-H1- 2H), 7.34 – 7.26 (m, 1H), 6.71 – 6.62 (m, pyrazolo[3,4d-]pyrimidin-6- 2H). yl)amino)-5-fluorophenol Pale brown solid. Yield: (0.031 g, 35%). LC- MS [M+H]+: 361, Rt = 12.84 min (Method- D).1H NMR (400 MHz, DMSO-d6 δ,): 8.56 – 8.51 (m, 1H), 8.22 – 8.16 (m, 3H), 7.70 (s, 2H), 7.61 – 7.51 (m, 3H), 7.35 – 7.28 (m, 9 N6-(2-isopropoxyphenyl)-1- 1H), 7.08 – 7.02 (m, 1H), 6.99 – 6.91 (m, phenyl-1H-pyrazolo[3,4- 2H), 4.74 – 4.61 (m, 1H), 1.33 (d, J = 6.0 Hz, d]pyrimidine-4,6-diamine 6H). Off-white solid. Yield: (0.036 g, 42%). LC- MS [M+H]+: 347.2, Rt = 10.22 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 8.53 (s, 1H), 8.25 – 8.20 (m, 2H), 8.15 (s, 1H), 10 7.50 – 7.40 (m, 2H), 7.28 – 7.17 (m, 2H), N6-(benzo[d][1,3]dioxol-4-yl)-1- 6.81 (t, J = 8.0 Hz, 1H), 6.70 (dd, J = 7.8, 1.2 phenyl-1H-pyrazolo[3,4- Hz, 1H), 5.99 (s, 2H). d]pyrimidine-4,6-diamine Brown + solid. Yield: (0.020 g, 23%). LC-MS [M+H] : 353.0 / 354.9, Rt = 10.58 min(Method-C).1H NMR (400 MHz, DMSO-d6, 11 δ): 10.61 (s, 1H), 8.26 – 8.10 (m, 4H), 7.84 (s, 1H), 7.60 – 7.50 (m, 2H), 7.36 – 7.26 (m, 1H), 6.91 – 6.83 (m, 2H). Ex. # Structure and name Characterization and procedure 2-((4-amino-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)-5-chlorophenol Off-wh +ite solid.Yield: (0.007 g, 9%). LC-MS [M+H] : 337.0, Rt = 9.90 min (Method-C).1H NMR (400 MHz, DMSO-d6 δ,): 10.54 (s, 1H), 8.36 (s, 1H), 8.20 (s, 1H), 8.16 (d, J = 12 2-((4-amino-1-phenyl-H1- 7.4 Hz, 2H), 7.79 (d, J = 8.1 Hz, 1H), 7.56 – pyrazolo[3,4d-]pyrimidin-6- 7.48 (m, 2H), 7.34 – 7.28 (m, 1H), 6.88 – yl)amino)-6-fluorophenol 6.73 (m, 2H). Pale brown solid. Yield: (0.017 g, 12%). LC- MS [M+H]+: 337.1, Rt = 9.81 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.76 (s, 1H), 8.15 (d, J = 8.1 Hz, 2H), 8.12 (s, 1H), 13 8.09 (s, 1H), 7.45 – 7.37 (m, 2H), 7.25 – 7.18 2-((4-amino-1-phenyl-H1- (m, 1H), 7.11 – 7.01 (m, 1H), 6.76 – 6.66 (m, pyrazolo[3,4d-]pyrimidin-6- 2H). yl)amino)-3-fluorophenol Pale yellow solid. Yield: (0.018 g, 22%).LC- MS [M+H]+: 342.0, Rt = 10.30 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 11.01 (s, 1H), 8.88 (s, 1H), 8.22 – 8.11 (m, 3H), 6 7.74 (d, J = 7.6 Hz, 1H), 7.41 (t, J = 7.9 Hz, 14 N -(1H-indol-7-yl)-1-phenyl-1H- 2H), 7.32 – 7.18 (m, 3H), 6.97 (t, J = 7.7 Hz, pyrazolo[3,4d-]pyrimidine-4,6- 1H), 6.49 – 6.40 (m, 1H). diamine Brown solid. Yield: (0.008 g, 10%).LC-MS [M+H] +: 333.0, Rt = 10.10 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.93 (s, 1H), 8.20 – 8.15 (m, 3H), 7.97 (d, J = 8.1 Hz, 15 1H), 7.84 (s, 1H), 7.56 – 7.49 (m, 2H), 7.33 2-((4-amino-1-phenyl-H1- – 7.26 (m, 1H), 6.70 – 6.67 (m, 1H), 6.65 – pyrazolo[3,4d-]pyrimidin-6- 6.61 (m, 1H), 2.21 (s, 3H). yl)amino)-5-methylphenol Off-white solid. Yield: (0.015 g, 18%).LC- MS [M+H]+: 345.2, Rt = 10.71 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 8.24 – 8.18 (m, 2H), 8.15 (s, 1H), 7.82 – 7.76 (m, 16 2H), 7.52 – 7.44 (m, 2H), 7.30 – 7.23 (m, N6-(2,3-dihydrobenzofuran-7-yl)- 1H), 6.97 – 6.92 (m, 1H), 6.86 – 6.78 (m, 1-phenyl-1H-pyrazolo[3,4- 1H), 4.57 (t, J = 8.7 Hz, 2H), 3.25 (t, J = 8.7 d]pyrimidine-4,6-diamine Hz, 2H). Ex. # Structure and name Characterization and procedure Brown solid. Yield: (0.025 g, 29%).LC-MS [M+H] +: 349.0, Rt = 9.45 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.56 (s, 1H), 8.21 – 8.14 (m, 3H), 7.97 (d, J = 3.0 Hz, 17 1H), 7.77 (s, 1H), 7.54 – 7.48 (m, 2H), 7.35 2-((4-amino-1-phenyl-H1- – 7.29 (m, 1H), 6.76 (d, J = 8.6 Hz, 1H), 6.41 pyrazolo[3,4d-]pyrimidin-6- (dd, J = 8.7, 3.0 Hz, 1H), 3.69 (s, 3H). yl)amino)-4-methoxyphenol Off-white solid. Yield: (0.063 g, 47%). LC- MS [M+H]+: 333.1, Rt = 11.00 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 8.48 – 8.41 (m, 1H), 8.24 – 8.15 (m, 3H), 7.64 (s, 18 N6-(2-methoxyphenyl)-1-phenyl- 1H), 7.57 – 7.50 (m, 2H), 7.34 – 7.27 (m, 1H-pyrazolo[3,4d-]pyrimidine- 1H), 7.07 – 7.01 (m, 1H), 7.01 – 6.94 (m, 4,6-diamine 2H), 3.88 (s, 3H). Pale-brown solid. Yield: (0.037 g, 45%). LC- MS [M+H]+: 333.4, Rt = 10.32 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.18 (s, 1H), 8.24 – 8.20 (m, 2H), 8.18 (s, 1H), 7.64 (t, J = 2.2 Hz, 1H), 7.54 – 7.48 (m, 2H), 19 N6-(3-methoxyphenyl)-1-phenyl- 7.35 – 7.27 (m, 2H), 7.15 (t, J = 8.1 Hz, 1H), 1H-pyrazolo[3,4d-]pyrimidine- 6.50 (ddd, J = 8.2, 2.5, 0.9 Hz, 1H), 3.73 (s, 4,6-diamine 3H). Grey solid. Yield: (0.053 g, 17%). LC-MS [M+H] +: 375.8, Rt = 10.31 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.24 – 8.18 (m, 2H), 8.12 (s, 1H), 7.94 (d, J = 8.8 20 N6-(4-(dimethylamino)-2- Hz, 1H), 7.55 – 7.46 (m, 3H), 7.31 – 7.24 (m, methoxyphenyl)-1-phenyl-H1- 1H), 6.43 (d, J = 2.6 Hz, 1H), 6.34 (dd, J = pyrazolo[3,4d-]pyrimidine-4,6- 8.8, 2.7 Hz, 1H), 3.84 (s, 3H), 2.89 (s, 6H). diamine Pale brown solid. Yield: (0.013 g, 15%). LC- MS [M+H]+: 343.1, Rt = 8.13 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 12.43 (s, 1H), 8.39 (s, 1H), 8.25 – 8.19 (m, 3H), 21 8.17 (s, 1H), 8.12 (s, 1H), 7.64 – 7.48 (m, N6-(1H-benzo[d]imidazol-7-yl)-1- 4H), 7.30 (t, J = 7.4 Hz, 1H), 7.25 – 7.14 (m, phenyl-1H-pyrazolo[3,4- 2H). d]pyrimidine-4,6-diamine Pale yellow solid. Yield: (0.027 g, 19%). LC- MS [M+H]+: 344.3, Rt = 3.66 min (Method- A).1H NMR (400 MHz, DMSO-d6 δ,): 8.61 (d, J = 8.4 Hz, 1H), 8.23 (s, 1H), 8.16 (d, J = 22 8.0 Hz, 2H), 7.98 (s, 1H), 7.58 (t, J = 7.8 Hz, 2H), 7.37 – 7.26 (m, 2H), 7.14 (s, 1H). Ex. # Structure and name Characterization and procedure 4-((4-amino-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)-3-hydroxybenzonitrile Brown + solid. Yield: (0.058 g, 42%). LC-MS [M+H] : 337.0, Rt = 9.91 min (Method-C).1H NMR (400 MHz, DMSO-d6 δ,): 10.06 (s, 1H), 8.29 (dd, J = 11.8, 3.1 Hz, 1H), 8.21 (s, 1H), 8.16 (d, J = 8.0 Hz, 2H), 7.75 (s, 1H), 23 2-((4-amino-1-phenyl-H1- 7.53 (t, J = 7.8 Hz, 2H), 7.33 (t, J = 7.4 Hz, pyrazolo[3,4d-]pyrimidin-6- 1H), 6.82 (dd, J = 8.8, 5.6 Hz, 1H), 6.62 (td, yl)amino)-4-fluorophenol J = 8.5, 3.1 Hz, 1H). White + solid. Yield: (0.013 g, 17%). LC-MS [M+H] : 321.1, Rt = 10.70 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.52 (s, 1H), 8.21 – 8.11 (m, 3H), 7.92 (td, J = 8.1, 24 N6-(2-fluorophenyl)-1-phenyl-H1- 1.8 Hz, 1H), 7.44 (t, J = 7.9 Hz, 2H), 7.30 – pyrazolo[3,4d-]pyrimidine-4,6- 7.04 (m, 4H). diamine Pale grey solid. Yield: (0.031 g, 23%). LC- MS [M+H]+: 342.0, Rt = 9.60 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 11.02 (s, 1H), 8.67 (s, 1H), 8.26 (d, J = 7.4 Hz, 2H), 25 8.18 (s, 1H), 7.82 (dd, J = 6.9, 1.7 Hz, 1H), N6-(1H-indol-4-yl)-1-phenyl-1H- 7.50 – 7.43 (m, 2H), 7.29 – 7.22 (m, 2H), pyrazolo[3,4d-]pyrimidine-4,6- 7.12 – 7.03 (m, 2H), 6.75 (t, J = 2.7 Hz, 1H). diamine Off-white solid. Yield: (0.039 g, 25%). LC- MS [M+H]+: 387.0, Rt = 11.01 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 10.85 (s, 1H), 8.56 (d, J = 8.5 Hz, 1H), 8.22 (s, 1H), 26 2-((4-amino-1-phenyl-H1- 8.16 (d, J = 8.0 Hz, 2H), 7.92 (s, 1H), 7.57 (t, pyrazolo[3,4d-]pyrimidin-6- J = 7.8 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.18 yl)amino)-5- (d, J = 8.9 Hz, 1H), 7.12 (s, 1H). (trifluoromethyl)phenol Yellowish solid. Yield: (0.015 g, 9%). LC- MS [M+H]+: 387.0, Rt = 11.73 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.56 (s, 1H), 8.24 – 8.10 (m, 4H), 7.74 – 7.64 (m, 27 1-phenyl-N6-(3- 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.41 – 7.28 (m, (trifluoromethoxy)phenyl)-1H- 2H), 6.88 (d, J = 8.1 Hz, 1H). pyrazolo[3,4d-]pyrimidine-4,6- diamine Ex. # Structure and name Characterization and procedure Yellowish solid. Yield: (0.047 g, 32%). LC- MS [M+H]+: 361.2, Rt = 11.28 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.15 (s, 1H), 8.24 – 8.15 (m, 3H), 7.63 – 7.57 (m, 1H), 7.52 (t, J = 7.9 Hz, 2H), 7.35 – 7.27 (m, 28 N6-(3-isopropoxyphenyl)-1- 2H), 7.13 (t, J = 8.1 Hz, 1H), 6.48 (dd, J = phenyl-1H-pyrazolo[3,4- 8.2, 2.4 Hz, 1H), 4.53 (hept, J = 6.0 Hz, 1H), d]pyrimidine-4,6-diamine 1.25 (d, J = 6.0 Hz, 6H). Brown + solid. Yield: (0.048 g, 35%). LC-MS [M+H] : 342.2, Rt = 10.31 min (Method-C).1H NMR (400 MHz, DMSO-d6 δ,): 10.87 (s, 1H), 9.04 (s, 1H), 8.33 – 8.26 (m, 2H), 8.16 (s, 1H), 7.90 (s, 1H), 7.59 – 7.50 (m, 2H), 29 N6-(1H-indol-6-yl)-1-phenyl-1H- 7.42 (d, J = 8.5 Hz, 1H), 7.36 (dd, J = 8.5, 1.8 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 1H), 7.31 – 7.24 (m, 1H), 7.22 (t, J = 2.7 diamine Hz, 1H), 6.34 (t, J = 2.6 Hz, 1H). Pale brown solid. Yield: (0.082 g, 43%). LC- MS [M+H]+: 333.3, Rt = 10.41 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 10.08 (s, 1H), 8.31 – 8.13 (m, 5H), 7.93 (s, 1H), 30 7.53 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 7.4 Hz, 2-((4-(methylamino)-1-phenyl- 1H), 6.92 – 6.78 (m, 3H), 3.01 (d, J = 4.5 Hz, 1H-pyrazolo[3,4d-]pyrimidin-6- 3H). yl)amino)phenol White powder. Yield: (0.025 g, 31%). LC- MS [M+H]+: 347, Rt = 2.43 min (Method-F). 1H NMR (400 MHz, DMSO-d6 δ,): 8.46 (dd, J = 6.0, 3.6 Hz, 1H), 8.24 (d, J = 4.6 Hz, 1H), 31 8.22 – 8.14 (m, 3H), 7.72 (s, 1H), 7.54 (t, J = N6-(2-methoxyphenyl)N-4-methyl- 7.9 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.08 – 1-phenyl-1H-pyrazolo[3,4- 7.02 (m, 1H), 7.01 – 6.96 (m, 2H), 3.89 (s, d]pyrimidine-4,6-diamine 3H), 3.01 (d, J = 4.5 Hz, 3H). Yellow + solid. Yield: (0.101 g, 76%). LC-MS [M+H] : 351.1 / 353.0, Rt = 12.18 min(Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.54 (s, 1H), 8.38 (s, 1H), 8.31 – 8.12 (m, 32 4H), 7.62 – 7.50 (m, 3H), 7.30 (dt, J = 16.2, N6-(3-chlorophenyl)N-4-methyl-1- 7.8 Hz, 2H), 6.97 (dd, J = 7.9, 2.1 Hz, 1H), phenyl-1H-pyrazolo[3,4- 3.04 (d, J = 4.5 Hz, 3H). d]pyrimidine-4,6-diamine Yellow + solid. Yield: (0.101 g, 76%). LC-MS [M+H] : 347.2, Rt = 11.20 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.26 33 (s, 1H), 8.28 – 8.10 (m, 4H), 7.78 – 7.64 (m, 1H), 7.55 – 7.46 (m, 2H), 7.37 – 7.25 (m, Ex. # Structure and name Characterization and procedure N6-(3-methoxyphenyl)N-4-methyl- 2H), 7.16 (t, J = 8.1 Hz, 1H), 6.54 – 6.47 (m, 1-phenyl-1H-pyrazolo[3,4- 1H), 3.74 (s, 3H), 3.04 (d, J = 4.5 Hz, 3H). d]pyrimidine-4,6-diamine Pale yellow solid. Yield: (0.084 g, 54%). LC- MS [M+H]+: 401.1, Rt = 12.63 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.62 (s, 1H), 8.28 (s, 2H), 8.21 – 8.15 (m, 3H), 467.65 (d, J = 8.3 Hz, 1H), 7.55 – 7.48 (m, 2H), 34 N -methyl-1-phenylN- -(3- 7.40 – 7.28 (m, 2H), 6.92 – 6.84 (m, 1H), (trifluoromethoxy)phenyl)-1H- 3.04 (d, J = 4.4 Hz, 3H). pyrazolo[3,4d-]pyrimidine-4,6- diamine White solid. Yield: (0.085 g, 59%). LC-MS [M+H] +: 375.4, Rt = 12.25 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.22 (s, 1H), 8.28 – 8.11 (m, 4H), 7.67 (s, 1H), 7.52 6 (t, J = 7.9 Hz, 2H), 7.37 – 7.26 (m, 2H), 7.13 35 N -(3-isopropoxyphenyl)N-4- (t, J = 8.1 Hz, 1H), 6.48 (dd, J = 8.1, 2.4 Hz, methyl-1-phenyl-1H- 1H), 4.52 (h, J = 6.0 Hz, 1H), 3.04 (d, J = 4.5 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 3H), 1.25 (d, J = 6.0 Hz, 6H). diamine Off-white solid. Yield: (0.044 g, 32%). LC- MS [M+H]+: 356.3, Rt = 11.42 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 11.00 (s, 1H), 8.97 (s, 1H), 8.19 – 8.09 (m, 4H), 7.75 (d, J = 8.0 Hz, 1H), 7.45 – 7.38 (m, 2H), 36 N6-(1H-indol-7-yl)-N4-methyl-1- 7.30 (t, J = 2.8 Hz, 1H), 7.28 – 7.20 (m, 2H), phenyl-1H-pyrazolo[3,4- 6.97 (t, J = 7.7 Hz, 1H), 6.45 (dd, J = 3.0, 1.9 d]pyrimidine-4,6-diamine Hz, 1H), 3.02 (d, J = 4.5 Hz, 3H). Brown solid. Yield: (0.019 g, 14%). LC-MS [M+H] +: 356.1, Rt = 10.70 min (Method-C).1H NMR (400 MHz, DMSO-d6 δ,): 10.90 (s, 1H), 9.13 (s, 1H), 8.33 – 8.27 (m, 2H), 8.15 – 8.03 (m, 3H), 7.58 – 7.51 (m, 2H), 7.41 (d, 6 J = 8.5 Hz, 1H), 7.34 (dd, J = 8.5, 1.8 Hz, 37 N -(1H-indol-6-yl)-N4-methyl-1- 1H), 7.31 – 7.25 (m, 1H), 7.21 (t, J = 2.7 Hz, phenyl-1H-pyrazolo[3,4- 1H), 6.36 – 6.32 (m, 1H), 3.06 (d, J = 4.5 Hz, d]pyrimidine-4,6-diamine 3H). Pale brown solid. Yield: (0.063 g, 51%). LC-MS [M+H]+: 401.2, Rt = 11.67 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 11.05 (s, 1H), 9.29 (s, 1H), 8.51 (d, J 38 = 5.0 Hz, 1H), 8.19 (s, 1H), 8.06 (d, J = 8.0 Hz, 2H), 7.67 – 7.58 (m, 1H), 7.52 – 7.42 2-((4-(methylamino)-1-phenyl- (m, 2H), 7.37 – 7.26 (m, 2H), 6.97 (t, J = 7.9 1H-pyrazolo[3,4d-]pyrimidin-6- Hz, 1H), 3.00 (d, J = 4.6 Hz, 3H). Ex. # Structure and name Characterization and procedure yl)amino)-6- (trifluoromethyl)phenol Brown solid. Yield: (0.022 g, 20%). LC-MS [M+H] +: 363.3, Rt = 10.43 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.33 (s, 1H), 8.25 (d, J = 4.5 Hz, 1H), 8.21 – 8.10 (m, 39 3H), 7.94 – 7.83 (m, 2H), 7.56 – 7.45 (m, 2-methoxy-6-((4-(methylamino)- 2H), 7.29 (t, J = 7.4 Hz, 1H), 6.78 (t, J = 8.2 1-phenyl-1H-pyrazolo[3,4- Hz, 1H), 6.70 – 6.61 (m, 1H), 3.79 (s, 3H), d]pyrimidin-6-yl)amino)phenol 2.99 (d, J = 4.5 Hz, 3H). White + solid. Yield: (0.061 g, 50%). LC-MS [M+H] : 317.5, Rt = 11.35 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.27 (s, 1H), 8.24 (d, J = 8.0 Hz, 2H), 8.21 – 8.13 (m, 40 4 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 7.9 N -methyl-N6,1-diphenyl-1H- Hz, 2H), 7.34 – 7.23 (m, 3H), 6.93 (t, J = 7.3 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 1H), 3.04 (d, J = 4.5 Hz, 3H). diamine Off-white solid. Yield: (0.005 g, 4%). LC- MS [M+H]+: 357.2, Rt = 3.72 min (Method- A).1H NMR (400 MHz, DMSO-d6 δ,): 12.07 (s, 1H), 8.35 (s, 1H), 7.41 – 7.36 (m, 1H), 7.35 (s, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.27 – 41 N6-(1H-indazol-7-yl)-N4-methyl- 7.23 (m, 1H), 7.14 (d, J = 7.5 Hz, 1H), 6.66 – 1-phenyl-1H-pyrazolo[3,4- 6.55 (m, 3H), 6.43 (t, J = 7.4 Hz, 1H), 6.27 d]pyrimidine-4,6-diamine (t, J = 7.7 Hz, 1H), 2.19 (d, J = 4.5 Hz, 3H). Brown + solid. Yield: (0.012 g, 9%). LC-MS [M+H] : 363.3, Rt = 3.82 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 9.60 (s, 1H), 8.34 – 8.24 (m, 1H), 8.22 – 8.14 (m, 3H), 8.09 – 8.02 (m, 1H), 7.82 (s, 1H), 7.51 42 (t, J = 7.8 Hz, 2H), 7.31 (t, J = 7.4 Hz, 1H), 4-methoxy-2-((4-(methylamino)- 6.77 (d, J = 8.6 Hz, 1H), 6.41 (dd, J = 8.6, 3.0 1-phenyl-1H-pyrazolo[3,4- Hz, 1H), 3.69 (s, 3H), 3.02 (d, J = 4.5 Hz, d]pyrimidin-6-yl)amino)phenol 3H). Brown solid. Yield: (0.005 g, 4%). LC-MS [M+H] +: 347.3, Rt = 4.38 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 9.24 (s, 1H), 8.29 – 8.09 (m, 2H), 8.05 (s, 1H), 8.01 43 – 7.85 (m, 1H), 7.46 – 7.26 (m, 2H), 7.22 – 2-(methyl(4-(methylamino)-1- 7.05 (m, 3H), 6.93 (d, J = 8.0 Hz, 1H), 6.84 phenyl-1H-pyrazolo[3,4- (t, J = 7.6 Hz, 1H), 3.42 (s, 3H), 2.86 (s, 3H). d]pyrimidin-6-yl)amino)phenol Ex. # Structure and name Characterization and procedure Pale pink solid. Yield: (0.029 g, 21%). LC- MS [M+H]+: 367.1 / 369.0, Rt = 11.50 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 10.62 (s, 1H), 8.34 – 8.22 (m, 2H), 8.20 – 44 8.12 (m, 3H), 7.89 (s, 1H), 7.55 (t, J = 7.8 Hz, 5-chloro-2-((4-(methylamino)-1- 2H), 7.31 (t, J = 7.4 Hz, 1H), 6.92 – 6.86 (m, phenyl-1H-pyrazolo[3,4- 2H), 3.00 (d, J = 4.6 Hz, 3H). d]pyrimidin-6-yl)amino)phenol Pale re +d solid. Yield: (0.058 g, 41%). LC-MS [M+H] : 367.1 / 368.9, Rt = 11.25 min(Method-C).1H NMR (400 MHz, DMSO-d6, δ): 10.40 (s, 1H), 8.60 (s, 1H), 8.42 – 8.27 45 (m, 1H), 8.25 – 8.14 (m, 3H), 7.78 (s, 1H), 4-chloro-2-((4-(methylamino)-1- 7.55 (t, J = 7.9 Hz, 2H), 7.33 (t, J = 7.4 Hz, phenyl-1H-pyrazolo[3,4- 1H), 6.89 – 6.84 (m, 2H), 3.01 (d, J = 4.5 Hz, d]pyrimidin-6-yl)amino)phenol 3H). Pale brown solid. Yield: (0.070 g, 47%). LC- MS [M+H]+: 390.1 / 392.0, Rt = 12.07 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 11.36 (s, 1H), 9.15 (s, 1H), 8.31 – 8.16 46 (m, 5H), 7.54 – 7.47 (m, 2H), 7.41 (t, J = 2.7 N6-(5-chloro-1H-indol-7-yl)-N4- Hz, 1H), 7.33 – 7.27 (m, 1H), 7.26 (d, J = 1.9 methyl-1-phenyl-1H- Hz, 1H), 6.44 (dd, J = 3.0, 1.9 Hz, 1H), 3.07 pyrazolo[3,4d-]pyrimidine-4,6- (d, J = 4.5 Hz, 3H). diamine Pale-brown solid. Yield: (0.049 g, 33%). LC- MS [M+H]+: 390.1 / 392.0, Rt = 11.89 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 11.35 (s, 1H), 9.07 (s, 1H), 8.22 – 8.09 64(m, 4H), 7.74 (d, J = 8.3 Hz, 1H), 7.46 – 7.39 47 N -(4-chloro-1H-indol-7-yl)-N - (m, 3H), 7.29 – 7.21 (m, 1H), 7.03 (d, J = 8.2 methyl-1-phenyl-1H- Hz, 1H), 6.51 – 6.46 (m, 1H), 3.01 (d, J = 4.5 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 3H). diamine Grey solid. Yield: (0.028 g, 20%). LC-MS [M+H] +: 370.5, Rt = 11.23 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.93 (s, 1H), 8.14 – 7.85 (m, 4H), 7.44 – 7.36 (m, 48 N4-methyl-N6-(1-methyl-1H- 1H), 7.28 – 7.17 (m, 3H), 7.16 – 7.08 (m, indol-7-yl)-1-phenyl-1H- 1H), 7.05 – 6.89 (m, 2H), 6.46 – 6.41 (m, pyrazolo[3,4d-]pyrimidine-4,6- 1H), 3.80 (s, 3H), 2.89 (s, 3H). diamine Ex. # Structure and name Characterization and procedure Brown + solid. Yield: (0.028 g, 20%). LC-MS [M+H] : 357.3, Rt = 7.77 min (Method-C).1H NMR (400 MHz, DMSO-d6 δ,): 12.28 (s, 49 1H), 9.25 (s, 1H), 8.35 – 8.21 (m, 3H), 8.12 N6-(1H-benzo[d]imidazol-6-yl)- 4 (d, J = 17.5 Hz, 3H), 7.60 – 7.44 (m, 4H), N -methyl-1-phenyl-1H- 7.32 – 7.26 (m, 1H), 3.06 (d, J = 4.5 Hz, 3H). pyrazolo[3,4d-]pyrimidine-4,6- diamine Orange + solid. Yield: (0.057 g, 40%). LC-MS [M+H] : 371.4, Rt = 8.09 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.23 (s, 1H), 8.33 – 8.26 (m, 3H), 8.18 – 8.07 (m, 50 N4-methyl-N6-(1-methyl-1H- 3H), 7.67 (d, J = 8.6 Hz, 1H), 7.57 – 7.49 (m, benzo[d]imidazol-5-yl)-1-phenyl- 2H), 7.45 (d, J = 8.7 Hz, 1H), 7.34 – 7.26 (m, 1H-pyrazolo[3,4d-]pyrimidine- 1H), 3.82 (s, 3H), 3.05 (d, J = 4.6 Hz, 3H). 4,6-diamine Pale purple solid. Yield: (0.040 g, 28%). LC- MS [M+H]+: 371.9, Rt = 9.08 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 8.92 (s, 1H), 8.25 (d, J = 8.0 Hz, 2H), 8.09 (s, 1H), 8.02 (s, 1H), 7.68 (s, 1H), 7.50 (t, J = 8.0 Hz, 2H), 7.36 (d, J = 8.5 Hz, 1H), 7.27 (t, J = 7.4 51 N4-methyl-N6-(1-methylindolin-5- Hz, 1H), 6.46 (d, J = 8.4 Hz, 1H), 3.20 (t, J = yl)-1-phenyl-1H-pyrazolo[3,4- 8.0 Hz, 2H), 3.00 (d, J = 4.5 Hz, 3H), 2.87 (t, d]pyrimidine-4,6-diamine J = 8.1 Hz, 2H), 2.66 (s, 3H). Off-white solid. Yield: (0.014 g, 9%). LC- MS [M+H]+: 386.5, Rt = 11.56 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 8.59 (s, 1H), 8.18 (d, J = 8.0 Hz, 2H), 8.14 – 8.04 (m, 2H), 7.44 (t, J = 7.8 Hz, 2H), 7.32 (d, J = 52 N6-(3,3-dimethylindolin-7-yl)N-4- 7.9 Hz, 1H), 7.25 (t, J = 7.4 Hz, 1H), 6.81 (d, methyl-1-phenyl-1H- J = 7.2 Hz, 1H), 6.63 (t, J = 7.6 Hz, 1H), 5.26 pyrazolo[3,4d-]pyrimidine-4,6- (s, 1H), 3.18 (d, J = 2.6 Hz, 2H), 2.98 (d, J = diamine 4.6 Hz, 3H), 1.25 (s, 6H). White + solid. Yield: (0.024 g, 18%). LC-MS [M+H] : 382.4, Rt = 4.51 min (Method-A).1H NMR (400 MHz, DMSO-d6 δ,): 11.04 (s, 1H), 9.04 – 8.69 (m, 1H), 8.16 (d, J = 8.1 Hz, 53 4H), 7.96 – 7.60 (m, 1H), 7.42 (t, J = 7.7 Hz, 4 2H), 7.34 – 7.20 (m, 3H), 6.96 (t, J = 7.7 Hz, N -cyclopropyl-N6-(1H-indol-7- 1H), 6.46 – 6.43 (m, 1H), 3.03 (s, 1H), 0.83 yl)-1-phenyl-1H-pyrazolo[3,4- (s, 2H), 0.67 (s, 2H). d]pyrimidine-4,6-diamine Ex. # Structure and name Characterization and procedure Off-white solid. Yield: (0.047 g, 36%). LC- MS [M+H]+: 400.5, Rt = 11.32 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 10.98 (s, 1H), 8.94 (s, 1H), 8.23 (d, J = 0.5 Hz, 2H), 8.16 (d, J = 7.3 Hz, 2H), 7.70 (d, J = 7.6 Hz, 1H), 7.42 (t, J = 7.9 Hz, 2H), 54 N6-(1H-indol-7-yl)-N4-(2- 7.30 (t, J = 2.8 Hz, 1H), 7.28 – 7.20 (m, methoxyethyl)-1-phenyl-H1- 2H), 6.96 (t, J = 7.7 Hz, 1H), 6.47 – 6.41 pyrazolo[3,4d-]pyrimidine-4,6- (m, 1H), 3.68 (q, J = 5.5 Hz, 2H), 3.56 (t, J diamine = 5.6 Hz, 2H), 3.30 (s, 3H). Pale brown solid. Yield: (0.019 g, 25%). LC-MS [M+H]+: 347, Rt = 11.94 min (Method-F and Method-G1).H NMR (400 MHz, DMSO-d6, δ): 9.97 (s, 1H), 8.33 – 55 8.27 (m, 1H), 8.25 – 8.16 (m, 3H), 7.83 (s, 2-((4-(dimethylamino)-1-phenyl- 1H), 7.58 – 7.49 (m, 2H), 7.36 – 7.28 (m, 1H-pyrazolo[3,4d-]pyrimidin-6- 1H), 6.91 – 6.78 (m, 3H), 3.36 (s, 6H). yl)amino)phenol Off-white solid. Yield: (0.023 g, 25%).LC- MS [M+H]+: 361.4, Rt = 12.80 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 8.40 – 8.36 (m, 1H), 8.31 – 8.29 (m, 1H), 8.22 – 56 N6-(2-methoxyphenyl)N-4,N4- 8.18 (m, 2H), 7.72 (s, 1H), 7.58 – 7.51 (m, dimethyl-1-phenyl-1H- 2H), 7.35 – 7.29 (m, 1H), 7.07 – 6.93 (m, pyrazolo[3,4d-]pyrimidine-4,6- 3H), 3.88 (s, 3H), 3.43 – 3.34 (m, 6H). diamine Pale pink solid. Yield: (0.035 g, 38%). LC- MS [M+H]+: 361.2, Rt = 12.01 min (Method- C).1H NMR (400 MHz, DMSO-d6, δ): 9.20 (s, 1H), 8.29 (s, 1H), 8.23 (d, J = 8.5 Hz, 2H), 5767.63 (t, J = 2.3 Hz, 1H), 7.53 (t, J = 7.8 Hz, N -(3-methoxyphenyl)N-4,N4- 2H), 7.35 – 7.27 (m, 2H), 7.16 (t, J = 8.1 Hz, dimethyl-1-phenyl-1H- 1H), 6.50 (dd, J = 8.3, 2.5 Hz, 1H), 3.72 (s, pyrazolo[3,4d-]pyrimidine-4,6- 3H), 3.38 (s, 6H). diamine Off-white solid.Yield: (0.054 g, 40%).LC- MS [M+H]+: 365.1 / 366.9, Rt = 13.10 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.47 (s, 1H), 8.34 – 8.28 (m, 2H), 8.25 – 58 N6-(3-chlorophenyl)N-4,N4- 8.18 (m, 2H), 7.60 – 7.51 (m, 3H), 7.37 – dimethyl-1-phenyl-1H- 7.31 (m, 1H), 7.28 (t, J = 8.1 Hz, 1H), 7.00 – pyrazolo[3,4d-]pyrimidine-4,6- 6.92 (m, 1H), 3.38 (s, 6H). diamine Ex. # Structure and name Characterization and procedure Grey solid. Yield: (0.022 g, 16%). LC-MS [M+H]+: 370.1, Rt = 11.80 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 10.98 (s, 1H), 8.90 (s, 1H), 8.28 (s, 1H), 8.17 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 7.6 Hz, 59 N6-(1H-indol-7-yl)-N4,N4- 1H), 7.44 (t, J = 7.8 Hz, 2H), 7.33 – 7.22 (m, dimethyl-1-phenyl-1H- 3H), 6.96 (t, J = 7.7 Hz, 1H), 6.44 (t, J = 2.5 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 1H), 3.34 (s, 6H). diamine Pale pink solid. Yield: (0.043 g, 60%). LC-MS [M+H]+: 432.3, Rt = 8.00 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 10.01 (s, 1H), 8.26 (t, J = 5.6 Hz, 1H), 8.23 – 8.16 (m, 4H), 7.88 (s, 1H), 7.56 60 2-((4-((2- – 