Compounds and compositions for the treatment of coronavirus-related diseases

Abstract

Provided herein are compounds and compositions for treating, managing or preventing coronavirus-related disease. Specifically, provided herein are compounds that are inhibitors of SARS-CoV-2 main protease (Mpro), pharmaceutical compositions comprising such compounds, methods of synthesizing such compounds, and methods of using such compounds and compositions for treating, managing or preventing coronavirus-related disease.

Description

[Technical Field]

[0001] Related Applications This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 224793, filed July 22, 2021, and U.S. Provisional Patent Application No. 63 / 289009, filed December 13, 2021, the contents of each of which are incorporated by reference in their entirety herein.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format and is incorporated herein by reference in its entirety. Said XML copy, created on June 30, 2022, is titled PAT059164-WO-PCT Sequence listing.xml and is 3930 bytes in size.

[0003] The present invention relates to compounds and compositions for the treatment, management and / or prevention of coronavirus-related diseases. Specifically, the present invention relates to compounds and compositions that inhibit the SARS-CoV-2 main protease (M pro The present invention relates to compounds that are inhibitors of coronavirus-associated leukemia (CoV), pharmaceutical compositions containing such compounds, methods for synthesizing such compounds, and methods of using such compounds and compositions for the treatment, management, or prevention of coronavirus-associated disease. [Background technology]

[0004] SARS-CoV-2 is a single-stranded, positive-stranded RNA virus belonging to the genus Coronavirus β. The SARS-CoV-2 genome is approximately 30 kb in length and contains untranslated regions (UTRs) at both ends and at least six complete open reading frame genes (ORFs). Among these ORFs, ORF 1a / b directly encodes two polyproteins: polyprotein 1a (pp1a) and polyprotein 1ab (pp1ab). These polypeptides encode the main protease (M pro), also known as 3C-like protease (3CLpro) and papain-like protease (PLpro), into 16 nonstructural proteins (nsp). These nsp play an important role in the generation of subgenomic RNAs that encode the four major structural proteins: surface spike glycoprotein (S), envelope protein (E), membrane protein (M), and nucleocapsid protein (N). Therefore, M pro plays a crucial role in the replication cycle of SARS-CoV-2. pro Inhibition of the activity of β-lactamase inhibitors (CLAs) may block viral replication and provide an effective therapeutic approach for treating COVID-19, the disease caused by SARS-CoV-2, or diseases caused by other betacoronaviruses.

[0005] M proThe identification of inhibitors has been the subject of several reports. The majority of these inhibitors are peptidomimetics, generally derived from previously studied protease inhibitors (Dai, W. et al. (2020) Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 368(6497), 1331-1335; Zhang, L., et al. (2020) Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors. Science, 368(6489), 409-412; Ma, C. et al. (2020) Boceprevir, GC-376, and calpain inhibitors II and XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Research, 30(8), 678-692; Jin, Z. et al. (2020) Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors.Nature, 582(7811), 289-293).

[0006] Peptidomimetics, originally developed for the SARS-CoV virus, are now in the clinic as intravenous treatments for COVID-19 (Hoffman, RLet et al. (2020). Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19. Journal of Medicinal Chemistry, 63(21), 12725-12747).

[0007] A few publications describe non-peptide small molecule inhibitors (Riva, L. et al. (2020). Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature, 586(7827), 113-119; Ghahremanpour, MM et al. (2020). Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2. ACS Med Chem Lett, 11, 2526; Guenther, S. et al. (2021). X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease. Science. https: / / doi.org / 10.1126 / science.abf7945; Douangamath, A. et al. (2020). Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease. Nature Communications, 11(1):5047), there remains a need for effective treatments for diseases caused by betacoronaviruses, particularly COVID-19. Summary of the Invention

[0008] Thus, in one aspect, the present invention provides a compound of formula (I): [ka] (In the formula, X1, X2, R 1 and R 2 is as defined herein) or a stereoisomer or a pharmaceutically acceptable salt thereof.

[0009] Another aspect of the present invention is a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0010] Another aspect of the present invention is a pharmaceutical composition comprising a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0011] In another aspect, the present invention provides methods for treating, preventing, and / or managing a coronavirus-related disease or disorder, comprising administering to a subject in need of such treatment, prevention, or management a therapeutically or prophylactically effective amount of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In certain embodiments, the coronavirus-related disease is COVID-19, other acute respiratory syndromes, non-respiratory coronavirus syndromes, and post-infectious coronavirus syndromes.

[0012] In another aspect, the present invention provides methods for treating, preventing, and / or managing a coronavirus-related disease or disorder, the methods comprising administering to a subject in need of such treatment, prevention, or management a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In certain embodiments, the coronavirus-related disease is COVID-19.

[0013] In another aspect, the present invention provides the use of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating, preventing, and / or managing a coronavirus-related disease or disorder.

[0014] In another aspect, the present invention provides the use of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating, preventing, and / or managing COVID-19.

[0015] In another aspect, the present invention provides the use of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, in the treatment, prevention, and / or management of a coronavirus-related disease or disorder.

[0016] In another aspect, the present invention provides the use of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, in the treatment, prevention and / or management of COVID-19.

[0017] In another aspect, the present invention provides a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention, and / or management of a coronavirus-related disease or disorder.

[0018] In another aspect, the present invention provides the use of a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof for use in the treatment, prevention and / or management of COVID-19.

[0019] In another aspect, the present invention provides a kit comprising a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for treating, preventing, and / or managing a coronavirus-related disease.

[0020] In another aspect, the present invention provides a kit comprising a compound of the present invention, its stereoisomer, or a pharmaceutically acceptable salt thereof, for treating, preventing, and / or managing COVID-19.

[0021] In another aspect, the present invention provides a combination for treating, preventing, and / or managing coronavirus-related diseases, in which a compound of the present invention, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is used in combination with one or more other active agents. In certain embodiments, the active agent is selected from a neutralizing antibody and an antiviral agent. In certain embodiments, the active agent is selected from a neutralizing antibody, an antiviral agent, and other agents selected from alvelestat, lenzilumab, octagam, remestemcel-L, RPH-104 + olokizumab, bucillamine, CD24FC (MK-7110), tradipitant, ifenprodil, tocilizumab, leronlimab, fenretinide, ATYR-1923, CYTO-205, APN-01, and Ampion. In certain embodiments, the neutralizing antibody is selected from the group consisting of bamlanivimab, bamlanivimab + etesevimab, bamlanivimab + VIR-7831, REGN-COV2, VIR-7831, AZD7442, regdanvimab / CT-P59, ABP 300, COVI-AM / STI-2020, VIR-7832, SAB-185, JS016 / etesevimab, C-135LS / C-144LS, BRII-196, BRII-198, SCTA-01, MW-33, DXP593, HFB-30132A, ADG20, COVI-GUARD (STI-1499), and convalescent plasma. Antiviral agents include remdesivir, Avigan / favipiravir, EIDD-2801 / molnupiravir, AT-527, PF-00835231, PF-07321332, Ens Selected from ovibep / DARPin, galidesivir, lopinavir-ritonavir, Virazole (ribavirin), levovir, elsulfavirine, thimerosal, UNI91103, silmitasertib / CX-4945, RBT-9, AT-301, Traneurocin / Neurosivir, opaganib, ABX-464, SNG001, alisporivir, nafamostat mesylate, vidofludimus / IMU-838, emvodostat / PTC299, brequinar, ATR-002, and maraviroc.

[0022] In another aspect, the invention provides a combination for treating, preventing, and / or managing a coronavirus-related disease, wherein a compound of the invention is used in combination with remdesivir (also known as 2-ethylbutyl((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate). [Brief explanation of the drawings]

[0023] [Figure 1] Figure 1 shows a representative powder X-ray diffractogram (PXRD) curve of (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile modification A. The x-axis shows the scattering angle in 2θ, and the y-axis shows the intensity of the scattered X-ray beam in detected photon counts. [Figure 2] 1 shows a representative differential scanning calorimetry (DSC) curve for (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile modification A. The x-axis shows temperature in degrees Celsius (°C), and the y-axis shows heat flow in watts per gram (W / g) associated with the rise of the endothermic peak. [Figure 3] 1 shows a representative thermogravimetric analysis (TGA) curve for (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile modification A. The x-axis shows temperature in degrees Celsius (°C) and the y-axis shows sample mass (loss) in weight percent (wt%). [Figure 4] Figure 1 shows a representative powder X-ray diffractogram (PXRD) curve of (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile modification B. The x-axis shows the scattering angle in 2θ, and the y-axis shows the intensity of the scattered X-ray beam in detected photon counts. [Figure 5]1 shows a representative differential scanning calorimetry (DSC) curve for (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile modification B. The x-axis shows temperature in degrees Celsius (°C) and the y-axis shows heat flow in watts per gram (W / g) associated with the rise of the endothermic peak. [Figure 6] 1 shows a representative thermogravimetric analysis (TGA) curve for (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile modification B. The x-axis shows temperature in degrees Celsius (°C) and the y-axis shows mass (loss) of the sample in weight percent (wt%). DETAILED DESCRIPTION OF THE INVENTION

[0024] definition As used herein, the term "alkyl" refers to a fully saturated branched or straight hydrocarbon chain. In certain embodiments, an alkyl group is selected from the group consisting of "C1-C2 alkyl," "C1-C3 alkyl," "C1-C4 alkyl," "C1-C5 alkyl," "C1-C6 alkyl," "C1-C7 alkyl," "C1-C8 alkyl," "C1-C9 alkyl," or "C1-C 10 alkyl," and the terms "C1-C2 alkyl," "C1-C3 alkyl," "C1-C4 alkyl," "C1-C5 alkyl," "C1-C6 alkyl," "C1-C7 alkyl," "C1-C8 alkyl," "C1-C9 alkyl," and "C1-C 10 "Alkyl," as used herein, refers to an alkyl group containing at least 1 and at most 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, respectively. Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.

[0025] As used herein, the term "alkenyl" refers to a partially saturated branched or straight hydrocarbon chain having one or more double bonds. In certain embodiments, an alkenyl group is defined as "C2-C3 alkenyl," "C2-C4 alkenyl," "C2-C5 alkenyl," "C2-C6 alkenyl," "C2-C7 alkenyl," "C2-C8 alkenyl," "C2-C9 alkenyl," or "C2-C 10 alkenyl," and the terms "C2-C3 alkenyl," "C2-C4 alkenyl," "C2-C5 alkenyl," "C2-C6 alkenyl," "C2-C7 alkenyl," "C2-C8 alkenyl," "C2-C9 alkenyl," and "C2-C 10 "Alkenyl," as used herein, refers to an alkenyl group containing at least 2, and at most 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, respectively. Non-limiting examples of alkenyl groups include ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, sec-butenyl, tert-butenyl, n-pentenyl, isopentenyl, n-hexenyl, n-heptenyl, n-octenyl, n-nonenyl, and n-decenyl.

[0026] As used herein, the term "alkoxy" refers to -O-alkyl or -alkyl-O-, where "alkyl" is as defined herein. In certain embodiments, an alkoxy group is selected from the group consisting of "C1-C2 alkoxy," "C1-C3 alkoxy," "C1-C4 alkoxy," "C1-C5 alkoxy," "C1-C6 alkoxy," "C1-C7 alkoxy," "C1-C8 alkoxy," "C1-C9 alkoxy," or "C1-C 10 alkoxy," and the terms "C1-C3 alkoxy," "C1-C4 alkoxy," "C1-C5 alkoxy," "C1-C6 alkoxy," "C1-C7 alkoxy," "C1-C8 alkoxy," "C1-C9 alkoxy," and "C1-C 10"Alkoxy," as used herein, means, respectively, -O-C1-C2 alkyl, -O-C1-C3 alkyl, -O-C1-C4 alkyl, -O-C1-C5 alkyl, -O-C1-C6 alkyl, -O-C1-C7 alkyl, -O-C1-C8 alkyl, -O-C1-C9 alkyl or -O-C1-C 10 Non-limiting examples of "alkoxy" groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, hexoxy, heptoxy, octoxy, nonoxy, and decoxy.

[0027] As used herein, the term "C3-C8 cycloalkyl" refers to a fully saturated monocyclic hydrocarbon ring system having from 3 to 8 carbon atoms as ring members. Non-limiting examples of such "C3-C8 cycloalkyl" groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0028] As used herein, the term "bicyclic C3-C8 cycloalkyl" refers to a fully saturated, fused bicyclic hydrocarbon ring system having from 3 to 8 carbon atoms as ring members, or as used herein, the term "bicyclic C3-C8 cycloalkyl" refers to a fully saturated, bridged bicyclic hydrocarbon ring system having from 3 to 8 carbon atoms as ring members, or as used herein, the term "bicyclic C3-C8 cycloalkyl" refers to a fully saturated, spiro bicyclic hydrocarbon ring system having from 3 to 8 carbon atoms as ring members. Non-limiting examples of such "bicyclic C3-C8 cycloalkyl" groups include bicyclo[1.1.1]pentanyl, spiro[3.3]heptanyl, spiro[2.3]hexanyl, and the like.

[0029] As used herein, the term "C5-C6 cycloalkenyl" refers to a partially saturated (but not aromatic) monocyclic hydrocarbon ring system having 5 to 6 carbon atoms as ring members. Non-limiting examples of "C5-C6 cycloalkenyl" as used herein include cyclopent-1-enyl, cyclopenta-1,3-dienyl, cyclohex-1-enyl, and cyclohexa-1,3-dienyl.

[0030] As used herein, the term "C1-C6 alkyl-phenyl" refers to a C1-C6 alkyl as defined above substituted with a phenyl group. A non-limiting example of a C1-C6 alkyl-phenyl is benzyl.

[0031] As used herein, the term "haloalkyl" refers to an alkyl group, as defined herein, in which at least one of the alkyl's hydrogen atoms is replaced by a halo group (as defined herein). The haloalkyl can be a monohaloalkyl, dihaloalkyl, trihaloalkyl, or polyhaloalkyl, including perhaloalkyl. A monohaloalkyl can have one iodo, bromo, chloro, or fluoro within the alkyl group. Dihaloalkyl and polyhaloalkyl groups can have two or more of the same halo atoms or a combination of different halo groups within the alkyl. Typically, a polyhaloalkyl contains up to six, four, three, or two halo groups. Non-limiting examples of haloalkyl include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, and dichloropropyl. Perhalo-alkyl refers to an alkyl in which all hydrogen atoms have been replaced with halo atoms, e.g., trifluoromethyl. Unless otherwise specified, preferred haloalkyl groups include monofluoro-, difluoro-, and trifluoro-substituted methyl and ethyl groups, e.g., CF, CHF, CHF, CHCHF, and CHCF.

[0032] As used herein, the term "C1-C6 haloalkyl" refers to each "C1-C6 alkyl" as defined herein, wherein at least one of the hydrogen atoms of the "C1-C6 alkyl" is replaced by a halo group (as defined herein). A C1-C6 haloalkyl group can be a mono-C1-C6 haloalkyl, where such a C1-C6 haloalkyl group has one iodo, one bromo, one chloro, or one fluoro. Furthermore, a C1-C6 haloalkyl group can be a di-C1-C6 haloalkyl, where such a C1-C6 haloalkyl group has two halo atoms independently selected from iodo, bromo, chloro, or fluoro. Furthermore, a C1-C6 haloalkyl group can be a poly-C1-C6 haloalkyl, where such a C1-C6 haloalkyl group can have two or more of the same halo atoms or a combination of two or more different halo atoms. Such poly C1-C6 haloalkyls may be perhalo C1-C6 haloalkyls, in which all hydrogen atoms of each C1-C6 alkyl are replaced with halo atoms, and the halo atoms may be the same or a combination of different halo atoms. Non-limiting examples of "C1-C6 haloalkyl" groups include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, dichloroethyl, and dichloropropyl.

[0033] As used herein, the term "haloalkoxy" refers to the group -O-haloalkyl, where the term "haloalkyl" is as defined herein. Non-limiting examples of haloalkoxy include fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, pentafluoroethoxy, heptafluoropropoxy, difluorochloromethoxy, dichlorofluoromethoxy, difluoroethoxy, difluoropropoxy, dichloroethoxy, and dichloropropoxy. Perhaloalkoxy refers to an alkoxy in which all hydrogen atoms are replaced with halo atoms, such as trifluoromethoxy. Unless otherwise specified, preferred haloalkoxy groups include monofluoro, difluoro, and trifluoro-substituted methoxy and ethoxy groups, such as -OCF, -OCHF, -OCHF, -OCHCHF, and -OCHCF.

[0034] As used herein, the term "C1-C6 haloalkoxy" refers to the group -O-C1-C6 haloalkyl, where the term C1-C6 haloalkyl is as defined herein. Non-limiting examples of "C1-C6 haloalkoxy" groups include fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, pentafluoroethoxy, heptafluoropropoxy, difluorochloromethoxy, dichlorofluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, difluoropropoxy, dichloroethoxy, and dichloropropoxy.

[0035] As used herein, the term "halogen" or "halo" refers to fluoro (F), chloro (Cl), bromo (Br) and iodo (I).

[0036] As used herein, the term "heteroatom" refers to a nitrogen (N), oxygen (O), or sulfur (S) atom.

[0037] As used herein, the term "heteroaryl" refers to an aromatic ring system containing one or more heteroatoms, which may be the same or different. As used herein, the term "heteroaryl" refers to N, NR 6 , O, and S; R 6 is as defined herein. Heteroaryl groups can be monocyclic ring systems or fused bicyclic ring systems. Monocyclic heteroaryl rings have 5 to 6 ring atoms. Bicyclic heteroaryl rings have 7 to 12 ring atoms. Bicyclic heteroaryl rings include ring systems in which a heteroaryl ring is fused to a phenyl ring. Non-limiting examples of heteroaryl groups as used herein include benzofuranyl, benzo[c]thiophenyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, cinnolinyl, furazanyl, furyl, imidazolyl, indolyl, indolizinyl, indazolyl, isoindolyl, isoquinolinyl, isoxazolyl, isothiazolyl, oxazolyl, oxaindolyl, oxadiazolyl (1,3,4-oxadiazolyl), and the like. Examples include diazolyl and 1,2,4-oxadiazolyl), purinyl, pyrazolyl, pyrrolyl, phthalazinyl, pyridyl (including 2-, 3- and 4-pyridyl), pyridazinyl, pyrazinyl, pyrimidinyl, quinoxalinyl, quinolinyl, quinazolinyl, tetrazinyl, tetrazolyl, tetrazolo[1,5-a]pyridinyl, thiazolyl, thiadiazolyl (including 1,3,4-thiadiazolyl), thienyl, triazinyl and triazolyl.

[0038] As used herein, the term "5- or 6-membered heteroaryl" refers to an aromatic 5- or 6-membered monocyclic ring system in which 1, 2, 3, or 4 ring members are N, NR 6 R is independently selected from O and S; 6is as defined herein. Non-limiting examples of such 5- or 6-membered heteroaryl groups as used herein include furyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyrazolyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, tetrazolyl, pyridyl (including 2-, 3-, and 4-pyridyl), pyridazinyl, pyrazinyl, and pyrimidinyl. In certain embodiments, the term "5- or 6-membered heteroaryl" as used herein refers to a heteroaryl group in which one, two, or three ring members are N, NR 6 R is independently selected from O and S; 6 as defined herein. Non-limiting examples of such 5- or 6-membered heteroaryl groups as used herein include furyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyrazolyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, pyridyl (including 2-, 3- and 4-pyridyl), pyridazinyl, pyrazinyl and pyrimidinyl.

[0039] As used herein, the term "6-membered heteroaryl" refers to an aromatic 6-membered monocyclic ring system in which 1, 2, or 3 ring members are each independently selected from N, O, and S. Non-limiting examples of such 6-membered heteroaryl groups as used herein include pyridyl (including 2-, 3-, and 4-pyridyl), pyridazinyl, pyrazinyl, and pyrimidinyl.

[0040] As used herein, the term "5-membered heteroaryl" refers to an aromatic 5-membered monocyclic ring system in which 1, 2, 3, or 4 ring members are N, NR 6 R is independently selected from O and S; 6is as defined herein. As used herein, non-limiting examples of such 5-membered heteroaryl groups include furyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyrazolyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, and tetrazolyl. In certain embodiments, as used herein, the term "5-membered heteroaryl" refers to a heteroaryl group in which one, two, or three ring members are N, NR 6 R is independently selected from O and S; 6 As used herein, "heteroaryl" also refers to an aromatic 5-membered monocyclic ring system, wherein: is as defined herein. Non-limiting examples of such 5-membered heteroaryl groups include furyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyrazolyl, thiadiazolyl, thiazolyl, thienyl, and triazolyl.

