Dimeric compounds as inhibitors of glycogen synthase 1 (GYS1) and methods of use thereof

Abstract

Provided herein are compounds of formula (I): (G1-Z1)-L-(G2-Z2)(I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, where G1, G2, Z1, Z2, and L are as defined elsewhere herein. Also provided herein are methods of preparing compounds of formula (I). Also provided herein are methods of inhibiting GYS1 and treating GYS1-mediated diseases, disorders, or conditions in individuals in need thereof.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 406,683, filed September 14, 2022, the entire contents of which are incorporated herein by reference for all purposes. [Background technology]

[0002] Pathological accumulation of glycogen is a hallmark of several serious and chronic human diseases. For some of these disorders, the cellular etiology driving this abnormal accumulation has a clear genetic basis; for others, the mechanical drivers are more complex. Nevertheless, elevated glycogen levels result in altered cellular homeostasis and impaired tissue function over time. The rate-limiting enzyme in the glycogen synthesis pathway is the protein glycogen synthase (GYS). In humans, there are two isoforms: GYS1 and GYS2. The former is ubiquitously expressed but highly abundant in muscle cells, while the latter is expressed exclusively in the liver. Glycogen synthesis ultimately begins with the transport of glucose into cells via the GLUT family of transporters. The conversion of glucose to glycogen follows a well-characterized biochemical pathway, leading to the covalent attachment of glucose molecules via α1,4-glycosidic bonds to long, branched structures by GYS. Glycogen's final globular structure results from the action of glycogen branching enzyme (GBE), which introduces α1,6-linked branch points along the chain. This biochemical chain results in the production of an energy-dense, highly soluble molecule that can be stored in the cellular cytosol and rapidly catabolized to glucose for energy use as needed. An imbalance in the equilibrium of either glycogen synthesis or glycogen degradation can result in abnormal accumulation of cellular glycogen stores. It has long been hypothesized that substrate-reducing therapies targeting inhibition of glycogen synthase could be an effective treatment for disorders of glycogen storage.Indeed, substrate reduction therapeutics have been highly successful in modifying the disease course in patients with other storage disorders, including Gaucher disease and Fabry disease (Platt FM, Butters TD. Substrate Reduction Therapy. Lysosomal Storage Disorders, Springer US chapter 11, pp. 153-168, 2007; Shemesh E, et al. Enzyme replacement and substrate reduction therapy for Gaucher disease. Cochrane Database of Systematic Reviews, Issue 3, 2015). The objective of the present invention is to inhibit glycogen synthase enzyme activity, resulting in a reduction in tissue glycogen stores, with therapeutic benefit to patients suffering from the consequences of abnormal cellular glycogen accumulation.

[0003] GYS1 exists as a homotetramer in a complex with glycogenin (Fastman NM, et al. The structural mechanism of human glycogen synthesis by the GYS1-GYG1 complex. Cell Reports, vol. 40, 2022; McCorvie, TJ, et al. Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate. Nature Structural & Molecular Biology, vol. 29, 2022).

[0004] Pompe disease is a rare genetic disorder caused by a loss-of-function (LOF) mutation in the lysosomal enzyme α-glucosidase (GAA), resulting in the pathological accumulation of cellular glycogen. GAA degrades lysosomal glycogen, and in its absence, glycogen accumulates in lysosomes. This triggers a disease cascade that begins with lysosomal and autophagosome dysfunction, ultimately resulting in cell death and muscle atrophy over time (Young SP, et al. Genetics in Medicine, vol. 11, no. 11, 2009). In humans, the clinical manifestations of the disease range in severity and occur with a prevalence of 1 in 40,000 births (Meena NK, Raben N. Pompe disease: new developments in an old lysosomal storage disorder. Biomolecules, vol. 10, 2020). Infantile-onset patients are born with cellular pathology and rapidly develop severe disabilities, including myopathy, cardiac defects, organ enlargement, and hypotension, which, if left untreated, can ultimately kill a child within a year. Late-onset children may develop cardiac hypertrophy but are consistently characterized by progressive loss of motor function, skeletal muscle degeneration, and eventual respiratory failure, leading to early death. Late-onset adult Pompe patients exhibit normal cardiac function but develop progressive muscle weakness and respiratory weakness, followed by respiratory failure. The current standard of care for Pompe patients is enzyme replacement therapy (ERT) with recombinant human GAA. While ERT treatment has been successful in slowing disease progression, significant unmet needs remain in the majority of patients (Schoser B, et al. The humanistic burden of Pompe disease: are there still unmet needs? A systematic review. BMC Neurology, vol. 17, 2017). For over a decade, substrate reduction therapies targeting GYS1 have been hypothesized to be beneficial in the treatment of Pompe disease.Indeed, three separate preclinical studies have demonstrated that genetic LOF of GYS1 in Pompe disease mouse models effectively reduces tissue glycogen and improves disease outcomes in mice (Douillard-Guilloux G, et al. Modulation of glycogen synthesis by RNA interference: toward a new therapeutic approach for glycogenosis type II. Human Molecular Genetics, vol. 17, no. 24, 2008; Douillard-Guilloux G, et al. Restoration of muscle function by genetic suppression of glycogen synthesis in a murine model of Pompe disease. Human Molecular Genetics, vol. 19, no. 4, 2010; Clayton NP, et al. Antisense oligonucleotide-mediated suppression of muscle glycogen synthase 1 synthesis as an approach for substrate reduction therapy of Pompe disease. Molecular Therapy - Nucleic Acids, vol. 3, 2014). Small molecule GYS1 inhibitors may be used to address the current unmet needs of Pompe patients, either as monotherapy or in combination with standard of care ERT.

[0005] Pompe disease is only one of more than a dozen diseases caused by inborn errors of metabolism that result in abnormal accumulation of glycogen in various tissues of the body. While specific dietary treatments effectively manage some glycogen storage diseases (GSDs), for others, there are no clinically approved therapeutic interventions to alter the disease course. Therefore, inhibiting glycogen synthesis and the concomitant reduction of tissue glycogen levels may be a viable treatment option for these patients. Cori's disease, GSD III, is caused by mutations in glycogen debranching enzyme (GDE), which leads to pathological glycogen accumulation in the heart, skeletal muscle, and liver (Kishnani P, et al. Glycogen storage disease type III diagnosis and management guidelines. Genetics in Medicine, vol. 12, no. 7, 2010). While dietary management can be effective in ameliorating disease symptoms, there is currently no treatment to prevent progressive myopathy in GSD III. Adult polyglucosan body disease (APBD) is an adult-onset disorder caused by loss of glycogen branching enzyme (GBE1) activity. GBE deficiency leads to the accumulation of long chains of unbranched glycogen that precipitate in the cytosol, generating polyglucosan bodies, ultimately inducing neurological deficits in both the central and peripheral nervous systems. Genetic deletion of GYS1 in an APBD mouse model rescued the deleterious accumulation of glycogen, improved lifespan, and neuromuscular function (Chown EE, et al. GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease. Annals of Clinical and Translational Neurology, vol. 7, no. 11, 2020). Lafora disease (LD) is a highly debilitating early-onset epilepsy disorder similarly characterized by the accumulation of polyglucasone bodies.Genetic crossing of the LD mouse model with GYS1 knockout (KO) mice resulted in rescue of the disease phenotype (Pedersen B, et al. Inhibiting glycogen synthesis prevents Lafora disease in a mouse model. Annals of Neurology, vol. 74, no. 2, 2013; Varea O, et al. Suppression of glycogen synthesis as a treatment for Lafora disease: establishing the window of opportunity. Neurobiology of Disease, 2020).

[0006] Recently, the dependence of clear cell carcinoma on high levels of glycogen has emerged as a novel therapeutic target. Ewing sarcoma (ES), clear cell renal cell carcinoma (ccRCC), glycogen-rich clear cell carcinoma of the breast (GRCC), acute myeloid leukemia (AML), and non-small cell lung cancer (NSCLC) are all examples of cancers histopathologically defined by abnormally high levels of PAS+ cellular glycogen. Increased GYS1 transcript levels have been significantly correlated with poor disease outcomes in NSCLC (Giatromanolaki A, et al. Expression of enzymes related to glucose metabolism in non-small cell lung cancer and prognosis. Experimental Lung Research, vol. 43, no. 4-5, 2017) and AML (Falantes JF, et al. Overexpression of GYS1, MIF, and MYC is associated with adverse outcome and poor response to azacitidine in myelodysplastic syndromes and acute myeloid leukemia. Clinical Lymphoma, Myeloma & Leukemia, vol. 15, no. 4, 2015). Lentiviral knockdown of GYS1 in cultured myeloid leukemia cells strongly inhibited cancer cell proliferation in vitro and tumor formation in vivo (Bhanot H, et al. Pathological glycogenesis through glycogen synthase I and suppression of excessive AMP kinase activity in myeloid leukemia cells. Leukemia, vol. 29, no. 7, 2015).Genetic knockdown of GYS1 in a ccRCC cell model both inhibits tumor growth in vivo and increases the synthetic lethality of sunitinib (Chen S, et al. GYS1 induces glycogen accumulation and promotes tumor progression via the NF-kB pathway in clear cell renal carcinoma. Theranostics, vol. 10, no. 20, 2020).

[0007] The reduction in GYS1 enzyme activity and reduction in cellular glycogen stores in preclinical models of Pompe disease, APBD, LD, AML, ccRCC, and NSCLC all provide strong evidence of the potential therapeutic benefit of inhibiting glycogen synthesis. The objective of the present invention is to inhibit glycogen synthase activity, resulting in a reduction in tissue glycogen stores, which will provide therapeutic benefit to patients suffering from the consequences of accumulated cellular glycogen. Summary of the Invention

[0008] As used herein, in one aspect, there is provided a compound of formula (I): (G1-Z1)-L-(G2-Z2)(I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: (i) G1 and / or G1-Z1, and (ii) G2 and / or G2-Z2 are each independently a GYS1 inhibitory moiety; and L is a linker.