7.49 (m, 2H), 7.30 (tt, J = 7.3, 1.2 Hz, morpholinoethyl)amino)-1- 1H), 6.90 – 6.78 (m, 3H), 3.63 (q, J = 6.5 phenyl-1H-pyrazolo[3,4- Hz, 2H), 3.58 (t, J = 4.6 Hz, 4H), 2.57 (t, J = d]pyrimidin-6-yl)amino)phenol 6.9 Hz, 2H), 2.45 (t, J = 4.6 Hz, 4H). White solid. Yield: (0.060 g, 81%). LC-MS [M+H]+: 446.5, Rt = 9.01 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 8.40 – 8.35 (m, 1H), 8.26 – 8.15 (m, 4H), 7.72 (s, 1H), 7.55 – 7.48 (m, 2H), 7.32 61 – 7.26 (m, 1H), 7.05 – 7.01 (m, 1H), 7.01 – N6-(2-methoxyphenyl)N-4-(2- 6.90 (m, 2H), 3.86 (s, 3H), 3.64 – 3.52 (m, morpholinoethyl)-1-phenyl-H1- 6H), 2.55 (t, J = 6.9 Hz, 2H), 2.46 – 2.38 pyrazolo[3,4d-]pyrimidine-4,6- (m, 4H). diamine Off-white solid. Yield: (0.023 g, 22%). LC-MS [M+H]+: 377.3, Rt = 10.69 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 8.45 – 8.40 (m, 1H), 8.29 (t, J = 5.4 Hz, 1H), 8.25 (s, 1H), 8.22 – 8.17 (m, 2H), 7.70 (s, 1H), 7.58 – 7.48 (m, 2H), 7.34 – 62 2-((6-((2-methoxyphenyl)amino)- 7.27 (m, 1H), 7.07 – 7.01 (m, 1H), 7.01 – 1-phenyl-1H-pyrazolo[3,4- 6.94 (m, 2H), 4.88 – 4.81 (m, 1H), 3.89 (s, d]pyrimidin-4-yl)amino)ethan-1- 3H), 3.68 – 3.61 (m, 2H), 3.61 – 3.55 (m, ol 2H). Off-white solid. Yield: (0.016 g, 13%). LC- MS [M+H]+: 386.4, Rt = 3.91 min (Method- A).1H NMR (400 MHz, DMSO-d6 δ,): 11.00 (s, 1H), 8.92 (s, 1H), 8.23 (s, 1H), 63 8.21 – 8.12 (m, 3H), 7.73 (d, J = 7.6 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 2.8 Hz, 1H), 7.28 – 7.20 (m, 2H), 6.97 (t, J = Ex. # Structure and name Characterization and procedure 2-((6-((1H-indol-7-yl)amino)-1- 7.8 Hz, 1H), 6.48 – 6.40 (m, 1H), 4.90 – phenyl-1H-pyrazolo[3,4- 4.75 (m, 1H), 3.71 – 3.55 (m, 4H). d]pyrimidin-4-yl)amino)ethan-1- ol Pink solid. Yield: (0.047 g, 39%). LC-MS [M+H]+: 427.2, Rt = 13.16 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 10.04 (s, 1H), 8.29 – 8.16 (m, 5H), 7.88 (s, 1H), 7.57 – 7.49 (m, 2H), 7.30 (tt, J 64 2-((4-((2-(cyclohex-1-en-1- = 7.4, 1.2 Hz, 1H), 6.91 – 6.75 (m, 3H), yl)ethyl)amino)-1-phenyl-H1- 5.48 (s, 1H), 3.63 – 3.53 (m, 2H), 2.26 (t, J pyrazolo[3,4d-]pyrimidin-6- = 7.5 Hz, 2H), 2.03 – 1.91 (m, 4H), 1.62 – yl)amino)phenol 1.46 (m, 4H). White solid. Yield: (0.038 g, 40%). LC-MS [M+H]+: 450.5, Rt = 13.64 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 11.01 (s, 1H), 8.89 (s, 1H), 8.26 – 8.07 (m, 4H), 7.76 (d, J = 7.7 Hz, 1H), 7.50 – 7.37 (m, 2H), 7.36 – 7.21 (m, 3H), 7.01 – 65 N4-(2-(cyclohex-1-en-1-yl)ethyl)- 6.90 (m, 1H), 6.50 – 6.43 (m, 1H), 5.46 (s, N6-(1H-indol-7-yl)-1-phenyl-1H- 1H), 3.66 – 3.53 (m, 2H), 2.25 (t, J = 7.7 pyrazolo[3,4d-]pyrimidine-4,6- Hz, 2H), 2.03 – 1.90 (m, 4H), 1.63 – 1.44 diamine (m, 4H). White solid. Yield: (0.017 g, 18%). LC-MS [M+H]+: 457.4, Rt = 5.11 min (Method-A).1H NMR (400 MHz, DMSO- d6, δ): 9.55 (s, 1H), 8.29 – 8.10 (m, 4H), 8.01 (s, 1H), 7.79 (s, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 6.77 (d, J 66 2-((4-((2-(cyclohex-1-en-1- = 8.7 Hz, 1H), 6.47 – 6.34 (m, 1H), 5.48 (s, yl)ethyl)amino)-1-phenyl-H1- 1H), 3.68 (s, 3H), 3.64 – 3.53 (m, 2H), 2.32 pyrazolo[3,4d-]pyrimidin-6- – 2.21 (m, 2H), 1.97 (d, J = 24.3 Hz, 4H), yl)amino)-4-methoxyphenol 1.54 (d, J = 30.5 Hz, 4H). Pale red solid. Yield: (0.054 g, 42%). LC-MS [M+H]+: 461.3, Rt = 13.89 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 10.55 (s, 1H), 8.28 (t, J = 5.6 Hz, 1H), 8.23 – 8.13 (m, 4H), 7.86 (s, 1H), 7.58 – 7.50 (m, 2H), 7.35 – 7.27 (m, 1H), 6.89 67 5-chloro-2-((4-((2-(cyclohex-1- (d, J = 2.4 Hz, 1H), 6.84 (dd, J = 8.6, 2.4 en-1-yl)ethyl)amino)-1-phenyl- Hz, 1H), 5.49 – 5.43 (m, 1H), 3.62 – 3.50 1H-pyrazolo[3,4d-]pyrimidin-6- (m, 2H), 2.25 (t, J = 7.5 Hz, 2H), 2.02 – yl)amino)phenol 1.91 (m, 4H), 1.62 – 1.47 (m, 4H). Ex. # Structure and name Characterization and procedure Off-white solid. Yield: (0.033 g, 26%). LC-MS [M+H]+: 452.4, Rt = 14.09 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 11.01 (s, 1H), 8.88 (s, 1H), 8.21 – 8.14 (m, 3H), 8.08 (t, J = 5.4 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.43 (t, J = 7.9 Hz, 2H), 7.30 (t, J = 2.8 Hz, 1H), 7.28 – 7.21 (m, 68 N4-(2-cyclohexylethyl)N-6-(1H- 2H), 6.95 (t, J = 7.8 Hz, 1H), 6.46 – 6.41 indol-7-yl)-1-phenyl-1H- (m, 1H), 3.57 – 3.48 (m, 2H), 1.80 – 1.59 pyrazolo[3,4d-]pyrimidine-4,6- (m, 5H), 1.53 (q, J = 7.2 Hz, 2H), 1.44 – diamine 1.30 (m, 1H), 1.29 – 1.10 (m, 3H), 1.00 – 0.87 (m, 2H). Purple solid. Yield: (0.008 g, 6%). LC-MS [M+H]+: 412.6, Rt = 12.98 min (Method-C).1H NMR (400 MHz, DMSO- d6, δ): 11.01 (s, 1H), 8.89 (s, 1H), 8.21 – 8.13 (m, 3H), 8.11 – 8.04 (m, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.43 (t, J = 7.9 Hz, 2H), 7.30 (t, J = 2.8 Hz, 1H), 7.28 – 7.20 (m, 2H), 69 N6-(1H-indol-7-yl)-N4-isopentyl- 6.95 (t, J = 7.7 Hz, 1H), 6.47 – 6.42 (m, 1-phenyl-1H-pyrazolo[3,4- 1H), 3.59 – 3.47 (m, 2H), 1.76 – 1.63 (m, d]pyrimidine-4,6-diamine 1H), 1.59 – 1.48 (m, 2H), 0.94 (d, J = 6.6 Hz, 6H). White solid. Yield: (0.059 g, 47%). LC-MS [M+H]+: 397.0, Rt = 21.42 min (Method-K).1H NMR (400 MHz, DMSO- d6, δ): 9.53 (s, 1H), 8.56 (t, J = 2.1 Hz, 1H), 70 8.39 – 8.13 (m, 4H), 7.57 (qd, J = 7.5, 1.8 N6-(3-bromophenyl)N-4-methyl-1- Hz, 3H), 7.43 – 7.28 (m, 1H), 7.22 (t, J = phenyl-1H-pyrazolo[3,4- 8.0 Hz, 1H), 7.14 – 7.01 (m, 1H), 3.04 (d, J d]pyrimidine-4,6-diamine = 4.6 Hz, 3H). White solid. Yield: (0.039 g, 27%). LC-MS [M+H]+: 427.0, Rt = 20.57 min (Method-K).1H NMR (400 MHz, DMSO- d6, δ): 9.49 (s, 1H), 8.52 (s, 1H), 8.32 (t, J = 5.4 Hz, 1H), 8.27 (s, 1H), 8.25 – 8.11 (m, 71 2-((6-((3-bromophenyl)amino)-1- 2H), 7.69 – 7.49 (m, 3H), 7.41 – 7.28 (m, phenyl-1H-pyrazolo[3,4- 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.10 (ddd, J = d]pyrimidin-4-yl)amino)ethan-1- 7.9, 2.0, 0.9 Hz, 1H), 4.85 (d, J = 5.4 Hz, ol 1H), 3.83 – 3.47 (m, 4H). White solid. Yield: (0.027 g, 35%). LC-MS [M+H]+: 363.1, Rt = 17.90 min (Method-K).1H NMR (400 MHz, DMSO- d6, δ): 10.03 (s, 1H), 8.30 (t, J = 5.4 Hz, 72 1H), 8.25 (d, J = 0.9 Hz, 1H), 8.24 – 8.11 (m, 3H), 7.86 (s, 1H), 7.61 – 7.47 (m, 2H), 7.31 (td, J = 7.4, 1.1 Hz, 1H), 6.94 – 6.70 Ex. # Structure and name Characterization and procedure 2-((4-((2-hydroxyethyl)amino)-1- (m, 3H), 4.84 (t, J = 5.2 Hz, 1H), 3.61 (dq, J phenyl-1H-pyrazolo[3,4- = 28.3, 6.1 Hz, 4H). d]pyrimidin-6-yl)amino)phenol White solid. Yield: (0.034 g, 19%). LC-MS [M+H]+: 491.0, Rt = 23.94 min (Method-K).1H NMR (400 MHz, DMSO- d6, δ): 9.46 (s, 1H), 8.51 (s, 1H), 8.22 (ddt, J = 6.6, 2.1, 1.3 Hz, 4H), 7.68 – 7.45 (m, 3H), 7.32 (ddt, J = 7.4, 5.9, 1.2 Hz, 1H), 7.21 (td, 73 6 J = 8.1, 1.3 Hz, 1H), 7.10 (ddd, J = 7.9, 2.0, N -(3-bromophenyl)N-4-(2- 1.0 Hz, 1H), 5.49 (s, 1H), 3.74 – 3.52 (m, (cyclohex-1-en-1-yl)ethyl)-1- 2H), 2.28 (t, J = 7.7 Hz, 2H), 1.97 (d, J = phenyl-1H-pyrazolo[3,4- 23.9 Hz, 4H), 1.72 – 1.41 (m, 4H). d]pyrimidine-4,6-diamine Example 74: 2-((4-amino-1-phenyl-H1-pyrazolo[3,4d-]pyrimidin-6-yl)amino)-5- (dimethylamino)phenol To a solution of N6-(4-(dimethylamino)-2-methoxyphenyl)-1-phenyHl--1pyrazolo[3,4- d]pyrimidine-4,6-diamine (0.04 g, 0.11 mmol, 1.0) e inq 3 mL of DCM was added 1 M BB3r in DCM (0.21 mL, 0.21 mmol, 2.0 eq). The solution w satisrred at RT for 24 h. Then, an additional portion of 1 M BBr3in DCM (0.21 mL, 0.21 mmol, 2.0 eq) was added t ahned mixture was stirredat RT for an additional 4 h. The reaction was quhen dc with water, neutralized with saturatedNaHCO3 aqueous solution to pH 9 and stirred at RT for m 3in0. The aqueous layer was extracted with EtOAc (3 x 15 mL). The combined organic laye wresre washed with water (2 x 10 mL) and brine (10 mL). The resulting organic layer was dr oiever anhydrous N2SaO4, filtered and volatiles were removed under reduced pressure. Purificatifon the o crude product by flash column chromatography (Silica gel, DCM / MeOH with 2% of N3,H 0-6%) afforded 2-((4-amino-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin-6-yl)amino)-5-(dimethylamino)phenol as g arey solid. Yield: (0.048 g, 35%). LC-MS [M+H+]: 362.0, Rt = 8.97 min (Method-C). 1H NMR (400 MHz, DMSO-d6 δ,): 9.74 (s, 1H), 8.18 (d, J = 8.1 Hz, 2H), 8.141 (Hs,), 7.90 (s, 1H), 7.62 (s, 1H), 7.50 (t, J = 7.9 Hz, 2H2),87 (.t, J = 7.4 Hz, 1H), 6.29 (s, 1H), 6.28 – 6.m22, ( 1H), 2.83 (s, 6H). Intermediate 27: tert-butyl (6-chloro-1-phenyl-H1-pyrazolo[3,4d-]pyrimidin-4- yl)(methyl)carbamate To a stirred solution o tfert-butyl N-methylcarbamate (0.16 g, 1.24 mmol, 1.1 eq) in DMF (1 mL) was added NaH (0.050 g of a 60% suspensnio mnin i eral oil, 1.24 mmol, 1.1 eq). The resulting mixture was stirred at RT for 30 min. Tnh, e 4,6-dichloro-1-phenyl-H1-pyrazolo[3,4-d]pyrimidine (0.300 g, 1.13 mmol, 1.0 eq) was add aend the mixture was stirred at RT for anadditional 22 h. The reaction was then quenchehd w aitter and diluted with EtOAc. The aqueous layer was extracted with EtOAc (3 x 10 mL). The cboinmed organic layers were washed with water (3 x 10 mL) and with saturated LiCl aqueous solnut (i3o x 10 mL), dried over anhydrous2NSaO4, filtered and concentrated. Purification of the ceru pdroduct by flash column chromatography (Silica gel, hexane / EtOAc 0-20%) afforde tedrt-butyl (6-chloro-1-phenyl-H1-pyrazolo[3,4d-]pyrimidin- 4-yl)(methyl)carbamate as a yellow oil, which wahsen t used in the next step without further purification. Yield: (0.212 g, 52%). LC-MS [M+H+]: 304.1 / 305.9, Rt = 3.86 min (Method-H). General Procedure E To a degassed solution of the appropriate arylri cdhelo or aryl dichloride (ex: 6-chlorNo- methyl-1-phenyl-1H-pyrazolo[3,4d-]pyrimidin-4-amine) (1.0 eq), the corresponding n aemi (ex: methyl 3-aminobenzoate) (1.3 eq) an3dP KO4or Cs2CO3(3.0 eq) in dioxane (4 mL / mmol) were added Pd(OAc2) (0.03 eq) and dppf or BINAP (0.05 eq). The solnut wioas degassed again and stirred at 100 °C for 16 h. After the reaction muirxet was cooled to room temperature, water and EtOAc were added. The aqueous layer was extracittehd E wtOAc (x3). The combined organic layers were washed with water (x1) and brine (x d1ri)e,d over anhydrous N2SaO4, filtered and volatiles were removed under reduced pressure. re Tshuelting crude was purified by flash column chromatography (Silica gel, hexane / EtOAc) or reeve prhsase flash column chromatography (C18, 10 mM aqueous N4HOAc (pH 7) / ACN) or semi-preparative HPLC (10 mMH N4HCO3 (pH 7 with HCOOH) / ACN) to obtain the desired producxt: (e methyl 3-((4-(methylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin-6-yl)amino)benzoate). The following Examples (Ex.) or Intermediates ()In wt.ere prepared according to the general procedure E: Ex.# or Structure and name Characterization and procedure Int.# Off-white solid. Yield: (0.232 g, 52%). LC-MS [M+H]+: 375.1, Rt = 3.54 min Int. 28 methyl 3-((4-(methylamino)- (Method-B). 1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)benzoate Pale yellow solid. Yield: (0.039 g, 27%). Int. 29 LC-MS [M+H]+: 375.3, Rt = 3.92 min methyl 2-((4-(methylamino)- (Method-B). 