[0041] As used herein, the term "9- or 10-membered bicyclic heteroaryl" refers to a 9- or 10-membered fused bicyclic aromatic ring system in which 1, 2, 3, 4, or 5 ring members are N, NR 6 R is independently selected from O and S; 6 is as defined herein. Non-limiting examples of such bicyclic heteroaryl groups as used herein include indolyl, quinolinyl, isoquinolinyl, indazolyl, purinyl, phthalazinyl, naphthyridinyl, quinazolinyl, cinnolinyl, thieno[2,3-b]furanyl, 1H-pyrazolo[4,3-d]-oxazolyl, imidazo[2,1-b]thiazolyl, imidazo[1,2-c]pyrimidinyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyrazinyl, pyrazino[2,3-d]pyridazinyl, imidazo[1,2-b][1,2,4]triazinyl, benzoxazolyl, benzimidazolyl, imidazopyridinyl, benzo[c]isoxazolyl, and benzothiazolyl.

[0042] As used herein, the term "4- to 7-membered heterocycloalkyl" refers to a 4- to 7-membered saturated hydrocarbon ring, in which 1, 2, 3, or 4 ring members are selected from the group consisting of N, NR 6 R is independently selected from O or S; 6is as defined herein. A heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. As used herein, non-limiting examples of 4- to 6-membered heterocycloalkyl groups include azetadinyl (including azetadin-1-yl, azetadin-2-yl, and azetadin-3-yl), oxetanyl (including oxetan-2-yl, oxetan-3-yl, and oxetan-4-yl), thietanyl (including thietan-2-yl, thietan-3-yl, and thietan-4-yl), pyrrolidinyl (including pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-4-yl, and pyrrolidin- tetrahydrofuranyl (including tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrofuran-4-yl and tetrahydrofuran-5-yl), tetrahydrothienyl (including tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydrothien-4-yl and tetrahydrothien-5-yl), piperidinyl (including piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-5-yl and piperidin- tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl and tetrahydropyran-6-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (piperazin-1-yl, piperazin-2-yl, piperazin-2-yl), tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1 ...pyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin- yl, piperazin-3-yl, piperazin-4-yl, piperazin-5-yl and piperazin-6-yl), morpholinyl (including morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-5-yl and morpholin-6-yl), thiomorpholinyl (including thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), oxathiani (oxathian-2-yl, oxathian-3-yl,dithianyl (including dithian-2-yl, dithian-3-yl, dithian-5-yl and dithian-6-yl), dioxolanyl (including dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl), thioxanyl (including thioxan-2-yl, thioxan-3-yl, thioxan-4-yl and thioxan-5-yl), dithiola pyrazolidinyl (including dithiolan-2-yl, dithiolan-4-yl and dithiolan-5-yl) and pyrazolidinyl (including pyrazolidin-1-yl, pyrazolidin-2-yl, pyrazolidin-3-yl, pyrazolidin-4-yl and pyrazolidin-5-yl), azepanyl, diazepanyl, triazepanyl, ozazepanyl, oxadiazepanyl, oxepanyl, thiepanyl, thiazepanyl and thiadiazepanyl.

[0043] As used herein, the term "3- to 6-membered heterocycloalkyl" refers to a 3- to 6-membered saturated hydrocarbon ring, in which 1, 2, or 3 of the ring members are N, NR 6 R is independently selected from O or S; 6is as defined herein. A heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. Non-limiting examples of 3- to 6-membered heterocycloalkyl groups as used herein include oxiranyl, aziridinyl, thiiranyl, azetadinyl (including azetadin-1-yl, azetadin-2-yl, and azetadin-3-yl), oxetanyl (including oxetan-2-yl, oxetan-3-yl, and oxetan-4-yl), thietanyl (including thietan-2-yl, thietan-3-yl, and thietan-4-yl), pyrrolidinyl (including pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin ... tetrahydrofuranyl (including tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrofuran-4-yl and tetrahydrofuran-5-yl), tetrahydrothienyl (including tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydrothien-4-yl and tetrahydrothien-5-yl), piperidinyl (including piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-5-yl), yl and piperidin-6-yl), tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl and tetrahydropyran-6-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (piperazin-1-yl, piperazin-1-yl, piperazin-1-yl, piperazin-1-yl), tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl and tetrahydrothiopyran-6-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1-yl, piperazin-1-yl, piperazin-1-yl, piperazin-1-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6 ... piperazinyl (including piperazin-1-yl, piperazin-1-yl, piperazin-1-yl, piperazin-1-yl thiomorpholinyl (including thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), oxathianiyl (including oxathian-2-yl, oxathian-3-yl,Examples of the alkyl group include oxathian-5-yl and oxathian-6-yl), dithianyl (including dithian-2-yl, dithian-3-yl, dithian-5-yl and dithian-6-yl), dioxolanyl (including dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl), thioxanyl (including thioxan-2-yl, thioxan-3-yl, thioxan-4-yl and thioxan-5-yl), dithiolanyl (including dithiolan-2-yl, dithiolan-4-yl and dithiolan-5-yl), pyrazolidinyl (including pyrazolidin-1-yl, pyrazolidin-2-yl, pyrazolidin-3-yl, pyrazolidin-4-yl and pyrazolidin-5-yl), hexahydropyridazinyl and hexahydropyrimidinyl.

[0044] As used herein, the term "4- to 6-membered heterocycloalkyl" refers to a 4- to 6-membered saturated hydrocarbon ring, in which 1, 2, 3, or 4 ring members are selected from the group consisting of N, NR 6 R is independently selected from O or S; 6is as defined herein. A heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. As used herein, non-limiting examples of 4- to 6-membered heterocycloalkyl groups include azetadinyl (including azetadin-1-yl, azetadin-2-yl, and azetadin-3-yl), oxetanyl (including oxetan-2-yl, oxetan-3-yl, and oxetan-4-yl), thietanyl (including thietan-2-yl, thietan-3-yl, and thietan-4-yl), pyrrolidinyl (including pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-4-yl, and pyrrolidin- tetrahydrofuranyl (including tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrofuran-4-yl and tetrahydrofuran-5-yl), tetrahydrothienyl (including tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydrothien-4-yl and tetrahydrothien-5-yl), piperidinyl (including piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-5-yl and piperidin- tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl and tetrahydropyran-6-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (piperazin-1-yl, piperazin-2-yl, piperazin-2-yl), tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1 ...pyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl), piperazinyl (including piperazin-1-yl, piperazin- yl, piperazin-3-yl, piperazin-4-yl, piperazin-5-yl and piperazin-6-yl), morpholinyl (including morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-5-yl and morpholin-6-yl), thiomorpholinyl (including thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), oxathiani (oxathian-2-yl, oxathian-3-yl,Examples of the alkyl group include oxathian-5-yl and oxathian-6-yl), dithianyl (including dithian-2-yl, dithian-3-yl, dithian-5-yl and dithian-6-yl), dioxolanyl (including dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl), thioxanyl (including thioxan-2-yl, thioxan-3-yl, thioxan-4-yl and thioxan-5-yl), dithiolanyl (including dithiolan-2-yl, dithiolan-4-yl and dithiolan-5-yl), pyrazolidinyl (including pyrazolidin-1-yl, pyrazolidin-2-yl, pyrazolidin-3-yl, pyrazolidin-4-yl and pyrazolidin-5-yl), hexahydropyridazinyl and hexahydropyrimidinyl.

[0045] As used herein, the term "5- or 6-membered heterocycloalkyl" refers to a 5- or 6-membered saturated hydrocarbon ring, in which 1, 2, 3, or 4 ring members are selected from the group consisting of N, NR 6 R is independently selected from O or S; 6is as defined herein. A heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. Non-limiting examples of 5- or 6-membered heterocycloalkyl groups as used herein include pyrrolidinyl (including pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-4-yl, and pyrrolidin-5-yl), tetrahydrofuranyl (including tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrofuran-4-yl, and tetrahydrofuran-5-yl), tetrahydrothienyl (including tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydrothien-4-yl, and tetrahydrothien ... -yl and tetrahydrothien-5-yl), piperidinyl (including piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-5-yl and piperidin-6-yl), tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl and tetrahydropyran-6-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-6-yl), yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, piperazin-4-yl, piperazin-5-yl and piperazin-6-yl), morpholinyl (including morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-5-yl and morpholin-6-yl), thiomorpholinyl (including thiomorpholin-2-yl, thiomorpholin-3-yl, yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), oxathiani (including oxathian-2-yl, oxathian-3-yl, oxathian-5-yl and oxathian-6-yl), dithianil (including dithian-2-yl, dithian-3-yl, dithian-5-yl and dithian-6-yl), dioxolanyl (including dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl), thioxanyl (thioxan-2-yl, thioxan-3-yl,thioxan-4-yl and thioxan-5-yl), dithiolanyl (including dithiolan-2-yl, dithiolan-4-yl and dithiolan-5-yl), pyrazolidinyl (including pyrazolidin-1-yl, pyrazolidin-2-yl, pyrazolidin-3-yl, pyrazolidin-4-yl and pyrazolidin-5-yl), hexahydropyridazinyl and hexahydropyrimidinyl.

[0046] As used herein, the term "6-membered heterocycloalkyl" refers to a 6-membered saturated hydrocarbon ring, in which 1, 2, 3, or 4 ring members are selected from the group consisting of N, NR 6 R is independently selected from O or S; 6is as defined herein. A heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. As used herein, non-limiting examples of 6-membered heterocycloalkyl groups include piperidinyl (including piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-5-yl, and piperidin-6-yl), tetrahydropyranyl (including tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl, and tetrahydropyran-6-yl), tetrahydrothiopyranyl (including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl, and tetrahydrothiopyran-6-yl), piperazinyl (including piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, piperazin-4-yl, piperazin- morpholinyl (including morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-5-yl and morpholin-6-yl), thiomorpholinyl (including thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), oxathiane (oxathiane-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), -yl, oxathian-3-yl, oxathian-5-yl and oxathian-6-yl), dithianyl (including dithian-2-yl, dithian-3-yl, dithian-5-yl and dithian-6-yl), oxanyl (including thioxan-2-yl, thioxan-3-yl, thioxan-4-yl and thioxan-5-yl), hexahydropyridazinyl and hexahydropyrimidinyl.

[0047] As used herein, the term "3-membered heterocycloalkyl" refers to a 3-membered saturated hydrocarbon ring, in which one or two ring members are N, NR 6 R is independently selected from O or S; 6is as defined herein. A heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. Non-limiting examples of 3-membered heterocycloalkyl groups as used herein include oxiranyl, aziridinyl, and thiiranyl.

[0048] As used herein, the term "5- or 6-membered heterocyclyl" refers to a partially saturated (but not aromatic) 5- or 6-membered monocyclic ring system in which one, two, or three ring members are N, NR 6 R is independently selected from O or S; 6 is as defined herein. In certain embodiments, as used herein, the term "5- or 6-membered heterocyclyl" refers to a heterocyclic ring in which one, two, or three ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, where the 5- or 6-membered heterocyclyl is optionally substituted with oxo. A 5- or 6-membered heterocyclyl group can be attached to another group at a nitrogen or carbon atom. Non-limiting examples of 5- or 6-membered heterocyclyl groups as used herein include 1,2-dihydropyridinyl and 2,3-dihydro-1H-pyrrolyl.

[0049] As used herein, the term "6-membered heterocyclyl" refers to a partially saturated (but not aromatic) 6-membered monocyclic ring system in which one, two, or three ring members are N, NR 6 R is independently selected from O or S; 6 is as defined herein. In certain embodiments, as used herein, the term "6-membered heterocyclyl" refers to a 6-membered heterocyclyl in which one, two, or three ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6, O, or S, where the 6-membered heterocyclyl is optionally substituted with oxo. A 6-membered heterocyclyl group can be attached to another group at a nitrogen or carbon atom. Non-limiting examples of 6-membered heterocyclyl groups as used herein include 1,2-dihydropyridinyl.

[0050] As used herein, the term "5-membered heterocyclyl" refers to a partially saturated (but not aromatic) 5-membered monocyclic ring system in which 1, 2, or 3 ring members are N, NR 6 R is independently selected from O or S; 6 is as defined herein. In certain embodiments, as used herein, the term "5-membered heterocyclyl" refers to a 5-membered heterocyclyl in which one, two, or three ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, where the 5-membered heterocyclyl is optionally substituted with oxo. A 5-membered heterocyclyl group can be attached to another group at a nitrogen or carbon atom. Non-limiting examples of 5-membered heterocyclyl groups as used herein include 2,3-dihydro-1H-pyrrolyl.

[0051] As used herein, the term "9- or 10-membered bicyclic heterocyclyl" refers to a partially saturated (but not aromatic) 9- or 10-membered bicyclic ring system in which 1, 2, 3, 4, or 5 ring members are N, NR 6 R is independently selected from O or S; 6 is as defined herein. A C5-C6 heterocycloalkenyl group can be attached to another group at a nitrogen or a carbon atom. Non-limiting examples of 9- or 10-membered bicyclic heterocyclyl groups as used herein include isochromanyl, 1,2-dihydroquinolinyl, 3a,7a-dihydro-1H-pyrrolo[2,3-c]pyridinyl, and 3a,7a-dihydro-1H-indazolyl.

[0052] As used herein, the term "oxo" refers to the group =O.

[0053] As used herein, the term "spiro-linked" refers to one ring system being linked to another ring system through a carbon atom that is common to both rings.

[0054] As used herein, the term "positioned beta (β) to the point of attachment" refers to the attachment of an R 2 For example, in the structure below, the N heteroatom is located in the beta (β) position relative to the point of attachment, indicated by the asterix (*). [ka]

[0055] Similarly, in the structure below, the carbon atom that is the ring member substituted with oxo is located in the beta (β) position relative to the point of attachment, indicated by the asterix (*). [ka]

[0056] As used herein, the term "isomer" refers to various compounds that have the same molecular formula but differ in the arrangement and configuration of atoms. Also, as used herein, the terms "optical isomer" or "stereoisomer" refer to any of the various stereoisomeric configurations, including geometric isomers, that may exist for a given compound of the present invention. It is understood that a substituent may be attached at a chiral center of a carbon atom. The term "chiral" refers to a molecule that has the property of not being superimposable on its mirror-image partner, while the term "achiral" refers to a molecule that is superimposable on its mirror-image partner. Thus, the present invention includes enantiomers, diastereomers, or racemates of a compound. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. This term is used to refer to a racemic mixture where appropriate. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is designated according to the Cahn-Ingold-Prelog RS system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be designated by either R or S. Resolved compounds of unknown absolute configuration can be designated (+) or (-) according to the direction (dextrorotatory or levorotatory) they rotate plane-polarized light at the wavelength of the sodium D line. Certain compounds described herein may contain one or more asymmetric centers or axes and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined in terms of absolute stereochemistry as (R)- or (S)-.

[0057] As used herein, the term "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial, antifungal), isotonicity agents, absorption delaying agents, salts, preservatives, drug stabilizers, binders, excipients, disintegrants, lubricants, sweeteners, flavoring agents, dyes, and the like, and combinations thereof, as known to those skilled in the art (see, e.g., Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in the therapeutic or pharmaceutical compositions is contemplated.

[0058] As used herein, the term "optionally substituted" means unsubstituted or substituted with the substituents listed thereafter.

[0059] The term "coronavirus-related disease" refers to a disease caused by a member of the coronavirus family (i.e., it may belong to the Coronaviridae family). Coronaviruses (CoVs) are positive-stranded RNA viruses that have a crown-like appearance under an electron microscope due to the presence of spike glycoproteins on their envelopes. Any member of the coronavirus family with a respiratory component (e.g., belonging to the alphacoronavirus, betacoronavirus, deltacoronavirus, or gammacoronavirus genera) is contemplated for the methods and uses described herein. As a non-limiting set of examples, the respiratory virus may be a betacoronavirus such as severe acute respiratory syndrome-related coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome-related coronavirus (MERS-CoV), OC43, and HKU1, or an alphacoronavirus such as 229E and NL63. The respiratory virus may also be a coronavirus other than SARS-CoV, SARS-CoV-2, MERS-CoV, OC43, HKU1, 229E, or NL63. Patients infected with SARS-CoV-2 present with a range of clinical severity, from asymptomatic interstitial pneumonia to severe interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS), severe acute lung injury (ALI), and a form of diffuse alveolar damage, a severe lung disease that can cause symptoms and death related to decreased blood oxygenation and respiratory failure and / or multiple organ failure (MOF). Clinical symptoms in COVID-19 patients include fever, cough, fatigue, loss of smell, and shortness of breath within 2–14 days after exposure. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV and spreads primarily through the respiratory tract. Cytokine profiling of patients with severe COVID-19 shows elevated levels of interleukin (IL)-2, IL-7, IL-6, IL-1, granulocyte colony-stimulating factor, interferon-γ-inducible protein 10, monocyte chemotactic protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α.

[0060] As used herein, the terms "inhibit," "inhibition," or "inhibiting" refer to the alleviation or suppression of a given condition, symptom, or disorder or disease, or a significant decrease in the baseline activity of a biological activity or process.

[0061] As used herein, the term "subject" can refer to an animal. The animal can be a mammal. A subject can also refer to, for example, a primate (e.g., a male or female human), cow, sheep, goat, horse, dog, cat, rabbit, rat, mouse, fish, bird, etc. In certain embodiments, the subject is a primate. In yet other embodiments, the subject is a human. Unless noted, the terms "patient" or "subject" are used interchangeably herein.

[0062] As used herein, the terms "treat," "treating," or "treatment," in reference to any disease or disorder, refer, in one embodiment, to ameliorating the disease or disorder (i.e., slowing or arresting or reducing the development of the disease or at least one of its clinical symptoms). In another embodiment, "treat," "treating," or "treatment" refers to alleviating or improving at least one physical parameter, including those that may not be discernible by the patient. In yet another embodiment, "treat," "treating," or "treatment" refers to modulating the disease or disorder either physically (e.g., stabilization of discernible symptoms), physiologically (e.g., stabilization of physical parameters), or both.

[0063] As used herein, the terms "prevent," "preventing," or "prevention," in reference to any disease or disorder, refers to the prophylactic treatment of the disease or disorder or the delay in the onset or progression of the disease or disorder.

[0064] As used herein, and unless otherwise indicated, the terms "manage," "managing," and "management" include preventing the recurrence of a particular disease or disorder in a patient already suffering from the disease or disorder and / or extending the time that a patient suffering from the disease or disorder remains in remission. The term also includes modulating the onset, progression, and / or duration of the disease or disorder, or altering the way a patient responds to the disease or disorder.

[0065] The term "therapeutically effective amount" of a compound of the invention refers to an amount of a compound of the invention that, when administered to a subject, elicits a biological or medical response, such as a reduction or inhibition of enzyme or protein activity, or ameliorates a symptom, manages a condition, relieves a condition, slows or delays the progression of a disease, or prevents a disease. In one non-limiting embodiment, the term "therapeutically effective amount" refers to an amount of a compound of the invention that, when administered to a subject, elicits a biological or medical response, such as a reduction or inhibition of an enzyme or protein activity, or ameliorates a symptom, manages a condition, relieves a condition, slows or delays the progression of a disease, or prevents a disease. pro ) or (ii) SARS-CoV-2 main protease (M pro ) activity associated with or mediated by SARS-CoV-2 main protease (M pro or (2) at least partially alleviate, inhibit, prevent, manage, and / or ameliorate a condition or disorder or disease characterized by activity (normal or abnormal) of SARS-CoV-2 main protease (M pro In another non-limiting embodiment, the term "therapeutically effective amount" refers to an amount of a compound of the invention that is effective to reduce or inhibit the activity of SARS-CoV-2 main protease (Mpro) when administered to a cell, or tissue, or non-cellular biological material, or culture medium.

[0066] The term "co-administered" refers to the presence of two active agents in the blood of an individual. Co-administered active agents can be delivered simultaneously or sequentially.

[0067] As used herein, the terms "a," "an," and "the," and similar terms used in connection with the present invention (particularly in connection with the claims), should be construed to encompass both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0068] Unless otherwise specified, the terms "compound of the invention", "compounds of the invention", "compound of the invention" or "compounds of the invention" refer to compounds of Formula (I) or subformulas thereof, such as Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie), Formula (If), Formula (Ig), Formula (Ih) and Formula (Ii) and exemplified compounds and salts thereof, and all stereoisomers (including diastereomers and enantiomers) thereof.