[0009] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently represented by formula (I-1) or (I-2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y 2 and Y 3 are each C, or Y 2 and Y 3 One of them is N and Y 2 and Y 3 the other of which is C, X 1 and X 2 However, independently, H, C 1~6 Alkyl, or C 1~6 is an alkoxy, X 3 and X 4 are each independently H, halo, C 1~6 Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; X 3 and X 4 C 1~6 the alkyl is optionally substituted with one or more halo; X 5 But H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 is cycloalkyl, (1)L 1 does not exist, and Q 1 However, (i)~(iv): (i) phenyl, where Q 1 The phenyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 substituted with cycloalkyl or 5- to 20-membered heteroaryl; C 1~6 The alkyl may be one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6 Alkyl, or -NH-C(O)-C 1~6optionally substituted with alkoxy; C 3~10 Cycloalkyl may contain one or more halo or C 1~6 optionally substituted with alkyl, and 5-20 membered heteroaryl is one or more C 1~6 phenyl optionally substituted with alkyl; (ii) 3- to 15-membered heterocyclyl, where Q 1 The 3- to 15-membered heterocyclyl is selected from one or more oxo, or C 1~6 3- to 15-membered heterocyclyl optionally substituted with alkyl; (iii) 5- to 20-membered heteroaryl, where Q 1 wherein the 5-20 membered heteroaryl is one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl; C 1~6 alkyl is optionally substituted with one or more halo; and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 5- to 20-membered heteroaryl optionally substituted with alkyl, and (iv) C 3~10 cycloalkyl; or or (2)L 1 is -CH2-, and Q 1 C 3~10 or cycloalkyl; L 2 is —C(O)— or —S(O)—; R 1 But H or C 1~6 is alkyl, R k is H, halo, -OH, -NH2, or -NH-C(O)C 1~6 is alkyl, R m is H, -OH, or C1~6 is alkyl, R n But H, C 1~6 Alkyl or C 3~10 cycloalkyl or R n together with the carbon atom to which it is attached, C 3~5 forming a cycloalkyl, or R k But R m or R n together with the atom to which they are attached form a cyclopropyl; R 2 However, (i)~(vii): (I C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a and optionally substituted with R a but, (a) -OH, (b) cyano, (c)C 2~6 Alkynyl, (d)C 6~20 Aryl, R a C 6~20 The aryl may be one or more of halo, cyano, C 1~6 Alkoxy or -NH-C(O)-C 1~6 C optionally substituted with alkyl 6~20 aryl, (e) 3- to 15-membered heterocyclyl, where R a 3-15 membered heterocyclyl is one or more R c and optionally substituted with R c But, halo, oxo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(O)-C 1~6 Alkyl or -C(O)-C 1~6 is an alkoxy, R c C 1~6 The alkyl may be one or more halo or C 2~6optionally substituted with alkynyl, and R c -C(O)-C 1~6 alkoxy is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo; (f)-N(R c )(R d ) and -N(R c )(R d )R c and R d However, independently of each other, H, C 1~6 Alkyl, -C(O)-C 1~6 Alkyl, -C(O)-C 1~6 Alkoxy, -C(O)-NH2, -C(O)-NH(C 1~6 alkyl), -C(O)-N(C 1~6 alkyl), -C(O)-(3- to 15-membered heterocyclyl), -CH-C(O)-NH, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R c or R d C 1~6 the alkyl is optionally substituted with one or more -C(O)-NH; R c or R d -C(O)-C 1~6 the alkyl is optionally substituted with one or more halo; R c or R d The 3- to 15-membered heterocyclyl and the 5- to 20-membered heteroaryl are independently one or more C 1~6 optionally substituted with alkyl; R c or R d -C(O)-(3 to 15-membered heterocyclyl) is one or more halo, -C(O)-C 1~6 Alkoxy or C 1~6 optionally substituted with alkyl, C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 optionally substituted with cycloalkyl, and Rc or R d -C(O)-N(C 1~6 C of alkyl)2 1~6 The alkyl may, independently of each other, be one or more halo or C 6~20 -N(R c )(R d ), (g)-OR e and R e But C 1~6 Alkyl, C 6~20 Aryl, -C(O)-(3- to 15-membered heterocyclyl), -C(O)-N-(C 1~6 alkyl) 2- or 5- to 20-membered heteroaryl; R e C 1~6 Alkyl is one or more C 1~6 optionally substituted with alkoxy, C 1~6 Alkoxy is one or more C 2~6 optionally substituted with alkynyl; R e C 6~20 The aryl may have one or more C 1~6 optionally substituted with alkyl, and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 Alkyl, C 1~6 Alkoxy or -C(O)-C 1~6 optionally substituted with alkoxy, C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 -OR optionally substituted with cycloalkyl e , (h)-C(O)-R e and R e is —NH2, —OH, or 3- to 15-membered heterocyclyl; —C(O)—R e , or (i)-S(O)2-R f and R f But C 1~6alkyl or 3- to 15-membered heterocyclyl, -S(O)2-R f C 1~6 Alkyl (ii) C 3~10 Cycloalkyl, R 2 C 3~10 Cycloalkyl may be one or more R q and optionally substituted with R q is 5 to 20-membered heteroaryl or C 6~20 aryl, and R q C 6~20 The aryl may have one or more C 1~6 C optionally substituted with alkoxy 3~10 cycloalkyl, (iii) 3- to 15-membered heterocyclyl, where R 2 The 3- to 15-membered heterocyclyl may be substituted with one or more halo, oxo, C 1~6 Alkyl, -C(O)-C 1~6 3- to 15-membered heterocyclyl optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iv) 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), 1~4 The alkyl group may be one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 optionally substituted with -(C alkyl)2, 5-20 membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl) is one or more R s and optionally substituted with R s But, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6is an alkoxy, R s C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, and R s wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C 1~6 5-20 membered heteroaryl optionally substituted with alkoxy or -(C 1~4 alkyl)(5-20 membered heteroaryl), (v)-N(R g )(R h ) and R g and R h are independently H or C 1~6 alkyl, -N(R g )(R h ), (vi)-C(O)-R j and R j But C 3~10 Cycloalkyl, -NH(C 1~6 alkyl), -N(C 1~6 -C(O)-R is -C(O)-R(alkyl), or -NH(5-20 membered heteroaryl); j ,and (vii)C 6~20 Aryl, R 2 C 6~20 The aryl is one or more 5- to 20-membered heteroaryl or -OR p and optionally substituted with R p is a 3- to 15-membered heterocyclyl, and R p 3-15 membered heterocyclyl is one or more -C(O)-C 1~6 C optionally substituted with alkyl 6~20 aryl, (G1-Z1) and (Z2-G2) are each independently substituted with a group attached to L.

[0010] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group of formula (IA): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y 1 , R 2 , R k , R x , R y , and R z is as defined elsewhere herein.

[0011] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group represented by formula (IB): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y 1 , R 2 , R k , R m , R n , R x , and R y is as defined elsewhere herein.

[0012] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group represented by formula (IC): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X 4 , X 5 , R 2 , R k , R v , and R w is as defined elsewhere herein.

[0013] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group represented by formula (ID): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X 4 , X 5 , R 2 , R k , R u , and R t is as defined elsewhere herein.

[0014] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group represented by formula (I-D1): [ka] and X of formula (I-D1) 4 , X 5 , R 2 , R K , R U , and R Z is as defined elsewhere herein.

[0015] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently represented by formula (I-D2): [ka] and X of formula (I-D2) 4 , X 5 , R 2 , R K , R T , and R U is as defined elsewhere herein.

[0016] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group of formula (IE): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 2 , R k , and R m is as defined elsewhere herein.

[0017] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group represented by formula (IF): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y 1 , R 2 , R k , R n , R x , and R yis as defined elsewhere herein.

[0018] In one aspect, provided herein is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group of formula (IG): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein rings A, L 1 , Y 2 , Y 3 , R 2 , R k , X 1 , X 2 , X 3 , X 4 , and X 5 is as defined elsewhere herein.

[0019] Provided herein in one aspect is a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a group of formula (IH): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y 1 , R 2 , R k , R n , R x , and R y is as defined elsewhere herein.

[0020] As used herein, in one aspect, the compound is represented by formula (II): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L, L 1 , L 2 , Y 2 , Y 3 , R 1 , R 2 , R k , R m , R n , X 1 , X 2 , X 3 , X 4 , X 5 , and Q 1 is as defined elsewhere herein.

[0021] As used herein, in one aspect, a compound is described having formula (III): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L, L 1 , L 2 , Y 2 , Y 3 , R 2 , X 1 , X 2 , X 3 , X 4 , X 5 , and Q 1 is as defined elsewhere herein.

[0022] As used herein, in one aspect, the compound is represented by formula (IV): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L, L 1 , L 2 , Y 2 , Y 3 , R 2 , Rk , R m , R n , X 1 , X 2 , X 3 , X 4 , X 5 , and Q 1 is as defined elsewhere herein.

[0023] As used herein, in one aspect, a compound is described having the formula (V): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L, L 1 , L 2 , Y 2 , Y 3 , R 2 , R k , R m , R n , X 1 , X 2 , X 3 , X 4 , X 5 , and Q 1 is as defined elsewhere herein.

[0024] Provided herein, in one aspect, is a pharmaceutical composition comprising: (i) a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

[0025] Provided herein, in one aspect, is a method for modulating GYS1 in a cell, the method comprising exposing the cell to (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0026] Provided herein, in one aspect, is a method for inhibiting GYS1 in a cell, the method comprising exposing the cell to (i) a composition comprising an effective amount of a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0027] Provided herein, in one aspect, are methods for reducing tissue glycogen stores in an individual in need thereof, comprising administering to the individual an effective amount of (i) a compound of Formula (I) or (ii) a pharmaceutical composition comprising a compound of Formula (I) and one or more pharmaceutically acceptable excipients. In some embodiments, the GYS1 inhibitor is selective for GYS1 over GYS2. In some embodiments, the compound of Formula (I) is 500-fold, 1,000-fold, 1,500-fold, or 1,700-fold selective for GYS1 over GYS2.

[0028] Provided herein, in one aspect, is a method of reducing tissue glycogen stores in an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0029] Provided herein, in one aspect, is a method of modulating GYS1 in the cells of an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0030] Provided herein, in one aspect, are methods for treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising subjecting the individual to glycogen substrate-reducing therapy. In some embodiments, the glycogen substrate-reducing therapy comprises administering a compound of Formula (I). In some embodiments, the compound of Formula (I) is selective for GYS1 over GYS2. In some embodiments, the compound of Formula (I) is 500-fold, 1,000-fold, 1,500-fold, or 1,700-fold selective for GYS1 over GYS2.

[0031] Provided herein, in one aspect, is a method of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients.

[0032] Provided herein, in one aspect, are methods of treating a glycogen storage disease, disorder, or condition in an individual in need thereof, comprising subjecting the individual to glycogen substrate-reducing therapy. In some embodiments, the glycogen substrate-reducing therapy comprises administering a compound of Formula (I). In some embodiments, the compound of Formula (I) is selective for GYS1 over GYS2. In some embodiments, the compound of Formula (I) is 500-fold, 1,000-fold, 1,500-fold, or 1,700-fold selective for GYS1 over GYS2.

[0033] In one aspect, provided herein is a kit comprising: (i) a composition comprising an effective amount of a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition comprising a compound of formula (I), or any variant or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use thereof in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

[0034] Provided herein in some aspects are methods for preparing a compound of formula (I), or any embodiment or variation thereof, such as a compound of formula (II), (II-A), (III), (II-A), (IV), (IV-A), (V), or (VA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. [Brief explanation of the drawings]

[0035] [Figure 1] Figure 1 shows the pathway by which PPP1R3A loss of function (LoF) leads to reduced muscle glycogen.

[0036] [Figure 2A] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and left ventricular ejection fraction (LVEF) (%) and left ventricular wall thickness (mm) in UK Biobank. [Figure 2B] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and left ventricular ejection fraction (LVEF) (%) and left ventricular wall thickness (mm) in UK Biobank.

[0037] [Figure 2C] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTV) and exercise power (watts), and maximum heart rate (HR) exercise (bpm) in UK Biobank. [Figure 2D] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTV) and exercise power (watts), and maximum heart rate (HR) exercise (bpm) in UK Biobank.

[0038] [Figure 2E] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and PQ interval (ms) and QRS duration (ms) in UK Biobank. [Figure 2F]Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and PQ interval (ms) and QRS duration (ms) in UK Biobank.