1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)benzoate White solid. Yield: (0.022 g, 16%). LC-MS [M+H]+: 358.2, Rt = 11.36 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.74 (s, 1H), 8.43 (s, 1H), 8.37 – 8.31 (m, Ex. 75 2H), 8.24 – 8.18 (m, 3H), 7.54 (t, J = 7.9 Hz, N6-(benzo[d]oxazol-4-yl)-N4- 2H), 7.44 (t, J = 8.1 Hz, 1H), 7.38 (d, J = 8.1 methyl-1-phenyl-1H- Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H), 3.05 (d, J = pyrazolo[3,4d-]pyrimidine- 4.5 Hz, 3H). 4,6-diamine Pale yellow solid. Yield: (0.041 g, 29%). LC-MS [M+H]+: 367.2, Rt = 4.48 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 8.79 (s, 1H), 8.22 – 8.06 (m, 4H), 7.78 (d, J Ex. 76 = 8.2 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 7.8 Hz, 1H), 7.47 – 7.07 (m, 5H), 2.94 (d, J = 4.5 Hz, 3H). Ex.# or Structure and name Characterization and procedure Int.# N6-(2- (difluoromethyl)phenyl)N-4- methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine- 4,6-diamine Off-white solid. Yield: (1.180 g, 52%). LC-MS [M+H]+: 458.4, Rt = 4.19 minInt. 30tert-butyl 7-((4-(Method-B). (methylamino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.004 g, 3%). LC-MS [M+H]+: 361.2, Rt = 4.33 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 8.10 (s, 2H), 8.05 (d, J = 6.6 Hz, 2H), 7.92 Ex. 77 N6-(2-methoxy-6- (s, 1H), 7.34 (s, 2H), 7.15 (dt, J = 15.9, 7.7 Hz, methylphenyl)N-4-methyl-1- 2H), 6.87 (t, J = 8.4 Hz, 2H), 3.70 (s, 3H), 2.90 phenyl-1H-pyrazolo[3,4- (s, 3H), 2.20 (s, 3H). d]pyrimidine-4,6-diamine Brown solid. Yield: (0.044 g, 33%). LC-MS [M+H]+: 346.6, Rt = 10.87 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.28 (s, 1H), 8.18 (d, J = 8.1 Hz, 2H), 8.13 – Ex. 78 8.01 (m, 2H), 7.45 – 7.36 (m, 3H), 7.21 (t, J = N4-methyl-N6-(2- 7.4 Hz, 1H), 7.06 – 6.99 (m, 1H), 6.66 – 6.59 (methylamino)phenyl)-1- (m, 2H), 5.14 (d, J = 5.4 Hz, 1H), 2.95 (d, J = phenyl-1H-pyrazolo[3,4- 4.5 Hz, 3H), 2.73 (d, J = 5.1 Hz, 3H). d]pyrimidine-4,6-diamine Pale yellow solid. Yield: (0.017 g, 16%). LC-MS [M+H]+: 358.2, Rt = 10.33 min (Method-C)1.H NMR (400 MHz, DMSO-d6, δ): 9.36 (s, 1H), 8.74 (s, 1H), 8.24 – 8.18 (m, Ex. 79 641H), 8.15 (s, 1H), 8.08 (d, J = 8.1 Hz, 2H), 7.67 N -(benzo[d]oxazol-7-yl)-N - (d, J = 7.8 Hz, 1H), 7.54 – 7.49 (m, 1H), 7.40 – methyl-1-phenyl-1H- 7.31 (m, 3H), 7.26 – 7.18 (m, 1H), 2.95 (d, J = pyrazolo[3,4d-]pyrimidine- 4.6 Hz, 3H). 4,6-diamine Ex.# or Structure and name Characterization and procedure Int.# Yellow wax. Yield: (0.190 g, 72%). LC-MS [M+H]+: 458.6, Rt = 3.93 min tert-butyl 6-((4- (Method-B). Int. 31 (methylamino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate Light brown solid. Yield: (0.035 g, 25%). LC-MS [M+H]+: 358.4, Rt = 10.20 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.45 (s, 1H), 8.65 (s, 1H), 8.50 (d, J = 2.1 Hz, 1H), 8.27 – 8.23 (m, 2H), 8.20 (d, J = 5.0 Ex. 80 N6-(benzo[d]oxazol-5-yl)-N4- Hz, 1H), 8.16 (s, 1H), 7.76 (dd, J = 8.9, 2.1 Hz, methyl-1-phenyl-1H- 1H), 7.66 (d, J = 8.9 Hz, 1H), 7.55 – 7.50 (m, pyrazolo[3,4d-]pyrimidine- 2H), 7.34 – 7.27 (m, 1H), 3.05 (d, J = 4.5 Hz, 4,6-diamine 3H). White solid. Yield: (0.011 g, 8%). LC-MS [M+H]+: 356.4, Rt = 3.84 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 10.89 (s, 1H), 9.03 (s, 1H), 8.30 (d, J = 8.0 Ex. 816 4Hz, 2H), 8.21 – 8.16 (m, 1H), 8.11 (s, 1H), 8.03 N -(1H-indol-5-yl)-N - (s, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.44 – 7.38 (m, methyl-1-phenyl-1H- 1H), 7.31 – 7.26 (m, 3H), 6.37 – 6.34 (m, 1H), pyrazolo[3,4d-]pyrimidine- 3.03 (d, J = 4.5 Hz, 3H). 4,6-diamine Off-white solid. Yield: (0.023 g, 16%). LC-MS [M+H]+: 372.3, Rt = 10.48 min (Method-C).1H NMR (400 MHz, DMSO-d6, Ex. 82 δ): 9.52 (s, 1H), 8.48 (d, J = 1.9 Hz, 1H), 8.32 – N4-methyl-N6-(2- 8.20 (m, 3H), 8.17 (s, 1H), 7.62 – 7.49 (m, 4H), methylbenzod[]oxazol-6-yl)- 7.33 (t, J = 7.5 Hz, 1H), 3.06 (d, J = 4.6 Hz, 1-phenyl-1H-pyrazolo[3,4- 3H), 2.58 (s, 3H). d]pyrimidine-4,6-diamine HN N N N Purple solid. Yield: (0.014 g, 10%). O N N N LC-MS [M+H]+: 358.2, Rt = 10.19 min H (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.59 (s, 1H), 8.61 (s, 1H), 8.57 (s, 1H), 8.28 Ex. 83 N6-(benzo[d]oxazol-6-yl)-N4- – 8.12 (m, 4H), 7.64 (s, 2H), 7.53 (t, J = 7.9 Hz, methyl-1-phenyl-1H- 2H), 7.32 (t, J = 7.4 Hz, 1H), 3.05 (d, J = 4.5 pyrazolo[3,4d-]pyrimidine- Hz, 3H). 4,6-diamine Ex.# or Structure and name Characterization and procedure Int.# Grey solid. Yield: (0.031 g, 22%). LC-MS [M+H]+: 371.4, Rt = 8.42 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.42 (s, 1H), 8.59 (s, 1H), 8.31 – 8.26 (m, Ex. 84 N4-methyl-N6-(1-methyl-1H- 2H), 8.23 – 8.19 (m, 1H), 8.14 (s, 1H), 7.61 – benzo[d]imidazol-6-yl)-1- 7.49 (m, 3H), 7.41 (dd, J = 8.7, 2.0 Hz, 1H), phenyl-1H-pyrazolo[3,4- 7.39 – 7.32 (m, 1H), 3.83 (s, 3H), 3.11 (d, J = d]pyrimidine-4,6-diamine 4.5 Hz, 3H). White solid. Yield: (0.011 g, 8%). LC-MS [M+H]+: 372.4, Rt = 10.54 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.38 (s, 1H), 8.35 (s, 1H), 8.29 – 8.23 (m, Ex. 85 N4-methyl-N6-(2- 2H), 8.22 – 8.11 (m, 2H), 7.67 (dd, J = 8.8, 2.1 methylbenzod[]oxazol-5-yl)- Hz, 1H), 7.52 (t, J = 8.6 Hz, 3H), 7.31 (t, J = 1-phenyl-1H-pyrazolo[3,4- 7.3 Hz, 1H), 3.05 (d, J = 4.5 Hz, 3H), 2.59 (s, d]pyrimidine-4,6-diamine 3H). White solid. Yield: (0.027 g, 20%). LC-MS [M+H]+: 346.6, Rt = 10.67 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.02 (s, 1H), 8.33 – 8.27 (m, 2H), 8.18 (s, Ex.864 62H), 7.58 – 7.51 (m, 2H), 7.32 (t, J = 7.4 Hz, N -methyl-N -(3- 1H), 7.22 (s, 1H), 7.06 – 6.97 (m, 2H), 6.21 (dt, (methylamino)phenyl)-1- J = 7.5, 1.9 Hz, 1H), 5.49 (d, J = 5.3 Hz, 1H), phenyl-1H-pyrazolo[3,4- 3.08 (d, J = 4.5 Hz, 3H), 2.71 (d, J = 4.9 Hz, d]pyrimidine-4,6-diamine 3H). Brown solid. Yield: (0.076 g, 43%).Int. 32tert-butyl 4-((4-LC-MS [M+H]+: 458.3, Rt = 3.62 min (methylamino)-1-phenyl-H1- (Method-H). pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.022 g, 15%). LC-MS [M+H]+: 372.6, Rt = 9.66 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.55 (s, 1H), 8.27 – 8.23 (m, 2H), 8.07 (s, 1H), 7.97 (s, 1H), 7.36 (t, J = 7.8 Hz, 2H), 7.18 Ex. 87 N4-methyl-N6-(1- (t, J = 7.4 Hz, 1H), 6.94 – 6.89 (m, 2H), 6.59 (t, methylindolin-7-yl)-1- J = 7.5 Hz, 1H), 3.26 (t, J = 8.4 Hz, 2H), 3.00 – phenyl-1H-pyrazolo[3,4- 2.91 (m, 5H), 2.67 (s, 3H). d]pyrimidine-4,6-diamine Ex.# or Structure and name Characterization and procedure Int.# White solid. Yield: (0.046 g, 33%). LC-MS [M+H]+: 370.4, Rt = 11.27 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.07 (s, 1H), 8.30 (d, J = 7.3 Hz, 2H), 8.15 N4-methyl-N6-(1-me (d, J = 24.2 Hz, 2H), 8.05 (s, 1H), 7.55 – 7.46 Ex. 88 thyl-1H- indol-5-yl)-1-phenyl-1H- (m, 3H), 7.38 – 7.22 (m, 3H), 6.34 (d, J = 3.0 pyrazolo[3,4d-]pyrimidine- Hz, 1H), 3.77 (s, 3H), 3.03 (d, J = 4.5 Hz, 3H). 4,6-diamine Yellowish oil. Yield: (0.065 g, 38%). tert-butyl 6 LC-MS [M+H]+: 484.7, Rt = 3.76 min Int. 33 -((4- (cyclopropylamino)-1- (Method-H). phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Off-white solid. Yield: (0.019 g, 15%). LC-MS [M+H]+: 414.4, Rt = 4.22 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 11.00 (s, 1H), 8.90 (s, 1H), 8.35 (s, 1H), 8.17 (d, J = 8.0 Hz, 2H), 7.99 (t, J = 6.0 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.43 (t, J = 7.9 Ex. 89 1-((6-((1H-indol-7-yl)amino)- Hz, 2H), 7.30 (t, J = 2.8 Hz, 1H), 7.29 – 7.21 1-phenyl-1H-pyrazolo[3,4- (m, 2H), 6.96 (t, J = 7.7 Hz, 1H), 6.44 (t, J = d]pyrimidin-4-yl)amino)-2- 2.4 Hz, 1H), 4.61 (s, 1H), 3.53 (d, J = 5.9 Hz, methylpropan-2-ol 2H), 1.17 (s, 6H). Colorless wax. Yield: (0.076 g, 47%). tert-butyl 7-((4-(( LC-MS [M+H]+: 516.7, Rt = 3.73 min Int. 34 2-hydroxy- 2-methylpropyl)amino)-1- (Method-H). phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Yellowish solid. Yield: (0.139 g, 85%). Int. 35 LC-MS [M+H]+: 516.5, Rt = 3.56 min (Method-H). Ex.# or Structure and name Characterization and procedure Int.# tert-butyl 6-((4-((2-hydroxy- 2-methylpropyl)amino)-1- phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Green wax. Yield: (0.063 g, 55%). tert-b LC-MS [M+H]+: 502.7, Rt = 4.24 min Int. 36 utyl 7-((4-((2- methoxyethyl)amino)-1- (Method-B). phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Yellow solid. Yield: (0.100 g, 61%). Int. 37 tert-butyl 6-((4-((2- LC-MS [M+H]+: 502.6, Rt = 3.67 min methoxyethyl)amino)-1- (Method-H). phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Pale brown solid. Yield: (0.037 g, 27%). LC-MS [M+H]+: 386.3, Rt = 9.99 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 10.88 (s, 1H), 9.10 (s, 1H), 8.33 – 8.26 (m, 2H), 8.22 (s, 1H), 8.17 – 8.09 (m, 1H), 8.00 (s, 1H), 7.57 – 7.51 (m, 2H), 7.41 (d, J = 8.5 Hz, Ex. 90 2-((6-((1H-indol-6-yl)amino)- 1H), 7.34 (dd, J = 8.5, 1.8 Hz, 1H), 7.31 – 7.24 1-phenyl-1H-pyrazolo[3,4- (m, 1H), 7.21 (t, J = 2.7 Hz, 1H), 6.36 – 6.32 d]pyrimidin-4- (m, 1H), 4.82 (t, J = 5.0 Hz, 1H), 3.66 (dt, J = yl)amino)ethan-1-ol 16.4, 5.4 Hz, 4H). Pale brown solid. Yield: (0.037 g, 27%). Int. 38 LC-MS [M+H]+: 488.7, Rt = 3.82 min (Method-B). tert-butyl 7-((4-((2- hydroxyethyl)amino)-1- Ex.# or Structure and name Characterization and procedure Int.# phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Off-white solid. Yield: (0.025 g, 19%). LC-MS [M+H]+: 388.2, Rt = 9.30 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.31 (s, 1H), 8.72 (s, 1H), 8.30 – 8.21 (m, Ex. 91 2H), 8.08 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 7.9 2-((6-(benzod[]oxazol-7- Hz, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.41 – 7.32 ylamino)-1-phenyl-1H- (m, 3H), 7.22 (t, J = 7.4 Hz, 1H), 4.82 (s, 1H), pyrazolo[3,4d-]pyrimidin-4- 3.64 – 3.46 (m, 4H). yl)amino)ethan-1-ol Yellow solid. Yield: (0.091 g, 53%). tert-butyl 6-((4-((2- LC-MS [M+H]+: 488.5, Rt = 3.68 min Int. 39 hydroxyethyl)amino)-1- (Method-H). phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Yellowish oil. Yield: (0.050 g, 30%). LC-MS [M+H]+: 500.7, Rt = 4.30 min tert-butyl 7-((4- (Method-H). Int. 40 (isobutylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate Yellow solid. Yield: (0.140 g, 85%). Int. 41 LC-MS [M+H]+: 500.7, Rt = 4.01 min tert-butyl 6-((4- (Method-H). (isobutylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate Ex.# or Structure and name Characterization and procedure Int.# Yellowish oil. Yield: (0.045 g, 26%). Int. 42 LC-MS [M+H]+: 472.7, Rt = 3.96 min tert-butyl 7-((4-(ethylamino)- (Method-H). 1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Off-white solid. Yield: (0.140 g, 81%).Int. 43tert-butyl 6-((4-(ethylamino)-LC-MS [M+H]+: 472.5, Rt = 3.78 min 1-phenyl-1H-pyrazolo[3,4- (Method-H). d]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.140 g, 87%). LC-MS+. 44 ter [M+H] : 524.5, Rt = 3.82 min Int t-butyl 6-((1-phenyl-4- ((2,2,2-trifluoroethyl)amino)- (Method-H). 