[0069] Various enumerated embodiments of the invention are described herein, and it will be recognized that the features specified in each embodiment may be combined with other specified features to provide further embodiments of the invention.

[0070] Compounds of the Invention The present invention relates to a compound of formula (I) [ka] (In the formula, X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; ii) unsubstituted or containing 1 to 4 R 5phenyl substituted with a group; iii) 1, 2, 3 or 4 ring members are N, NR 6 4, 5, or 6-membered heterocycloalkyl selected from each independently from O and S, which is unsubstituted or has 1 to 4 R 5 a 4-, 5-, or 6-membered heterocycloalkyl optionally substituted by an oxo group, wherein the 5- or 6-membered heterocycloalkyl is optionally substituted by oxo; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) unsubstituted C1-C6 alkyl, vi) 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, and the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; vii) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heterocyclyl substituted by a group; viii) unsubstituted or 1 to 4 R 5 spiro-linked C3-C8 cycloalkyl substituted with a group; ix) unsubstituted or 1 to 4 R 5 bicyclic C3-C8 cycloalkyl substituted with a group; x) C5-C6 cycloalkenyl, and xi) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and which is unsubstituted or has 1 to 4 R 59- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 2 teeth, i)-(CH2) 0-6 CHR 13 R 14 , ii) is unsubstituted or contains 1, 2, 3 or 4 R 12 benzyl substituted with a group, iii) 6-membered heteroaryl in which 1, 2, or 3 ring members are each independently selected from N, O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group; iv) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, with 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; v) a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, further having 0, 1, 2, 3, or 4 ring members each independently selected from N, O, and S, and which is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; vi) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, 3, or 4 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; vii) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, such as N, NR 6, O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; viii) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 and 5- or 6-membered heterocycloalkyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; ix) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 5- or 6-membered heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; x) NR as a ring member having a point of attachment at a carbon atom ring member and located beta (β) to the point of attachment 6 and 9- or 10-membered bicyclic heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xi) a 9- or 10-membered bicyclic heterocyclyl having an attachment point at a carbon atom ring member and an O heteroatom as a ring member positioned beta (β) to the attachment point, and 6, O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xii) 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S; and 12 a 9- or 10-membered bicyclic heteroaryl substituted with a group; xiii) 1, 2 or 3 ring members are N, NR 6 , O and S, and is substituted with 1 or 2 oxo or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; xiv) 1, 2 or 3 ring members are N, NR 6 , O and S, which are substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xv) a 6-membered heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; xvi) 1, 2, 3, 4 or 5 ring members are N, NR 69- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3, or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xvii) one ring member is NR 6 a 6-membered heterocyclyl selected from the group consisting of: xviii) 6-membered heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, or 2 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group, and xix) a 10-membered bicyclic heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 10-membered bicyclic heterocyclyl substituted with a group and optionally substituted with an additional oxo is selected from the group consisting of R 3a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —C(═O)OH, —OH, CN, or NH2; R 3b is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —C(═O)OH, —OH, CN, or NH2; R 4a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —C(═O)OH, —OH, CN, or NH2; R 4bis H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —C(═O)OH, —OH, CN, or NH2; R 3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 C1-C6 alkyl substituted with a group, Each R 5 -CN, -OH, -NR 7 R 8 , N.R. 6 C(=O)C2-C6 alkenyl, -SF5, S(=O)2C1-C6 alkyl, -C(=O)N(R 7 )2, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; 4-6 membered heterocycloalkyl having 1, 2, or 3 ring members each independently selected from N, O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl that is unsubstituted or substituted with CN, NH2, or OH, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3, or 4 R 9 is substituted with a group, Each R 6 is H, C1-C6 haloalkyl, C1-C6 haloalkoxy, -S(=O)2N(R 7)2, S(=O)2C1-C6 alkyl, S(=O)2C1-C6 haloalkyl, -S(=O)2C3-C6 cycloalkyl, -C(=O)R 7 , -C(=O)N(R 7 )2, C3-C6 cycloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —OH, CN, or —C(═O)OH; Each R 7 are independently selected from the group consisting of H and C1-C6 alkyl that is unsubstituted or substituted with OH or C1-C6 alkoxy; R 8 is H, unsubstituted C1-C6 alkyl, C3-C8 cycloalkyl, or 1, 2, 3, or 4 ring members are N, NR 6 , O, and S; and 4- to 6-membered heterocycloalkyl, each independently selected from R 9 is substituted with a group, Each R 9 is NR 10 R 11 , -C(=O)N(R 7 )2 and -OH or -N(R 7 ) C1-C6 alkyl substituted with 2; R 10 is H or unsubstituted C1-C6 alkyl, R 11 is H, unsubstituted C1-C6 alkyl, or —S(═O)2C1-C6 alkyl, Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, -S(=O)2R 6 , -S(=O)2R 7 , -S(=O)2N(R 7 )2, [ka] , halo, phenyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , 4-6 membered heterocycloalkyl each independently selected from O and S, 5- or 6-membered heteroaryl each independently selected from N, O and S, and C1-C6 alkyl unsubstituted or substituted with NH2, CN or OH, wherein phenyl, heterocycloalkyl and heteroaryl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH; R 13 is H, -C(=O)N(R 7 ) 2 or 1, 2, 3 or 4 ring members are N, NR 6 , 5- or 6-membered heteroaryl independently selected from O and S; R 14 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 5- or 6-membered heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo, and ii) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or contains 1, 2, 3, or 4 R 12 5- or 6-membered heteroaryl substituted with a group and Each R 15 is CN, NH2, -OH, -C(=O)OH, -C(=O)N(R 7 )2, -C(=O)C(=O)OH, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR 6, O, and S, wherein the cycloalkyl, heteroaryl, and heterocycloalkyl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, and unsubstituted C-C alkyl; However, R 3a , R 3b , R 4a or R 4b (provided that at least one of the is not hydrogen) or a stereoisomer or a pharmaceutically acceptable salt thereof.

[0071] Various embodiments of the compounds of the present invention are described herein. It will be appreciated that the features specified in each embodiment can be combined with other specified features to provide further embodiments. The embodiments listed below are representative of the compounds of formula (I) of the present invention.

[0072] Embodiment 1. Formula (I) [ka] (In the formula, X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; ii) unsubstituted or containing 1 to 4 R 5 phenyl substituted with a group; iii) 1, 2, 3 or 4 ring members are N, NR 64, 5, or 6-membered heterocycloalkyl selected from each independently from O and S, which is unsubstituted or has 1 to 4 R 5 a 4-, 5-, or 6-membered heterocycloalkyl optionally substituted by an oxo group, wherein the 5- or 6-membered heterocycloalkyl is optionally substituted by oxo; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) unsubstituted C1-C6 alkyl, vi) 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, and the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; vii) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heterocyclyl substituted by a group; viii) unsubstituted or 1 to 4 R 5 spiro-linked C3-C8 cycloalkyl substituted with a group; ix) unsubstituted or 1 to 4 R 5 bicyclic C3-C8 cycloalkyl substituted with a group; x) C5-C6 cycloalkenyl, and xi) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R2 teeth, i)-(CH2) 0-6 CHR 13 R 14 , ii) is unsubstituted or contains 1, 2, 3 or 4 R 12 benzyl substituted with a group, iii) 6-membered heteroaryl in which 1, 2, or 3 ring members are each independently selected from N, O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group; iv) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, with 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; v) a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, further having 0, 1, 2, 3, or 4 ring members each independently selected from N, O, and S, and which is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; vi) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, 3, or 4 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; vii) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12a 9-membered bicyclic heteroaryl substituted with a group; viii) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 and 5- or 6-membered heterocycloalkyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; ix) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 5- or 6-membered heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; x) NR as a ring member having a point of attachment at a carbon atom ring member and located beta (β) to the point of attachment 6 and 9- or 10-membered bicyclic heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xi) a 9- or 10-membered bicyclic heterocyclyl having an attachment point at a carbon atom ring member and an O heteroatom as a ring member positioned beta (β) to the attachment point, and 6, O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xii) 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S; and 12 a 9- or 10-membered bicyclic heteroaryl substituted with a group; xiii) 1, 2 or 3 ring members are N, NR 6 , O and S, and is substituted with 1 or 2 oxo or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; xiv) 1, 2 or 3 ring members are N, NR 6 , O and S, which are substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xv) a 6-membered heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; xvi) 1, 2, 3, 4 or 5 ring members are N, NR 69- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3, or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xvii) one ring member is NR 6 a 6-membered heterocyclyl selected from the group consisting of: xviii) 6-membered heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, or 2 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group, and xix) a 10-membered bicyclic heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 10-membered bicyclic heterocyclyl substituted with a group and optionally substituted with an additional oxo is selected from the group consisting of R 3a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3b is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4bis H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 C1-C6 alkyl substituted with a group, Each R 5 -CN, -OH, -NR 7 R 8 , N.R. 6 C(=O)C2-C6 alkenyl, -SF5, S(=O)2C1-C6 alkyl, -C(=O)N(R 7 )2, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; 4-6 membered heterocycloalkyl having 1, 2, or 3 ring members each independently selected from N, O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl that is unsubstituted or substituted with CN, NH2, or OH, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3, or 4 R 9 is substituted with a group, Each R 6 is H, C1-C6 haloalkyl, C1-C6 haloalkoxy, -S(=O)2N(R 7)2, S(=O)2C1-C6 alkyl, S(=O)2C1-C6 haloalkyl, -S(=O)2C3-C6 cycloalkyl, -C(=O)R 7 , -C(=O)N(R 7 )2, C3-C6 cycloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —OH, CN, or —C(═O)OH; Each R 7 are independently selected from the group consisting of H and C1-C6 alkyl that is unsubstituted or substituted with OH or C1-C6 alkoxy; R 8 is H, unsubstituted C1-C6 alkyl, C3-C8 cycloalkyl, or 1, 2, 3, or 4 ring members are N, NR 6 , O, and S; and 4- to 6-membered heterocycloalkyl, each independently selected from R 9 is substituted with a group, Each R 9 is NR 10 R 11 , -C(=O)N(R 7 )2 and -OH or -N(R 7 ) C1-C6 alkyl substituted with 2; R 10 is H or unsubstituted C1-C6 alkyl, R 11 is H, unsubstituted C1-C6 alkyl, or —S(═O)2C1-C6 alkyl, Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, -S(=O)2R 7 , -S(=O)2N(R 7 )2, [ka] , halo, phenyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6, 4-6 membered heterocycloalkyl each independently selected from O and S, 5- or 6-membered heteroaryl each independently selected from N, O and S, and C1-C6 alkyl unsubstituted or substituted with NH2, CN or OH, wherein phenyl, heterocycloalkyl and heteroaryl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH; R 13 is H, -C(=O)N(R 7 ) 2 or 1, 2, 3 or 4 ring members are N, NR 6 , 5- or 6-membered heteroaryl independently selected from O and S; R 14 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 5- or 6-membered heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo, and ii) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or contains 1, 2, 3, or 4 R 12 5- or 6-membered heteroaryl substituted with a group and Each R 15 is CN, NH2, -OH, -C(=O)OH, -C(=O)N(R 7 )2, -C(=O)C(=O)OH, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR 6, O, and S, wherein the cycloalkyl, heteroaryl, and heterocycloalkyl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, and unsubstituted C-C alkyl; However, R 3a , R 3b , R 4a or R 4b (provided that at least one of the is not hydrogen) a compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0073] Embodiment 2. [ka] (In the formula, X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 teeth, i) unsubstituted or 1 to 4 R 5 phenyl substituted with a group; ii) unsubstituted or containing 1 to 4 R 5 spiro-linked C3-C8 cycloalkyl substituted with a group; iii) unsubstituted or containing 1 to 4 R 5 bicyclic C3-C8 cycloalkyl substituted with a group; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; vi) unsubstituted C1-C6 alkyl; vii) C5-C6 cycloalkenyl, viii) 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O or S, wherein the 5- or 6-membered heterocyclyl is optionally substituted by oxo; ix) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heterocyclyl substituted by a group; x) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heterocycloalkyl, each independently selected from R 5 5- or 6-membered heterocycloalkyl substituted with a group and optionally substituted with oxo, and xi) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 2 teeth, i)-(CH2) 0-6 CHR 13 R 14 , ii) is unsubstituted or contains 1, 2, 3 or 4 R 12 benzyl substituted with a group, iii) 6-membered heteroaryl in which 1, 2, or 3 ring members are each independently selected from N, O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12a 6-membered heteroaryl substituted with a group; iv) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, with 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; v) a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, further having 0, 1, 2, 3, or 4 ring members each independently selected from N, O, and S, and which is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; vi) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, 3, or 4 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; vii) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; viii) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 and 5- or 6-membered heterocycloalkyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; ix) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 5- or 6-membered heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; x) NR as a ring member having a point of attachment at a carbon atom ring member and located beta (β) to the point of attachment 6 and 9- or 10-membered bicyclic heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xi) a 9- or 10-membered bicyclic heterocyclyl having an attachment point at a carbon atom ring member and an O heteroatom as a ring member positioned beta (β) to the attachment point, and 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xii) 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S; and 12 a 9- or 10-membered bicyclic heteroaryl substituted with a group; xiii) 1, 2 or 3 ring members are N, NR 6 , O and S, and is substituted with 1 or 2 oxo or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; xiv) 1, 2 or 3 ring members are N, NR 6 , O and S, which are substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xv) a 6-membered heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; xvi) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3, or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xvii) one ring member is NR 6 a 6-membered heterocyclyl selected from the group consisting of: xviii) 6-membered heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, or 2 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group, and xix) a 10-membered bicyclic heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 10-membered bicyclic heterocyclyl substituted with a group and optionally substituted with an additional oxo is selected from the group consisting of R 3a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3b is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4b is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 C1-C6 alkyl substituted with a group, Each R 5 -OH, -NR 7 R 8 , N.R. 6 C(=O)C2-C6 alkenyl, -SF5, -C(=O)N(R 7 )2, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; 4-6 membered heterocycloalkyl having 1, 2, or 3 ring members each independently selected from N, O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl that is unsubstituted or substituted with CN, NH2, or OH, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3, or 4 R 9 is substituted with a group, Each R 6 is H, -S(=O)2N(R 7 )2, -C(=O)N(R 7 )2 and C1-C6 alkyl that is unsubstituted or substituted with —OH, —CN, or —C(═O)OH; Each R 7 are independently selected from the group consisting of H and unsubstituted C1-C6 alkyl; R 8 is H, unsubstituted C1-C6 alkyl, C3-C8 cycloalkyl, or 1, 2, 3, or 4 ring members are N, NR 6 , O, and S; and 4- to 6-membered heterocycloalkyl, each independently selected from R 9 is substituted with a group, Each R 9 is NR 10 R 11 , -C(=O)N(R 7 )2 and -OH or -N(R 7) C1-C6 alkyl substituted with 2; R 10 is H or unsubstituted C1-C6 alkyl, R 11 is H, unsubstituted C1-C6 alkyl, or —S(═O)2C1-C6 alkyl, Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, -S(=O)2R 6 , -S(=O)2N(R 7 )2, [ka] , halo, phenyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , 4-6 membered heterocycloalkyl each independently selected from O and S, 5- or 6-membered heteroaryl each independently selected from N, O and S, and C1-C6 alkyl unsubstituted or substituted with NH2, CN or OH, wherein phenyl, heterocycloalkyl and heteroaryl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH; R 13 is H, -C(=O)N(R 7 ) 2 or 1, 2, 3 or 4 ring members are N, NR 6 , 5- or 6-membered heteroaryl independently selected from O and S; R 14 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 5- or 6-membered heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo, and ii) 1, 2, 3 or 4 ring members are N, NR6 , O, and S, and is unsubstituted or contains 1, 2, 3, or 4 R 12 5- or 6-membered heteroaryl substituted with a group and Each R 15 is CN, NH2, -OH, -C(=O)OH, -C(=O)N(R 7 )2, -C(=O)C(=O)OH, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR 6 , O, and S, wherein the cycloalkyl, heteroaryl, and heterocycloalkyl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, and unsubstituted C-C alkyl; However, R 3a , R 3b , R 4a or R 4b (provided that at least one of the is not hydrogen) The compound of embodiment 1, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0074] Embodiment 3.X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; ii) unsubstituted or containing 1 to 4 R 5 phenyl substituted with a group; iii) 1, 2, 3 or 4 ring members are N, NR 6 4, 5, or 6-membered heterocycloalkyl selected from each independently from O and S, which is unsubstituted or has 1 to 4 R 5 a 4-, 5-, or 6-membered heterocycloalkyl optionally substituted by an oxo group, wherein the 5- or 6-membered heterocycloalkyl is optionally substituted by oxo; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) unsubstituted C1-C6 alkyl, vi) 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, and the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; vii) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heterocyclyl substituted by a group; viii) unsubstituted or 1 to 4 R 5 spiro-linked C3-C8 cycloalkyl substituted with a group; ix) unsubstituted or 1 to 4 R 5 bicyclic C3-C8 cycloalkyl substituted with a group; x) C5-C6 cycloalkenyl, and xi) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 2 teeth, i)-(CH2) 0-6 CHR 13 R 14 , ii) is unsubstituted or contains 1, 2, 3 or 4 R 12 benzyl substituted with a group, iii) 6-membered heteroaryl in which 1, 2, or 3 ring members are each independently selected from N, O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group; iv) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, with 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; v) a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, further having 0, 1, 2, 3, or 4 ring members each independently selected from N, O, and S, and which is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; vi) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, 3, or 4 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; vii) 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; viii) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 and 5- or 6-membered heterocycloalkyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; ix) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 5- or 6-membered heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; x) NR as a ring member having a point of attachment at a carbon atom ring member and located beta (β) to the point of attachment 6 and 9- or 10-membered bicyclic heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xi) a 9- or 10-membered bicyclic heterocyclyl having an attachment point at a carbon atom ring member and an O heteroatom as a ring member positioned beta (β) to the attachment point, and 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xii) 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S; and 12 a 9- or 10-membered bicyclic heteroaryl substituted with a group; xiii) 1, 2 or 3 ring members are N, NR 6 , O and S, and is substituted with 1 or 2 oxo or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocycloalkyl substituted by a group and optionally substituted by 1 or 2 oxo; xiv) 1, 2 or 3 ring members are N, NR 6 , O and S, which are substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3 or 4 R 12 a 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xv) a 6-membered heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 126-membered heterocyclyl substituted by a group and optionally substituted by oxo; xvi) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3, or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; xvii) one ring member is NR 6 a 6-membered heterocyclyl selected from the group consisting of: xviii) 6-membered heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, or 2 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 6-membered heteroaryl substituted with a group, and xix) a 10-membered bicyclic heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, such as N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 10-membered bicyclic heterocyclyl substituted with a group and optionally substituted with an additional oxo is selected from the group consisting of R 3a is -CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3b is H, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4a is H, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4bis H, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 C1-C6 alkyl substituted with a group, Each R 5 -CN, -OH, -NR 7 R 8 , N.R. 6 C(=O)C2-C6 alkenyl, -SF5, S(=O)2C1-C6 alkyl, -C(=O)N(R 7 )2, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; 4-6 membered heterocycloalkyl having 1, 2, or 3 ring members each independently selected from N, O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl that is unsubstituted or substituted with CN, NH2, or OH, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3, or 4 R 9 is substituted with a group, Each R 6 is H, C1-C6 haloalkyl, C1-C6 haloalkoxy, -S(=O)2N(R 7)2, S(=O)2C1-C6 alkyl, S(=O)2C1-C6 haloalkyl, -S(=O)2C3-C6 cycloalkyl, -C(=O)R 7 , -C(=O)N(R 7 )2, C3-C6 cycloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —OH, CN, or —C(═O)OH; Each R 7 are independently selected from the group consisting of H and C1-C6 alkyl that is unsubstituted or substituted with OH or C1-C6 alkoxy; R 8 is H, unsubstituted C1-C6 alkyl, C3-C8 cycloalkyl, or 1, 2, 3, or 4 ring members are N, NR 6 , O, and S; and 4- to 6-membered heterocycloalkyl, each independently selected from R 9 is substituted with a group, Each R 9 is NR 10 R 11 , -C(=O)N(R 7 )2 and -OH or -N(R 7 ) C1-C6 alkyl substituted with 2; R 10 is H or unsubstituted C1-C6 alkyl, R 11 is H, C1-C6 alkyl, or —S(═O)2C1-C6 alkyl, Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, -S(=O)2R 7 , -S(=O)2N(R 7 )2, [ka] , halo, phenyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6, 4-6 membered heterocycloalkyl each independently selected from O and S, 5- or 6-membered heteroaryl each independently selected from N, O and S, and C1-C6 alkyl unsubstituted or substituted with NH2, CN or OH, wherein phenyl, heterocycloalkyl and heteroaryl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH; R 13 is H, -C(=O)N(R 7 ) 2 or 1, 2, 3 or 4 ring members are N, NR 6 , 5- or 6-membered heteroaryl independently selected from O and S; R 14 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 5- or 6-membered heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo, and ii) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or contains 1, 2, 3, or 4 R 12 5- or 6-membered heteroaryl substituted with a group and Each R 15 is CN, NH2, -OH, -C(=O)OH, -C(=O)N(R 7 )2, -C(=O)C(=O)OH, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR 6, O, and S, wherein cycloalkyl, heteroaryl, and heterocycloalkyl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, and unsubstituted C1-C6 alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0075] Embodiment 4.X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; ii) unsubstituted or containing 1 to 4 R 5 phenyl substituted with a group; iii) 1, 2, 3 or 4 ring members are N, NR 6 4, 5, or 6-membered heterocycloalkyl selected from each independently from O and S, which is unsubstituted or has 1 to 4 R 5 a 4-, 5-, or 6-membered heterocycloalkyl optionally substituted by an oxo group, wherein the 5- or 6-membered heterocycloalkyl is optionally substituted by oxo; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) unsubstituted C1-C6 alkyl, vi) 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6, O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, and the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; vii) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heterocyclyl substituted by a group; viii) unsubstituted or 1 to 4 R 5 spiro-linked C3-C8 cycloalkyl substituted with a group; ix) unsubstituted or 1 to 4 R 5 bicyclic C3-C8 cycloalkyl substituted with a group; x) C5-C6 cycloalkenyl, and xi) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 2 teeth, i) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; ii) a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, further having 0, 1, 2, 3, or 4 ring members each independently selected from N, O, and S, and which is unsubstituted or has 1, 2, 3, or 4 R 12a 10-membered bicyclic heteroaryl substituted with a group; iii) a 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, 3, or 4 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; iv) a 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, wherein N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 9-membered bicyclic heteroaryl substituted with a group; v) NR as a ring member having a point of attachment at a carbon atom ring member and positioned beta (β) to the point of attachment 6 and 9- or 10-membered bicyclic heterocyclyl having the formula: 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; vi) a 9- or 10-membered bicyclic heterocyclyl having an attachment point at a carbon atom ring member and an O heteroatom as a ring member located beta (β) to the attachment point, such as N, NR 6 , O and S, and is substituted with 1 or 2 oxo, or unsubstituted, or is substituted with 1, 2, 3 or 4 R 12 a 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo; vii) 1, 2, 3, 4 or 5 ring members are N, NR 6, O, and S; and 12 a 9- or 10-membered bicyclic heteroaryl substituted with a group; viii) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, substituted by 1 or 2 oxo or unsubstituted, or substituted by 1, 2, 3, or 4 R 12 9- or 10-membered bicyclic heterocyclyl substituted by a group and optionally substituted by 1 or 2 oxo, and ix) a 10-membered bicyclic heterocyclyl having a carbon atom as a ring member at the point of attachment and substituted with oxo and positioned beta (β) to the point of attachment, wherein N, NR 6 , O, and S, and is unsubstituted or has 1, 2, 3, or 4 R 12 10-membered bicyclic heterocyclyl substituted with a group and optionally substituted with an additional oxo is selected from the group consisting of R 3a is -CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3bis H, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4a is H, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 4b is H, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15C2-C6 alkenyl substituted by a group, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted by 1 or 2 substituents independently selected from the group consisting of CN, —C(═O)OH, NH2, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH2; R 3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 C1-C6 alkyl substituted with a group, Each R 5 -CN, -OH, -NR 7 R 8 , N.R. 6 C(=O)C2-C6 alkenyl, -SF5, S(=O)2C1-C6 alkyl, -C(=O)N(R 7 )2, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; 4-6 membered heterocycloalkyl having 1, 2, or 3 ring members each independently selected from N, O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl that is unsubstituted or substituted with CN, NH2, or OH, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3, or 4 R 9 is substituted with a group, Each R 6 is H, C1-C6 haloalkyl, C1-C6 haloalkoxy, -S(=O)2N(R 7 )2, S(=O)2C1-C6 alkyl, S(=O)2C1-C6 haloalkyl, -S(=O)2C3-C6 cycloalkyl, -C(=O)R 7 , -C(=O)N(R 7 )2, C3-C6 cycloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —OH, CN, or —C(═O)OH; Each R 7are independently selected from the group consisting of H and C1-C6 alkyl that is unsubstituted or substituted with OH or C1-C6 alkoxy; R 8 is H, unsubstituted C1-C6 alkyl, C3-C8 cycloalkyl, or 1, 2, 3, or 4 ring members are N, NR 6 , O, and S; and 4- to 6-membered heterocycloalkyl, each independently selected from R 9 is substituted with a group, Each R 9 is NR 10 R 11 , -C(=O)N(R 7 )2 and -OH or -N(R 7 ) C1-C6 alkyl substituted with 2; R 10 is H or unsubstituted C1-C6 alkyl, R 11 is H, unsubstituted C1-C6 alkyl, or —S(═O)2C1-C6 alkyl, Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, -S(=O)2R 7 , -S(=O)2N(R 7 )2, [ka] , halo, phenyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6, 4-6 membered heterocycloalkyl each independently selected from O and S, 5- or 6-membered heteroaryl each independently selected from N, O and S, and C1-C6 alkyl unsubstituted or substituted with NH2, CN, or OH, wherein phenyl, heterocycloalkyl, and heteroaryl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH, and Each R 15 is CN, NH2, -OH, -C(=O)OH, -C(=O)N(R 7 )2, -C(=O)C(=O)OH, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR 6 , O, and S, and 3-6 membered heterocycloalkyl, wherein cycloalkyl, heteroaryl, and heterocycloalkyl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, and unsubstituted C1-C6 alkyl; or a pharmaceutically acceptable salt, or stereoisomer thereof.