[0039] [Figure 2G] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and QT interval (ms) and serum glucose (mmol / L) in UK Biobank. [Figure 2H] Figure 1 shows the association between PPP1R3A protein-truncating variants (PTVs) and QT interval (ms) and serum glucose (mmol / L) in UK Biobank. DETAILED DESCRIPTION OF THE INVENTION

[0040] "Individual" refers to mammals, including humans and non-human mammals. Examples of individuals include, but are not limited to, mice, rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs, goats, sheep, cows, and humans. In some embodiments, individual refers to a human.

[0041] As used herein, "about" in reference to a parameter or value includes and describes the parameter or value itself. For example, "about X" includes and describes X itself.

[0042] As used herein, an "at risk" individual is an individual at risk of developing a disease or condition. An "at risk" individual may or may not have a detectable disease or condition, and may or may not exhibit detectable disease prior to the treatment methods described herein. "At risk" means that an individual has one or more so-called risk factors, which are measurable parameters that correlate with the development of a disease or condition and are known in the art. Individuals who have one or more of these risk factors have a higher likelihood of developing a disease or condition than individuals who do not have these risk factors.

[0043] "Treatment" or "treating" is an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired results may include one or more of the following: reducing one or more symptoms resulting from a disease or condition; reducing the severity of a disease or condition; delaying or preventing the onset of one or more symptoms associated with a disease or condition (e.g., stabilizing a disease or condition, preventing or slowing the worsening or progression of a disease or condition); and alleviating the disease, such as by causing regression of clinical symptoms (e.g., ameliorating a disease state, enhancing the effect of another drug, slowing the progression of a disease, improving quality of life, and / or prolonging survival).

[0044] As used herein, "delaying the onset of a disease or condition" means to postpone, inhibit, slow, decelerate, stabilize, and / or postpone the onset of the disease or condition. This delay can be of varying lengths of time, depending on the disease being treated and / or the medical history of the individual. As will be apparent to one of skill in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease or condition.

[0045] As used herein, the term "therapeutically effective amount" or "effective amount" refers to a compound of the present disclosure or a pharmaceutical salt thereof sufficient to provide treatment when administered to an individual. As understood in the art, an effective amount may be one or more administrations, e.g., a single administration or multiple administrations may be required to achieve a desired therapeutic endpoint. An effective amount may be considered in the context of administering one or more therapeutic agents; a single agent may be considered to be administered in an effective amount if, in conjunction with one or more other agents, a desired or beneficial result may be obtained or achieved.

[0046] As used herein, "unit dosage form" refers to physically discrete units suitable as unit dosages, each containing a predetermined amount of active ingredient or compound, which may be in a pharmaceutically acceptable carrier.

[0047] As used herein, "pharmaceutically acceptable" means a substance that is not biologically or otherwise undesirable, e.g., the substance can be incorporated into a pharmaceutical composition administered to an individual without causing significant undesired biological effects.

[0048] The term "alkyl," as used herein, refers to an unbranched or branched monovalent saturated hydrocarbon chain. As used herein, alkyl refers to an alkyl group having 1 to 20 carbons (i.e., C 1~20 alkyl), 1 to 16 carbons (i.e., C 1~16 alkyl), 1 to 12 carbons (i.e., C 1~12 alkyl), 1 to 10 carbons (i.e., C 1~10 alkyl), 1 to 8 carbons (i.e., C 1~8 alkyl), 1 to 6 carbons (i.e., C 1~6 alkyl), 1 to 4 carbons (i.e., C 1~4 alkyl), or 1 to 3 carbons (i.e., C 1~3 alkyl). Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbons is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms are encompassed (e.g., "butyl" includes n-butyl, sec-butyl, isobutyl, and tert-butyl, and "propyl" includes n-propyl and isopropyl). Certain commonly used alternative names may be used and will be understood by those skilled in the art. For example, a divalent group, such as a divalent "alkyl" group, may be referred to as an "alkylene."

[0049] As used herein, the term "alkenyl" refers to a branched or unbranched monovalent hydrocarbon chain containing at least one carbon-carbon double bond. As used herein, alkenyl refers to a hydrocarbon chain having 2 to 20 carbons (i.e., C2~20 alkenyl), 2 to 16 carbons (i.e., C 2~16 alkenyl), 2 to 12 carbons (i.e., C 2~12 alkenyl), 2 to 10 carbons (i.e., C 2~10 alkenyl), 2 to 8 carbons (i.e., C 2~8 alkenyl), 2 to 6 carbons (i.e., C 2~6 alkenyl), 2 to 4 carbons (i.e., C 2~4 alkenyl), or 2-3 carbons (i.e., C 2~3 alkenyl). Examples of alkenyl include, but are not limited to, ethenyl, prop-1-enyl, prop-2-enyl-1,2-butadienyl, and 1,3-butadienyl. When an alkenyl residue having a specific number of carbon atoms is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms can be encompassed (e.g., "propenyl" includes prop-1-enyl and prop-2-enyl). Certain commonly used alternative names may be used and will be understood by those skilled in the art. For example, a divalent group such as a divalent "alkenyl" group can be referred to as "alkenylene."

[0050] As used herein, the term "alkynyl" refers to a branched or unbranched monovalent hydrocarbon chain containing at least one carbon-carbon triple bond. As used herein, alkynyl refers to a hydrocarbon chain having 2 to 20 carbons (i.e., C 2~20 alkynyl), 2 to 16 carbons (i.e., C 2~16 alkynyl), 2 to 12 carbons (i.e., C 2~12 alkynyl), 2 to 10 carbons (i.e., C 2~10 alkynyl), 2 to 8 carbons (i.e., C 2~8 alkynyl), 2 to 6 carbons (i.e., C 2~6 alkynyl), 2 to 4 carbons (i.e., C 2~4 alkynyl), or 2-3 carbons (i.e., C 2~3alkynyl). Examples of alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, and but-3-ynyl. When an alkynyl residue having a specific number of carbons is named by a chemical name or molecular formula, all positional isomers having that number of carbon atoms can be included (e.g., "propynyl" includes prop-1-ynyl and prop-2-ynyl). Certain commonly used alternative names may be used and will be understood by those skilled in the art. For example, a divalent group such as a divalent "alkynyl" group can be referred to as an "alkynylene."

[0051] The term "alkoxy" as used herein refers to an -O-alkyl moiety. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy.

[0052] The term "aryl," as used herein, refers to a fully unsaturated carbocyclic ring moiety. The term "aryl" encompasses monocyclic and polycyclic fused ring moieties. As used herein, aryl refers to, for example, a ring of 6 to 20 ring carbon atoms (i.e., C 6~20 aryl), 6 to 16 ring carbon atoms (i.e., C 6~16 aryl), 6 to 12 ring carbon atoms (i.e., C 6~12 aryl), or 6 to 10 ring carbon atoms (i.e., C 6~10 Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, fluorenyl, and anthryl.

[0053] The term "cycloalkyl," as used herein, refers to a saturated or partially unsaturated carbocyclic ring moiety. The term "cycloalkyl" encompasses monocyclic and polycyclic ring moieties, which may be fused, branched, or spiro. Cycloalkyl includes cycloalkenyl groups, where the ring moiety contains at least one cyclic double bond. Cycloalkyl includes any polycyclic carbocyclic ring moiety containing at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. As used herein, cycloalkyl refers to, for example, a ring having 3 to 20 ring carbon atoms (i.e., C 3~20 cycloalkyl), 3 to 16 ring carbon atoms (i.e., C 3~16 cycloalkyl), 3 to 12 ring carbon atoms (i.e., C 3~12 cycloalkyl), 3 to 10 ring carbon atoms (i.e., C 3~10 cycloalkyl), 3 to 8 ring carbon atoms (i.e., C 3~8 cycloalkyl), 3 to 6 ring carbon atoms (i.e., C 3~6 cycloalkyl), or 3 to 5 ring carbon atoms (i.e., C 3~5 Cycloalkyl includes rings containing cycloalkyl groups. Monocyclic cycloalkyl ring moieties include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Furthermore, cycloalkyl also includes spirocycloalkyl ring moieties, for example, spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro[5.5]undecanyl.

[0054] The term "halo," as used herein, refers to those atoms occupying Group VIIA of the periodic table and includes fluorine (fluoro), chlorine (chloro), bromine (bromo), and iodine (iodo).

[0055] The term "heteroaryl," as used herein, refers to an aromatic (fully unsaturated) ring moiety containing one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heteroaryl" includes both monocyclic and polycyclic fused ring moieties. As used herein, heteroaryl includes, for example, 5 to 20 ring atoms (i.e., 5-20-membered heteroaryl), 5 to 16 ring atoms (i.e., 5-16-membered heteroaryl), 5 to 12 ring atoms (i.e., 5-12-membered heteroaryl), 5 to 10 ring atoms (i.e., 5-10-membered heteroaryl), 5 to 8 ring atoms (i.e., 5-8-membered heteroaryl), or 5 to 6 ring atoms (i.e., 5-6-membered heteroaryl). Any monocyclic or polycyclic aromatic ring moiety containing one or more ring heteroatoms is considered heteroaryl, regardless of the point of attachment to the remainder of the molecule (i.e., the heteroaryl moiety can be attached to the remainder of the molecule through any ring carbon or any ring heteroatom of the heteroaryl moiety). Examples of heteroaryl groups include acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzofuranyl, benzothiazolyl, benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolyl, Including, but not limited to, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, and triazinyl.Examples of fused heteroaryl rings include, but are not limited to, benzo[d]thiazolyl, quinolinyl, isoquinolinyl, benzo[b]thiophenyl, indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl, and imidazo[1,5-a]pyridinyl, and the heteroaryl may be attached via either ring of the fused system.

[0056] The term "heterocyclyl," as used herein, refers to a saturated or partially unsaturated cyclic moiety containing one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heterocyclyl" includes both monocyclic and polycyclic ring moieties, which may be fused, bridged, or spiro. Any non-aromatic monocyclic or polycyclic aromatic ring moiety containing at least one ring heteroatom is considered to be heterocyclyl, regardless of the point of attachment to the rest of the molecule (i.e., the heterocyclyl moiety can be attached to the rest of the molecule through any ring carbon or any ring heteroatom of the heterocyclyl moiety). Furthermore, the term heterocyclyl is intended to encompass any polycyclic ring moiety containing at least one ring heteroatom, provided that the polycyclic ring moiety contains at least one non-aromatic ring, regardless of the point of attachment to the rest of the molecule. As used herein, heterocyclyl includes, for example, 3 to 20 ring atoms (i.e., 3-20-membered heterocyclyl), 3 to 16 ring atoms (i.e., 3-16-membered heterocyclyl), 3 to 12 ring atoms (i.e., 3-12-membered heterocyclyl), 3 to 10 ring atoms (i.e., 3-10-membered heterocyclyl), 3 to 8 ring atoms (i.e., 3-8-membered heterocyclyl), 3 to 6 ring atoms (i.e., 3-6-membered heterocyclyl), 3 to 5 ring atoms (i.e., 3-5-membered heterocyclyl), 5 to 8 ring atoms (i.e., 5-8-membered heterocyclyl), or 5 to 6 ring atoms (i.e., 5-6-membered heterocyclyl).Examples of heterocyclyl groups are, for example, azetidinyl, azepinyl, benzodioxolyl, benzo[b][l,4]dioxepinyl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyranonyl, benzofuranonyl, dioxolanyl, dihydropyranyl, hydropyranyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, furanonyl, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoquinol ... Includes isoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thiophenyl (i.e., thienyl), thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Examples of spiroheterocyclyl rings include, but are not limited to, bicyclic and tricyclic ring systems such as oxabicyclo[2.2.2]octanyl, 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of fused heterocyclyl rings include, but are not limited to, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl, and isoindolinyl, where the heterocyclyl may be attached via either ring of the fused system.