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate Yellowish oil. Yield: (0.070 g, 44%). LC-MS [M+H]+: 526.5, Rt = 3.99 minInt. 45tert-butyl 7-((1-phenyl-4-(Method-H). ((2,2,2-trifluoroethyl)amino)- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate Ex.# or Structure and name Characterization and procedure Int.# White solid. Yield: (0.070 g, 41%). LC-MS [M+H]+: 486.6, Rt = 4.11 min Int. 46 tert-butyl 7-((4- (Method-H). (isopropylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate Off-white solid. Yield: (0.150 g, 89%). LC-MS [M+H]+: 486.6, Rt = 3.91 min Int. 47 tert-butyl 6-((4- (Method-H). (isopropylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate Off-white solid. Yield: (0.027 g, 21%). LC-MS [M+H]+: 426.9 / 428.8, Rt = 4.63 min Int. 48 N-(2-(benzyloxy)phenyl)-4- (Method-B). chloro-1-phenyl-1H- pyrazolo[3,4b-]pyridin-6- amine Off-white solid. Yield: (0.082 g, 26%). LC-MS [M+H]+: 339.1 / 340.9, Rt = 4.04 min Int. 49 4-chloro-N-(2-fluorophenyl)- (Method-B). 1-phenyl-1H-pyrazolo[3,4- b]pyridin-6-amine Ex.# or Structure and name Characterization and procedure Int.# White + solid. Yield: (0.060 g, 61%). LC 1-MS [M+H] : 348.7, Rt = 12.22 min (Method-C)H.NMR (400 MHz, DMSO-d6, δ): 8.64 (s, 1H), 8.26 – 8.21 (m, 2H), 8.14 (s, 1H), 8.08 – 8.02 6 (m, 1H), 7.48 – 7.41 (m, 2H), 7.26 – 7.19 (m, Ex. 92 N -(2-fluoro-3- 2H), 7.04 (t, J = 7.9 Hz, 1H), 6.89 (t, J = 7.1 Hz, methylphenyl)N-4-methyl-1- 1H), 5.93 (s, 1H), 2.86 (d, J = 4.7 Hz, 3H), 2.28 phenyl-1H-pyrazolo[3,4- (d, J = 2.1 Hz, 3H). b]pyridine-4,6-diamine Off-wh +ite solid. Yield: (0.040 g, 38%). LC-MS [M+H] : 334.6, Rt = 11.74 min (Method-C 1)H.NMR (400 MHz, DMSO-d6, δ): 8.71 (s, 1H), 8.29 (t, J = 8.2 Hz, 1H), 8.23 (d, J = 7.6 Hz, 2H), Ex.93 N6-(2-fluorophenyl)-N4- 8.14 (s, 1H), 7.46 (t, J = 7.9 Hz, 2H), 7.28 – 7.20 methyl-1-phenyl-1H- (m, 3H), 7.17 (t, J = 7.7 Hz, 1H), 7.05 – 6.97 (m, pyrazolo[3,4b-]pyridine-4,6- 1H), 5.95 (s, 1H), 2.86 (d, J = 4.8 Hz, 3H). diamine Colorless wax. Yield: (0.100 g, 62%). LC-MS [M+H]+: 457.6, Rt = 3.80 min tert-butyl 7-((4- (Method-H). Int. 50 (methylamino)-1-phenyl-H1- pyrazolo[3,4b-]pyridin-6- yl)amino)indoline-1- carboxylate Yellowish wax. Yield: (0.152 g, 86%) LC-MS [M+H]+: 457.5, Rt = 3.60 min (Method-H).Int. 51tert-butyl 6-((4-(methylamino)-1-phenyl-H1- pyrazolo[3,4b-]pyridin-6- yl)amino)indoline-1- carboxylate White + solid. Yield: (0.068 g, 64%). LC 1-MS [M+H] : 369.6, Rt = 11.56 min (Method-C)H.NMR (400 MHz, DMSO-d6, δ): 8.60 (s, 1H), 8.08 (s, 1H), 8.05 – 8.04 (m, 1H), 8.03 – 8.01 Ex. 94 (m, 1H), 7.44 – 7.40 (m, 1H), 7.24 – 7.18 (m, 3H), 7.13 (q, J = 4.7 Hz, 1H), 7.11 – 7.06 (m, 1H), 7.01 – 6.96 (m, 2H), 6.47 (d, J = 3.1 Hz, Ex.# or Structure and name Characterization and procedure Int.# N4-methyl-N6-(1-methyl-1H- 1H), 5.49 (s, 1H), 3.80 (s, 3H), 2.78 (d, J = 4.8 indol-7-yl)-1-phenyl-1H- Hz, 3H). pyrazolo[3,4b-]pyridine-4,6- diamine White solid. Yield: (0.130 g, 79%). tert-butyl 7-((4-((2,2- LC-MS [M+H]+: 508.5, Rt = 3.91 min Int. 52 difluoroethyl)amino)-1- (Method-H). phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Colorless wax. Yield: (0.060 g, 36%). LC-MS [M+H]+: 490.4, Rt = 3.84 minInt. 53tert-butyl 7-((4-((2-(Method-H). fluoroethyl)amino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate White solid. Yield: (0.148 g, 45%). LC-MS [M+H]+: 558.4, Rt = 7.58 minInt. 54tert-butyl 7-((4-((tert-(Method-L). butoxycarbonyl)(methyl)amin o)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Brown solid. Yield: (0.053 g, 36%). LC-MS [M+H]+: 388.3, Rt = 11.48 min (Method-C).1H NMR (400 MHz, DMSO-d6, Ex. 162 δ): 8.91 (s, 1H), 8.12 – 7.99 (m, 2H), 8.00 – 7.84 (m, 2H), 7.35 – 7.17 (m, 3H), 7.17 – 7.08 (m, 1H), 6.96 – 6.86 (m, 1H), 6.79 – 6.70 (m, Ex.# or Structure and name Characterization and procedure Int.# N6-(4-fluoro-1-methyl-1H- 1H), 6.50 (d, J = 3.1 Hz, 1H), 3.79 (s, 3H), 2.88 indol-7-yl)-N4-methyl-1- (s, 3H). phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine White solid. Yield: (0.046 g, 31%). LC-MS [M+H]+: 388.3, Rt = 11.53 min (Method-C). Ex. 1631H NMR (400 MHz, DMSO-d6, δ): 9.05 (s, 1H), 8.17 – 8.07 (m, 2H), 7.97 (d, J = 8.0 Hz, N6-(5-fluoro-1-methyl-1H- 2H), 7.36 – 7.22 (m, 3H), 7.21 – 7.11 (m, 2H), indol-7-yl)-N4-methyl-1- 6.94 (dd, J = 10.8, 2.5 Hz, 1H), 6.43 (d, J = 3.0 phenyl-1H-pyrazolo[3,4- Hz, 1H), 3.81 (s, 3H), 2.91 (s, 3H). d]pyrimidine-4,6-diamine Pale yellow wax. Yield: (0.041 g, 22%). LC-MS [M+H]+: 492.0, Rt = 4.16 min (Method-H). Int. 63 tert-butyl 5-chloro-7-((4- (methylamino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate Brown oil. Yield: (0.060 g, 65%). LC-MS [M+H]+: 483.2, Rt = 3.82 min (Method-H). Int. 64 tert-butyl 5-cyano-7-((4- (methylamino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.009 g, 6%). LC-MS [M+H]+: 372.4, Rt = 11.70 min (Method-C)1.H NMR (400 MHz, DMSO-d6, δ): 8.44 (s, 1H), 8.23 (d, J = 7.5 Hz, 2H), 8.15 – 8.03 (m, 2H), 7.44 (t, J = 7.9 Hz, 2H), 7.24 (t, J Ex. 164 N4-methyl-N6-(1- = 7.4 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.00 (t, methylindolin-4-yl)-1- J = 7.9 Hz, 1H), 6.26 (d, J = 7.6 Hz, 1H), 3.24 – phenyl-1H-pyrazolo[3,4- 3.19 (m, 2H), 2.98 (d, J = 4.5 Hz, 3H), 2.91 (t, J d]pyrimidine-4,6-diamine = 8.2 Hz, 2H), 2.69 (s, 3H). Ex.# or Structure and name Characterization and procedure Int.# Brown oil. Yield: (0.090 g, 47%). LC-MS [M+H]+: 498.6, Rt = 4.08 min (Method-H). Int. 65 tert-butyl 5-cyclopropyl-7- ((4-(methylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)indoline-1- carboxylate White solid. Yield: (0.038 g, 30%). LC-MS [M+H]+: 390.4, Rt = 12.69 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 9.22 (s, 1H), 8.21 (dt, J = 7.1, 1.7 Hz, 3H), 8.15 (s, 1H), 7.53 – 7.47 (m, 2H), 7.30 (tt, J = Ex. 165 N6-(4-fluoro-1-methylindolin- 7.3, 1.5 Hz, 1H), 7.08 (s, 1H), 6.96 (d, J = 11.9 6-yl)-N4-methyl-1-phenyl- Hz, 1H), 3.31 – 3.28 (m, 2H), 3.03 (d, J = 4.5 1H-pyrazolo[3,4- Hz, 3H), 2.85 (t, J = 8.1 Hz, 2H), 2.69 (s, 3H). d]pyrimidine-4,6-diamine Green solid. Yield: (0.038 g, 40%). LC-MS [M+H]+: 490.4, Rt = 4.25 min (Method-H). Int. 66 tert-butyl 4-fluoro-5-methyl- 7-((4-(methylamino)-1- phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.052 g, 35%). LC-MS [M+H]+: 390.6, Rt = 11.57 min (Method-C).1H NMR (400 MHz, DMSO-d6, Ex. 166 δ): 8.56 (s, 1H), 8.28 – 8.23 (m, 2H), 8.14 – 8.00 (m, 2H), 7.46 – 7.36 (m, 2H), 7.25 – 7.19 N6-(5-fluoro-1-methylindolin- (m, 1H), 6.94 (dd, J = 11.0, 2.6 Hz, 1H), 6.83 – 7-yl)-N4-methyl-1-phenyl- 6.76 (m, 1H), 3.28 (t, J = 8.3 Hz, 2H), 3.11 – 1H-pyrazolo[3,4- 2.83 (m, 5H), 2.64 (s, 3H). d]pyrimidine-4,6-diamine Ex.# or Structure and name Characterization and procedure Int.# White solid. Yield: (0.210 g, 82%). LC-MS [M+H]+: 560.2 / 562.1, Rt = 4.34 min (Method-H). Int. 67 tert-butyl 5-chloro-7-((1- phenyl-4-((2,2,2- trifluoroethyl)amino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate Pale brown solid. Yield: (0.155 g, 54%). LC- MS [M+H]+: 420.3, Rt = 10.24 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 9.08 (s, Ex. 167 1H), 8.50 – 8.42 (m, 1H), 8.18 (s, 1H), 8.00 (s, 2H), 7.41 (dd, J = 7.2, 1.8 Hz, 1H), 7.29 (s, N4-(2,2-difluoroethyl)-N6-(1- 2H), 7.23 – 7.13 (m, 2H), 7.03 – 6.92 (m, 2H), methyl-1H-indol-7-yl)-1- 6.44 (d, J = 3.1 Hz, 1H), 6.34 – 5.67 (m, 1H), phenyl-1H-pyrazolo[3,4- 3.78 (s, 3H), 3.78 – 3.57 (m, 2H). d]pyrimidine-4,6-diamine White solid. Yield: (0.070 g, 44%). LC-MS [M+H]+: 540.3, Rt = 4.14 min (Method-H). Int. 68 tert-butyl (R)-7-((1-phenyl-4- ((1,1,1-trifluoropropan-2- yl)amino)-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.110 g, 70%). LC-MS [M+H]+: 540.5, Rt = 4.12 min (Method-H). Int. 69 tert-butyl (S)-7-((1-phenyl-4- ((1,1,1-trifluoropropan-2- yl)amino)-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Ex.# or Structure and name Characterization and procedure Int.# Brown solid. Yield: (0.070 g, 43%). LC-MS [M+H]+: 558.5, Rt = 4.17 min (Method-H).Int. 70tert-butyl 4-fluoro-7-((1- phenyl-4-((3,3,3- trifluoropropyl)amino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.160 g, 96%). LC-MS [M+H]+: 536.4, Rt = 4.16 min (Method-H).Int. 71tert-butyl 4-fluoro-7-((4-((2- fluoro-2- methylpropyl)amino)-1- phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Brown solid. Yield: (0.165 g, 63%). LC-MS [M+H]+: 462.7, Rt = 3.82 min (Method-H). Int. 72 N4-benzyl-N4-methyl-N6-(1- methylindolin-7-yl)-1- phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine White solid. Yield: (0.184 g, 47%). LC-MS [M+H]+: 558.4, Rt = 4.39 min (Method-H). Int. 73 tert-butyl 6-((4-((tert- butoxycarbonyl)(methyl)amin o)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- Ex.# or Structure and name Characterization and procedure Int.# yl)amino)indoline-1- carboxylate Yellow solid. Yield: (0.210 g, 92%). LC-MS [M+H]+: 578.5, Rt = 4.04 min (Method-H).Int. 74tert-butyl 5-((4-((4- methoxybenzyl)(methyl)amin o)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6- yl)amino)indoline-1- carboxylate Yellow oil. Yield: (0.237 g, 93%). LC-MS [M+H]+: 598.7, Rt = 4.08 min (Method-H). Int. 75 N4-(4-methoxybenzyl)N-6-(1- (4-methoxybenzyl)indolin-7- yl)-N4-methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine- 4,6-diamine White solid. Yield: (0.030 g, 22%). LC-MS [M+H]+: 488.7, Rt = 3.78 min (Method-H). Int. 76 tert-butyl 7-((1-(4- methoxyphenyl)-4- (methylamino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate White solid. Yield: (0.012 g, 9%) LC-MS [M+H]+: 369.3, Rt = 4.29 min (Method-A).1H NMR (400 MHz, DMSO-d6, δ): 8.88 (s, 1H), 8.40 – 8.30 (m, 2H), 8.18 (s, 1H), 8.10 (s, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.39 Ex. 168 N4-methyl-N6-(1-methyl-1H- – 7.30 (m, 2H), 7.26 (t, J = 6.2 Hz, 2H), 7.10 indol-5-yl)-1-phenyl-1H- (q, J = 4.7 Hz, 1H), 6.34 (d, J = 3.1 Hz, 1H), Ex.# or Structure and name Characterization and procedure Int.# pyrazolo[3,4b-]pyridine-4,6- 5.66 (s, 1H), 3.77 (s, 3H), 2.85 (d, J = 4.8 Hz, diamine 3H). Yellow solid. Yield: (0.044 g, 34%). LC-MS [M+H]+: 389.5, Rt = 10.46 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.37 (s, 1H), 8.34 – 8.32 (m, 1H), 8.31 – 8.30 (m, 1H), 8.10 (s, 1H), 7.42 – 7.36 (m, 2H), Ex. 169 N6-(5-fluoro-1-methylindolin- 7.22 – 7.13 (m, 2H), 7.07 (dd, J = 11.2, 2.7 Hz, 7-yl)-N4-methyl-1-phenyl- 1H), 6.80 – 6.76 (m, 1H), 5.63 (s, 1H), 3.29 (t, 1H-pyrazolo[3,4b-]pyridine- J = 8.3 Hz, 2H), 2.96 (t, J = 8.3 Hz, 2H), 2.83 4,6-diamine (d, J = 4.8 Hz, 3H), 2.65 (s, 3H). White solid. Yield: (0.038 g, 30%). LC-MS [M+H]+: 389.5, Rt = 11.71 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.32 – 8.29 (m, 2H), 8.19 (s, 1H), 8.06 (s, 1H), 7.39 – 7.34 (m, 2H), 7.18 – 7.14 (m, 1H), Ex. 170 N6-(4-fluoro-1-methylindolin- 7.08 (q, J = 4.7 Hz, 1H), 6.90 (dd, J = 8.7, 5.5 7-yl)-N4-methyl-1-phenyl- Hz, 1H), 6.43 (t, J = 8.4 Hz, 1H), 5.41 (s, 1H), 1H-pyrazolo[3,4b-]pyridine- 3.36 (t, J = 8.5 Hz, 2H), 2.97 (t, J = 8.5 Hz, 4,6-diamine 2H), 2.79 (d, J = 4.7 Hz, 3H), 2.72 (s, 3H). Brown oil. Yield: (0.095 g, 64%) . LC-MS [M+H]+: 507.4, Rt = 3.83 min (Method-H).Int. 77tert-butyl 7-((4-((2,2- difluoroethyl)amino)-1- phenyl-1H-pyrazolo[3,4- b]pyridin-6- yl)amino)indoline-1- carboxylate Brown oil. Yield: (0.093 g, 71%). LC-MS [M+H]+: 577.5, Rt = 4.48 min (Method-H). Int. 78 tert-butyl 7-((4-((4- methoxybenzyl)(methyl)amin o)-1-phenyl-1H-pyrazolo[3,4- b]pyridin-6- yl)amino)indoline-1- carboxylate Ex.