[0076] Embodiment 5.X1 is a CR 3a R 3b and X2 is CR 4a R 4b and R 1 teeth, i) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; ii) unsubstituted or containing 1 to 4 R 5 phenyl substituted with a group; iii) 1, 2, 3 or 4 ring members are N, NR 6 , O and S, wherein the 5- or 6-membered heterocycloalkyl is unsubstituted or has 1 to 4 R 5 a 4-, 5-, or 6-membered heterocycloalkyl substituted with a group; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) unsubstituted C1-C6 alkyl, vi) 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z, and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O or S, and the 5- or 6-membered heterocyclyl is unsubstituted or has one or two R 12 5- or 6-membered heterocyclyl substituted by a group and optionally substituted by oxo; vii) one or two ring members are N and NR 6 and a 9- or 10-membered bicyclic heterocyclyl selected from the group consisting of: 5 9- or 10-membered bicyclic heterocyclyl substituted by a group, and viii) unsubstituted or 1 to 4 R 5 Bicyclic C3-C8 cycloalkyl substituted with a group is selected from the group consisting of R 2 teeth, i) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1, 2, 3, or 4 R 12 a 10-membered bicyclic heteroaryl substituted with a group; and ii) 1, 2, 3, 4 or 5 ring members are N, NR 6, O, and S; and 12 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 3a is -CN, R 3b is H or unsubstituted C1-C6 alkyl, R 4a is H or unsubstituted C1-C6 alkyl, R 4b is H or unsubstituted C1-C6 alkyl, Each R 5 is independently selected from the group consisting of CN, —OH, S(═O)C1-C6 alkyl, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, unsubstituted C3-C8 cycloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with OH; Each R 6 is H, C1-C6 haloalkyl, C1-C6 haloalkoxy, S(=O)2C1-C6 alkyl, S(=O)2C1-C6 haloalkyl, -S(=O)2C3-C6 cycloalkyl, -C(=O)R 7 , C3-C6 cycloalkyl, and C1-C6 alkyl that is unsubstituted or substituted with —OH; Each R 7 is independently selected from the group consisting of H and C1-C6 alkyl that is unsubstituted or substituted with OH or C1-C6 alkoxy, and Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -CN, -S(=O)2R 7 and C1-C6 alkyl substituted with OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of embodiment 4.

[0077] Embodiment 6.X1 is a CR 3a R 3b, C═O or NR 3c 6. The compound according to any one of embodiments 1 to 5, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0078] Embodiment 7.X1 is a CR 3a R 3b 6. The compound according to any one of embodiments 1 to 5, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0079] Embodiment 8. A compound according to any one of embodiments 1 to 5, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein X1 is C=O.

[0080] Embodiment 9.X1 is NR 3c 6. The compound according to any one of embodiments 1 to 5, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0081] Embodiment 10.X2 is a CR 4a R 4b or C═O, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0082] Embodiment 11.X2 is a CR 4a R 4b 11. The compound according to any one of embodiments 1 to 10, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0083] Embodiment 12. A compound according to any one of embodiments 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein X2 is C=O.

[0084] Embodiment 13. A compound of formula (I) according to any one of embodiments 1 to 5, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, selected from compounds having the structure of the following subformulas: Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie), Formula (If) and Formula (Ig). [ka]

[0085] Embodiment 14. A compound according to any one of embodiments 1 to 5, selected from compounds having the structure of formula (Ig), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. [ka]

[0086] Embodiment 15. A compound according to any one of embodiments 1 to 5, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from a compound having the structure of Formula (Ih) or Formula (Ii): [ka]

[0087] Embodiment 16. The compound of any one of embodiments 1 to 5, its stereoisomer, or pharmaceutically acceptable salt thereof, selected from compounds having the structure of formula (Ii): [ka]

[0088] Embodiment 17.R 2 is -(CH2) 0-6 CHR 13 R 14 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0089] Embodiment 18.R 2 is -CHR 13 R 14 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0090] Embodiment 19.R 2 is unsubstituted or has 1, 2, 3 or 4 R12 17. The compound of any one of embodiments 1 to 16, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound is benzyl substituted with a group.

[0091] Embodiment 20.R 2 is unsubstituted or contains one R 12 17. The compound of any one of embodiments 1 to 16, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound is benzyl substituted with a group.

[0092] Embodiment 21.R 2 is a 6-membered heteroaryl in which 1, 2, or 3 ring members are each independently selected from N, O, and S, and the 6-membered heteroaryl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0093] Embodiment 22.R 2 is a 6-membered heteroaryl in which one ring member is selected from N, and the 6-membered heteroaryl is unsubstituted or contains one or two R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0094] Embodiment 23.R 2 is unsubstituted or has 1, 2, 3 or 4 R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyridyl substituted with a group.

[0095] Embodiment 24.R 2 is unsubstituted or contains one or two R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is pyrid-3-yl substituted with a group.

[0096] Embodiment 25.R 2is a ring in which 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S, wherein the 9- or 10-membered bicyclic heteroaryl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0097] Embodiment 26.R 2 has 1, 2 or 3 ring members N, NR 6 and 9- or 10-membered bicyclic heteroaryl, each independently selected from O and S, wherein the 9- or 10-membered bicyclic heteroaryl is unsubstituted or contains one or two R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0098] Embodiment 27.R 2 are each unsubstituted or 1, 2, 3 or 4 R 12 17. The compound of any one of embodiments 1 to 16, wherein the compound is isoquinolinyl, phthalazinyl, cinnolinyl, imidazo[1,2-c]pyrimidinyl, pyrazolo[1,5-a]pyrazinyl, benzo[c]isoxazolyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-a]pyridinyl, or naphthyridinyl substituted with a group, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0099] Embodiment 28.R 2 are each unsubstituted or 1, 2, 3 or 4 R 1217. The compound of any one of embodiments 1 to 16, its stereoisomer, or a pharmaceutically acceptable salt thereof, which is isoquinolin-4-yl, phthalazin-4-yl, cinnolin-4-yl, imidazo[1,2-c]pyrimidin-8-yl, pyrazolo[1,5-a]pyrazin-7-yl, benzo[c]isoxazol-3-yl, imidazo[1,2-a]pyrazin-5-yl, imidazo[1,2-a]pyridin-3-yl, or naphthyridin-4-yl substituted with a group.

[0100] Embodiment 29.R 2 are each unsubstituted or one or two R 12 substituted with a group [ka] 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0101] Embodiment 30.R 2 is unsubstituted or contains one or two R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is isoquinolinyl substituted with a group.

[0102] Embodiment 31.R 2 is unsubstituted or contains one or two R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is isoquinolin-4-yl substituted with a group.

[0103] Embodiment 32.R 2 is unsubstituted or contains one or two R 12 17. The compound of any one of embodiments 1 to 16, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the compound is 3-(isoquinolin-4-yl) substituted with a group.

[0104] Embodiment 33.R 2The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted isoquinolin-4-yl.

[0105] Embodiment 34.R 2 The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted 3-(isoquinolin-4-yl).

[0106] Embodiment 35.R 2 is unsubstituted or contains one or two R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is phthalazinyl substituted with a group.

[0107] Embodiment 36.R 2 is unsubstituted or contains one or two R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is phthalazin-4-yl substituted with a group.

[0108] Embodiment 37.R 2 The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted phthalazin-4-yl.

[0109] Embodiment 38.R 2 has 1, 2 or 3 ring members N, NR 6 , O, and S, wherein the 5- or 6-membered heterocycloalkyl is substituted with 1 or 2 oxo, or the 5- or 6-membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0110] Embodiment 39.R2 has 1, 2 or 3 ring members N, NR 6 , O, and S, wherein the 5- or 6-membered heterocyclyl is substituted with 1 or 2 oxo, or the 5- or 6-membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0111] Embodiment 40.R 2 is a ring with one ring member NR 6 and wherein the 6-membered heterocyclyl is substituted with oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0112] Embodiment 41.R 2 is unsubstituted or has 1, 2, 3 or 4 R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyridinyl-2(1H)-one substituted with a group.

[0113] Embodiment 42.R 2 are each unsubstituted or 1, 2, 3 or 4 R 12 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyridin-3-yl-2(1H)-one or pyridin-4-yl-2(1H)-one substituted with a group.

[0114] Embodiment 43.R 2 are each unsubstituted or one or two R 12 substituted with a group [ka] 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0115] Embodiment 44.R 2 is a ring in which 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S, wherein the 9- or 10-membered bicyclic heterocyclyl is substituted by 1 or 2 oxo, or the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or is substituted by 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0116] Embodiment 45.R 2 has one ring member N, NR 6 and O, wherein the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or substituted with oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0117] Embodiment 46.R 2 are each unsubstituted or 1, 2, 3 or 4 R 12 17. The compound according to any one of embodiments 1 to 16, wherein the compound is isochromanyl, quinolinyl-2(1H)-one, 3a,7a-dihydro-1H-pyrrolo[2,3-c]pyridinyl, or 3a,7a-dihydro-1H-indazolyl substituted with a group, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0118] Embodiment 47.R 2 are each unsubstituted or 1, 2, 3 or 4 R 1217. The compound according to any one of embodiments 1 to 16, wherein the compound is isochroman-4-yl, quinolin-4-yl-2(1H)-one, 3a,7a-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl, or 3a,7a-dihydro-1H-indazol-4-yl substituted with a group, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0119] Embodiment 48.R 2 are each unsubstituted or one or two R 12 substituted with a group [ka] 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0120] Embodiment 49.R 2 are each unsubstituted or one or two R 12 17. The compound of any one of embodiments 1 to 16, wherein the compound is isoquinolinyl, isochromanyl, pyridyl, phthalazinyl, cinnolinyl, imidazo[1,2-c]pyrimidinyl, pyrazolo[1,5-a]pyrazinyl, 3a,7a-dihydro-1H-pyrrolo[2,3-c]pyridinyl, benzo[c]isoxazolyl, imidazo[1,2-a]pyrazinyl, pyridinyl-2(1H)-one, quinolinyl-2(1H)-one, imidazo[1,2-a]pyridinyl, naphthyridinyl, or 3a,7a-dihydro-1H-indazolyl substituted with a group, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0121] Embodiment 50.R 2 are each unsubstituted or one or two R 12 substituted with a group [ka] 17. The compound according to any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0122] Embodiment 51.R 2 is a 6-membered heteroaryl having a point of attachment at a carbon atom ring member and having a N heteroatom as a ring member positioned beta (β) to the point of attachment, wherein the 6-membered heteroaryl has 0, 1, or 2 additional N heteroatoms as ring members, and the 6-membered heteroaryl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0123] Embodiment 52.R 2 is a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and having a N heteroatom as a ring member positioned beta (β) to the point of attachment, the 10-membered bicyclic heteroaryl having 0, 1, 2, or 3 additional N heteroatoms as ring members, the 10-membered bicyclic heteroaryl being unsubstituted or having 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0124] Embodiment 53.R 2 is a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and having a N heteroatom as a ring member positioned beta (β) to the point of attachment, the 10-membered bicyclic heteroaryl further having 0, 1, 2, 3, or 4 ring members each independently selected from N, O, and S, the 10-membered bicyclic heteroaryl being unsubstituted or having 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0125] Embodiment 54.R 2is a 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and having a N heteroatom as a ring member located beta (β) to the point of attachment, the 9-membered bicyclic heteroaryl having 0, 1, 2, 3, or 4 additional N heteroatoms as ring members, the 9-membered bicyclic heteroaryl being unsubstituted or having 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0126] Embodiment 55.R 2 is a 9-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, and the 9-membered bicyclic heteroaryl is N, NR 6 , O, and S; and the 9-membered bicyclic heteroaryl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0127] Embodiment 56.R 2 has a point of attachment at a carbon atom ring member and has NR as the ring member located beta (β) to the point of attachment. 6 and 5- or 6-membered heterocycloalkyl having the formula: 6 , O, and S, wherein the 5- or 6-membered heterocycloalkyl is substituted with 1 or 2 oxo, or the 5- or 6-membered heterocycloalkyl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0128] Embodiment 57.R 2has a point of attachment at a carbon atom ring member and has NR as the ring member located beta (β) to the point of attachment. 6 and the 5- or 6-membered heterocyclyl is N, NR 6 , O, and S, and the 5- or 6-membered heterocyclyl is substituted with 1 or 2 oxo, or the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0129] Embodiment 58.R 2 has a point of attachment at a carbon atom ring member and has NR as the ring member located beta (β) to the point of attachment. 6 and 9- or 10-membered bicyclic heterocyclyl having the formula: 6 , O, and S, wherein the 9- or 10-membered heterocyclyl is substituted with 1 or 2 oxo, or the 9- or 10-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0130] Embodiment 59.R 2 is a 9- or 10-membered bicyclic heterocyclyl having the point of attachment at a carbon atom ring member and having an O heteroatom as a ring member positioned beta (β) to the point of attachment, and the 9- or 10-membered heterocyclyl is selected from N, NR 6 , O, and S, wherein the 9- or 10-membered heterocyclyl is substituted with 1 or 2 oxo, or the 9- or 10-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with one or two oxo.

[0131] Embodiment 60.R 2 is a 6-membered heterocyclyl having a carbon atom as a ring member that has the point of attachment at a carbon atom ring member and is substituted with oxo and that is positioned beta (β) to the point of attachment, and the 6-membered heterocyclyl is N, NR 6 , O, and S; and the 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally substituted with oxo.

[0132] Embodiment 61.R 2 is a 10-membered bicyclic heterocyclyl having a carbon atom as a ring member that has the point of attachment at a carbon atom ring member and is substituted with oxo and that is positioned beta (β) to the point of attachment, and the 10-membered heterocyclyl is selected from N, NR 6 , O, and S, and the 10-membered heterocyclyl is unsubstituted or the 10-membered heterocyclyl further has 1, 2, 3, or 4 ring members each independently selected from R 12 17. The compound of any one of embodiments 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with a group and optionally with an additional oxo.

[0133] Embodiment 62. Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, [ka] , halo and 1, 2, 3 or 4 ring members are N, NR 6 , O and C1-C6 alkyl that is unsubstituted or substituted with NH2, CN, or OH, wherein heterocycloalkyl is unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of the compound of any one of embodiments 1 to 61.