[0057] As used herein, the term "oxo" refers to a =O moiety.

[0058] The terms "optional" and "optionally," as used herein, mean that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not occur. Thus, the term "optionally substituted" infers that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms at the specified atom, moiety, or group may or may not be replaced by atoms, moieties, or groups other than hydrogen. By way of example, and not limitation, the phrase "methyl optionally substituted with one or more chloro" encompasses the moieties -CH, -CHCl, -CHCl, and -CCl.

[0059] Aspects and embodiments described herein as "comprising" are to be understood to include "consisting of" and "consisting essentially of" embodiments.

[0060] The term "pharmaceutically acceptable salt" of a given compound, as used herein, refers to a salt that retains the biological effectiveness and properties of the given compound and is not biologically or otherwise undesirable. "Pharmaceutically acceptable salt" includes, for example, salts with inorganic acids and salts with organic acids. Furthermore, if a compound described herein is obtained as an acid addition salt, the free base can be obtained by basifying a solution of the acid salt. Conversely, if the product is a free base, an addition salt, particularly a pharmaceutically acceptable addition salt, can be produced by dissolving the free base in a suitable organic solvent and treating the solution with an acid according to conventional procedures for preparing acid addition salts from base compounds. See, for example, "Handbook of Pharmaceutical Salts Properties, Selection, and Use," International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), incorporated herein by reference. Those skilled in the art will recognize various synthetic methods that can be used to prepare non-toxic pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Salts derived from inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Salts derived from organic acids include, for example, acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, trifluoroacetic acid, and the like. Similarly, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines.Specific examples of suitable amines include, by way of example only, isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like.

[0061] Isotopically labeled forms of the compounds described herein can be prepared. Isotopically labeled compounds have the structures shown herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, for example, 2 H, 3 H, 11 C. 13 C. 14 C. 13 N, 15 N, 15 O. 17 O. 18 O. 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 I. In some embodiments, compounds of Formula (A) are provided in which one or more hydrogens are replaced with deuterium or tritium.

[0062] Some of the compounds provided herein may exist as tautomers. Tautomers are in equilibrium with each other. By way of example, an amide-containing compound may exist in equilibrium with an imidic acid tautomer. Regardless of which tautomer is shown and the nature of the equilibrium between the tautomers, the compounds of this disclosure will be understood by those skilled in the art to include both the amide and imidic acid tautomers. Thus, for example, an amide-containing compound is understood to include its imidic acid tautomer. Similarly, an imidic acid-containing compound is understood to include its amide tautomer.

[0063] Prodrugs of the compounds disclosed herein or pharmaceutically acceptable salts thereof are also provided herein. Prodrugs are compounds that can be administered to an individual and release the compounds disclosed herein as parent drug compounds in vivo. It should be understood that prodrugs can be prepared by modifying functional groups in the parent drug compound so that the modifications are cleaved in vitro or in vivo to release the parent drug compound. See, for example, Rautio, J., Kumpulainen, H., Heimbach, T. et al. Prodrugs: design and clinical applications. Nat Rev Drug Discov 7, 255-270 (2008), which is incorporated herein by reference.

[0064] The compounds of the present disclosure, or their pharmaceutically acceptable salts, may contain asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined in terms of absolute stereochemistry as (R)- or (S)- (or, in the case of amino acids, (D)- or (L)-). The present disclosure is intended to include all such possible isomers, as well as their racemic and optically pure forms, and mixtures thereof, in any proportion. Optically active (+)- and (−), (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents or resolved using conventional techniques, for example, chromatography and / or fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of the racemates (or racemates of salts or derivatives) using, for example, chiral high-pressure liquid chromatography (HPLC) and chiral supercritical fluid chromatography (SFC). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, unless otherwise specified, the present disclosure is intended to include both E and Z geometric isomers. Similarly, cis and trans are used in their conventional sense to describe relative spatial relationships.

[0065] "Stereoisomers" refer to compounds consisting of the same atoms connected by the same bonds but having different three-dimensional structures that are not interchangeable. The present disclosure contemplates various stereoisomers, or mixtures thereof, and includes "enantiomers," which refer to two stereoisomers whose structures are non-superimposable mirror images of each other. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other.

[0066] Where enantiomeric and / or diastereomeric forms of a given structure exist, a planar bond indicates that all stereoisomeric forms of the structure shown may exist, for example: [ka]

[0067] Where enantiomeric and / or diastereomeric forms of a given structure exist, the presence of a planar bond and "*" symbol indicates that the composition consists of at least 90% by weight of a single isomer of unknown stereochemistry, for example, [ka]

[0068] Where enantiomeric and / or diastereomeric forms of a given structure exist, a wedge or hash bond indicates that the composition consists of at least 90% by weight of a single enantiomer or diastereomer of the known stereochemistry, for example, [ka]

[0069] Combinations of the above notations may be used where applicable. Exemplary species may contain stereocenters with known stereochemistry and stereocenters with unknown stereochemistry, such as: [ka]

[0070] Combinations of the above notations may be used where applicable. Exemplary species may contain stereocenters with known stereochemistry and stereocenters with mixtures of isomers, such as: [ka]

[0071] compound As used herein, in one aspect, there is provided a compound of formula (I): (G1-Z1)-L-(G2-Z2)(I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: (i) G1 and / or G1-Z1, and (ii) G2 and / or G2-Z2 are each independently a GYS1 inhibitory moiety, and L is a linker.

[0072] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is a bond or (C1-C 50 ) alkyl; (C1~C 50 )Alkyl is an alkyl group containing one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R x )(R y )-, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 optionally substituted with aryl, or 5- to 20-membered heteroaryl; and (C1~C 50 One or more of the C atoms in the alkyl may be bonded to one or more —C(R x )=C(R x)-, -C≡C-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -OC(O)N(R x )-, -N(R x )C(O)O-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -S(O) n O-, -OS(O) n -, -OS(O) n O-, -OS(O) n N(R x )-, -N(R x )S(O) n O-, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 optionally substituted with aryl, or 5- to 20-membered heteroaryl; Each C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 Aryl or 5- to 20-membered heteroaryl may be substituted with one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -OC(O)OR z , -OC(O)N(R xx )(R yy ), -N(R xx )C(O)OR z , -N(R xx )C(O)N((R xx)(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )C(O)R z , -N(R xx )(R yy ), -S(O) n R z , -S(O) n OR z , -OS(O) n R z , -OS(O) n OR z , -OS(O) n N(R xx )(R yy ), -N(R xx )S(O) n OR z , -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0073] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is one or more of deuterium, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C═O), —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —O(C1-C6)cycloalkyl, —N(R x )(R y )-, C3~C 15Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 aryl, or 5- to 20-membered heteroaryl optionally substituted (C1-C 50 ) alkyl, (C1~C 50 One or more of the C atoms of the alkyl may be substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 optionally substituted with aryl, or 5- to 20-membered heteroaryl; Each C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 Aryl and 5- to 20-membered heteroaryl are substituted with one or more deuterium atoms, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo(C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )(R yy ), -S(O) n R z, -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0074] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1~C 20 )Alkyl is an alkyl group containing one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R x )(R y )-, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 optionally substituted with aryl, or 5- to 20-membered heteroaryl; and (C1~C 20 One or more of the C atoms of the alkyl may be substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(Rx )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 optionally substituted with aryl, or 5- to 20-membered heteroaryl; Each C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 Aryl and 5- to 20-membered heteroaryl may each be substituted with one or more of deuterium, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )(R yy ), -S(O) n R z , -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0075] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1-C 20 )Alkyl is an alkyl group containing one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R x )(R y )-, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 optionally substituted with aryl, or 5- to 10-membered heteroaryl; and (C1~C 20 One or more of the C atoms of the alkyl may be substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 optionally substituted with aryl, or 5- to 10-membered heteroaryl; Each C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10Aryl and 5- to 10-membered heteroaryl are substituted with one or more deuterium atoms, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo(C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )(R yy ), -S(O) n R z , -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0076] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1-C 20 )Alkyl is an alkyl group containing one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(Rx )(R y )-, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 optionally substituted with aryl, or 5- to 10-membered heteroaryl; and (C1~C 20 One or more of the C atoms of the alkyl may be substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 optionally substituted with aryl, or 5- to 10-membered heteroaryl; Each R x and R y are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0077] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1-C 20 ) alkyl is one or more deuterium, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo(C=O), —O(C1-C6) alkyl, —O(C1-C6) haloalkyl, —O(C1-C6) cycloalkyl, or —N(R x )(R y )-, and (C1~C 20 ) alkyl, one or more of the C atoms may be substituted with one or more of -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 optionally substituted with aryl, or 5- to 10-membered heteroaryl; Each R x and R y are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0078] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1-C 20 ) alkyl is optionally substituted with one or more deuterium, halo, (C1-C4) alkyl, (C1-C4) haloalkyl, oxo(C=O), -O(C1-C4) alkyl, -O(C1-C4) haloalkyl, or -O(C1-C4) cycloalkyl; and (C1~C 20 ) alkyl, one or more of the C atoms may be substituted with one or more of -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, 3-8 membered heterocyclyl, C6-C 10optionally substituted with aryl, or 5- to 10-membered heteroaryl; Each R x and R y are independently H, (C1-C3) alkyl, (C1-C3) haloalkyl, or (C1-C3) cycloalkyl, and Each n is independently 0 to 2.

[0079] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1-C 20 ) alkyl, one or more C atoms may be substituted with one or more -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)- or -N(R x )-, and Each R x and R y are independently H, (C1-C3) alkyl, (C1-C3) haloalkyl, or (C1-C3) cycloalkyl, and Each n is independently 0 to 2.

[0080] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (C1-C 20 ) alkyl, (C1-C 20 ) One or more of the C atoms of the alkyl is replaced by one or more -O-.

[0081] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is —(—O—CH2CH2) m -O-, and m is 1 to 12.