# or Structure and name Characterization and procedure Int.# Colourless oil. Yield: (0.070 g, 45%). LC-MS [M+H]+: 472.4, Rt = 3.98 min (Method-H). Int. 79 tert-butyl 7-((3-methyl-4- (methylamino)-1-phenyl-H1- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate Brownish solid. Yield: (0.080 g, 31%). LC-MS [M+H]+: 476.1, Rt = 2.67 min (Method-N). Int. 80 tert-butyl 7-((1-(3- fluorophenyl)-4- (methylamino)-1H- pyrazolo[3,4-d]pyrimidin-6- yl)amino)indoline-1- carboxylate Brownish solid. Yield: (0.080 g, 46%). LC-MS [M+H]+: 476.1, Rt = 2.11 min (Method-N). Int. 81 tert-butyl 7-((1-(2- fluorophenyl)-4- (methylamino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate Brownish solid. Yield: (0.050 g, 58%). LC-MS [M+H]+: 476.4, Rt = 2.13 min (Method-N). Int. 82 tert-butyl 7-((1-(4- fluorophenyl)-4- (methylamino)-1H- pyrazolo[3,4d-]pyrimidin-6- Ex.# or Structure and name Characterization and procedure Int.# yl)amino)indoline-1- carboxylate Yellow + wax. Yield: (0.014 g, 21%). LC-MS [M+H] : 510.4, Rt = 3.77 min (Method-H).Int. 83N6-(6-fluoro-1-methylindolin-7-yl)-N4-(4-methoxybenzyl)- N4-methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine- 4,6-diamine Pale br +own solid. Yield: (0.004 g, 3%). LC-MS [M+H] : 372.1, Rt = 7.46 min (Method-C 1)H.NMR (300 MHz, DMSO-d6, δ): 8.64 (s, 1H), 8.28 – 8.16 (m, 2H), 8.15 – 8.02 (m, 2H), 7.60 71N4(d, J = 8.1 Hz, 1H), 7.44 (t, J = 7.9 Hz, 2H),Ex. 1-methyl-N6-(2-7.25 (t, J = 7.3 Hz, 1H), 7.16 (t, J = 7.7 Hz, methylisoindolin-4-yl)-1- 1H), 6.94 (d, J = 7.3 Hz, 1H), 3.88 – 3.78 (m, phenyl-1H-pyrazolo[3,4- 4H), 2.98 (d, J = 4.4 Hz, 3H), 2.41 (s, 3H). d]pyrimidine-4,6-diamine White solid. Yield: (0.047 g, 34%). LC-MS [M+H]+: 359.4, Rt = 12.40 min (Method-C).1H NMR (400 MHz, DMSO-d6, Ex. 172 δ): 8.24 – 8.20 (m, 2H), 8.19 – 8.10 (m, 2H), 7.91 – 7.81 (m, 2H), 7.51 – 7.46 (m, 2H), 7.29 N6-(2,3-dihydrobenzofuran-7- – 7.24 (m, 1H), 6.94 (dq, J = 7.3, 1.1 Hz, 1H), yl)-N4-methyl-1-phenyl-1H- 6.83 (t, J = 7.7 Hz, 1H), 4.57 (t, J = 8.7 Hz, pyrazolo[3,4d-]pyrimidine- 2H), 3.25 (t, J = 8.7 Hz, 2H), 2.99 (d, J = 4.5 4,6-diamine Hz, 3H). Off-white wax. Yield: (0.163 g, 72%). LC-MS [M+H]+: 616.5, Rt = 4.24 min (Method-H).Int. 84N6-(4-fluoro-1-(4- methoxybenzyl)indolin-7-yl)- N4-(4-methoxybenzyl)N-4- methyl-1-phenyl-1H- pyrazolo[3,4d-]pyrimidine- 4,6-diamine Ex.# or Structure and name Characterization and procedure Int.# Off-white solid. Yield: (0.017 g, 11%). LC-MS [M+H]+: 402.2, Rt = 12.14 min (Method-C).1H NMR (400 MHz, DMSO-d6, δ): 8.86 (s, 1H), 8.21 – 7.85 (m, 4H), 7.32 – 7.18 (m, 3H), 7.18 – 7.09 (m, 1H), 6.86 J (d =, Ex. 173 N6-(4-fluoro-1,5-dimethyl-6.8 Hz, 1H), 6.42 (d J, = 3.1 Hz, 1H), 3.77 (s,1H-indol-7-yl)-N4-methyl-1- 3H), 2.90 (s, 3H), 2.27 (s, 3H). phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine Pale pink oil. Yield: (0.062 g, 24%). LC-MS [M+H]+: 488.2, Rt = 4.43 min (Method-H). Int. 85 tert-butyl 4-fluoro-5-methyl- 7-((4-(methylamino)-1- phenyl-1H-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-1H- indole-1-carboxylate Brown oil. Yield: (0.077 g, 65%). LC-MS [M+H]+: 489.4, Rt = 4.34 min (Method-H). Int. 86 tert-butyl 4-fluoro-5-methyl- 7-((4-(methylamino)-1- phenyl-1H-pyrazolo[3,4- b]pyridin-6- yl)amino)indoline-1- carboxylate Brownish solid. Yield: (0.150 g, 27%). LC-MS [M+H] +: 488.3, Rt = 2.79 min (Method-N).Int. 87 tert-butyl 7-((1-(3- methoxyphenyl)-4- (methylamino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)indoline-1- carboxylate Ex.# or Structure and name Characterization and procedure Int.# White solid. Yield: (0.060 g, 41%). LC-MS [M+H]+: 414.1, Rt = 12.28 min (Method-C).1H NMR (400 MHz, DMSO-d6, Ex. 174 δ): 9.06 – 8.81 (m, 1H), 8.34 – 8.15 (m, 1H), 8.12 – 7.90 (m, 3H), 7.28 – 7.27 (m, 3H), 7.19 – 7.15 (m, 2H), 7.03 – 6.86 (m, 1H), 6.42 (d, J N4-cyclopropyl-N6-(5-fluoro- = 3.1 Hz, 1H), 3.82 (s, 3H), 2.95 – 2.81 (m, 1-methyl-1H-indol-7-yl)-1- 1H), 1.03 – 0.48 (m, 4H). phenyl-1H-pyrazolo[3,4- d]pyrimidine-4,6-diamine Colorless wax. Yield: (0.037 g, 21%). LC-MS [M+H]+: 500.2, Rt = 4.50 min (Method-H). Int. 88 tert-butyl 7-((4- (cyclopropylamino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin- 6-yl)amino)-5-fluoro-1H- indole-1-carboxylate Off-white solid. Yield: (0.019 g, 15%). LC-MS [M+H]+: 492.3, Rt = 4.40 min (Method-H). Int. 89 tert-butyl 5-fluoro-7-((1-(4- fluorophenyl)-4- (methylamino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)-1H-indole-1- carboxylate Off-white solid. Yield: (0.040 g, 22%). LC-MS [M+H]+: 514.1, Rt = 4.46 min (Method-H). Int. 90 tert-butyl 7-((4- (cyclopropylamino)-1- phenyl-1H-pyrazolo[3,4- d]pyrimidin-6-yl)amino)-5- fluoro-4-methyl-1H-indole-1- carboxylate Ex.# or Structure and name Characterization and procedure Int.# Orange wax. Yield: (0.042 g, 23%). LC-MS [M+H]+: 506.1, Rt = 4.35 min (Method-H). Int. 91 tert-butyl 5-fluoro-7-((1-(4- fluorophenyl)-4- (methylamino)-1H- pyrazolo[3,4d-]pyrimidin-6- yl)amino)-4-methyl-1H- indole-1-carboxylate Intermediate 55: tert-butyl 7-((4-((tert-butoxycarbonyl)(methyl)amino)-1-phenyHl-1- pyrazolo[3,4d-]pyrimidin-6-yl)(methyl)amino)indoline-1-carboxyleat To a stirred solution o tfert-butyl 7-((4-((tert-butoxycarbonyl)(methyl)amino)-1-phenyl- 1H-pyrazolo[3,4d-]pyrimidin-6-yl)amino)indoline-1-carboxylate 50%.1 (048 g, 0.13 mmol, 1.0 eq) in DMF (1.5 mL) was added NaH (0.006 g, 0.14o ml,m 1.1 eq). The solution was stirred at 0°C for 30 min. Then, MeI (10 µL, 0.160 mmol, 1.2) e wqas added and the solution was stirred atRT for 40 h. The reaction was then quenched withter wa nd diluted with EtOAc. The aqueous layer was extracted with EtOAc (3 x 10 mL). The cboinmed organic layers were washed with water (3 x 10 mL) and brine (3 x 10 mL), dried over anrhoyuds Na2SO4, filtered and concentrated. Purification of the crude product by flash columhnro cmatography (Silica gel, hexane / EtOAc 0- 40%) afforded tert-butyl 7-((4-((tert-butoxycarbonyl)(methyl)amino)-1-phenyHl-1-pyrazolo[3,4- d]pyrimidin-6-yl)(methyl)amino)indoline-1-carboxyleat as a white solid. Yield: (0.061 g, 80%). LC-MS [M+H+]: 572.5, Rt = 6.99 min (Method-L). To a degassed solution of the appropriate arylri cdhelo (ex: N-(2-(benzyloxy)phenyl)-4- chloro-1-phenyl-1H-pyrazolo[3,4b-]pyridin-6-amine) (1.0 eq) t,ert-butylcarbamate (3.0 eq) and Cs2CO3 (3.0 eq) in dioxane (14 mL / mmol) were added XP (h0o.0s5 eq) and P2d(dba)3 (0.03 eq). The resulting mixture was stirred at 100 °C for h 1.6 The reaction mixture was allowed to cool to RT and diluted with water. The aqueous layer watsra ectxed with EtOAc (x2). The combined organic layers were washed with water (x2) ande b (rxin1), dried over anhydrous 2 NSaO4, filtered and concentrated to dryness. The resulting crudse p wuarified by flash column chromatography (Silica gel, hexane / EtOAc) to obtain the desiredod purct (ex: tert-butyl (6-((2- (benzyloxy)phenyl)amino)-1-phenylH-1-pyrazolo[3,4b-]pyridin-4-yl)carbamate). The following intermediates were prepared accord toin tghe general procedure F: Characterization and Int # Structure and name procedure Off-white solid. Yield: (0.033 g, quantitative yield). LC-MS [M+H]+: 508.1, Rt = 56 4.44 min (Method-B). tert-butyl (6-((2-(benzyloxy)phenyl)amino)-1- phenyl-1H-pyrazolo[3,4b-]pyridin-4-yl)carbamate Pale yellow solid. Yield: (0.087 g, 96%). LC-MS [M+H]+: 420.3, Rt = 57 4.00 min (Method-B). tert-butyl (6-((2-fluorophenyl)amino)-1-phenylH-1- pyrazolo[3,4b-]pyridin-4-yl)carbamate General Procedure G To a solution of appropriate ester (ex: 3-((4-(myelatmhino)-1-phenyl-1H-pyrazolo[3,4- d]pyrimidin-6-yl)amino)benzoate) (1.0 eq) in THF ( m40L / mmol) was added LiBH4(13.3 eq). The solution was stirred at 50 °C for 16 h unde2r a Ntmosphere. After the reaction mixture was cooled to RT, water was added, and the crude was acid tiofie pdH 3 with 1 M HCl. The aqueous layer was extracted with EtOAc (x3). The combined organice lrasy were washed with water (x2) and brine (x1), dried over anhydrous N2SaO4, filtered and volatiles were removed under redu pcreedssure. The resulting crude was purified by flash columnro cmhatography (Silica gel, hexane / EtOAc) to obtain the desired compound (ex: (3-((4-(methylaom)-i1n-phenyl-1H-pyrazolo[3,4d-]pyrimidin-6- yl)amino)phenyl)methanol). The following Examples (Ex.) were prepared accogrd toin the general procedure G: Ex.# Structure and name Characterization and procedure Off-white solid. Yield: (0.042 g, 76%). LC-MS [M+H]+: 347.2, Rt = 9.36 min (Method- C).1H NMR (400 MHz, DMSO-d6 δ,): 9.26 (s, 1H), 8.29 – 8.23 (m, 2H), 8.18 – 8.05 (m, 3H), 95 7.58 – 7.50 (m, 3H), 7.33 – 7.27 (m, 1H), 7.22 (t, (3-((4-(methylamino)-1-phenyl- J = 7.8 Hz, 1H), 6.93 – 6.89 (m, 1H), 5.14 (t, J = 1H-pyrazolo[3,4d-]pyrimidin-6- 5.7 Hz, 1H), 4.50 (d, J = 5.6 Hz, 2H), 3.04 (d, J yl)amino)phenyl)methanol = 4.5 Hz, 3H). Off-white solid. Yield: (0.024 g, 67%). LC-MS [M+H]+: 347.1, Rt = 10.37 min (Method-C).1H NMR (400 MHz, DMSO-d6 δ,): 8.72 (s, 1H), 8.24 – 8.11 (m, 5H), 7.48 (t, J = 7.9 96 Hz, 2H), 7.35 – 7.23 (m, 3H), 7.04 – 6.96 (m, (2-((4-(methylamino)-1-phenyl- 1H), 5.56 (t, J = 5.2 Hz, 1H), 4.59 (d, J = 5.2 Hz, 1H-pyrazolo[3,4d-]pyrimidin-6- 2H), 2.98 (d, J = 4.5 Hz, 3H). yl)amino)phenyl)methanol General Procedure H The appropriate carboxylate (ex: Tert-butyl 7-((4-(methylamino)-1-phenylH-1- pyrazolo[3,4d-]pyrimidin-6-yl)amino)indoline-1-carboxylate) (1. e0q) was dissolved in HCl 4 M in dioxane (27 mL / mmol). The solution was stirretd R aT between 1 h and 16 h. The crude volatiles were removed under reduced pressure. Then, Na3H aCnOd EtOAc were added, and the mixture was stirred at RT for 1 h. The aqueous layer watrsac etxed with more EtOAc (x3). The combined organic layers were washed with water (x1) ande b (rxin1). The resulting organic layer was dried over anhydrous N2aSO4, filtered and concentrated. The resulting crudes w puarified by flash column chromatography (Silica gel, hexane / EtOAc) r oerverse phase flash column chromatography (C18, 10 mM aqueous4 NOHAc (pH 7) / ACN) to obtain the desired product: (ex N6-(indolin-7-yl)-N4-methyl-1-phenyl-1H-pyrazolo[3,4d-]pyrimidine-4,6-diamine). The following Examples (Ex.) were prepared accogrd toin the general procedure H: Ex.# Structure and name Characterization and procedure White solid. Y...