[0134] Embodiment 63. Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -N(R 7 )2, -CN, -OH, [ka] , a stereoisomer thereof, or a pharmaceutically acceptable salt thereof of the compound of any one of embodiments 1 to 61, wherein R is independently selected from the group consisting of unsubstituted C1-C6 alkyl and halo.

[0135] Embodiment 64. Each R 12 is -C(=O)N(R 7 )2, -C(=O)OH, -CN, -S(=O)2R 7 and C1-C6 alkyl substituted with OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-61.

[0136] Embodiment 65. Each R 12 is independently selected from the group consisting of -C(=O)NH2, -C(=O)NH(CH2)2OCH3, -C(=O)OH, -CN, -S(=O)2CH3 and -C(CH3)2OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1 to 61.

[0137] Embodiment 66. Each R 12 is -S(=O)2R 6, -S(=O)2N(R 7 )2, phenyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , 4-6 membered heterocycloalkyl each independently selected from O and S, and 5- or 6-membered heteroaryl each independently selected from N, O and S, wherein phenyl, heterocycloalkyl, and heteroaryl are unsubstituted or substituted with 1 or 2 substituents independently selected from the group consisting of OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0138] Embodiment 67.R 1 are each unsubstituted or 1 to 4 R 5 67. The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is phenyl or pyridyl substituted with a group.

[0139] Embodiment 68.R 1 is phenyl or one or two ring members are N, NR 6 , O, and S; and phenyl or heteroaryl is unsubstituted or has one to two R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0140] Embodiment 69.R 1 are each unsubstituted or 1 to 2 R independently selected from Cl, F, CF, -CHF, -CH, -CH(CH), -OCH, -OCHF, -OCF, CN, -SOCH, and -C(CH)OH; 5 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is phenyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl substituted with a group.

[0141] Embodiment 70.R1 are each unsubstituted or 1 to 2 R independently selected from Cl, F, CF, -CHF, -CH, -CH(CH), -OCH, -OCHF, -OCF, CN, -SOCH, and -C(CH)OH; 5 67. The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is phenyl or pyridyl substituted with a group.

[0142] Embodiment 71.R 1 is unsubstituted or is substituted with 1 to 2 R independently selected from Cl, F, CF, -CHF, -CH, -CH(CH), -OCH, -OCHF, -OCF, CN, -SOCH, and -C(CH)OH; 5 67. The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyridyl substituted with a group.

[0143] Embodiment 72.R 1 The compound according to any one of embodiments 1-66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is pyridyl that is unsubstituted or substituted with CF3.

[0144] Embodiment 73.R 1 The compound of any one of embodiments 1-66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is pyridyl substituted with CF3.

[0145] Embodiment 74.R 1 are each unsubstituted or 1 to 2 R independently selected from Cl, F, CF, -CHF, -CH, -CH(CH), -OCH, -OCHF, -OCF, CN, -SOCH, and -C(CH)OH; 5 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyrazolyl or imidazolyl substituted with a group.

[0146] Embodiment 75.R 1are each unsubstituted or substituted with 1 to 2 R independently selected from the group consisting of Cl, —CH, and —CH(CH) 5 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyrazolyl or imidazolyl substituted with a group.

[0147] Embodiment 76.R 1 is unsubstituted or has 1 to 4 R 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is phenyl substituted with a group.

[0148] Embodiment 77.R 1 is unsubstituted or contains 1 to 2 R 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is phenyl substituted with a group.

[0149] Embodiment 78.R 1 are each unsubstituted or 1 to 2 R independently selected from -CN, -OH, -S(=O)2C1-C6 alkyl, C1-C6 alkyl, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, and C1-C6 alkyl substituted with OH; 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is phenyl substituted with a group.

[0150] Embodiment 79.R 1 are each unsubstituted or 1 to 2 R independently selected from Cl, F, —CF, —OCF, —CH, —OCH, —CN, —CHF, —OCHF, —SOCH, —CH(CH) and —C(CH)OH; 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is phenyl substituted with a group.

[0151] Embodiment 80.R 1 are each unsubstituted or 1 to 2 R independently selected from Cl, F, —CF, —OCF, —CH, —OCH, —CN, —CHF, —OCHF, —SOCH, and —C(CH)OH; 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is phenyl substituted with a group.

[0152] Embodiment 81.R 1 teeth, [ka] 67. The compound of any one of embodiments 1 to 66, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0153] Embodiment 82.R 1 is unsubstituted or has 1 to 4 R 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a spiro-linked C3-C8 cycloalkyl substituted with a group.

[0154] Embodiment 83.R 1 is unsubstituted or has 1 to 4 R 5 67. The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a bicyclic C3-C8 cycloalkyl substituted with a group.

[0155] Embodiment 84.R 1 is unsubstituted or contains 1 to 2 R 5 67. The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a bicyclic C3-C8 cycloalkyl substituted with a group.

[0156] Embodiment 85.R 1 is unsubstituted or contains 1 to 2 R 5 and each R is a bicyclic C3-C8 cycloalkyl substituted with a5 is independently selected from the group consisting of halo, C1-C6 haloalkyl, and unsubstituted C1-C6 alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-66.

[0157] Embodiment 86.R 1 are each unsubstituted or 1 to 2 R 5 bicyclo[1.1.1]pentan-1-yl), (spiro[3.3]heptan-2-yl), or (spiro[2.3]hexan-5-yl) substituted with a group, 5 is independently selected from the group consisting of F, —CF 3 and —CH 3 , a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 66.

[0158] Embodiment 87.R 1 is unsubstituted or has 1 to 4 R 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C3-C8 cycloalkyl substituted with a group.

[0159] Embodiment 88.R 1 is unsubstituted or contains 1 to 2 R 5 67. The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C3-C8 cycloalkyl substituted with a group.

[0160] Embodiment 89.R 1 is unsubstituted or contains 1 to 2 R 5 is a C3-C8 cycloalkyl substituted with a group, and each R 5 is independently selected from the group consisting of halo, OH, C1-C6 haloalkyl, unsubstituted C1-C6 alkyl, and unsubstituted C3-C8 cycloalkyl, a compound, a stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-66.

[0161] Embodiment 90.R 1are each unsubstituted or 1 to 2 R 5 cyclobutyl, cyclopentyl, or cyclohexyl substituted with a group, and each R 5 is independently selected from the group consisting of F, -CF3, -CH3, -CH(CH3)2 and cyclopropyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 66.

[0162] Embodiment 91.R 1 are each unsubstituted or 1 to 2 R 5 67. The compound according to any one of embodiments 1 to 66, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein R is C3-C8 cycloalkyl or bicyclic C3-C8 cycloalkyl substituted with a group.

[0163] Embodiment 92.R 1 are each unsubstituted or 1 to 2 R 5 C3-C8 cycloalkyl or bicyclic C3-C8 cycloalkyl substituted with a group, and each R 5 is independently selected from the group consisting of halo, OH, C1-C6 haloalkyl, unsubstituted C1-C6 alkyl, and unsubstituted C3-C8 cycloalkyl, a compound, a stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-66.

[0164] Embodiment 93.R 1 are each unsubstituted or 1 to 2 R 5 cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentan-1-yl), (spiro[3.3]heptan-2-yl), or (spiro[2.3]hexan-5-yl) substituted with a group, 5 is independently selected from the group consisting of F, -CF3, -CH3, -CH(CH3)2 and cyclopropyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 66.

[0165] Embodiment 94.R 1is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, wherein the 5- or 6-membered heteroaryl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0166] Embodiment 95.R 1 has one or two ring members N, NR 6 , O, and S, wherein the 5- or 6-membered heteroaryl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0167] Embodiment 96.R 1 has one or two ring members N, NR 6 , O and S, wherein the 5- or 6-membered heteroaryl is unsubstituted or has 1 to 2 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0168] Embodiment 97.R 1 has one ring member N, NR 6 , O and S, wherein the 5- or 6-membered heteroaryl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0169] Embodiment 98.R 1 are each unsubstituted or 1 to 4 R 567. The compound of any one of embodiments 1 to 66, wherein the compound is pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, pyrrolyl, imidazolyl, thienyl, furyl, thiazolyl, oxazolyl, isoxazolyl, or triazolyl substituted with a group, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0170] Embodiment 99.R 1 teeth, [ka] 67. The compound of any one of embodiments 1 to 66, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0171] Embodiment 100.R 1 are each unsubstituted or 1 to 4 R 5 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, which is pyridyl or pyrazolyl substituted with a group.

[0172] Embodiment 101.R 1 teeth, [ka] 67. The compound of any one of embodiments 1 to 66, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0173] Embodiment 102.R 1 The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is C1-C6 alkyl.

[0174] Embodiment 103.R 1 The compound of any one of embodiments 1-66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is neopentyl.

[0175] Embodiment 104.R 1The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is C5-C6 cycloalkenyl.

[0176] Embodiment 105.R 1 The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is C5 cycloalkenyl.

[0177] Embodiment 106.R 1 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is cyclopent-1-enyl or cyclopenta-1,3-dienyl.

[0178] Embodiment 107.R 1 The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is C6 cycloalkenyl.

[0179] Embodiment 108.R 1 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is cyclohex-1-enyl or cyclohexa-1,3-dienyl.

[0180] Embodiment 109.R 1 is a 5- or 6-membered heterocyclyl having 1, 2, or 3 ring members independently selected from W, Y, and Z; W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O, or S, and the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 12 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group and optionally substituted with oxo.

[0181] Embodiment 110.R 1is a 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z; and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O or S, wherein the 5- or 6-membered heterocyclyl is substituted with oxo, and R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0182] Embodiment 111.R 1 is a 5- or 6-membered heterocyclyl in which 1, 2, or 3 ring members are each independently selected from W, Y, and Z; and W is NR 6 , O, S, S=O or S(=O)2, and Y is NR 6 , O, S, S=O or S(=O)2, and Z is NR 6 , O or S, and the 5- or 6-membered heterocyclyl is substituted with oxo, and R 6 is H or -CH3, and R 5 The compound of any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is —CF 3 .

[0183] Embodiment 112.R 1 The compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is 1,2-dihydropyridinyl substituted with oxo, -CH3, and -CF3.

[0184] Embodiment 113.R 1 is 1,2-dihydropyridinyl, pyridinyl-2(1H)-one, 2,3-dihydro-1H-pyrrolyl, or 1,3-dihydro-2H-pyrrolyl-2-one, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0185] Embodiment 114.R 1is a 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and the 9- or 10-membered bicyclic heteroaryl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0186] Embodiment 115.R 1 is a ring in which 1, 2, 3, 4 or 5 ring members are N, NR 6 , O and S, wherein the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0187] Embodiment 116.R 1 is a ring in which 1, 2, 3, 4 or 5 ring members are N, NR 6 , O and S, wherein the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or has 1 to 2 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0188] Embodiment 117.R 1 has one or two ring members N and NR 6 and wherein the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or has 1 to 2 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0189] Embodiment 118.R 1 The compound according to any one of embodiments 1 to 66, wherein is 1H-indazolyl) or indazolyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0190] Embodiment 119.R 1 has one ring member N, NR 6 , O and S, wherein the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or has 1 to 2 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0191] Embodiment 120.R 1 is a ring with one ring member NR 6 and wherein the 9- or 10-membered bicyclic heterocyclyl is unsubstituted or has 1 to 2 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0192] Embodiment 121.R 1 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O and S, wherein the 5- or 6-membered heterocycloalkyl is optionally substituted with oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0193] Embodiment 122.R 1 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, wherein the 4-, 5-, or 6-membered heterocycloalkyl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0194] Embodiment 123.R 1 has one or two ring members N, NR 6, O, and S, wherein the 4-, 5-, or 6-membered heterocycloalkyl is unsubstituted; a stereoisomer thereof; or a pharmaceutically acceptable salt thereof.

[0195] Embodiment 124.R 1 has one ring member N, NR 6 , O, and S; R is a 4- or 5-membered heterocycloalkyl selected from 6 is —C(═O)CH2OH, —(CH2)2OH, —(CH2)2CF3, —CH2CF3, —C(═O)CH3, —SO2CH3, —SO2CF3, —SO2-cyclopropyl, or cyclopropyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0196] Embodiment 125.R 1 is azetidinyl or pyrrolidinyl substituted with a group selected from -C(=O)CH2OH, -(CH2)2OH, -(CH2)2CF3, -CH2CF3, -C(=O)CH3, -SO2CH3, -SO2CF3, -SO2-cyclopropyl, and cyclopropyl, respectively, a compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1 to 66.

[0197] Embodiment 126.R 1 The compound of any one of embodiments 1-66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is pyrrolidinyl-2-one.

[0198] Embodiment 127.R 1 is a 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, O, and S, and the 9- or 10-membered bicyclic heteroaryl is unsubstituted or has 1 to 4 R 5 67. A compound according to any one of embodiments 1 to 66, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0199] Embodiment 128. Each R 5 is NR 6 C(═O)C2-C6 alkenyl, —SF5, unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, wherein cycloalkyl is unsubstituted or has 1, 2, 3, or 4 R 9 The compound of any one of embodiments 1 to 127, its stereoisomer, or a pharmaceutically acceptable salt thereof, substituted with:

[0200] Embodiment 129. Each R 5 is NR 6 C(═O)C2-C6 alkenyl, —SF5, unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, wherein cycloalkyl is unsubstituted or is substituted with one R 9 The compound of any one of embodiments 1 to 127, its stereoisomer, or a pharmaceutically acceptable salt thereof, substituted with:

[0201] Embodiment 130. Each R 5 is NR 6 C(═O)C2-C6 alkenyl, —SF5, unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, wherein cycloalkyl is unsubstituted or is substituted with one or two R 9 The compound of any one of embodiments 1 to 127, its stereoisomer, or a pharmaceutically acceptable salt thereof, substituted with:

[0202] Embodiment 131. Each R 5 -OH, -NR 7 R 8 , -C(=O)N(R 7 ) 2, 1, 2, 3 or 4 ring members are N, NR 6, O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl substituted with CN, NH2, or OH, wherein heterocycloalkyl is unsubstituted or substituted with 1, 2, 3, or 4 R 9 128. A compound according to any one of embodiments 1 to 127, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0203] Embodiment 132. Each R 5 -OH, -NR 7 R 8 , -C(=O)N(R 7 ) 2, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; 5- or 6-membered heteroaryl having 1, 2, or 3 ring members each independently selected from N, O, and S; and C1-C6 alkyl substituted with CN, NH2, or OH, wherein heterocycloalkyl is unsubstituted or substituted with 1 or 2 R 9 128. A compound according to any one of embodiments 1 to 127, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0204] Embodiment 133. Each R 5 is independently selected from the group consisting of CN, —OH, S(═O)C1-C6 alkyl, C1-C6 haloalkyl, halo, C1-C6 haloalkoxy, C1-C6 alkoxy, C3-C8 cycloalkyl, and C1-C6 alkyl unsubstituted or substituted with OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-127.

[0205] Embodiment 134. Each R 5The compound, its stereoisomer or pharmaceutically acceptable salt thereof described in any one of embodiments 1 to 127, wherein the groups are independently selected from Cl, F, CF3, -CHF2, -CH3, -CH(CH3)2, -OCH3, -OCHF2, -OCF3, CN, -SO2CH3 and -C(CH3)2OH.

[0206] Embodiment 135.R 5 The compound, stereoisomer, or pharmaceutically acceptable salt thereof of any one of embodiments 1-127, wherein is C1-C6 haloalkyl, halo, or C1-C6 haloalkoxy.

[0207] Embodiment 136.R 5 The compound according to any one of embodiments 1 to 127, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is -CF3, F, Cl, -OCHF2, or -OCF3.

[0208] Embodiment 137. Each R 5 is independently selected from the group consisting of halo, OH, C1-C6 haloalkyl, unsubstituted C1-C6 alkyl, and unsubstituted C3-C8 cycloalkyl, a compound, a stereoisomer, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-127.

[0209] Embodiment 138. Each R 5 is independently selected from the group consisting of F, —CF3, —CH3, —CH(CH3)2, and cyclopropyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1 to 127.

[0210] Embodiment 139. Each R 6 is independently selected from the group consisting of H and unsubstituted C1-C6 alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-138.

[0211] Embodiment 140. Each R 6is H, C1-C6 haloalkyl, C1-C6 haloalkoxy, S(=O)2C1-C6 alkyl, S(=O)2C1-C6 haloalkyl, -S(=O)2C3-C6 cycloalkyl, -C(=O)R 7 , C3-C6 cycloalkyl, and C1-C6 alkyl unsubstituted or substituted with —OH or C1-C6 haloalkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 138.

[0212] Embodiment 141. Each R 6 is independently selected from the group consisting of H, -CH3, -C(=O)CH2OH, -(CH2)2OH, -(CH2)2CF3, -CH2CF3, -C(=O)CH3, -SO2CH3, -SO2CF3, -SO2-cyclopropyl, or cyclopropyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0213] Embodiment 142.R 3a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 The compound of any one of embodiments 1-141, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with one or two substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH.

[0214] Embodiment 143.R 3a is H, -CN, 1, 2 or 3 ring members are N, NR6 , 4-7 membered heterocycloalkyl selected from O and S, or one or more R 15 The compound according to any one of embodiments 1 to 141, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0215] Embodiment 144.R 3a is -CN or one or more R 15 The compound according to any one of embodiments 1 to 141, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0216] Embodiment 145.R 3a The compound according to any one of embodiments 1 to 141, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is -CN or -CH3.

[0217] Embodiment 146.R 3a The compound of any one of embodiments 1-141, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is —CN.

[0218] Embodiment 147.R 3b is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 The compound of any one of embodiments 1-146, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with one or two substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH.

[0219] Embodiment 148.R 3b is H, -CN, 1, 2 or 3 ring members are N, NR 6 , O, and S, or unsubstituted or one or more R 15 The compound according to any one of embodiments 1 to 146, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0220] Embodiment 149.R 3b is H, —CN, or unsubstituted or contains one or more R 15 The compound according to any one of embodiments 1 to 146, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0221] Embodiment 150.R 3b The compound according to any one of embodiments 1-146, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is H or unsubstituted C1-C6 alkyl.

[0222] Embodiment 151.R 3b The compound of any one of embodiments 1-146, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein is H or —CH 3 .

[0223] Embodiment 152.R 4a is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 6 4 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15The compound of any one of embodiments 1-151, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with one or two substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH.

[0224] Embodiment 153.R 4a is H, -CN, 1, 2 or 3 ring members are N, NR 6 , O, and S, or unsubstituted or one or more R 15 The compound according to any one of embodiments 1 to 151, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0225] Embodiment 154.R 4a is H, —CN, or unsubstituted or contains one or more R 15 The compound according to any one of embodiments 1 to 151, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0226] Embodiment 155.R 4a The compound according to any one of embodiments 1-151, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is H or unsubstituted C1-C6 alkyl.

[0227] Embodiment 156.R 4a The compound, stereoisomer, or pharmaceutically acceptable salt thereof of any one of embodiments 1-151, wherein is H or —CH 3 .

[0228] Embodiment 157.R 4b is H, —CN, C3-C8 cycloalkyl, 1, 2 or 3 ring members are N, NR 64 to 7-membered heterocycloalkyl, each independently selected from O and S, unsubstituted or containing one or more R 15 C1-C6 alkyl substituted with a group or unsubstituted or with one or more R 15 The compound of any one of embodiments 1-156, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with one or two substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, C1-C6 haloalkyl, C1-C6 alkyl, or C1-C6 alkyl substituted with —C(═O)OH, —OH, CN, or NH.

[0229] Embodiment 158.R 4b is H, -CN, 1, 2 or 3 ring members are N, NR 6 , O, and S, or unsubstituted or one or more R 15 The compound according to any one of embodiments 1 to 156, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0230] Embodiment 159.R 4b is H, —CN, or unsubstituted or contains one or more R 15 The compound according to any one of embodiments 1 to 156, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0231] Embodiment 160.R 4b The compound according to any one of embodiments 1-156, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is H or unsubstituted C1-C6 alkyl.

[0232] Embodiment 161.R 4bThe compound, stereoisomer, or pharmaceutically acceptable salt thereof of any one of embodiments 1-156, wherein is H or —CH 3 .

[0233] Embodiment 162.R 3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 The compound according to any one of embodiments 1 to 161, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0234] Embodiment 163.R 3c is —C(═O)C2-C6 alkenyl or one or more R 15 The compound according to any one of embodiments 1 to 161, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0235] Embodiment 164.R 3c The compound according to any one of embodiments 1-161, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is —C(═O)C2-C6 alkenyl.