[0082] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is alkyl. In some embodiments, alkyl is selected from the group consisting of C1-C2, C1-C3, C1-C4, C1-C5, C1-C6, C1-C8, C1-C9, C1-C10, C1-C11, C1-C12, C1-C13, C1-C14, C1-C15, C1-C16, C1-C17, C1-C18, C1-C19, C1-C20, C1-C21, C1-C22, C1-C23, C1-C24, C1-C25, C1-C26, C1-C28, C1-C29, C1-C29, C1-C21, C1-C22, C1-C23, C 10 , C1~C 12 , C1~C 15 , C1~C 20 , C1~C 30 , C1~C 40 , or C1~C 50 In some embodiments, alkyl is C1-C 50 In some embodiments, alkyl is C1-C 40 In some embodiments, alkyl is C1-C 30 In some embodiments, alkyl is C1-C 20 In some embodiments, alkyl is C1-C 15 In some embodiments, alkyl is C1-C 12 In some embodiments, alkyl is C1-C 10 In some embodiments, alkyl is C1-C8. In some embodiments, alkyl is C1-C6. In some embodiments, alkyl is C1-C4. In some embodiments, alkyl is C1-C3. In some embodiments, alkyl is methyl or ethyl. In some embodiments, alkyl is methyl. In some embodiments, alkyl is ethyl. In some embodiments, alkyl is unbranched. In some embodiments, alkyl is branched.

[0083] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, alkyl in L is selected from the group consisting of one or more of deuterium, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C═O), —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —O(C1-C6)cycloalkyl, —N(R x )(R y )-, C3~C15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 In some embodiments, the alkyl is optionally substituted with one or more deuterium, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —O(C1-C6)cycloalkyl, —N(R x )(R y )-, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 Optionally substituted aryl or 5-10 membered heteroaryl.

[0084] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, alkyl in L is one or more of deuterium, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C═O), —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —O(C1-C6)cycloalkyl, or —N(R x )(R y In some embodiments, alkyl is optionally substituted with one or more deuterium, halo, (C1-C4)alkyl, (C1-C4)haloalkyl, oxo(C═O), —O(C1-C4)alkyl, —O(C1-C4)haloalkyl, or —O(C1-C4)cycloalkyl.

[0085] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, one or more of the C atoms of the alkyl of L is substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -OC(O)N(R x )-, -N(R x )C(O)O-, -N(R x )C(O)N(R y )-, -C(O)N(Rx )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -S(O) n O-, -OS(O) n -, -OS(O) n O-, -OS(O) n N(R x )-, -N(R x )S(O) n O-, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 In some embodiments, one or more of the C atoms of the alkyl are optionally substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 In some embodiments, one or more of the C atoms of the alkyl are optionally substituted with one or more —C(R x )=C(R x )-, -C≡C-, -O-, -C(O)-, -N(R x )C(O)N(R y)-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 In some embodiments, one of the C atoms of the alkyl is optionally substituted with one or more of -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3-C8 cycloalkyl, 3-8 membered heterocyclyl, C6-C 10 In some embodiments, one or more of the C atoms of the alkyl are optionally substituted with one or more of -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, 3-8 membered heterocyclyl, C6-C 10 In some embodiments, one or more of the C atoms of the alkyl are optionally substituted with one or more of -O-, -C(O)-, -N(R x )C(O)N(R y )-, -C(O)N(Rx )-, -N(R x )C(O)- or -N(R x In some embodiments, one or more of the C atoms of the alkyl are optionally replaced with one or more —O— or —N(R x In some embodiments, one or more of the C atoms of the alkyl is optionally replaced with one or more -O-.

[0086] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, each C3-C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 Aryl or 5- to 20-membered heteroaryl may be substituted with one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -OC(O)OR z , -OC(O)N(R xx )(R yy ), -N(R xx )C(O)OR z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )C(O)R z , -N(R xx )(R yy ), -S(O) n R z , -S(O) n OR z , -OS(O) n R z , -OS(O) n OR z , -OS(O) nN(R xx )(R yy ), -N(R xx )S(O) n OR z , -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z is independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl, and each n is independently 0 to 2.

[0087] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, each C3-C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 Aryl and 5- to 20-membered heteroaryl are substituted with one or more deuterium atoms, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo(C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )(R yy ), -S(O) n R z , -N(R xx )S(O)n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0088] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, each L is C3-C8 cycloalkyl, 3- to 8-membered heterocyclyl, C6 ... 10 Aryl and 5- to 10-membered heteroaryl are substituted with one or more deuterium atoms, halo, (C1-C6) alkyl, (C1-C6) haloalkyl, oxo(C=O), -O(C1-C6) alkyl, -O(C1-C6) haloalkyl, -O(C1-C6) cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )(R yy ), -S(O) n R z , -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx)S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0089] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is —(—O—CH2CH2) m -O- and m is 1 to 25. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 20. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 15. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 10. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 6. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 4. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 3. In some embodiments, L is -(-O-CH2CH2) m In some embodiments, L is -O-, and m is 1 to 2. In some embodiments, L is -(-O-CH2CH2)-O-. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 10. In some embodiments, m is 11.

[0090] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is —(—O—CH2CH2) m -O- and m is 1 to 25. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 20. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 15. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 10. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 6. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 4. In some embodiments, L is -(-O-CH2CH2) m -O- and m is 1 to 3. In some embodiments, L is -(-O-CH2CH2) m In some embodiments, L is -O-, and m is 1 to 2. In some embodiments, L is -(-O-CH2CH2)-O-. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 10. In some embodiments, m is 11.

[0091] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is —(—O—CH2CH2) m -O- and m is 1 to 25. In some embodiments, L is -(-O-CH2CH2) m In some embodiments, L is —O—, m is 1 to 20, and one or more O is replaced with NH. ... mIn some embodiments, L is —O—, m is 1 to 15, and one or more O is replaced with NH. In some embodiments, L is —(—O—CHCH) m In some embodiments, L is —O—, m is 1 to 10, and one or more O is replaced with NH. In some embodiments, L is —(—O—CHCH) m In some embodiments, L is —O—, m is 1 to 6, and one or more O is replaced with NH. ... m In some embodiments, L is —O—, m is 1 to 4, and one or more O is replaced with NH. ... m In some embodiments, L is —O—, m is 1 to 3, and one or more O is replaced with NH. In some embodiments, L is —(—O—CHCH) m In some embodiments, L is -O-, m is 1 to 2, and one or more O are replaced with NH. In some embodiments, L is -(-O-CH2CH2)-O-. In some embodiments, m is 1, and one O is replaced with NH. In some embodiments, m is 2, and one O is replaced with NH. In some embodiments, m is 3, and one O is replaced with NH. In some embodiments, m is 4, and one O is replaced with NH. In some embodiments, m is 5. In some embodiments, m is 6, and one O is replaced with NH. In some embodiments, m is 10, and one O is replaced with NH. In some embodiments, m is 11, and one O is replaced with NH. In some embodiments, L is -O-CH2CH2-O-CH2CH2-O-CH2CH2-NH-CH2CH2-O-CH2CH2-O-.

[0092] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L comprises an optionally substituted alkylene, an optionally substituted heteroalkylene, an optionally substituted alkenylene, an optionally substituted heteroalkenylene, an optionally substituted alkynylene, an optionally substituted heteroalkynylene, an optionally substituted carbocyclylene, an optionally substituted heterocyclylene, an optionally substituted arylene, an optionally substituted heteroarylene, or any combination thereof.

[0093] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is selected from the group consisting of ethylene glycol, polyethylene glycol (PEG), and a PEG derivative. In some embodiments, the PEG derivative comprises polyethylene glycol (PEG), wherein one or more of the C atoms of PEG are substituted with one or more groups and / or one or more of the C atoms of PEG are substituted with one or more groups. In some embodiments, one or more C atoms in PEG are each independently selected from one or more of deuterium, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C═O), —O(C1-C6)alkyl, —O(C1-C6)haloalkyl, —O(C1-C6)cycloalkyl, —N(R x )(R y )-, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 aryl, or 5- to 20-membered heteroaryl, and / or one or more of the C atoms in the PEG moiety are each independently substituted with one or more —C(R x )=C(R x )-, -C≡C-,, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -OC(O)N(R x )-, -N(R x )C(O)O-, -N(R x )C(O)N(R y)-, -C(O)N(R x )-, -N(R x )C(O)-, -N(R x )-, -S(O) n -, -S(O) n O-, -OS(O) n -, -OS(O) n O-, -OS(O) n N(R x )-, -N(R x )S(O) n O-, -N(R x )S(O) n N(R y )-, -S(O) n N(R x )-, -N(R x )S(O) n -, C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 substituted with an aryl or 5- to 20-membered heteroaryl; Each C3~C 15 Carbocyclyl, 3-15 membered heterocyclyl, C6-C 14 Aryl or 5- to 20-membered heteroaryl may be substituted with one or more deuterium atoms, halo, (C1-C6)alkyl, (C1-C6)haloalkyl, oxo(C=O), -O(C1-C6)alkyl, -O(C1-C6)haloalkyl, -O(C1-C6)cycloalkyl, -N(R xx )(R yy ), -C(O)R z , -C(O)OR z , -OC(O)R z , -OC(O)OR z , -OC(O)N(R xx )(R yy ), -N(R xx )C(O)OR z , -N(R xx )C(O)N((R xx )(R yy ), -C(O)N(R xx )(R yy ), -N(R xx )C(O)R z , -N(R xx )(R yy ), -S(O)n R z , -S(O) n OR z , -OS(O) n R z , -OS(O) n OR z , -OS(O) n N(R xx )(R yy ), -N(R xx )S(O) n OR z , -N(R xx )S(O) n N(R xx )(R yy ), -S(O) n N(R xx )(R yy ), or -N(R xx )S(O) n R z and optionally substituted with Each R x , R xx , R y , R yy , and R z are independently H, (C1-C6)alkyl, (C1-C6)haloalkyl, or (C1-C6)cycloalkyl; and Each n is independently 0 to 2.

[0094] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L comprises a polymer.

[0095] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L comprises a polymer. In some embodiments, the polymer is polyethylene glycol (PEG). In some embodiments, the polyethylene glycol comprises from about 2 to about 20 ethylene glycol units.

[0096] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is a bond.

[0097] In some embodiments of the compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is attached at any available position of G1 or Z1, and at any available position of G2 or Z2.

[0098] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (i) the Z1 portion of (G1-Z1), and (ii) The Z2 portion of (G2-Z2) is bound to the nucleotide.

[0099] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (i) the G1 portion of (G1-Z1), and (ii) G2 portion of (G2-Z2) is bound to the

[0100] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (i) the Z1 portion of (G1-Z1), and (ii) G2 portion of (G2-Z2) is bound to the

[0101] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L is (i) the G1 portion of (G1-Z1), and (ii) The Z2 portion of (G2-Z2) is bound to the nucleotide.

[0102] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is unsubstituted methyl, (1)Q 1 is a 5- to 20-membered heteroaryl; Q 1 The 5- to 20-membered heteroaryl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, C 3~10 optionally substituted with cycloalkyl or —OH; 1 is not unsubstituted pyridyl, or (2)Q 1 is phenyl and Q 1 The phenyl in (i) at least one C 3~6 Alkyl-substituted and at least one C 3~6 The alkyl may have at least one C optionally substituted with one or more halo. 3~6 alkyl, or (ii) at least one C 3~10 cycloalkyl-substituted with at least one C 3~10 Cycloalkyl may be one or more halo or C 1~6 at least one C optionally substituted with alkyl 3~10 cycloalkyl, or (iii) substituted with at least one 5- to 20-membered heteroaryl, wherein the at least one 5- to 20-membered heteroaryl is substituted with one or more C 1~6 or substituted with at least one 5-20 membered heteroaryl, optionally substituted with alkyl.