Claims

WHAT IS CLAIMED IS:

1. A compound having Formula (I):or a pharmaceutically acceptable salt or solvaetere tohf, wherein: A1 is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no morethan one of A2, A3, and A4is N; R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R2is selected from the group consisting of hydrog -Cen1-,6alkyl, -C(=O)-C1-4alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-4 alkyl-C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl, wherein said -1C-6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl- C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6- membered)-C2-5heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl groups are optionally substituted by 1, 2 or 3 substituse enatch independently selected from the group consisting of halogen, -N(R2,a a)nd -ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4alkyl, and -C3-6cycloalkyl, wherein said -1C-4alkyl and -C3-6cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydro agnedn -C1-4 alkyl, wherein said-C1-4alkyl is optionally substituted with 1 or 2 subtusetints each independently selected from the group consisting of halogen, -CN, and -O; oRra R2 and R3 together with the nitrogen atom to which they a trteached form an optionally substituted spirocyclic heterocyclicg r;in R4is selected from the group consisting of hydrog heanlo,gen, and -1C-4alkyl optionally substituted by 1, 2 or 3 halogen ato amnsd;each R5 is independently selected from the group consis otifn hgalogen, -CN, -ORa, -C1-4alkyl, -C3-6cycloalkyl, and -(3- to 6-membered)1--C5heterocyclyl, wherein said -1C-4alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the group consisting of halogen, hydroxy, -N(R2b, ) -C1-4alkyl, -C1-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -C1-4 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl groups are optionally substituted b,y 21 or 3 substituents each independently selected from the group consisting of1--4C alkyl, -C1-4alkoxy, and halogen; R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydro -xCy1,-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ringh,e wrein 1 or 2 carbon atoms of said heterocyclic ring are optionally replaced with ate hroeatom independently selected fromthe group consisting of O, N, and S, and whereind s haeterocyclic ring is optionallysubstituted with 1 or 2 substituents each indepnetnlyde selected form the group consisting of halogen and -1C-4alkyl; R7 is selected from the group consisting of hydrog heanlo,gen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb2), -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –C3-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a5- or 6-membered ring having at least one hetemro,at woherein the ring is optionallysubstituted by one or more substituents selecotemd t fhre group consisting of halogen, -CN,-C(=O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl is optionally substitut bedy 1, 2 or 3 fluorine atoms; orR6 and R7, together with adjacent carbon atoms to which tahrey attached, form a7-, 8-, 9-, or 10-membered spiroheterocyclyl gro thuapt is saturated or unsaturated, whereinthe spiroheterocyclyl group is optionally substeitdut by one or more substituents selected from the group consisting of halogen and1-4 -C alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atoms; and R6, R7, and R8 each take the place of a hydrogen atom that wo tuhlderwise be present in any position on the ring of Formula to (I) which R6, R7 and R8 are attached; with the proviso that the compound having FormuI)la is ( not: 2-((6-(benzo[d][1,3]dioxol-5-ylamino)-1-(p-tolyl)-H1-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(methyl(phenyl)amino)-1Hy-rpazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-fluorophenyl)-6-(indolin-1-yl)-1H-pyrazo[l3o,4-d]pyrimidin-4-yl)amino)ethan- 1-ol; 2-((1-(4-chlorophenyl)-6-(indolin-1-yl)-1H-pyrazo[l3o,4-d]pyrimidin-4-yl)amino)ethan- 1-ol; 2-((6-(indolin-1-yl)-1-(p-tolyl)-1H-pyrazolo[3,4-dp]yrimidin-4-yl)amino)ethan-1-ol; 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-14--(fluorophenyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(2,3-dihydro-4H-benzo[b,]4[1]oxazin-4-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-1p--(tolyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((6-(3,4-dihydroquinolin-1(2H)-yl)-1-(4-fluorophneyl)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(3,4-dihydroquinolin-1(2-Hy)l)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((6-(3,4-dihydroquinolin-1(2H)-yl)-1-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; N4-ethyl-N6,1-diphenyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine; N6,1-diphenyl-N4-propyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine; or N4-cyclohexyl-N6,1-diphenyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine.

2. The compound of claim 1 having Formula (I):(I) or a pharmaceutically acceptable salt or solvaetere tohf, wherein: A1 is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no morethan one of A2, A3, and A4is N; R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; R2is selected from the group consisting of hydrog -Cen1-,6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4alkyl-(3- to 6-membered)-2C-5heterocyclyl, wherein said -1C-6alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl- C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6- membered)-C2-5 heterocyclyl, and -C1-4 alkyl-(3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted by 1, 2 or 3 substituse enatch independently selected from the group consisting of halogen, -N(R2,a a)nd -ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4 alkyl, and -C3-6cycloalkyl, wherein said -1C-4alkyl and -C3-6cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydro agnedn -C1-4 alkyl, wherein said-C1-4alkyl is optionally substituted with 1 or 2 subtusetints each independently selected from the group consisting of halogen, -CN, and -O; Ra R4 is selected from the group consisting of hydrog heanlo,gen, and -1C-4 alkyl optionally substituted by 1, 2 or 3 halogen ato amnsd;each R5is independently selected from the group consis otifn hgalogen, -CN, -ORa, -C1-4 alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl, wherein said -1C-4 alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the groupconsisting of halogen, hydroxy, -N(R2b, ) -C1-4 alkyl, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -C1-4 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl groups are optionally substituted b,y 21 or 3 substituents each independently selected from the group consisting of1--4C alkyl, -C1-4alkoxy, and halogen; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydro -xCy1,-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ringh,e wrein 1 or 2 carbon atoms of said heterocyclic ring are optionally replaced with ate hroeatom independently selected fromthe group consisting of O, N, and S, and whereind s haeterocyclic ring is optionallysubstituted with 1 or 2 substituents each indepnetnlyde selected form the group consisting of halogen and -1C-4alkyl; R7is selected from the group consisting of hydrog heanlo,gen, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb2), -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –C3-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a5- or 6-membered ring having at least one hetemro,at woherein the ring is optionallysubstituted by one or more substituents selecotemd t fhre group consisting of halogen, -CN,-C(=O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl is optionally substitut bedy 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a7-, 8-, 9-, or 10-membered spiroheterocyclyl gro thuapt is saturated or unsaturated, whereinthe spiroheterocyclyl group is optionally substeitdut by one or more substituents selectedfrom the group consisting of halogen and1-4 -C alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atoms; and R6, R7, and R8 each take the place of a hydrogen atom that wo tuhlderwise be present in any position on the ring of Formula to (I) which R6, R7 and R8 are attached; with the proviso the compound having Formula (I n)o ist: 2-((6-(benzo[d][1,3]dioxol-5-ylamino)-1-(p-tolyl)-H1-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(methyl(phenyl)amino)-1Hy-rpazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-fluorophenyl)-6-(indolin-1-yl)-1H-pyrazo[l3o,4-d]pyrimidin-4-yl)amino)ethan- 1-ol; 2-((1-(4-chlorophenyl)-6-(indolin-1-yl)-1H-pyrazo[l3o,4-d]pyrimidin-4-yl)amino)ethan- 1-ol; 2-((6-(indolin-1-yl)-1-(p-tolyl)-1H-pyrazolo[3,4-dp]yrimidin-4-yl)amino)ethan-1-ol; 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-14--(fluorophenyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(2,3-dihydro-4H-benzo[b,]4[1]oxazin-4-yl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((6-(2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)-1p--(tolyl)-1H-pyrazolo[3,4- d]pyrimidin-4-yl)amino)ethan-1-ol; 2-((6-(3,4-dihydroquinolin-1(2H)-yl)-1-(4-fluorophneyl)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; 2-((1-(4-chlorophenyl)-6-(3,4-dihydroquinolin-1(2-Hy)l)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol; or 2-((6-(3,4-dihydroquinolin-1(2H)-yl)-1-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4- yl)amino)ethan-1-ol.

3. The compound of claim 1 or 2 having Formula: (II)or a pharmaceutically acceptable salt or solvaetere tohf.

4. The compound of claim 1 or 2 having Formula): (IIIor a pharmaceutically acceptable salt or and seol tvhaetreof.

5. The compound of any one of claims 1-4, or am phaacreutically acceptable salt or solvate thereof, wherein R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl.

6. The compound of claim 5, or a pharmaceuticaclclye aptable salt or solvate thereof, wherein R1is selected from the group consisting of hydro agnedn -C1-4alkyl.

7. The compound of claim 6, or a pharmaceuticaclclye aptable salt or solvate thereof, wherein R1 is hydrogen.

8. The compound of any one of claims 1-4, or am phaacreutically acceptable salt or solvate thereof, wherein R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ringh,e wrein 1 or 2 carbon atoms of said heterocyclic ring are optionally replaced with a heteroatom p inednedently selected from the group consisting of O, N, and S, and wherein said heterocyclic r isin ogptionally substituted with 1 or 2 substituents each independently selected form the group consgis otfi halogen and -1C-4alkyl.

9. The compound of claim 8, or a pharmaceuticaclclye aptable salt or solvate thereof, wherein R2 is selected from the group consisting of hydrog meent,hyl, -C3-6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said methyl,3 --C6 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl- (3- to 6-membered)-2C-5heterocyclyl groups are optionally substituted 1 b,y 2 or 3 substituents each independently selected from the group consgis otfi halogen, -N(Ra2,) and –ORa.

10. The compound of claim 8, wherein2i Rs not -CH2CH2OH.

11. The compound of any one of claims 1 or 8-10in hgav Formula (IV):or a pharmaceutically acceptable salt or solvaetere tohf.

12. The compound of any one of claims 1 or 8-10in hgav Formula (V):or a pharmaceutically acceptable salt or solvaetere tohf.

13. The compound of any one of claims 1 or 8-10in hgav Formula (VI):or a pharmaceutically acceptable salt or solvaetere tohf.

14. The compound of any one of claims 1 or 8-10in hgav Formula (VII):or a pharmaceutically acceptable salt or solvaetere tohf.

15. The compound of any one of claims 1-14, ora arm phaceutically acceptable salt or solvate thereof, wherein R2 is hydrogen.

16. The compound of any one of claims 1-14, ora arm phaceutically acceptable salt or solvate thereof, wherein R2 is selected from the group consisting of1-5 -C alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-2alkyl- (3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-2alkyl-(3- to 6- membered)-C2-5 heterocyclyl groups are optionally substituted 1 by or 2 substituents each independently selected from the group consisting ha olof gen and –ORa, wherein Ra is selected from the group consisting of hydrogen, methyl, a enthdyl, wherein said methyl and ethyl groups are optionally substituted with 1, 2, or 3 fluori anteoms.

17. The compound of any one of claims 1-16, ora arm phaceutically acceptable salt or solvate thereof, wherein R3is hydrogen.

18. The compound of any one of claims 1-16, ora arm phaceutically acceptable salt or solvate thereof, wherein R3is -C1-4alkyl.

19. The compound of any one of claims 1-18, ora arm phaceutically acceptable salt or solvate thereof, wherein R4is hydrogen.

20. The compound of any one of claims 1-19, ora arm phaceutically acceptable salt or solvate thereof, wherein n is 0.

21. The compound of any one of claims 1-7 or 15 o-2r0 a, pharmaceutically acceptable salt or solvate thereof, wherein6 R is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(Rb)2, and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydro -xCy1,-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-.

22. The compound of any one of claims 1-21, ohr a rm paceutically acceptable salt or solvatethereof, wherein R7is selected from the group consisting of hydrog heanlo,gen, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halong aetoms.

23. The compound of any one of claims 1-22, ora arm phaceutically acceptable salt or solvate thereof, wherein each8 R is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb2), -C1-4 alkyl optionally substituted with 1, 2, or 3 fluinoer atoms, and –3C-6 cycloalkyl.

24. The compound of any one of claims 1-23, whe mrei ins 1.

25. The compound of any one of claims 1-7 or 15 o-2r0 a, pharmaceutically acceptable salt or solvate thereof, wherein: R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from thegroup consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms.

26. The compound of claim 25, or a pharmaceutic aacllcyeptable salt or solvate thereof, having Formula (VIII):

27. The compound of claim 25, or a pharmaceutic aacllcyeptable salt or solvate thereof, having Formula (IX):

28. The compound of any one of claims 1-7, 15-2r02,5 o-27, or a pharmaceutically acceptable salt or solvate thereof, wherein6 R and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 5- or 6-membered ring havtin lgea ast one heteroatom, wherein the ring is optionally substituted by one or more substitue snetlsected from the group consisting of halogen, -CN, -C(=O)-C1-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms.

29. The compound of any one of claims 1-7, 15-2r02,5 o-27, or a pharmaceutically acceptable salt or solvate thereof, wherein6R and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a 5-membered ring having att l oenaes nitrogen atom, wherein the ring is optionally substituted by one or more substitue snetlsected from the group consisting of halogen, -CN, -C(=O)-C1-4 alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms.

30. The compound of any one of claims 1-7, 15-2r02,5 o-29, or a pharmaceutically acceptable salt or solvate thereof, wherein6 R and R7, together with the adjacent carbon atoms to wh thicehy are attached, form a ring selected from the groounpsi csting ofwherein is a single bond or a doublebond, and wherein x R and Ry are each independently selected from the groupsis ctoin g ofhydrogen, halogen, -CN, -C(=O)1--C4alkyl, and -C1-4alkyl, wherein said alkyl is optionally substituted by 1, 2 or 3 fluorine atoms, and whner Rexi and Ryeach take the place of a hydrogen atom that would otherwise be present in any ponsi otino the ring to whichxR and Ryare attached.

31. The compound of any one of claims 1-7 or 15 o-2r4 a, pharmaceutically acceptable salt or solvate thereof, having Formula (X):wherein R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1- -4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; R7 is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4 alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4 alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6 cycloalkyl; and m is 1, 2, or 3.

32. The compound of any one of claims 1-25 or 2,8 o-3r0 a pharmaceutically acceptable salt or solvate thereof, wherein2A is N; and A3and A4are CH.

33. The compound of any one of claims 1-25 or 2,8 o-3r0 a pharmaceutically acceptable salt or solvate thereof, wherein2 A and A4 are CH; and A3 is N.

34. The compound of any one of claims 1-25 or 2,8 o-3r0 a pharmaceutically acceptable salt or solvate thereof, wherein2 A and A3 are CH; and A4 is N.

35. The compound of any one of claims 1-25 or 2,8 o-3r0 a pharmaceutically acceptable salt or solvate thereof, wherein2, A A3, and A4are CH.

36. The compound of claim 1 or 2, or a pharmacealulytic acceptable salt or solvate thereof, that is any one or more of the compounds of Ta.ble 1 37. The compound of claim 1, or a pharmaceutic aacllcyeptable salt or solvate thereof, that is any one or more of the compounds of Table 2.

38. A pharmaceutical composition comprising the p co umnd of any one of claims 1-37, or apharmaceutically acceptable salt or solvate the,r aenodf at least one pharmaceutically acceptable excipient.

39. A compound of Formula (I):or a pharmaceutically acceptable salt or solvaetere tohf, wherein: A1 is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no morethan one of A2, A3, and A4is N; R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl;R2 is selected from the group consisting of hydrog -Cen1-,6 alkyl, -C(=O)-C1-4 alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)2-C-5 heterocyclyl, and -C1-4 alkyl-(3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl- C3-6 cycloalkyl, -C1-4 alkyl-C3-6 cycloalkenyl, -C1-4 alkyl-C3-6 cycloalkynyl, -(3- to 6- membered)-C2-5 heterocyclyl, and -C1-4 alkyl-(3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted by 1, 2 or 3 substituse enatch independently selected from the group consisting of halogen, -N(R2,a a)nd –ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4 alkyl, and -C3-6 cycloalkyl, wherein said -1C-4 alkyl and -C3-6 cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydro agnedn –C1-4 alkyl, wherein said–C1-4 alkyl is optionally substituted with 1 or 2 subtusetints each independently selected from the group consisting of halogen, -CN, and -O; oRra R2 and R3 together with the nitrogen atom to which they a trteached form an optionally substituted spirocyclic heterocyclicg r;in R4is selected from the group consisting of hydrog heanlo,gen, and -1C-4alkyloptionally substituted by 1, 2 or 3 halogen ato amnsd;each R5 is independently selected from the group consis otifn hgalogen, -CN, -ORa, -C1-4 alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl, wherein said -1C-4 alkyl, -C3-6cycloalkyl, and -(3- to 6-membered)1--C5heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the group consisting of halogen, hydroxy, -N(R2b, ) -C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -C1-4alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl groups are optionally substituted b,y 21 or 3 substituents each independently selected from the group consisting of1- -4C alkyl, -C1-4 alkoxy, and halogen; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selectedfrom the group consisting of halogen, -CN, hydro -xCy1,-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ringh,e wrein 1 or 2 carbon atoms of said heterocyclic ring are optionally replaced with ate hroeatom independently selected from the group consisting of O, N, and S, and whereind s haeterocyclic ring is optionallysubstituted with 1 or 2 substituents each indepnetnlyde selected form the group consisting of halogen and -1C-4alkyl; R7is selected from the group consisting of hydrog heanlo,gen, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb2), -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –C3-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a5- or 6-membered ring having at least one hetemro,at woherein the ring is optionally substituted by one or more substituents selecotemd t fhre group consisting of halogen, -CN,-C(=O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl is optionally substitut bedy 1, 2 or 3 fluorine atoms; or R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, forma 7-, 8-, 9-, or 10-membered spiroheterocyclyl gpro thuat is saturated or unsaturated, wherein the spiroheterocyclyl group is optionalulyb s tituted by one or more substituentsselected from the group consisting of halogen aCn1d-4 - alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atom ans;d R6, R7, and R8each take the place of a hydrogen atom that wo tuhledrwise be present in any position on the ring of Formula to (I) which R6, R7 and R8 are attached, for use as a medicament for treating or preven atin dgisease, condition, or disorder in a patient.