[0236] Embodiment 165.R 3c is one or more R 15 The compound according to any one of embodiments 1 to 161, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with a group.

[0237] Embodiment 166. Each R 6 is H, C1-C6 alkyl, -S(=O)2N(R 7 )2, -C(=O)N(R 7 )2, and C1-C6 alkyl substituted with —OH, —CN, or —C(═O)OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-165.

[0238] Embodiment 167. Each R 6is independently selected from the group consisting of H and unsubstituted C1-C6 alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-165.

[0239] Embodiment 168. Each R 6 is -S(=O)2N(R 7 )2, -C(=O)N(R 7 )2, and C1-C6 alkyl substituted with —OH, —CN, or —C(═O)OH, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-165.

[0240] Embodiment 169. Each R 7 is H, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0241] Embodiment 170. Each R 7 The compound according to any one of embodiments 1 to 168, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted C1-C6 alkyl.

[0242] Embodiment 171. Each R 7 is independently selected from the group consisting of H and C1-C6 alkyl that is unsubstituted or substituted with OH or C1-C6 alkoxy, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, of any one of embodiments 1-168.

[0243] Embodiment 172. Each R 7 is independently selected from the group consisting of H, —CH3, and —(CH2)2OCH3, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1 to 168.

[0244] Embodiment 173.R 8 The compound of any one of embodiments 1-172, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein is H.

[0245] Embodiment 174.R 8 The compound according to any one of embodiments 1 to 172, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted C1-C6 alkyl.

[0246] Embodiment 175.R 8 is a C3-C8 cycloalkyl, wherein the cycloalkyl is unsubstituted or has 1, 2, 3, or 4 R 9 173. A compound according to any one of embodiments 1 to 172, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0247] Embodiment 176.R 8 is a C3-C8 cycloalkyl, wherein the cycloalkyl is unsubstituted or has one or two R 9 173. A compound according to any one of embodiments 1 to 172, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0248] Embodiment 177.R 8 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; heterocycloalkyl is unsubstituted or has 1, 2, 3, or 4 R 9 173. A compound according to any one of embodiments 1 to 172, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0249] Embodiment 178.R 8 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; heterocycloalkyl is unsubstituted or has one or two R 9 173. A compound according to any one of embodiments 1 to 172, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, substituted with a group.

[0250] Embodiment 179.R 9 is NR 10R 11 179. The compound of any one of embodiments 1 to 178, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0251] Embodiment 180.R 9 is -C(=O)N(R 7 179. The compound of any one of embodiments 1 to 178, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0252] Embodiment 181.R 9 is -OH or -N(R 7 179. A compound according to any one of embodiments 1 to 178, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R is C1-C6 alkyl substituted with 2.

[0253] Embodiment 182.R 10 The compound of any one of embodiments 1-181, or a stereoisomer or pharmaceutically acceptable salt thereof, wherein is H.

[0254] Embodiment 183.R 10 The compound according to any one of embodiments 1 to 181, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted C1-C6 alkyl.

[0255] Embodiment 184.R 11 The compound of any one of embodiments 1-183, wherein is H, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0256] Embodiment 185.R 11 The compound according to any one of embodiments 1 to 183, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is unsubstituted C1-C6 alkyl.

[0257] Embodiment 186.R 11 The compound according to any one of embodiments 1 to 183, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is -S(=O)2C1-C6alkyl.

[0258] Embodiment 187.R 13 The compound of any one of embodiments 1-186, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein:

[0259] Embodiment 188.R 13 is -C(=O)N(R 7 187. The compound of any one of embodiments 1-186, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0260] Embodiment 189.R 13 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O and S; a stereoisomer thereof; or a pharmaceutically acceptable salt thereof.

[0261] Embodiment 190.R 14 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O and S, wherein the 5- or 6-membered heterocyclyl is unsubstituted or has 1, 2, 3 or 4 R 4 and optionally substituted with one or two oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-189.

[0262] Embodiment 191.R 14 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, wherein the 6-membered heterocyclyl is unsubstituted or has 1, 2, 3, or 4 R 4 and optionally substituted with one or two oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-189.

[0263] Embodiment 192.R 14 has one ring member N, NR6 , O and S, wherein the 6-membered heterocyclyl is substituted with oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0264] Embodiment 193.R 14 is a ring with one ring member NR 6 and wherein the 6-membered heterocyclyl is substituted with oxo, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0265] Embodiment 194.R 14 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, wherein the 5- or 6-membered heteroaryl is unsubstituted or has 1, 2, 3, or 4 R 4 189. The compound of any one of embodiments 1-189, its stereoisomer, or its pharmaceutically acceptable salt, substituted with:

[0266] Embodiment 195.R 14 is a ring in which 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, wherein the 5- or 6-membered heteroaryl is unsubstituted or has one or two R 4 189. The compound of any one of embodiments 1-189, its stereoisomer, or its pharmaceutically acceptable salt, substituted with:

[0267] Embodiment 196. Each R 15 is CN, NH2, -OH, -C(=O)OH, -C(=O)N(R 7 )2, -C(=O)C(=O)OH, C1-C6 alkoxy, halo, C1-C6 haloalkyl, C3-C8 cycloalkyl, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR6 , O, and S, and 3-6 membered heterocycloalkyl, wherein cycloalkyl, heteroaryl, and heterocycloalkyl are unsubstituted or substituted with 1, 2, or 3 substituents independently selected from the group consisting of CN, —C(═O)OH, NH, OH, and unsubstituted C1-C6 alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0268] Embodiment 197. Each R 15 is CN, 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heteroaryl in which 1, 2, or 3 ring members are N, NR 6 , O and S; a 3- to 6-membered heterocycloalkyl; a stereoisomer thereof; or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 195.

[0269] Embodiment 198. Each R 15 is CN and 1, 2 or 3 ring members are N, NR 6 , O and S; a 3- to 6-membered heterocycloalkyl; a stereoisomer thereof; or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 195.

[0270] Embodiment 199. Each R 15 is CN and 1, 2 or 3 ring members are N, NR 6 , O and S; a 3- to 6-membered heterocycloalkyl; a stereoisomer thereof; or a pharmaceutically acceptable salt thereof, of any one of embodiments 1 to 195.

[0271] Embodiment 200. Each R 15is independently selected from the group consisting of CN and oxiranyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to any one of embodiments 1-195.

[0272] Embodiment 201.X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 teeth, i) unsubstituted or 1 to 4 R 5 phenyl substituted with a group; ii) unsubstituted or containing 1 to 4 R 5 spiro-linked C3-C8 cycloalkyl substituted with a group; iii) unsubstituted or containing 1 to 4 R 5 bicyclic C3-C8 cycloalkyl substituted with a group; iv) unsubstituted or 1 to 4 R 5 C3-C8 cycloalkyl substituted by a group; v) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S, and is unsubstituted or has 1 to 4 R 5 a 5- or 6-membered heteroaryl substituted by a group; vi) unsubstituted C1-C6 alkyl; vii) 1, 2, 3, 4 or 5 ring members are N, NR 6 9- or 10-membered bicyclic heterocyclyl, each independently selected from O and S, which is unsubstituted or has 1 to 4 R 5 9- or 10-membered bicyclic heterocyclyl substituted by a group, and viii) 1, 2, 3 or 4 ring members are N, NR 6 , O, and S; and 5- or 6-membered heterocycloalkyl, each independently selected from R 55- or 6-membered heterocycloalkyl substituted with a group and optionally oxo is selected from the group consisting of R 2 teeth, i) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, or 3 additional N heteroatoms as ring members, and is unsubstituted or has 1 or 2 R 12 a 10-membered bicyclic heteroaryl substituted with a group; ii) a 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member positioned beta (β) to the point of attachment, and having 0, 1, 2, 3, or 4 additional ring members each independently selected from N, O, and S, and which is unsubstituted or has 1 or 2 R 12 a 10-membered bicyclic heteroaryl substituted with a group; and iii) 1, 2, 3, 4 or 5 ring members are N, NR 6 , O, and S; and 12 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 3a is -CN or one or more R 15 C1-C6 alkyl substituted with a group, R 3b is H or unsubstituted C1-C6 alkyl, R 4a is H or unsubstituted C1-C6 alkyl, R 4b is H, R 3c is H, —C(═O)C2-C6 alkenyl, or one or more R 15 C1-C6 alkyl substituted with a group, Each R 5is independently selected from the group consisting of unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, and halo, and Each R 6 is independently selected from the group consisting of H and unsubstituted C1-C6 alkyl, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0273] Embodiment 202.X1 is a CR 3a R 3b , C═O or NR 3c and X2 is CR 4a R 4b or C=O, R 1 are each unsubstituted or 1 to 4 R 5 phenyl or pyridyl substituted with a group; R 2 teeth, i) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, or 3 additional N heteroatoms as ring members, which are unsubstituted or have one R 12 a 10-membered bicyclic heteroaryl substituted with a group; and ii) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, and is unsubstituted or has one R 12 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 3a is -CN, R 3b is H, R 4a is H, and R 4b is H, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0274] Embodiment 203.R 1 are each unsubstituted or 1 to 4 R5 phenyl or pyridyl substituted with a group; R 2 teeth, i) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, or 3 additional N heteroatoms as ring members, which are unsubstituted or have one R 12 a 10-membered bicyclic heteroaryl substituted with a group; and ii) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, and is unsubstituted or has one R 12 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 3a is -CN, R 3b is H, R 4a is H, and R 4b is H, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0275] Embodiment 204.R 1 are each unsubstituted or one R 5 phenyl or pyridyl substituted with a group; R 2 teeth, i) 10-membered bicyclic heteroaryl having a point of attachment at a carbon atom ring member and a N heteroatom as a ring member located beta (β) to the point of attachment, and having 0, 1, 2, or 3 additional N heteroatoms as ring members, which are unsubstituted or have one R 12 a 10-membered bicyclic heteroaryl substituted with a group; and ii) 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4, or 5 ring members are each independently selected from N, and is unsubstituted or has one R 12 9- or 10-membered bicyclic heteroaryl substituted with a group is selected from the group consisting of R 3a is -CN, R 3b is H, R 4a is H, R 4b is H, and R 5 The compound of embodiment 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is C1-C6 haloalkyl, halo, or C1-C6 haloalkoxy.

[0276] Embodiment 205.R 1 is pyridin-3-yl substituted with -CF3, R 2 is unsubstituted 3-(isoquinolin-4-yl), and R 3a The compound of embodiment 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein is —CN.

[0277] Embodiment 206. 3-(Isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorophenyl)-3-(isoquinolin 1. The compound of embodiment 1, its stereoisomer, or a pharmaceutically acceptable salt thereof, is selected from 1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoro ...3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile,

[0278] Embodiment 207. 3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, and (S)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 2. The compound of embodiment 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from:

[0279] Embodiment 208. 3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, (R)-5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, (S)-5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, 1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, 1-(3,3-difluorocyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, (S)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, 1-(3-chlorophenyl)-3-(6-(2-hydroxypropan-2-yl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxamide, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)-N-(2-methoxyethyl)isoquinoline-6-carboxamide, 1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, (S)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, (4R,5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, (4S,5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,3R)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1s,3S)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, 1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, 1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, 1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, 1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-(trifluoromethyl)pyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, 1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-oxo-1,6-dihydropyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, (R)-4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, (S)-4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, 3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1s,3S)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1r,3R)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-((1s,3R)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-((1r,3S)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,4R)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,4S)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((1r,4S)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((1s,4R)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, 1-(3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((1s,3R)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((1r,3S)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((1r,3S)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((1s,3R)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, 1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-((1r,4r)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,4R)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,4S)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methylazetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, 1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, 1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, (S)-3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (S)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, and (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 2. The compound of embodiment 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from:

[0280] Embodiment 209. 3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, (R)-5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, 1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, 1-(3,3-difluorocyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, 1-(3-chlorophenyl)-3-(6-(2-hydroxypropan-2-yl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxamide, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)-N-(2-methoxyethyl)isoquinoline-6-carboxamide, 1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, (4R,5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,3R)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1s,3S)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, 1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, 1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, 1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, 1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-(trifluoromethyl)pyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, 1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-oxo-1,6-dihydropyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, (R)-4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, 3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1s,3S)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1r,3R)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,4R)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,4S)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, 1-(3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, 1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-((1r,4r)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,4R)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methylazetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, 1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, 1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, and (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 2. The compound of embodiment 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from:

[0281] Embodiment 210. 3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, 1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 1-(4-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, 1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, 1-(3,3-difluorocyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-hydroxy-3-(trifluoromethyl)cyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, 1-(3-chlorophenyl)-3-(6-(2-hydroxypropan-2-yl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxamide, 4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)-N-(2-methoxyethyl)isoquinoline-6-carboxamide, 1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (4R,5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,3R)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1s,3S)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, 1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, (R)-1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-2-(trifluoromethyl)pyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, (R)-1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, 3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1s,3S)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1r,3R)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,4R)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,4S)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, (R)-1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-((1r,4r)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,4R)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, (R)-1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, and (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 2. The compound of embodiment 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from:

[0282] Embodiment 211. (R)-3-(isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-5-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, (R)-1-(4-cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, (R)-1-(3-chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-4-(3-(3-chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, (R)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (4R,5S)-1-(3-chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,3R)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1s,3S)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-1-(4-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-1-(3-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1H-indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, (R)-1-(3-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-(difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(2-hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, (R)-1-(6-isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-1-(5,6-dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,6-dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-1-(5-fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-4-(4-cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile, (R)-3-(isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1s,3S)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-((1r,3R)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,4R)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,4S)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, (R)-1-(3,3-dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6,6-difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-((1r,4R)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-(cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-1-(1-acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, (R)-1-(4,4-difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, and (R)-1-((R or S)-3,3-difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 2. The compound of embodiment 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from:

[0283] Embodiment 212. The compound is (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, [ka] 17. The compound of formula (I) of any one of embodiments 1 to 5 or 16, having the structure:

[0284] Embodiment 213. The compound of embodiment 212 which is crystalline (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile.

[0285] Embodiment 214. When measured at temperatures in the range of 20 to 40°C using Cu-Kα radiation having a wavelength of 0.15418 nm, the values ​​are (6.85±0.2)°, (8.52±0.2)°, (10.41±0.2)°, (13.71±0.2)°, (16.90±0.2)°, (17.06±0.2)°, (18.40±0.2)°, and (19.05±0.2)°. 214. The compound of embodiment 213, characterized by having an X-ray powder diffractogram comprising at least four reflections at 2θ angles selected from the group consisting of: (21.76±0.2)°, (22.55±0.2)°, (23.50±0.2)°, (24.82±0.2)°, (26.89±0.2)°, and (28.17±0.2)°.

[0286] Embodiment 215. The compound of embodiment 213, characterized by having a powder X-ray diffractogram comprising reflections at 2θ angles of (10.41±0.2)°, (16.90±0.2)°, (17.06±0.2)°, and (21.76±0.2)°, when measured at a temperature in the range of 20 to 40°C using Cu-Kα radiation having a wavelength of 0.15418 nm.

[0287] Embodiment 216. The compound of any one of embodiments 213 to 215, characterized by having a differential scanning calorimetry curve comprising an endothermic peak having a peak temperature of (235.2°C ± 0.5)°C when measured at a heating rate of 10 K / min.

[0288] Embodiment 217. The compound of any one of embodiments 213-216, characterized by having a thermogravimetric analysis curve that exhibits a mass loss of 0.51 wt. % or less, based on the weight of the crystalline form, when heated from 30° C. to 210° C. at a rate of 10 K / min.

[0289] Embodiment 218. A compound according to embodiment 213 which is variation A of (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile.

[0290] Embodiment 219. The compound of embodiment 213, characterized by having an X-ray powder diffractogram comprising at least four reflections at 2θ angles selected from the group consisting of: (6.99±0.2)°, (9.11±0.2)°, (13.99±0.2)°, (15.96±0.2)°, (18.26±0.2)°, (19.82±0.2)°, (20.63±0.2)°, (22.03±0.2)°, (23.80±0.2)°, (25.29±0.2)°, (27.30±0.2)°, (30.57±0.2)°, and (33.47±0.2)°, when measured at a temperature in the range of 20 to 40°C using Cu-Kα radiation having a wavelength of 0.15418 nm.

[0291] Embodiment 220. The compound of embodiment 219, characterized by having a powder X-ray diffractogram comprising reflections at 2θ angles of (15.96±0.2)°, (18.26±0.2)°, (19.82±0.2)°, and (23.80±0.2)°, when measured at a temperature in the range of 20 to 40°C using Cu-Kα radiation having a wavelength of 0.15418 nm.

[0292] Embodiment 221. The compound of embodiment 219 or 220, characterized by having a differential scanning calorimetry curve comprising an endothermic peak having a peak temperature of (161.3°C ± 0.5)°C when measured at a heating rate of 10 K / min.

[0293] Embodiment 222. The compound of any one of embodiments 219-221, characterized by having a thermogravimetric analysis curve that exhibits a mass loss of 0.21 wt. % or less, based on the weight of the crystalline form, when heated from 30° C. to 150° C. at a rate of 10 K / min.

[0294] Embodiment 223. A compound according to embodiment 213 which is modification B of (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile.

[0295] Embodiment 224. The compound of embodiment 212 which is amorphous (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile.

[0296] Depending on the selection of starting materials and procedures, the compounds may exist in one form or as a mixture of possible isomers, e.g., as pure optical isomers or isomeric mixtures, such as racemic and diastereomeric mixtures, depending on the number of asymmetric carbon atoms. The present invention is intended to include all such possible isomers, including racemic mixtures, diastereomeric mixtures, and optically pure forms. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. When the compounds contain double bonds, the substituents may be in the E- or Z-configuration. When the compounds contain disubstituted cycloalkyl, the cycloalkyl substituent may have a cis- or trans-configuration. All tautomeric forms are also intended to be included.

[0297] As used herein, the term "salt" refers to an acid addition salt or a base addition salt of a compound of the present invention. "Salt" specifically includes "pharmaceutically acceptable salts." As used herein, the term "pharmaceutically acceptable salts" refers to salts that retain the biological effectiveness and properties of the compounds of the present invention and that are generally not biologically or otherwise undesirable. In many cases, the compounds of the present invention are capable of forming acid and / or base salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto.

[0298] Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Organic or inorganic acids that can be used to form pharmaceutically acceptable acid addition salts of the compounds of the present invention include acetic acid, adipic acid, ascorbic acid, aspartic acid, benzoic acid, benzenesulfonic acid, carbonic acid, camphorsulfonic acid, capric acid, chlorotheophyllinate, citric acid, ethanedisulfonic acid, fumaric acid, D-glycero-D-glucoheptonic acid, galactaric acid, galactaric / mucic acid, gluceptic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, isethione, and the like. Acids that can be used include, but are not limited to, lactic acid, lactobionic acid, lauryl sulfuric acid, malic acid, maleic acid, malonic acid, mandelic acid, mesylic acid, methanesulfonic acid, mucic acid, naphthoic acid, 1-hydroxy-2-naphthoic acid, naphthalenesulfonic acid, 2-naphthalenesulfonic acid, nicotinic acid, nitric acid, octadecanoic acid, oleic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, polygalacturonic acid, propionic acid, sebacic acid, stearic acid, succinic acid, sulfosalicylic acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, trifluoroacetic acid, and triphenylacetic acid.

[0299] The salt forms of the compounds of the present invention can be converted into the free compounds by treatment with a suitable basic agent.

[0300] Pharmaceutically acceptable acid addition salts of the compounds of the present invention include acetate, adipate, ascorbate, aspartate, benzoate, besylate, benzenesulfonate, bicarbonate / carbonate, bisulfate / sulfate, bromide / hydrobromide, camphorsulfonate, caprate, caprate, chloride / hydrochloride, chlorotheophyllinate, citrate, edisylate, ethanedisulfonate, fumarate, gluceptate, glucoheptonate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide / iodide, isethionate, lactate, lactobionate, lauryl sulfate, malate, maleate, malonate, mandelate, Salts include, but are not limited to, salts, mesylate, methanesulfonate, methylsulfate, mucate, naphthoate, napsylate, 2-napsylate, naphthalenesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate, p-toluenesulfonate, trifluoroacetate, trifenatate, triphenylacetate, and xinafoate salt forms.