[0103] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (i) G1 or G1-Z1, and (ii) G2 or G2-Z2 are the same. In some embodiments, G1 and G2 are the same, and / or G1-Z1 and G2-Z2 are the same. In some embodiments, (i) G1 and (ii) G2 are the same. In some embodiments, (i) G1-Z1 and (ii) G2 are the same.

[0104] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (i) G1 or G1-Z1, and (ii) G2 or G2-Z2 are different. In some embodiments, G1 and G2 are the same and / or G1-Z1 and G2-Z2 are different. In some embodiments, (i) G1 and (ii) G2 are different. In some embodiments, (i) G1-Z1 and (ii) G2-Z2 are different.

[0105] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (i) G1 or G1-Z1, and (ii) G2 or G2-Z2 have enhanced GYS1 inhibition compared to the other of (i) G1 or G1-Z1, and (ii) G2 or G2-Z2. In some embodiments, one of G1 and G2 has enhanced GYS1 inhibition compared to the other of G1 and G2. In some embodiments, one of G1-Z1 and G2-Z2 has enhanced GYS1 inhibition compared to the other of G1-Z1 and G2-Z2.

[0106] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound of Formula (I) has enhanced GYS1 inhibition relative to G1, G1-Z1, G2, and / or G2-Z2. In some embodiments, the compound of Formula (I) has enhanced GYS1 inhibition relative to G1. In some embodiments, the compound of Formula (I) has enhanced GYS1 inhibition relative to G1-Z1. In some embodiments, the compound of Formula (I) has enhanced GYS1 inhibition relative to G2. In some embodiments, the compound of Formula (I) has enhanced GYS1 inhibition relative to G2-Z2.

[0107] In some embodiments, (G1-Z1)-L-(G2-Z2) is a bivalent inhibitor with the potential to simultaneously engage two GYS1 monomers within a single tetrameric complex.

[0108] In some embodiments of a compound of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (G1-Z1) and (G2-Z2) are each independently a group represented by formula (I-1) or (I-2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y 2 and Y 3 are each C, or Y 2 and Y 3 One of them is N and Y 2 and Y 3 the other of which is C, X 1 and X 2 However, independently, H, C 1~6 Alkyl, or C 1~6 is an alkoxy, X 3 and X 4 are each independently H, halo, C 1~6Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; X 3 and X 4 C 1~6 the alkyl is optionally substituted with one or more halo; X 5 But H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 is cycloalkyl, (1)L 1 does not exist, and Q 1 However, (i)~(iv): (i) phenyl, where Q 1 The phenyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 substituted with cycloalkyl or 5- to 20-membered heteroaryl; C 1~6 The alkyl may be one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy; C 3~10 Cycloalkyl may contain one or more halo or C 1~6 optionally substituted with alkyl, and 5-20 membered heteroaryl is one or more C 1~6 phenyl optionally substituted with alkyl; (ii) 3- to 15-membered heterocyclyl, where Q 1 The 3- to 15-membered heterocyclyl is selected from one or more oxo, or C 1~6 3- to 15-membered heterocyclyl optionally substituted with alkyl; (iii) 5- to 20-membered heteroaryl, where Q 1 wherein the 5-20 membered heteroaryl is one or more halo, C 1~6 Alkyl, C2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl; C 1~6 alkyl is optionally substituted with one or more halo; and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 5- to 20-membered heteroaryl optionally substituted with alkyl, and (iv) C 3~10 cycloalkyl; or or (2)L 1 is -CH2-, and Q 1 C 3~10 or cycloalkyl; L 2 is —C(O)— or —S(O)—; R 1 But H or C 1~6 is alkyl, R k is H, halo, -OH, -NH2, or -NH-C(O)C 1~6 is alkyl, R m is H, -OH, or C 1~6 is alkyl, R n But H, C 1~6 Alkyl or C 3~10 cycloalkyl or R n together with the carbon atom to which it is attached, C 3~5 forming a cycloalkyl, or R k But R m or R n together with the atom to which they are attached form a cyclopropyl; R 2 However, (i)~(vii): (I C 1~6 alkyl, and R 2 C 1~6Alkyl is one or more R a and optionally substituted with R a but, (a) -OH, (b) cyano, (c)C 2~6 Alkynyl, (d)C 6~20 Aryl, R a C 6~20 The aryl may be one or more of halo, cyano, C 1~6 Alkoxy or -NH-C(O)-C 1~6 C optionally substituted with alkyl 6~20 aryl, (e) 3- to 15-membered heterocyclyl, where R a 3-15 membered heterocyclyl is one or more R c and optionally substituted with R c But, halo, oxo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(O)-C 1~6 Alkyl or -C(O)-C 1~6 is an alkoxy, R c C 1~6 The alkyl may be one or more halo or C 2~6 optionally substituted with alkynyl, and R c -C(O)-C 1~6 alkoxy is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo; (f)-N(R c )(R d ) and -N(R c )(R d )R c and R d However, independently of each other, H, C 1~6 Alkyl, -C(O)-C 1~6 Alkyl, -C(O)-C 1~6 Alkoxy, -C(O)-NH2, -C(O)-NH(C 1~6 alkyl), -C(O)-N(C 1~6alkyl), -C(O)-(3- to 15-membered heterocyclyl), -CH-C(O)-NH, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R c or R d C 1~6 the alkyl is optionally substituted with one or more -C(O)-NH; R c or R d -C(O)-C 1~6 the alkyl is optionally substituted with one or more halo; R c or R d The 3- to 15-membered heterocyclyl and the 5- to 20-membered heteroaryl are independently one or more C 1~6 optionally substituted with alkyl; R c or R d -C(O)-(3 to 15-membered heterocyclyl) is one or more halo, -C(O)-C 1~6 Alkoxy or C 1~6 optionally substituted with alkyl, C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 optionally substituted with cycloalkyl, and R c or R d -C(O)-N(C 1~6 C of alkyl)2 1~6 The alkyl may, independently of each other, be one or more halo or C 6~20 -N(R c )(R d ), (g)-OR e and R e But C 1~6 Alkyl, C 6~20 Aryl, -C(O)-(3- to 15-membered heterocyclyl), -C(O)-N-(C 1~6 alkyl) 2- or 5- to 20-membered heteroaryl; R e C 1~6Alkyl is one or more C 1~6 optionally substituted with alkoxy, C 1~6 Alkoxy is one or more C 2~6 optionally substituted with alkynyl; R e C 6~20 The aryl may have one or more C 1~6 optionally substituted with alkyl, and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 Alkyl, C 1~6 Alkoxy or -C(O)-C 1~6 optionally substituted with alkoxy, C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 -OR optionally substituted with cycloalkyl e , (h)-C(O)-R e and R e is —NH2, —OH, or 3- to 15-membered heterocyclyl; —C(O)—R e , or (i)-S(O)2-R f and R f But C 1~6 alkyl or 3- to 15-membered heterocyclyl, -S(O)2-R f C 1~6 Alkyl (ii) C 3~10 Cycloalkyl, R 2 C 3~10 Cycloalkyl may be one or more R q and optionally substituted with R q is 5 to 20-membered heteroaryl or C 6~20 aryl, and R q C 6~20 The aryl may have one or more C 1~6 C optionally substituted with alkoxy 3~10 cycloalkyl, (iii) 3- to 15-membered heterocyclyl, where R 2The 3- to 15-membered heterocyclyl may be substituted with one or more halo, oxo, C 1~6 Alkyl, -C(O)-C 1~6 3- to 15-membered heterocyclyl optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iv) 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), 1~4 The alkyl group may contain one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 optionally substituted with -(C alkyl)2, 5-20 membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl) is one or more R s and optionally substituted with R s But, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 is an alkoxy, R s C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, and R s wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C 1~6 5-20 membered heteroaryl optionally substituted with alkoxy or -(C 1~4 alkyl)(5-20 membered heteroaryl), (v)-N(Rg )(R h ) and R g and R h are independently H or C 1~6 alkyl, -N(R g )(R h ), (vi)-C(O)-R j and R j But C 3~10 Cycloalkyl, -NH(C 1~6 alkyl), -N(C 1~6 -C(O)-R is -C(O)-R(alkyl), or -NH(5-20 membered heteroaryl); j ,and (vii)C 6~20 Aryl, R 2 C 6~20 Aryl is one or more 5- to 20-membered heteroaryl or -OR p and optionally substituted with R p is a 3- to 15-membered heterocyclyl, and R p 3-15 membered heterocyclyl is one or more -C(O)-C 1~6 C optionally substituted with alkyl 6~20 aryl, (G1-Z1) and (Z2-G2) are each independently substituted with a group attached to L.

[0109] In some embodiments of a compound of Formula (I), (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the group bonded to L comprises a carbon, oxygen, nitrogen, or sulfur atom. In some embodiments, the group bonded to L comprises a carbon atom. In some embodiments, the group bonded to L comprises an oxygen atom. In some embodiments, the group bonded to L comprises a nitrogen atom. In some embodiments, the group bonded to L comprises a sulfur atom.

[0110] In some embodiments of a compound of Formula (I), (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the group attached to L is at any available position of G1 or Z1, and at any available position of G2 or Z2. In some embodiments, the group attached to L is at any available position of R 2 or R n In some embodiments, the group attached to L is R 2 In some embodiments, the group attached to L is R n is located.

[0111] In some embodiments of a compound of Formula (I), (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the group attached to L comprises a reactive site suitable for attachment to L. In some embodiments, the group attached to L comprises a sulfhydryl group that forms a disulfide or thioether bond, an aldehyde group, a ketone group, and a hydrazine group that form a hydrazone bond, a carboxylic acid group and an amino group that form a peptide bond, a carboxylic acid group and a hydroxy group that form an ester bond, a sulfonic acid that forms a sulfonamide bond, an alcohol that forms a carbamate bond, and an amine that forms an amide, sulfonamide, or carbamate bond.

[0112] In some embodiments of a compound of Formula (I), (I-1), or (I-2), e.g., a compound of Formula (II), (III), (IV), or (V), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, G1 and G2 are each independently: [ka] or a moiety of formula (I-1) represented by [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R k , R m , R n , R 1 , X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , Y 3 , L 1 , and Q 1 is as defined for compounds of formula (I-1) or (I-2). In some embodiments, R k , R m , R n , R 1 , X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , Y 3 , L 1 , and Q 1 is as defined for a compound of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH) as defined elsewhere herein.

[0113] In some embodiments of a compound of Formula (I), (I-1), or (I-2), e.g., a compound of Formula (II), (III), (IV), or (V), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, G1 and G2 are each independently: [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. In some embodiments, G1 and G2 are each independently: [ka] It is a part of formula (I-2) represented by:

[0114] In some embodiments of a compound of Formula (I), (I-1) or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Z and Z are each independently: [ka] and R is a moiety of formula (I-1) or (I-2) represented by 2 and L 2 is as defined for compounds of formula (I-1) or (I-2). In some embodiments, R 2 and L 2 is as defined for a compound of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH) as defined elsewhere herein.