40. The compound for use of claim 39 having Form (Iu)l:aor a pharmaceutically acceptable salt or solvaetere tohf, wherein: A1is N or CH; A2, A3, and A4 are each independently N or CH, with the provhisaot t no morethan one of A2, A3, and A4 is N; R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R2 is selected from the group consisting of hydrog -Cen1-,6 alkyl, -C(=O)-C1-4 alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl-C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6-membered)2-C-5heterocyclyl, and -C1-4 alkyl-(3- to 6-membered)-2C-5 heterocyclyl, wherein said -1C-6 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, -C3-6cycloalkenyl, -C3-6cycloalkynyl -C1-4alkyl- C3-6cycloalkyl, -C1-4alkyl-C3-6cycloalkenyl, -C1-4alkyl-C3-6cycloalkynyl, -(3- to 6- membered)-C2-5 heterocyclyl, and -C1-4 alkyl-(3- to 6-membered)-2C-5 heterocyclyl groups are optionally substituted by 1, 2 or 3 substituse enatch independently selected from the group consisting of halogen, -N(R2,a a)nd –ORa; each Ra is independently selected from the grounpsis ctoing of hydrogen, -1C-4alkyl, and -C3-6 cycloalkyl, wherein said -1C-4 alkyl and -C3-6 cycloalkyl groups are optionally substituted by 1, 2 or 3 halogen atoms; R3 is selected from the group consisting of hydro agnedn –C1-4 alkyl, wherein said–C1-4 alkyl is optionally substituted with 1 or 2 subtusetints each independently selected from the group consisting of halogen, -CN, and -O; Ra R4is selected from the group consisting of hydrog heanlo,gen, and -1C-4alkyloptionally substituted by 1, 2 or 3 halogen ato amnsd;each R5 is independently selected from the group consis otifn hgalogen, -CN, -ORa, -C1-4alkyl, -C3-6cycloalkyl, and -(3- to 6-membered)1--C5heterocyclyl, wherein said -1C-4alkyl, -C3-6 cycloalkyl, and -(3- to 6-membered)1--C5 heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each innddeepnetly selected from the groupconsisting of halogen, hydroxy, -N(R2b, ) -C1-4 alkyl , -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; n is 0, 1, or 2; each Rb is independently selected from the grounpsi csoting of hydrogen, -1C-4 alkyl, -C(=O)-C1-4alkyl, -C3-6cycloalkyl, and -(5- to 6-membered)2--C5heterocyclyl, wherein said -C1-4 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, and -(5- to 6-membered)2--C5 heterocyclyl groups are optionally substituted b,y 21 or 3 substituents each independently selected from the group consisting of1--4C alkyl, -C1-4alkoxy, and halogen; R6is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydro -xCy1,-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; or R1 and R6 together with the nitrogen and carbon atoms toch wh thiey are attached form an optionally substituted heterocyclic ringh,e wrein 1 or 2 carbon atoms of said heterocyclic ring are optionally replaced with ate hroeatom independently selected fromthe group consisting of O, N, and S, and whereind s haeterocyclic ring is optionallysubstituted with 1 or 2 substituents each indepnetnlyde selected form the group consisting of halogen and -1C-4alkyl; R7is selected from the group consisting of hydrog heanlo,gen, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb2), -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –C3-6 cycloalkyl; and m is 1, 2, or 3; or R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a5- or 6-membered ring having at least one hetemro,at woherein the ring is optionallysubstituted by one or more substituents selecotemd t fhre group consisting of halogen, -CN,-C(=O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl is optionally substitut bedy 1, 2 or 3 fluorine atoms; or R6 and R7, together with the adjacent carbon atoms to w thhicehy are attached, forma 7-, 8-, 9-, or 10-membered spiroheterocyclyl gpro thuat is saturated or unsaturated,wherein the spiroheterocyclyl group is optionalulyb s tituted by one or more substituentsselected from the group consisting of halogen aCn1d-4 - alkyl, wherein said alkyl, is optionally substituted by 1, 2 or 3 fluorine atom ans;d R6, R7, and R8 each take the place of a hydrogen atom that wo tuhledrwise be present in any position on the ring of Formula to (I) which R6, R7 and R8 are attached, for use as a medicament for treating or preven atin dgisease, condition, or disorder in a patient.

41. The compound for use of claim 40 or 41, wher tehien compound of Formula (I) is a compound having Formula (II):or a pharmaceutically acceptable salt or solvaetere tohf.

42. The compound for use of claim 40 or 41, wher tehien compound of Formula (I) is a compound having Formula (III):or a pharmaceutically acceptable salt or and seol tvhaetreof.

43. The compound for use of any one of claims 4,0 w-4h2erein R1 is selected from the group consisting of hydrogen, -1C-4 alkyl, -C3-6 cycloalkyl, and -C1-4 alkyl-C3-6 cycloalkyl.

44. The compound for use of claim 43, wherei1n is R selected from the group consisting of hydrogen and -C1-4 alkyl.

45. The compound for use of claim 43, where1in is R hydrogen.

46. The compound for use of any one of claims 4,0 w-4h2erein R1and R6together with the nitrogen and carbon atoms to which they are attdac fohrem an optionally substituted heterocyclic ring, wherein 1 or 2 carbon atoms of said heterloiccy rcing are optionally replaced with a heteroatom independently selected from the grounpsi csoting of O, N, and S, and wherein said heterocyclic ring is optionally substituted with or 12 substituents each independently selected form the group consisting of halogen and1- -4C alkyl.

47. The compound for use of any one of claims 410, o, 4r 46, wherein the compound of Formula (I) is a compound having Formula (IV):or a pharmaceutically acceptable salt or solvaetere tohf.

48. The compound for use of any one of claims 410, o, 4r 46, wherein the compound of Formula (I) is a compound having Formula (V):or a pharmaceutically acceptable salt or solvaetere tohf.

49. The compound for use of any one of claims 410 o,r 446, wherein the compound of Formula (I) is a compound having Formula (VI):or a pharmaceutically acceptable salt or solvaetere tohf.

50. The compound for use of any one of claims 410,, o 4r 46, wherein the compound of Formula (I) is a compound having Formula (VII):or a pharmaceutically acceptable salt or solvaetere tohf.

51. The compound for use of any one of claims 4,0 w-5h0erein R2 is hydrogen.

52. The compound for use of any one of claims 4,0 w-5h0erein R2is selected from the group consisting of -C1-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-2alkyl-C3-6cycloalkyl, -C1-2alkyl-C3-6cycloalkenyl, -C1-2alkyl-C3-6cycloalkynyl, -(3- to 6- membered)-C2-5heterocyclyl, and -C1-2alkyl-(3- to 6-membered)-2C-5heterocyclyl, wherein said -C1-5 alkyl, -C(=O)-C1-4 alkyl, -C3-6 cycloalkyl, -C3-6 cycloalkenyl, -C3-6 cycloalkynyl -C1-2 alkyl- C3-6 cycloalkyl, -C1-2 alkyl-C3-6 cycloalkenyl, -C1-2 alkyl-C3-6 cycloalkynyl, -(3- to 6-membered)- C2-5heterocyclyl, and -C1-2alkyl-(3- to 6-membered)-2C-5heterocyclyl groups are optionally substituted by 1 or 2 substituents each indepenlyd seenltected from the group consisting of halogenand –ORa, wherein Ra is selected from the groupsis ctoin g of hydrogen, methyl, and ethyl,wherein said methyl and ethyl groups are option saullbystituted with 1, 2, or 3 fluorine atoms.

53. The compound for use of any one of claims 4,0 w-5h2erein R3 is hydrogen.

54. The compound for use of any one of claims 4,0 w-5h2erein R3is -C1-4alkyl.

55. The compound for use of any one of claims 4,0 w-5h4erein R4is hydrogen.

56. The compound for use of any one of claims 4,0 w-5h5erein n is 0.

57. The compound for use of any one of claims 40 o-r4561-56, wherein 6 R is selected from the group consisting of hydrogen, halogen, -CN, a -O, R -N(Rb)2, and -C1-4 alkyl optionally substituted by 1, 2 or 3 substituents each indeepnetnlyd selected from the group consisting of halogen, -CN, hydroxy, -1C-4alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-.

58. The compound for use of any one of claims74,0 w-5herein R7 is selected from the group consisting of hydrogen, halogen, -ORa, an1d-4- aClkyl optionally substituted with 1, 2, or 3 haelong atoms.

59. The compound for use of any one of claims 4,0- w5h8erein each8R is independently selected from the group consisting of hydrogen,og heanl, -ORa, -CN, -N(Rb2,) -C1-4 alkyl optionally substituted with 1, 2 or 3 fluorine atso,m and –C3-6 cycloalkyl.

60. The compound for use of any one of claims 4,0 w-5h9erein m is 1.

61. The compound for use of any one of claims 40 o-r4521-56, wherein: R1is selected from the group consisting of hydrog -Cen1-,4alkyl, -C3-6cycloalkyl, and -C1-4alkyl-C3-6 cycloalkyl; each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6cycloalkyl; and R6 and R7, together with adjacent carbon atoms to which tahrey attached, form a 5- or 6-membered ring having at least one heteroatom, winh tehre ring is optionally substituted by one ormore substituents selected from the group consgis otfin halogen, -CN, -C(=O)-1C-4alkyl, and -C1-4 alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms; or R6 and R7, together with adjacent carbon atoms to which t ahrey attached, form a 7-, 8-,9-, or 10-membered spiroheterocyclyl group that sa isturated or unsaturated, wherein the spiroheterocyclyl group is optionally substituteyd o bne or more substituents selected from thegroup consisting of halogen and1 --4C alkyl, wherein said alkyl, is optionally substitudte by 1, 2 or 3 fluorine atoms.

62. The compound for use of claim 61, wherein tohmep cound of Formula (I) is a compound having Formula (VIII):or a pharmaceutically acceptable salt or solvaetere tohf.

63. The compound for use of claim 61, wherein tohmep cound of Formula (I) is a compound having Formula (IX):or a pharmaceutically acceptable salt or solvaetere tohf.

64. The compound for use of any one of claims 4,05-412-56, or 61-63, wherein6R and R7,together with the adjacent carbon atoms to whicehy t ahre attached, form a 5- or 6-membered ringhaving at least one heteroatom, wherein the ring op itsionally substituted by one or more substituents selected from the group consistin hga olofgen, -CN, -C(=O)-1C-4alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substituted by 21 o,r 3 fluorine atoms.

65. The compound for use of any one of claims 4,05-412-56, or 61-63, wherein6R and R7,together with the adjacent carbon atoms to whicehy a thre attached, form a 5-membered ring havingat least one nitrogen atom, wherein the ring isio onpatlly substituted by one or more substituents selected from the group consisting of halogen, -C -CN(=, O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl, is optionally substituted by 1, 2 o frlu 3orine atoms.

66. The compound for use of any one of claims 4,05-412-56, or 61-65, or a pharmaceutically acceptable salt or solvate thereof, where6in an Rd R7, together with the adjacent carbon atoms to which they are attached, form a ring selected f trhoem group consisting of:wherein is a single bond or a double bond, and wherexin an Rd Ryare each independently selected from the group consisting of hydrogeno,g heanl, -CN, -C(=O)-C1-4alkyl, and -C1-4alkyl, wherein said alkyl is optionally substituted by 21 o,r 3 fluorine atoms, and whereinxa Rnd Ryeachtake the place of a hydrogen atom that would othiserw be present in any position on the ring towhich Rxand Ryare attached.

67. The compound for use of any one of claims 40 o-r451-56, having Formula (X):or a pharmaceutically acceptable salt or solvaetere tohf, wherein R1 is selected from the group consisting of hydrog -Cen1-,4 alkyl, -C3-6 cycloalkyl, and -C1-4alkyl-C3-6cycloalkyl; R6 is selected from the group consisting of hydrog heanlo,gen, -CN, -ORa, -N(R2b,) and -C1-4 alkyl optionally substituted by 1, 2 or 3 subsetintuts each independently selected from the group consisting of halogen, -CN, hydroxy,1--4C alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; R7is selected from the group consisting of hydrog heanl,ogen, -ORa, and -1C-4alkyl optionally substituted with 1, 2, or 3 halogen asto;m each R8 is independently selected from the group consgis otifn hydrogen, halogen, -ORa, -CN, -N(Rb)2, -C1-4alkyl optionally substituted with 1, 2, or 3 haelong atoms, and –3C-6cycloalkyl; and m is 1, 2, or 3.

68. The compound for use of any one of claims 40 o-r6614-66, wherein A2 is N; and A3 and A4are CH.

69. The compound for use of any one of claims 40 o-r6614-66, wherein A2 and A4 are CH; and A3is N.

70. The compound for use of any one of claims 40 o-r6614-66, wherein A2 and A3 are CH; and A4is N.

71. The compound for use of any one of claims 40 o-r6614-66, wherein A2, A3, and A4 are CH.

72. The compound for use of claim 39 or 40, whe trheein compound of Formula (I) is any one or more of the compounds of Table 1.

73. The compound for use of claim 40, wherein tohmep cound of Formula (I) is any one or more of the compounds of Table 2.

74. The compound for use of any one of claims 4,0 w-7h3erein the disease, condition, or disorder is associated with the alteration of tchteiv aity of β-glucocerebrosidase (GBA).

75. The compound for use of any one of claims 4,0 w-7h3erein the disease, condition, or disorder is a lysosomal storage disease.

76. The compound for use of claim 75, wherein tyhseos lomal storage disease is Gaucher's disease.

77. The compound for use of any one of claims 4,0- w7h3erein the disease, condition or disorder is an α-synucleinopathy.

78. The compound for use of claim 77, wherein α t-hseynucleinopathy is Parkinson’s disease.

79. The compound for use of any one of claims 4,0- w7h3erein the disease, condition or disorder is a tauopathy.

80. The compound for use of claim 79, whereina thueop tathy is Alzheimer’s disease.

81. The compound for use of any one of claims 4,0 w-7h3erein the disease, condition, or disorder is selected from the group consisting G oafu:cher's disease, Parkinson's disease, dementia with Lewy bodies, diffuse Lewy body disease, muleltip system atrophy (MSA), epilepsy, bipolar disorder, schizophrenia, an anxiety disorder, m daejoprression, polycystic kidney disease, type 2 diabetes, open angle glaucoma, multiple scleroMsSis), ( multiple myeloma, Alzheimer's disease, non-Alzheimer’s tauopathies (Pick’s complex), amroypohtic lateral sclerosis (ALS), corticobasal degeneration, frontotemporal lobe dementia, GBAr1ki Pnsaon, neuronopathic Gaucher's disease, neuroaxonal dystrophy, neurodegenerative diseaisthes p warkinsonism, progressive supranuclear palsy, pure autonomic failure, sporadic Creutzf-eJladktob disease, and unimpaired aging.

82. The compound for use of any one of claims 40 fu-8rt1her comprising administering to the patient at least one other therapeutic agent.

83. The compound for use of claim 82, whereinh theera tpeutic agent is an effective amount of an enzyme for enzyme replacement therapy.

84. The compound for use of claim 83, wherein tnhzeym ee is β-glucocerebrosidase or an analog thereof.

85. The compound for use of claim 83, wherein tnhzeym e e is imiglucerase.

86. The compound for use of claim 82, whereinh theera tpeutic agent is an effective amount of a small molecule chaperone.

87. The compound for use of claim 86, wherein thmeal sl molecule chaperone binds competitively to an enzyme.

88. The compound for use of claims 86 or 87, whne trheei small molecule chaperone is selected from the group consisting of iminoalditols, iminogsaurs, aminosugars, thiophenylglycosides, glycosidase, sulfatase, glycosyl transferase, phhaotsapse, and peptidase inhibitors.

89. The compound for use of claim 87, wherein tmheal sl molecule chaperone is selected from the group consisting of isofagomine, N-non-ydl-e1oxynojirimycin (NN-DNJ), ambroxol, and miglustat.

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