[0301] Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Organic bases used to form pharmaceutically acceptable base addition salts of the compounds of the present invention include, but are not limited to, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like. Specific organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine, and tromethamine. Inorganic bases used to form pharmaceutically acceptable base addition salts of the compounds of the present invention include, but are not limited to, sodium hydroxide, potassium hydroxide, ammonium hydroxide, ammonium salts, and metals from columns I to XII of the periodic table. Pharmaceutically acceptable base addition salts of the compounds of the present invention include, but are not limited to, sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper salts, with particularly preferred salts being ammonium, potassium, sodium, calcium, and magnesium salts.

[0302] The pharmaceutically acceptable salts of the present invention can be synthesized from a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid form of these compounds with a stoichiometric amount of an appropriate base (such as hydroxide, carbonate, bicarbonate, Na, Ca, Mg, or K), or by reacting the free base form of these compounds with a stoichiometric amount of an appropriate acid. Such reactions are usually carried out in water or an organic solvent, or a mixture of the two. Generally, the use of non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile is desirable, where practicable.

[0303] Any formula given herein is intended to represent unlabeled forms of the compound as well as isotopically labeled forms. Isotopically labeled compounds have the structure depicted by the formula given herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Isotopes that can be incorporated into the compounds of the present invention include, for example, isotopes of hydrogen.

[0304] Furthermore, certain isotopes, particularly deuterium (i.e. 2 Incorporation of H or D) may result in certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life, or reduced dosage requirements, or improved therapeutic index or tolerability. It is understood that in this context deuterium is considered a substituent of the compounds of the present invention. The concentration of deuterium can be defined by the isotopic enrichment factor. As used herein, the term "isotopic enrichment factor" refers to the ratio between the isotopic abundance and the natural abundance of a particular isotope. When a substituent in a compound of the invention is designated as deuterium, such compound has an isotopic enrichment factor for each designated deuterium atom of at least 3500 (52.5% deuterium incorporation at each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation). It is understood that the term "isotopic enrichment factor" can be applied to any isotope in the same manner as described for deuterium.

[0305] Other examples of isotopes that may be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, e.g., 3 H, 11 C. 13 C. 14 C. 15 N, 18 F, 31 P, 32 P, 35 S, 36 Cl, 123 I, 124 I, 125 Therefore, the present invention provides, for example, 3 H and14 Radioactive isotopes such as C or 2 H and 13 It should be understood that this includes compounds incorporating one or more of any of the foregoing isotopes, including those in which non-radioactive isotopes such as C are present. Such isotopically labeled compounds may be used in metabolic studies ( 14 C), reaction rate tests (e.g. 2 H or 3 H), detection or imaging techniques such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), including drug or substrate tissue distribution assays, or in radiation treatment of patients. 18 F or labeled compounds may be particularly desirable for PET or SPECT studies. Isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by methods analogous to those described in the accompanying Examples and Preparations, substituting appropriate isotopically labeled reagents for previously used non-labeled reagents.

[0306] For example, the compounds of the present invention may exist in the deuterated forms shown below. [ka]

[0307] Any asymmetric atom (e.g., carbon, etc.) of the compounds of the present invention can be present in racemic or enantiomerically enriched form, for example, in the (R)-, (S)-, or (R,S)-configuration. In certain embodiments, each asymmetric atom has an enantiomeric excess of at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% in the (R)- or (S)-configuration. Substituents on atoms having unsaturated double bonds may, where possible, be present in cis-(Z)- or trans-(E)-form.

[0308] Thus, as used herein, the compounds of the present invention may be in the form of one of the possible isomers, rotamers, atropisomers, tautomers or mixtures thereof, for example, as substantially pure geometric (cis or trans) isomers, diastereomers, optical isomers (enantiomers), racemates or mixtures thereof.

[0309] Any resulting mixture of isomers can be separated on the basis of the physical chemical differences of the components into pure or substantially pure geometric or optical isomers, diastereomers, racemates, for example, by chromatography and / or fractional crystallization.

[0310] Any resulting racemic forms of final products or intermediates can be resolved into their optical antipodes by known methods, for example, by separation of their diastereomeric salts obtained with optically active acids or bases, and liberating the optically active acidic or basic compounds. In particular, compounds of the present invention can be resolved into their optical antipodes by, for example, fractional crystallization of salts formed with optically active acids, such as tartaric acid, dibenzoyltartaric acid, diacetyltartaric acid, di-O,O'-p-toluoyltartaric acid, mandelic acid, malic acid, or camphor-10-sulfonic acid, using basic moieties in this way. Racemic products can also be resolved by chiral chromatography, for example, high-pressure liquid chromatography (HPLC) using a chiral adsorbent.

[0311] Methods of Making the Compounds of the Invention General procedures for preparing compounds of the present invention are described below. In the reactions described, reactive functional groups, such as hydroxy, amino, imino, or carboxy groups, can be protected to avoid undesired participation in the reaction if desired in the final product. Within the scope of this specification, only readily removable groups that are not a component of the specifically desired final product of the compounds of the present invention are referred to as "protecting groups," unless the context dictates otherwise. The protection of functional groups by such protecting groups, the protecting groups themselves, and their cleavage reactions are described in standard reference works such as, for example, J.F.W.M. Comie, "Protective Groups in Organic Chemistry," Plenum Press, London and New York, 1973, and T.W. Greene and P.G.W. Buts, "Protective Groups in Organic Synthesis," Third Edition, Wiley, New York, 1999.

[0312] Unless otherwise indicated herein or clearly contradicted by context, all methods described herein can be performed in any suitable order. The use of any examples or exemplary language (e.g., "etc.") provided herein is intended merely to further clarify the invention and does not limit the scope of the invention as otherwise claimed.

[0313] Methods of synthesizing compounds of the present invention The compounds of the present invention were prepared by the processes described herein and illustrated in the Examples. The combination of various building blocks and intermediates described herein can be applied to obtain the compounds of the present invention. Non-limiting examples of synthetic schemes used to prepare the compounds of the present invention are illustrated in Schemes 1-8 below. More detailed guidance can be found in the Examples section.

[0314] [ka] Alkylation of primary alkyl, aryl, or heteroaryl amines can be achieved using a suitable electrophile, such as 2-bromoethanol, in the presence of a base, such as diisopropylethylamine, in an organic solvent, such as DMF. Protection of amines with a suitable protecting group, such as tert-butyl carbamate (Boc), can be achieved using standard conditions, such as treatment with BocO using EtN as a base in a solvent, such as CHCl. ​​Oxidation of primary alcohols to the corresponding aldehydes can be achieved using standard conditions with an oxidizing agent, such as the Dess-Martin reagent, in a solvent, such as CHCl. ​​Aldehydes can be converted to α-aminonitriles using the Strecker reaction, typically by using the desired amine, RNH, in the presence of a Lewis acid, such as Ti(OEt) in a nonpolar organic solvent, such as dichloroethane, followed by treatment of the formed imine with a cyanide source, such as TMSCN. Deprotection can be achieved using standard conditions, which, in the case of Boc carbamates, may include TFA in a solvent, such as DCM. Cyclization of the diamine can be achieved using conditions such as triphosgene with an organic base such as Et3N in an organic solvent such as THF.

[0315] [ka] Oxidation of primary alcohols to the corresponding aldehydes can be achieved using standard conditions with an oxidizing agent such as the Dess-Martin reagent in a solvent such as CHCl. ​​Aldehydes can be converted to α-aminonitriles using the Strecker reaction, typically achieved by using the desired amine, RNH, in the presence of a Lewis acid such as Ti(OEt) in a nonpolar organic solvent such as dichloroethane, followed by treatment of the resulting imine with a cyanide source such as TMSCN. Cyclization of diamines can be achieved using conditions such as carbonyldiimidazole with an organic base such as diisopropylethylamine in an organic solvent such as THF. Deprotection can be achieved using standard conditions, which, in the case of Boc carbamates, may include HCl in a solvent such as EtOAc. When R1 = Ar or Het-Ar, arylation can be achieved using Buchwald-Hartwig coupling under typical conditions, which involve using the required aryl or heteroaryl halide R1-X, a Cu(I) source such as (Bu4NICuI)2, and a diamine ligand such as DMBACH in the presence of an inorganic base such as Cs2CO3 in an organic solvent such as 1,4-dioxane, which may typically require heating.

[0316] [ka] where R = H or alkyl. Formation of α-aminonitriles using the Strecker reaction can typically be carried out by treating the desired amine, R1NH2, and a carbonyl compound in the presence of a Lewis acid such as Ti(OEt)4 in a non-polar organic solvent such as dichloroethane, followed by treatment of the intermediate with a cyanide source such as TMSCN. Deprotection can be achieved using standard conditions, which, in the case of Boc carbamates, may include TFA in a solvent such as DCM. Cyclization of the diamine can be achieved using conditions such as triphosgene with an organic base such as Et3N in an organic solvent such as THF. Alkylation of the cyclic urea can be achieved with the desired haloalkane, R1-Hal, in the presence of an inorganic base such as Cs2CO3 in a polar aprotic solvent such as DMF. When R1 = Ar or Het-Ar, arylation can be achieved using an Ullmann-Goldberg coupling, typically involving the use of the required aryl or heteroaryl halide R1-X, a Cu(I) source such as (Bu4NICuI)2, and a diamine ligand such as DMBACH in the presence of an inorganic base such as Cs2CO3 in an organic solvent such as 1,4-dioxane, typically requiring heating.

[0317] [ka] Alkylation of primary amines can be carried out by reacting a suitable carbonyl, R, with an optional acid catalyst, such as AcOH, in the presence of a suitable reducing agent, such as NaBH(OAc) in an organic solvent, such as CH2Cl2. 1 This can be achieved by reductive amination with =O compounds. Cyclization of the diamine can be achieved using conditions such as triphosgene with an organic base such as EtN in an organic solvent such as THF.

[0318] [ka] Alkylation of primary amines can be carried out by reacting a suitable carbonyl, R, with an optional acid catalyst, such as AcOH, in the presence of a suitable reducing agent, such as NaBH(OAc) in an organic solvent, such as CH2Cl2. 1 This can be achieved by reductive amination with a =O compound. Cyclization of the diamine can be achieved using conditions such as triphosgene with an organic base such as EtN in an organic solvent such as THF. Deprotection can be achieved using standard conditions, which in the case of Boc carbamates may include TFA in a solvent such as DCM. Subsequent functionalization of the deprotected amine can be achieved using standard conditions.

[0319] [ka] Arylation of cyclic ureas is typically carried out by S in the presence of a base such as Cs2CO3 in a polar aprotic solvent such as DMF under heating. N Ar arylation conditions, where R 1 -X is a stable electrophilic aryl or heteroaryl halide, R 1 -X.

[0320] [ka] Amide formation can be achieved using standard conditions, such as by using an amide coupling reagent such as N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate in the presence of a base such as N-methylimidazole in an organic solvent such as MeCN. Formation of α-aminonitriles using the Strecker reaction typically involves coupling the desired amine, R, to a nitrile in the presence of a Lewis acid such as Ti(OEt) in a non-polar organic solvent such as dichloroethane. 2 This can be achieved by treating the intermedia...

Claims

1. Formula (I) 【Chemical 1】 (wherein X １ is CR ３ａ R ３ｂ , C=O or NR ３ｃ and X ２ is CR ４ａ R ４ｂ or C=O, and R １ is i) one, two, three or four ring members are 5- or 6-membered heteroaryl independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with one to four R ５ groups and is 5- or 6-membered heteroaryl, ii) phenyl which is unsubstituted or substituted with 1 to 4 R ５ groups iii) 1, 2, 3 or 4 ring members are 4, 5 or 6-membered heterocycloalkyl independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with 1 to 4 R ５ groups, and the 5- or 6-membered heterocycloalkyl is optionally substituted with oxo, 4, 5 or 6-membered heterocycloalkyl, iv) unsubstituted or C substituted with 1 to 4 R ５ groups ３ ~C ８ cycloalkyl, v) C which is non-replaceable １ ~C ６ alkyl, vi) a 5- or 6-membered heterocyclyl in which 1, 2 or 3 ring members are each independently selected from W, Y and Z, where W is NR ６ , O, S, S=O or S(=O) ２ , Y is NR ６ , O, S, S=O or S(=O) ２ , and Z is NR ６ , O or S, and the 5- or 6-membered heterocyclyl is unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups and is optionally substituted with oxo, a 5- or 6-membered heterocyclyl vii) a 9- or 10-membered bicyclic heterocyclyl in which 1, 2, 3, 4 or 5 ring members are each independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with 1 to 4 R ５ groups, a 9- or 10-membered bicyclic heterocyclyl, viii) non-replaced or spiro-bonded C substituted with 1 to 4 R ５ groups to cycloalkyl ３ -C ８ ​ ix) bicyclic C which is unsubstituted or substituted with 1 to 4 R ５ groups to C ３ to C ８ cycloalkyl, x) C ５ ~C ６ cycloalkenyl, and (xi)1, 2, 3, 4 or 5 ring members are each independently selected from N, O and S, a 9- or 10-membered bicyclic heteroaryl which is unsubstituted or substituted with 1 to 4 R ５ groups, a 9- or 10-membered bicyclic heteroaryl selected from the group consisting of R ２ is i) A 10-membered bicyclic heteroaryl having a bonding point in a carbon atom ring member and having an N heteroatom as a ring member located at the beta (β) position relative to the bonding point, having 0, 1, 2 or 3 additional N heteroatoms as ring members, being unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, a 10-membered bicyclic heteroaryl ii) A 10-membered bicyclic heteroaryl having a bonding point in a carbon atom ring member and having an N heteroatom as a ring member located at the beta (β) position with respect to the bonding point, further having 0, 1, 2, 3 or 4 ring members independently selected from N, O and S, and being unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, a 10-membered bicyclic heteroaryl iii) A 9-membered bicyclic heteroaryl having a bonding point in a carbon atom ring member and having an N heteroatom as a ring member located at the beta (β) position with respect to the bonding point, having 0, 1, 2, 3 or 4 additional N heteroatoms as ring members, unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, a 9-membered bicyclic heteroaryl substituted with iv) A 9-membered bicyclic heteroaryl having a bonding point in a carbon atom ring member and having an N heteroatom as a ring member located at the beta (β) position with respect to the bonding point, wherein N, NR ６ , O and S each independently further have 0, 1, 2, 3 or 4 ring members selected from, and is unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, a 9-membered bicyclic heteroaryl v) A 9- or 10-membered bicyclic heterocyclyl having a bonding point in a carbon atom ring member and having NR as a ring member located at the beta (β) position with respect to the bonding point ６ which further has 0, 1, 2, 3 or 4 ring members independently selected from N, NR ６ , O and S, and which is substituted with 1 or 2 oxos, or is unsubstituted, or is substituted with 1, 2, 3 or 4 R １２ groups, and optionally substituted with 1 or 2 oxos, a 9- or 10-membered bicyclic heterocyclyl vi) A 9- or 10-membered bicyclic heterocyclyl having a bonding point in a carbon atom ring member and having an O heteroatom as a ring member located at the beta (β) position with respect to the bonding point, which is selected from N, NR ６ , O and S, further having 0, 1, 2, 3 or 4 ring members independently selected therefrom, being substituted with 1 or 2 oxo groups, or unsubstituted, or substituted with 1, 2, 3 or 4 R １２ groups, and optionally substituted with 1 or 2 oxo groups, a 9- or 10-membered bicyclic heterocyclyl, vii) a 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4 or 5 ring members are each independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, a 9- or 10-membered bicyclic heteroaryl viii) a 9- or 10-membered bicyclic heterocyclyl in which 1, 2, 3, 4 or 5 ring members are each independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with 1 or 2 oxo groups or with 1, 2, 3 or 4 R １２ groups and which is optionally substituted with 1 or 2 oxo groups, and ix) A 10-membered bicyclic heterocyclyl having a bonding point in a carbon atom ring member, being substituted with oxo, and having a carbon atom as a ring member located at the beta (β) position with respect to the bonding point, which is N, NR ６ , O and S, further having 1, 2, 3 or 4 ring members independently selected from each, being unsubstituted, or 1, 2, 3 or 4 R １２ groups substituted, and optionally substituted with additional oxo, a 10-membered bicyclic heterocyclyl selected from the group consisting of R ３ａ is -CN, C ３ to C ８ cycloalkyl, a 4 - to 7 - membered heterocycloalkyl in which 1, 2 or 3 ring members are each independently selected from N, NR ６ , O and S, unsubstituted or substituted with one or more R １５ groups, C １ to C ６ alkyl or unsubstituted or substituted with one or more R １５ groups, C ２ to C ６ alkenyl, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or the cycloalkyl and heterocycloalkyl are substituted with 1 or 2 substituents independently selected from the group consisting of CN, -C(=O)OH, NH ２ , OH, C １ to C ６ haloalkyl and unsubstituted or substituted with -C(=O)OH, -OH, CN or NH ２ and C １ to C ６ alkyl, and is substituted with 1 or 2 substituents independently selected from the group consisting of R ３ｂ is H, C ３ ~C ８ cycloalkyl, 4- to 7-membered heterocycloalkyl in which 1, 2 or 3 ring members are each independently selected from N, NR ６ , O and S, unsubstituted or substituted with one or more R １５ groups, C １ ~C ６ alkyl or unsubstituted or substituted with one or more R １５ groups, C ２ ~C ６ alkenyl, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or the cycloalkyl and heterocycloalkyl are substituted with 1 or 2 substituents independently selected from the group consisting of CN, -C(=O)OH, NH ２ , OH, C １ ~C ６ haloalkyl and unsubstituted or substituted with -C(=O)OH, -OH, CN or NH ２ and C １ ~C ６ alkyl, R ４ａ is H, C ３ ~C ８ cycloalkyl, a 4- to 7-membered heterocycloalkyl in which 1, 2 or 3 ring members are each independently selected from N, NR ６ , O and S, unsubstituted or substituted with one or more R １５ groups, C １ ~C ６ alkyl or unsubstituted or substituted with one or more R １５ groups, C ２ ~C ６ alkenyl, wherein the cycloalkyl and heterocycloalkyl are unsubstituted or the cycloalkyl and heterocycloalkyl are substituted with 1 or 2 substituents independently selected from the group consisting of CN, -C(=O)OH, NH ２ , OH, C １ ~C ６ haloalkyl and unsubstituted or substituted with -C(=O)OH, -OH, CN or NH ２ and C １ ~C ６ alkyl, and is substituted with 1 or 2 substituents independently selected from the group consisting of: R ４ｂ is H, C ３ ~C ８ cycloalkyl, a 4- to 7-membered heterocycloalkyl in which 1, 2 or 3 ring members are each independently selected from N, NR ６ , O and S, unsubstituted or substituted with one or more R １５ groups, C １ ~C ６ alkyl or unsubstituted or substituted with one or more R １５ groups, C ２ ~C ６ alkenyl, said cycloalkyl and heterocycloalkyl being unsubstituted or said cycloalkyl and heterocycloalkyl being substituted with 1 or 2 substituents independently selected from the group consisting of CN, -C(=O)OH, NH ２ , OH, C １ ~C ６ haloalkyl and unsubstituted or substituted with -C(=O)OH, -OH, CN or NH ２ and C １ ~C ６ alkyl, and is substituted with 1 or 2 substituents independently selected from the group consisting of R ３ｃ is H, -C(=O)C ２ ~C ６ alkenyl or C substituted with one or more R １５ groups, １ ~C ６ alkyl, and Each R ５ is selected independently from the group consisting of -CN, -OH, -NR ７ R ８ NR ６ C(=O)C ２ ~C ６ alkenyl, -SF ５ S(=O) ２ C １ ~C ６ alkyl, -C(=O)N(R ７ ) ２ C １ ~C ６ haloalkyl, halo, C １ ~C ６ haloalkoxy, C １ ~C ６ alkoxy, C ３ ~C ８ cycloalkyl, a 4- to 6-membered heterocycloalkyl in which 1, 2, 3 or 4 ring members are each independently selected from N, NR ６ O and S, a 5- or 6-membered heteroaryl in which 1, 2 or 3 ring members are each independently selected from N, O and S, and unsubstituted or substituted with CN, NH ２ or OH C １ ~C ６ alkyl, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3 or 4 R ９ groups, Each R ６ is H, C １ ~C ６ haloalkyl, C １ ~C ６ haloalkoxy, -S(=O) ２ N(R ７ ) ２ S(=O) ２ C １ ~C ６ alkyl, S(=O) ２ C １ ~C ６ haloalkyl, -S(=O) ２ C ３ ~C ６ cycloalkyl, -C(=O)R ７ , -C(=O)N(R ７ ) ２ C ３ ~C ６ cycloalkyl and is unsubstituted or substituted with -OH, CN or -C(=O)OH C １ ~C ６ alkyl, and is independently selected from the group consisting of Each R ７ is selected independently from the group consisting of H and being unsubstituted, or OH or C １ to C ６ alkyl substituted with alkoxy, １ to C ６ and is independently selected from the group consisting of alkyl, R ８ is H, unsubstituted C １ ~C ６ alkyl, C ３ ~C ８ cycloalkyl or 4- to 6-membered heterocycloalkyl in which 1, 2, 3 or 4 ring members are each independently selected from N, NR ６ , O and S, and the cycloalkyl and heterocycloalkyl are unsubstituted or substituted with 1, 2, 3 or 4 R ９ groups, Each R ９ is NR １０ R １１ , -C(=O)N(R ７ ) ２ and -OH or -N(R ７ ) ２ substituted C １ ~C ６ independently selected from the group consisting of alkyl, R １０ is H or unsubstituted C １ ~C ６ alkyl, R １１ is H, unsubstituted C １ to C ６ alkyl or -S(=O) ２ C １ to C ６ alkyl, Each R １２ is -C(=O)N(R ７ ) ２ , -C(=O)OH, -N(R ７ ) ２ , -CN, -OH, -S(=O) ２ R ７ , -S(=O) ２ N(R ７ ) ２ , 【Chemical Formula 2】 , halo, phenyl, C ３ ~C ８ cycloalkyl, 4- to 6-membered heterocycloalkyl in which 1, 2, 3 or 4 ring members are each independently selected from N, NR ６ , O and S, 5- or 6-membered heteroaryl in which 1, 2 or 3 ring members are each independently selected from N, O and S, and are substituted or NH ２ , CN or OH-substituted C １ ~C ６ alkyl, independently selected from the group consisting of, said phenyl, heterocycloalkyl and heteroaryl are unsubstituted or substituted with 1 or 2 OH groups, and Each R １５ is CN, NH ２ , -OH, -C(=O)OH, -C(=O)N(R ７ ) ２ , -C(=O)C(=O)OH, C １ ~C ６ alkoxy, halo, C １ ~C ６ haloalkyl, C ３ ~C ８ cycloalkyl, 5- or 6-membered heteroaryl in which 1, 2, 3 or 4 ring members are each independently selected from N, NR ６ , O and S, and 3- to 6-membered heterocycloalkyl in which 1, 2 or 3 ring members are each independently selected from N, NR ６ , O and S, and is independently selected from the group consisting of cycloalkyl, heteroaryl and heterocycloalkyl, and the cycloalkyl, heteroaryl and heterocycloalkyl are unsubstituted or are substituted with 1, 2 or 3 substituents independently selected from the group consisting of CN, -C(=O)OH, NH ２ , OH and unsubstituted C １ ~C ６ alkyl) a compound, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