[0115] In some embodiments of a compound of Formula (I-1) or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -C(O)- or -S(O)2-, and R 2 is C 1~3 alkyl, C 1~3 Alkyl or R 2 is optionally substituted with one or more 3- to 10-membered heterocyclic rings, and the 3- to 10-membered heterocyclic rings are optionally substituted with one or more oxo, or C 1~3In some embodiments, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -C(O)- and R 2 is C 1~3 alkyl, C 1~3 Alkyl or R 2 is optionally substituted with one or more 3- to 10-membered heterocyclic rings, and the 3- to 10-membered heterocyclic rings are optionally substituted with one or more oxo, or C 1~3 In some embodiments, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -S(O)2- and R 2 is C 1~3 alkyl, C 1~3 Alkyl or R 2 is optionally substituted with one or more 3- to 10-membered heterocyclic rings, and the 3- to 10-membered heterocyclic rings are optionally substituted with one or more oxo, or C 1~3 It is further optionally substituted with alkyl.

[0116] In some embodiments of a compound of Formula (I-1) or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -C(O)- or -S(O)2-, and R 2 is C 1~3 In some embodiments, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -C(O)- and R 2 is C 1~3 In some embodiments, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -S(O)2- and R 2 is C 1~3 It is alkyl.

[0117] In some embodiments of a compound of Formula (I-1) or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Z and Z are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is —C(O)— or —S(O)—. In some embodiments, Z and Z are each independently [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 In some embodiments, Z1 and Z2 are each independently: [ka] and L is a moiety of formula (I-1) or (I-2) represented by 2 is -S(O)2-.

[0118] In some embodiments of the compounds of Formula (I-1) or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 2is —C(O)— or —S(O)—. In some embodiments, L 2 is —C(O)—. In some embodiments, L 2 is -S(O)2-.

[0119] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is a 5- to 20-membered heteroaryl; Q 1 The 5- to 20-membered heteroaryl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl is one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl or halo. 1 is a 5- to 6-membered heteroaryl, and Q 1 The 5- to 6-membered heteroaryl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl is one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl or halo. 1 is pyridinyl and Q 1 The pyridinyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10Cycloalkyl is one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl or halo. 1 is 2-pyridinyl or 3-pyridinyl, and Q 1 2-pyridinyl or 3-pyridinyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl is one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl or halo. 1 is 2-pyridinyl and Q 1 2-pyridinyl may be one or more halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl is one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl or halo. 1 is 2-pyridinyl and Q 1 2-pyridinyl may be one or more halo, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl is one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl or halo. 1 is 2-pyridinyl and Q 1wherein the 2-pyridinyl is optionally substituted with one or more fluoro, chloro, methyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, or methoxy, wherein the methyl is optionally substituted with one or more fluoro, and the cyclopropyl and cyclobutyl are independently optionally substituted with one or more methyl or fluoro.

[0120] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 teeth, [ka] is selected from the group consisting of:

[0121] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 teeth, [ka] is selected from the group consisting of:

[0122] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is phenyl and Q 1 The phenyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), or C 3~10 cycloalkyl-substituted, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, Q is optionally substituted with alkyl.1 is phenyl and Q 1 The phenyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, or C 3~10 cycloalkyl-substituted, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, Q is optionally substituted with alkyl. 1 is phenyl and Q 1 wherein the phenyl is substituted with one or more fluoro, chloro, methyl, isopropyl, sec-butyl, tert-butyl, prop-1-en-2-yl, cyclopropyl, or cyclobutyl, wherein the methyl, isopropyl, sec-butyl, and tert-butyl are independently optionally substituted with one or more halo, and the cyclopropyl and cyclobutyl are independently optionally substituted with one or more fluoro or methyl.

[0123] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is phenyl and Q 1 The phenyl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 substituted with cycloalkyl or 5-20 membered heteroaryl, C 1~6 Alkyl is one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, C 3~10 Cycloalkyl may be one or more halo or C 1~6 and the 5-20 membered heteroaryl is optionally substituted with one or more C1~6 Optionally substituted with alkyl.

[0124] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 teeth, [ka] is selected from the group consisting of:

[0125] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 teeth, [ka] In some embodiments of the compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q is selected from the group consisting of: 1 teeth, [ka] is selected from the group consisting of:

[0126] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is a 3- to 15-membered heterocyclyl, and Q 1 In some embodiments, Q is optionally substituted with one or more oxo. 1 teeth, [ka] is.

[0127] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 (i) 3- to 15-membered heterocyclyl, and Q 1 The 3- to 15-membered heterocyclyl is selected from one or more oxo, or C 1~6 (ii) a 3- to 15-membered heterocyclyl optionally substituted with alkyl; (iii) a 5- to 20-membered heteroaryl, wherein Q 1 wherein the 5-20 membered heteroaryl is one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 (iii) a 5- to 20-membered heteroaryl optionally substituted with alkyl; or (iv) C 3~10 It is cycloalkyl.

[0128] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is a 3- to 15-membered heterocyclyl, and Q 1 The 3- to 15-membered heterocyclyl may be one or more oxo, or C 1~6 In some embodiments, Q is optionally substituted with alkyl. 1 teeth, [ka] is selected from the group consisting of:

[0129] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is a 5- to 20-membered heteroaryl; Q 1The 5- to 20-membered heteroaryl may be one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, Q is optionally substituted with alkyl. 1 is a 5- to 20-membered heteroaryl; Q 1 The 5- to 20-membered heteroaryl may have one or more C 1~6 In some embodiments, Q is optionally substituted with alkyl. 1 is a 5- to 20-membered heteroaryl; Q 1 In some embodiments, Q is a 5- to 20-membered heteroaryl containing one or more ring N atoms. 1 is a 5- to 20-membered heteroaryl; Q 1 In some embodiments, the 5-20 membered heteroaryl of Q contains two ring Ns. 1 is a 5- to 20-membered heteroaryl; Q 1 The 5-20 membered heteroaryl of Q is monocyclic or bicyclic. 1 is a 5- to 20-membered heteroaryl; Q 1 In some embodiments, the 5- to 20-membered heteroaryl of Q is monocyclic. 1 is a 5- to 20-membered heteroaryl; Q 1 In some embodiments, the 5- to 20-membered heteroaryl of Q is bicyclic. 1 teeth, [ka] is selected from the group consisting of:

[0130] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Q 1 is C 3~10In some embodiments, Q is cycloalkyl. 1 is C 3~6 In some embodiments, Q is cycloalkyl. 1 is cyclopropyl.

[0131] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, L 1 is absent or is -CH-. In some embodiments, L 1 is absent. In some embodiments, L 1 is -CH-. In some embodiments, L 1 does not exist, and Q 1 is C 3~10 In some embodiments, L is cycloalkyl. 1 does not exist, and Q 1 is C 3~6 In some embodiments, L is cycloalkyl. 1 does not exist, and Q 1 is cyclopropyl. In some embodiments, L 1 is -CH2- and Q 1 is C 3~10 In some embodiments, L is cycloalkyl. 1 is -CH2- and Q 1 is C 3~6 In some embodiments, L is cycloalkyl. 1 is -CH2- and Q 1 is cyclopropyl.

[0132] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 , X 2 , X 3 , X 4 , and X 5 are each H.

[0133] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is H or C 1~6 In some embodiments, R 1 is H. In some embodiments, R 1 is C 1~3 In some embodiments, R 1 is methyl.

[0134] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H, halo, -OH, -NH2, or -NH-C(O)C 1~6 In some embodiments, R k is H. In some embodiments, R k is halo. In some embodiments, R k is F.

[0135] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R m is H, -OH, or C 1~6 In some embodiments, R m is H.

[0136] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R n is H, C 1~6 Alkyl, or C 3~10 In some embodiments, R n is H.

[0137] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R m is H and R n is H and R k is H, halo, -OH, -NH2, or -NH-C(O)C 1~6 In some embodiments, R m is H and R n is H and R k is halo, —OH, or —NH. In some embodiments, R m is H and R n is H and R k is halo. In some embodiments, R m is H and R n is H and R k is fluoro.

[0138] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is R m or R n together with the atom to which they are attached form cyclopropyl.

[0139] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R n together with the carbon atom to which it is attached, C 3~5 In some embodiments, R n together with the carbon atom to which it is attached form a cyclopropyl.

[0140] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is H.

[0141] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0142] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), C 1~4 Alkyl is one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R 2 is a 5- to 20-membered heteroaryl, and C 1~4 Alkyl is one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R 2 is (methyl)(5-20 membered heteroaryl), and the methyl is selected from one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R s Ha, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 In some embodiments, R s C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy; R s The 3- to 15-membered heterocyclyl may have one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0143] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments of the compounds of Formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth [ka] is.

[0144] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] is selected from the group consisting of:

[0145] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] [ka] In some embodiments, R 2 teeth [ka] is.

[0146] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c is optionally substituted with

[0147] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c and optionally substituted with R c is oxo, C 1~6 Alkyl, or -C(O)-C1~6 is alkoxy, and R c C 1~6 The alkyl is optionally substituted with one or more halo, and R c -C(O)-C 1~6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0148] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)-(3- to 15-membered heterocyclyl), and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0149] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(Rd ) and R c and R d One of the is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0150] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, and R 2 The ethyl group has one or more R a is substituted with R a -N(R c )(R d ) and R c and R d One of the is H and R c and R d The other is -C(O)-C 1~6 In some embodiments, R 2 teeth [ka] is.

[0151] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 and X 2 are each independently H, C 1~6 Alkyl, or C 1~6 In some embodiments, X is alkoxy. 1 and X 2 are each H.

[0152] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 3 and X 4 are each independently H, halo, C 1~6 Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; X 3 and X 4 C 1~6 The alkyl is optionally substituted with one or more halo.

[0153] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 5 is H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 In some embodiments, X is cycloalkyl. 5 is H, C 1~4 Alkyl, C 1~3 Alkoxy or C 3~6 In some embodiments, X is cycloalkyl. 5 is H. In some embodiments, X 5 is isopropyl, n-butyl, isobutyl, or t-butyl.

[0154] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 1 ~X 5 are H and Q 1 is one or more halo, C 1~6 Alkyl, -NH2, or C 3~10 5-20 membered heteroaryl optionally substituted with cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, X is optionally substituted with alkyl. 1~X 5 are H and Q 1 is one or more halo, C 1~6 Alkyl, -NH2, or C 3~10 5-6 membered heteroaryl optionally substituted with cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, X is optionally substituted with alkyl. 1 ~X 5 are H and Q 1 is one or more halo, C 1~6 Alkyl, -NH2, or C 3~10 pyridinyl optionally substituted with cycloalkyl, 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, X is optionally substituted with alkyl. 1 ~X 5 are H and Q 1 is one or more halo, C 1~4 Alkyl, -NH2, or C 3~4 pyridinyl optionally substituted with cycloalkyl, 3~4 Cycloalkyl may be one or more halo or C 1~6 In some of the foregoing embodiments, R m is H and R n is H. In some of the foregoing embodiments, R 1 is H.

[0155] In some embodiments of a compound of formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (I-2), X 1 ~X 5 are H and Q 1 is one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), or C 3~10phenyl substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, X is optionally substituted with alkyl. 1 ~X 5 are H and Q 1 is one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 10-membered heterocyclyl), or C 3~10 phenyl substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, X is optionally substituted with alkyl. 1 ~X 5 are H and Q 1 is one or more halo, C 1~4 Alkyl, C 2~4 Alkenyl, -NH2, -NH-C(O)-(C 1~4 alkyl), -NH-C(O)-(3- to 10-membered heterocyclyl), or C 3~4 phenyl substituted with cycloalkyl, C 1~4 The alkyl is optionally substituted with one or more halo, and C 3~4 Cycloalkyl may be one or more halo or C 1~6 Optionally substituted with alkyl.