2. X １ is CR ３ａ R ３ｂ and X ２ is CR ４ａ R ４ｂ and R １ is i) one, two, three or four ring members are 5- or 6-membered heteroaryl independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with 1 to 4 R ５ groups and is 5- or 6-membered heteroaryl, ii) phenyl which is unsubstituted or substituted with 1 to 4 R ５ groups iii) one, two, three or four ring members are 4-, 5- or 6-membered heterocycloalkyl independently selected from N, NR ６ , O and S, said 5- or 6-membered heterocycloalkyl being unsubstituted or substituted with 1 to 4 R ５ groups, 4-, 5- or 6-membered heterocycloalkyl, iv) C which is unsubstituted or substituted with 1 to 4 R ５ groups ３ to C ８ cycloalkyl v) C which is non-replaceable １ ~C ６ alkyl, vi) a 5- or 6-membered heterocyclyl in which 1, 2 or 3 ring members are each independently selected from W, Y and Z, where W is NR ６ , O, S, S=O or S(=O) ２ , Y is NR ６ , O, S, S=O or S(=O) ２ , and Z is NR ６ , O or S, and the 5- or 6-membered heterocyclyl is unsubstituted or substituted with 1 or 2 R １２ groups and optionally substituted with oxo, a 5- or 6-membered heterocyclyl vii) a 9- or 10-membered bicyclic heterocyclyl in which one or two ring members are each independently selected from N and NR ６ which is unsubstituted or substituted with one or two R ５ groups, and viii) bicyclic C which is unsubstituted or substituted with 1 to 4 R ５ groups ３ to C ８ cycloalkyl selected from the group consisting of R ２ is i) A 10-membered bicyclic heteroaryl having a bonding point in a carbon atom ring member and having an N heteroatom as a ring member located at the beta (β) position with respect to the bonding point, having 0, 1, 2 or 3 additional N heteroatoms as ring members, being unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, and ii) a 9- or 10-membered bicyclic heteroaryl in which 1, 2, 3, 4 or 5 ring members are each independently selected from N, NR ６ , O and S, which is unsubstituted or substituted with 1, 2, 3 or 4 R １２ groups, a 9- or 10-membered bicyclic heteroaryl selected from the group consisting of R ３ａ is -CN, R ３ｂ is H or unsubstituted C １ to C ６ alkyl, R ４ａ is H or unsubstituted C １ to C ６ alkyl, R ４ｂ is H or unsubstituted C １ -C ６ to C alkyl, Each R ５ is independently selected from the group consisting of CN, -OH, S(=O) ２ C １ to C ６ alkyl, C １ to C ６ haloalkyl, halo, C １ to C ６ haloalkoxy, C １ to C ６ alkoxy, C ３ to C ８ cycloalkyl and C １ to C ６ alkyl which is unsubstituted or substituted with OH, Each R ６ is H, C １ ~C ６ haloalkyl, C １ ~C ６ haloalkoxy, S(=O) ２ C １ ~C ６ alkyl, S(=O) ２ C １ ~C ６ haloalkyl, -S(=O) ２ C ３ ~C ６ cycloalkyl, -C(=O)R ７ 、C ３ ~C ６ cycloalkyl and is unsubstituted or substituted with -OH, C １ ~C ６ is independently selected from the group consisting of alkyl, Each R ７ is selected independently from the group consisting of H and being unsubstituted, or OH or C １ to C ６ alkyl substituted with alkoxy, and １ to C ６ alkyl Each R １２ is independently selected from the group consisting of -C(=O)N(R ７ ), -C(=O)OH, -CN, -S(=O) ２ R ２ R ７ and C substituted with OH １ ~C ６ alkyl, the compound according to claim 1, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

3. R ２ is unsubstituted or 3-(isoquinolin-4-yl) substituted with one or two R １２ groups, the compound according to claim 1, its stereoisomers or its pharmaceutically acceptable salts.

4. Each R １２ is independently selected from the group consisting of -C(=O)N(R ７ ), -C(=O)OH, -CN, -S(=O) ２ R ２ and C ７ substituted with OH, the compound according to claim 3, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. １ ~C ６ alkyl, an alkyl group, an alkylene group, an alkynyl group, or an alkenyl group.

5. R １ is phenyl or a 5- or 6-membered heteroaryl in which one or two ring members are each independently selected from N, NR ６ , O and S, and the phenyl or heteroaryl is unsubstituted or substituted with one or two R ５ groups, the compound according to claim 1, its stereoisomers or its pharmaceutically acceptable salts.

6. R １ is each unsubstituted or is Cl, F, CF ３ , -CHF ２ , -CH ３ , -CH(CH ３ ), ２ , -OCH ３ , -OCHF ２ , -OCF ３ , CN, -SO ２ CH ３ and -C(CH ３ ), ２ OH, and is phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl substituted with one or two R ５ groups independently selected therefrom, a compound according to claim 5, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

7. R １ is unsubstituted or is substituted with 1 to 2 R ３ groups independently selected from Cl, F, CF ２ , -CHF ３ , -CH ３ ), -CH(CH ２ ), -OCH ３ , -OCHF ２ , -OCF ３ , CN, -SO ２ CH ３ and -C(CH ３ ), ２ and is pyridyl substituted with 1 to 2 R ５ groups, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, according to claim 6.

8. R １ is each unsubstituted or is Cl, F, CF ３ , -CHF ２ , -CH ３ , -CH(CH ３ ), ２ , -OCH ３ , -OCHF ２ , -OCF ３ , CN, -SO ２ CH ３ and -C(CH ３ ), ２ OH, and is pyrazolyl or imidazolyl substituted with 1 to 2 R ５ groups independently selected therefrom, a compound according to any one of claims 1 to 6, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.

9. i. R １ is each unsubstituted or substituted with 1 to 2 R ５ groups and is C ３ to C ８ cycloalkyl or bicyclic C ３ to C ８ cycloalkyl, and ii. R1 is a 5- or 6-membered heterocyclyl in which 1, 2 or 3 ring members are each independently selected from W, Y and Z, W is NR6, O, S, S=O or S(=O)2, Y is NR6, O, S, S=O or S(=O)2, and Z is NR6, O or S, and the 5- or 6-membered heterocyclyl is substituted with oxo and with an R5 group, or iii. R1 is a 4-, 5- or 6-membered heterocycloalkyl in which 1 or 2 ring members are each independently selected from N, NR6, O and S, and the 4-, 5- or 6-membered heterocycloalkyl is unsubstituted,[[]] The compound, stereoisomer thereof or pharmaceutically acceptable salt thereof according to Claim 1.

10. R ３ａ is -CN, R ３ｂ is H or unsubstituted C １ to C ６ alkyl, R ４ａ is H or unsubstituted C １ ~C ６ alkyl, and R ４ｂ is H or unsubstituted C １ to C ６ alkyl, the compound according to claim 1, its stereoisomer or its pharmaceutically acceptable salt.

11. R3a is -CN, R3b is H or C1-C6 alkyl which is unsubstituted,[[]] R4a is H or C1-C6 alkyl which is unsubstituted, and R4b is H or C1-C6 alkyl which is unsubstituted, the compound, stereoisomer thereof or pharmaceutically acceptable salt thereof according to Claim 6.

12. Formula (I-i) 【Chemical Formula 3】 (wherein R １ is a pyridin-3-yl substituted with -CF ３ and R ２ is unsubstituted 3-(isoquinolin-4-yl) and R ３ａ is -CN) having the structure of the compound or a pharmaceutically acceptable salt or stereoisomer thereof, the compound or a pharmaceutically acceptable salt or stereoisomer thereof according to Claim 1.

13. 3-(Isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile,[[]] (R)-3-(Isoquinolin-4-yl)-2-oxo-1-phenylimidazolidine-4-carbonitrile,[[]] 1-(3-Chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile,[[]] (R)-1-(3-Chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile,[[]] 3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile,[[]] 3-(Isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 1-(4-Chlorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-Fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-Fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-Chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methoxy-4-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-4-yl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Chloropyrimidin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 5-(4-Cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, (R)-5-(4-Cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-2-(trifluoromethyl)isonicotinonitrile, 1-(4-Cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-Cyano-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Fluoro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(Difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(Difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methoxypyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 1-((R)-1-(2-Hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-Hydroxyacetyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-((R)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-yl)imidazolidine-4-carbonitrile, 1-(3,3-Difluorocyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-Hydroxy-3-(trifluoromethyl)cyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-Difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(5-methoxy-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrazin-2-yl)imidazolidine-4-carbonitrile, 4-(3-(3-Chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, (R)-4-(3-(3-Chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxylic acid, 1-(3-Chlorophenyl)-3-(6-(2-hydroxypropan-2-yl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-Chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carboxamide, 4-(3-(3-Chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)-N-(2-methoxyethyl)isoquinoline-6-carboxamide, 1-(3-Chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-Chlorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-Methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-Methoxy-5-(trifluoromethyl)phenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 4-(3-(3-Chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, (R)-4-(3-(3-Chlorophenyl)-5-cyano-2-oxoimidazolidin-1-yl)isoquinoline-6-carbonitrile, 1-(3-Chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-Chlorophenyl)-3-(isoquinolin-4-yl)-4-methyl-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (5S)-1-(3-Chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, (4R,5S)-1-(3-Chlorophenyl)-3-(isoquinolin-4-yl)-5-methyl-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methylpyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-((1r,3R)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-((1s,3S)-3-(trifluoromethyl)cyclobutyl)imidazolidine-4-carbonitrile, 1-((R)-1-(2-Hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R)-1-(2-Hydroxyethyl)pyrrolidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(3-methoxy-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(3-(methylsulfonyl)phenyl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)pyrimidin-2-yl)imidazolidine-4-carbonitrile, 1-(4-Cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-Cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 1-(3-Cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-Cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(4-methylpyrimidin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Chloropyridazin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-Fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-Fluoropyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-Fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-Fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyridin-4-yl)imidazolidine-4-carbonitrile, 1-(5-Chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Chloro-3-methoxypyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(Difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(Difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-Chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-Chloro-2-cyanophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-Fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-Fluoropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyrimidin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1H-Indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1H-Indazol-7-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-Isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-Isopropyl-1H-pyrazol-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(1-methyl-1H-pyrazol-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,4-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,4-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)-1H-imidazol-2-yl)imidazolidine-4-carbonitrile, 1-(3-(2-Hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(2-Hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Chloro-2-(trifluoromethyl)pyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(5-methyl-2-(trifluoromethyl)pyridin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(Difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(Difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-Cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-Cyano-3-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methylpyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6-(Difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-(Difluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-Fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Fluoro-6-(trifluoromethyl)pyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(Difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(Difluoromethyl)pyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methylpyrimidin-5-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-Chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Chloro-3-methylpyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridazin-3-yl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(3-methyl-6-(trifluoromethyl)pyridin-2-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(Difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(Difluoromethoxy)-2-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-(2-Hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-(2-Hydroxypropan-2-yl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,4-Difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,4-Difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3,5-Difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,5-Difluorophenyl)-3-(6-(methylsulfonyl)isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-Chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-Chloro-4-fluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methyl-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-(Difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-(Difluoromethoxy)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2-Cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2-Cyano-5-(trifluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethoxy)phenyl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(2-(trifluoromethyl)pyrimidin-5-yl)imidazolidine-4-carbonitrile, 1-(6-Isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6-Isopropylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(1-methyl-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-2-yl)imidazolidine-4-carbonitrile, 1-(5,6-Dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5,6-Dimethylpyridin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(4-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(2-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(5-(Difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-(Difluoromethoxy)-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(2,6-Dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(2,6-Dimethylpyridin-4-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(4-Chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4-Chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(5-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, 1-(5-Fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(5-Fluoro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile (R)-3-(Isoquinolin-4-yl)-1-(4-methoxy-6-(trifluoromethyl)pyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile 1-(4-(Difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(4-(Difluoromethyl)phenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 1-(2,5-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(2,5-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 1-(3,5-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(3,5-Difluorophenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 1-(6-Chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(6-Chloropyridin-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 3-(Isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile (R)-3-(Isoquinolin-4-yl)-1-(6-methoxypyridin-3-yl)-2-oxoimidazolidine-4-carbonitrile 3-(Isoquinolin-4-yl)-2-oxo-1-(6-oxo-1,6-dihydropyridin-3-yl)imidazolidine-4-carbonitrile 1-(5-Chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(5-Chloro-2-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 1-(5-Chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(5-Chloro-2-methoxyphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 1-(2-Cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(2-Cyano-5-methylphenyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 4-(4-Cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile (R)-4-(4-Cyano-3-(isoquinolin-4-yl)-2-oxoimidazolidin-1-yl)-6-(trifluoromethyl)nicotinonitrile 3-(Isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile (R)-3-(Isoquinolin-4-yl)-1-(4-methyl-1H-imidazol-2-yl)-2-oxoimidazolidine-4-carbonitrile 1-(4-Chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-(4-Chloro-1H-imidazol-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile 3-(Isoquinolin-4-yl)-1-(3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile (R)-3-(Isoquinolin-4-yl)-1-((1s,3S)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile (R)-3-(Isoquinolin-4-yl)-1-((1r,3R)-3-methylcyclobutyl)-2-oxoimidazolidine-4-carbonitrile 1-(4-Fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-((1r,4R)-4-fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile (R)-1-((1s,4S)-4-Fluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(spiro[3.3]heptan-2-yl)imidazolidine-4-carbonitrile, 1-(3-Isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-Isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-Isopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-Cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1s,3S)-3-Cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((1r,3R)-3-Cyclopropylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(spiro[2.3]hexan-5-yl)imidazolidine-4-carbonitrile, 1-(3,3-Dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3,3-Dimethylcyclobutyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(6,6-Difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(6,6-Difluorospiro[3.3]heptan-2-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-((1r,4r)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-((1r,4R)-4-(trifluoromethyl)cyclohexyl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(1-((trifluoromethyl)sulfonyl)azetidin-3-yl)imidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-(1-(methylsulfonyl)azetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-(Cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-(Cyclopropylsulfonyl)azetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-(1-methylazetidin-3-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)imidazolidine-4-carbonitrile, 1-(1-Acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-Acetylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(1-Cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(1-Cyclopropylazetidin-3-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)imidazolidine-4-carbonitrile, 1-(4,4-Difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(4,4-Difluorocyclohexyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 1-(3-Fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-(3-Fluorobicyclo[1.1.1]pentan-1-yl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, 3-(Isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, (R)-3-(Isoquinolin-4-yl)-1-neopentyl-2-oxoimidazolidine-4-carbonitrile, 1-(3,3-Difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, (R)-1-((R or S)-3,3-Difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile, and (R)-1-((R or S)-3,3-Difluorocyclopentyl)-3-(isoquinolin-4-yl)-2-oxoimidazolidine-4-carbonitrile The compound according to claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, selected from

14. A pharmaceutical composition comprising the compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

15. A composition comprising the compound according to claim 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for the treatment, management, and / or prevention of coronavirus-related diseases.

16. The composition according to claim 15, wherein the coronavirus-related disease is COVID-19.

17. (R)-3-(Isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile, and 【Chemical Formula 4】 The compound of formula (I) according to claim 1, having the structure of.

18. The compound according to claim 17, which is crystalline (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile.

19. When measured at a temperature in the range of 20 to 40 °C using Cu-Kα radiation having a wavelength of 0.15418 nm, having a powder X-ray diffractogram comprising at least four reflections at 2θ angles selected from the group consisting of (6.85 ± 0.2)°, (8.52 ± 0.2)°, (10.41 ± 0.2)°, (13.71 ± 0.2)°, (16.90 ± 0.2)°, (17.06 ± 0.2)°, (18.40 ± 0.2)°, (19.05 ± 0.2)°, (21.76 ± 0.2)°, (22.55 ± 0.2)°, (23.50 ± 0.2)°, (24.82 ± 0.2)°, (26.89 ± 0.2)° and (28.17 ± 0.2)°, The compound according to claim 18, characterized by.

20. The compound according to claim 19, characterized by having a differential scanning calorimetry curve comprising an endothermic peak having a peak temperature of (235.2 °C ± 0.5) °C when measured at a heating rate of 10 K / min.

21. The compound according to claim 19, characterized by having a thermogravimetric analysis curve showing a mass loss of 0.51% by weight or less based on the weight of the crystalline form when heated from 30 °C to 210 °C at a rate of 10 K / min.

22. The compound according to claim 18, which is Modification A of (R)-3-(isoquinolin-4-yl)-2-oxo-1-(6-(trifluoromethyl)pyridin-3-yl)imidazolidine-4-carbonitrile.

23. When measured at a temperature in the range of 20 to 40 °C using Cu-Kα radiation having a wavelength of 0.15418 nm, the compound according to claim 18, characterized by having a powder X-ray diffractogram comprising at least four reflections at 2θ angles selected from the group consisting of (6.99 ± 0.2)°, (9.11 ± 0.2)°, (13.99 ± 0.2)°, (15.96 ± 0.2)°, (18.26 ± 0.2)°, (19.82 ± 0.2)°, (20.63 ± 0.2)°, (22.03 ± 0.2)°, (23.80 ± 0.2)°, (25.29 ± 0.2)°, (27.30 ± 0.2)°, (30.57 ± 0.2)° and (33.47 ± 0.2)°.

24. The compound according to claim 23, characterized by having a differential scanning calorimetry curve comprising an endothermic peak having a peak temperature of (161.3 °C ± 0.5) °C when measured at a heating rate of 10 K / min.

25. The compound according to claim 23, characterized by having a thermogravimetric analysis curve showing a mass loss of 0.21% by weight or less based on the weight of the crystalline form when heated from 30 °C to 150 °C at a rate of 10 K / min.

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