[0156] In some embodiments of a compound of Formula (I-1), or (I-2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 1 is H. In some of the foregoing embodiments, R m is H and R n is H. In some of the foregoing embodiments, R k is R mor R n together with the atom to which they are attached form cyclopropyl.

[0157] In some embodiments of a compound of formula (I-1), or any embodiment or variation thereof, e.g., a compound of formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] R k , R m , R n , and R 1 Along with the formula [ka] wherein X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , Y 3 , R 1 , R k , R m , and R n is as defined elsewhere herein.

[0158] In some embodiments of a compound of formula (I-1), or any embodiment or variation thereof, e.g., a compound of formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] R k , R m , R n , and R 1 Along with the formula [ka] wherein R 1 and R m But both are H and X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , Y 3 , R k , and R n is as defined elsewhere herein.

[0159] In some embodiments of a compound of formula (I-1), or any embodiment or variation thereof, e.g., a compound of formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] R k , R m , R n , and R 1 Along with the formula [ka] wherein R 1 , R m , and R n are H and X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , Y 3 , and R k is as defined elsewhere herein.

[0160] In some embodiments of a compound of formula (I-1), or any embodiment or variation thereof, e.g., a compound of formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] R k , R m , R n , and R 1 Along with the formula [ka] wherein R 1 , R m , and R n are H and R k is halo or H, and X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , and Y 3 is as defined elsewhere herein. In some embodiments, the moiety R k is fluoro.

[0161] In some embodiments of a compound of formula (I-1), or any embodiment or variation thereof, e.g., a compound of formula (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, [ka] The part represented by is a part with carbon atoms. [ka] R k , R m , R n , and R 1 Along with the formula [ka] wherein R 1 , R m , and R n are H and R k But it is fluoro and X 1 , X 2 , X 3 , X 4 , X 5 , Y 2 , and Y 3is as defined elsewhere herein. In some embodiments, Y 2 and Y 3 and each is C. In some embodiments, one Y 2 and Y 3 is C and Y 2 and Y 3 The other of these is N.

[0162] As used herein, in some embodiments, the compound has the formula (IA): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, of formula (I-1), wherein Y 1 is CH or N, and R x and R z However, independently, H, halo, C 1~6 alkyl, or -NH2, and Y 1 If is CH, R x or R z C 1~6 The alkyl may be optionally substituted with one or more halo, and R y However, (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 Optionally substituted with alkyl.

[0163] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x and R z are independently H, fluoro, chloro, or methyl; R y is (i) isopropyl, (ii) isopropenyl, or (iii) C 3~4 is cycloalkyl, C3~4 The cycloalkyl is optionally substituted with one or more fluoro or methyl. In some embodiments, R x and R z are independently H, fluoro, chloro, or methyl; R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, C 3~4 The cycloalkyl is optionally substituted with one or more fluoro or methyl. In some embodiments, R x is H, fluoro, chloro, or methyl, and R z is H and R y is (i) isopropyl, or (ii) C 3~4 is cycloalkyl, C 3~4 The cycloalkyl is optionally substituted with one or more fluoro or methyl.

[0164] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is fluoro or methyl optionally substituted with one or more fluoro, and R y is (i) isopropyl, (ii) isopropenyl, or (iii) one or more halo or C 1~6 C optionally substituted with alkyl 3~4 cycloalkyl, or (iv) butyl, and R z is fluoro or methyl, with the proviso that R x and R z At least one of is halo, CF2, or CF3.

[0165] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or halo. In some embodiments of the compound of formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R kis H or fluoro. In some embodiments of the compound of formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0166] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0167] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), C 1~4 Alkyl is one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R s Ha, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 In some embodiments, R s C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C1~6 optionally substituted with alkoxy; R s The 3- to 15-membered heterocyclyl may have one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0168] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] [ka] In some embodiments, R 2 teeth [ka] is.

[0169] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c and optionally substituted with R c is oxo, C 1~6 Alkyl, or -C(O)-C 1~6 is alkoxy, and R c C 1~6 The alkyl is optionally substituted with one or more halo, and R c -C(O)-C 1~6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0170] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)-(3- to 15-membered heterocyclyl), and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0171] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0172] In some embodiments of the compound of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, and R 2 The ethyl group has one or more R a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-C 1~6 In some embodiments, R 2 teeth [ka] is.

[0173] In some embodiments of the compounds of Formula (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Y 1 is CH or N, and R x and R z are independently H or halo, and R y is C 1~6 Alkyl or C 3~10 is cycloalkyl, and R k is H or halo, and R 2 is selected from (i) to (iii): (I C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a but, (a) -OH, (b)C 6~20 Aryl, R a C 6~20The aryl may be one or more of halo, cyano, C 1~6 Alkoxy or -NH-C(O)-C 1~6 optionally substituted with alkyl; (c) 3- to 15-membered heterocyclyl, where R a 3-15 membered heterocyclyl is one or more R c and optionally substituted with R c But, halo, oxo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(O)-C 1~6 Alkyl or -C(O)-C 1~6 is an alkoxy, R c C 1~6 The alkyl may be one or more halo or C 2~6 optionally substituted with alkynyl, and R c -C(O)-C 1~6 the alkoxy is optionally substituted with one or more halo; (d)-N(R c )(R d ) and -N(R c )(R d )R c and R d However, independently of each other, H, C 1~6 Alkyl, -C(O)-C 1~6 Alkyl, -C(O)-C 1~6 Alkoxy, -C(O)-NH2, -C(O)-NH(C 1~6 alkyl), -C(O)-N(C 1~6 alkyl), -C(O)-(3- to 15-membered heterocyclyl), -CH-C(O)-NH, 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R c or R d C 1~6 the alkyl is optionally substituted with one or more -C(O)-NH; R c or R d -C(O)-C 1~6the alkyl is optionally substituted with one or more halo; R c or R d The 3- to 15-membered heterocyclyl and the 5- to 20-membered heteroaryl are independently one or more C 1~6 optionally substituted with alkyl; R c or R d -C(O)-(3 to 15-membered heterocyclyl) is one or more halo, -C(O)-C 1~6 Alkoxy or C 1~6 optionally substituted with alkyl, C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 optionally substituted with cycloalkyl, and R c or R d -C(O)-N(C 1~6 C of alkyl)2 1~6 The alkyl may, independently of each other, be one or more halo or C 6~20 optionally substituted with aryl; (e)-OR e and R e But C 1~6 Alkyl, C 6~20 Aryl, -C(O)-(3- to 15-membered heterocyclyl), -C(O)-N-(C 1~6 alkyl) 2- or 5- to 20-membered heteroaryl; R e C 1~6 Alkyl is one or more C 1~6 optionally substituted with alkoxy, C 1~6 Alkoxy is one or more C 2~6 optionally substituted with alkynyl; R e C 6~20 The aryl may have one or more C 1~6 optionally substituted with alkyl, and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 Alkyl, C1~6 Alkoxy or -C(O)-C 1~6 optionally substituted with alkoxy, C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 optionally substituted with cycloalkyl; (f)-C(O)-R e and -C(O)-R e R e is —NH2, —OH, or 3- to 15-membered heterocyclyl; (ii) 3- to 15-membered heterocyclyl, where R 2 The 3- to 15-membered heterocyclyl may be substituted with one or more halo, oxo, C 1~6 Alkyl, -C(O)-C 1~6 optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iii) 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), 1~4 The alkyl group may contain one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5-20 membered heteroaryl is optionally substituted with one or more R s and optionally substituted with R s But, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 is an alkoxy, R s C 1~6 The alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, and R s wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0174] In some embodiments of formula (IA), Y 1 is CH or N, and R x and R z are independently H or halo, and R y is C 1~6 Alkyl or C 3~10 is cycloalkyl, and R k is H or halo, and R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a teeth, (a) -OH, (b) one or more halo, cyano, C 1~3 Alkoxy or -NH-C(O)-C 1~3 C optionally substituted with alkyl 6~10 aryl, or (c) one or more halo, oxo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(O)-C 1~6 Alkyl or -C(O)-C 1~6 3-15 membered heterocyclyl optionally substituted with alkoxy.

[0175] In some embodiments of formula (IA), Y 1 is CH or N, and R x and R z are independently H or halo, and R y is C 1~3 Alkyl or C 3~5 is cycloalkyl, and R k is the halo and R2 is one or more R a C is replaced by 1~4 alkyl, and R a teeth, (a) -OH, (b) one or more halo, cyano, C 1~3 Alkoxy or -NH-C(O)-C 1~3 C optionally substituted with alkyl 6~10 aryl, or (c) one or more halo, oxo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(O)-C 1~6 Alkyl or -C(O)-C 1~6 C optionally substituted with alkoxy 3~8 Heteroaryl.

[0176] As used herein, in some embodiments, the compound has the formula (I-A1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R x and R z However, independently, H, halo, C 1~6 alkyl, or -NH2, C 1~6 The alkyl is optionally substituted with one or more halo. In some embodiments, R x is H, halo, or C 1~6 alkyl, and R y is (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, and R z is H, halo, or C 1~6 In some embodiments, R z is H. In some embodiments, R x and Rz At least one of them is a halo.

[0177] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is fluoro or methyl, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, and R z is fluoro or methyl, with the proviso that R x and R z At least one of them is a halo.

[0178] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is fluoro or methyl optionally substituted with one or more fluoro, and R y is (i) isopropyl, (ii) one or more halo or C 1~6 C optionally substituted with alkyl 3~4 cycloalkyl, or (iii) butyl, and R z is fluoro or methyl, with the proviso that R x and R z At least one of is halo, CF2, or CF3.

[0179] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or halo. In some embodiments of the compounds of formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or fluoro. In some embodiments of the compounds of formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0180] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in ais substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0181] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), C 1~4 Alkyl is one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R s Ha, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 In some embodiments, R s C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy; R s The 3- to 15-membered heterocyclyl may have one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0182] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0183] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c and optionally substituted with R c is oxo, C 1~6 Alkyl, or -C(O)-C 1~6 is alkoxy, and R c C 1~6 The alkyl is optionally substituted with one or more halo, and R c -C(O)-C 1~6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 2 teeth, [ka] is.

[0184] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl ina is substituted with R a HA-OR e and R e is —C(O)-(3- to 15-membered heterocyclyl), and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 In some embodiments, R 2 teeth, [ka] is.

[0185] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 In some embodiments, R 2 teeth, [ka] is.

[0186] In some embodiments of the compound of Formula (I-A1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, and R 2 The ethyl group has one or more Ra is substituted with R a -N(R c )(R d ) and R c and R d One of the is H and R c and R d The other is -C(O)-C 1~6 In some embodiments, R 2 teeth [ka] is.

[0187] In some embodiments, the compound has formula (I-A2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R x But, H, Halo, C 1~6 alkyl, or -NH2, C 1~6 alkyl is optionally substituted with one or more halo, and R y However, (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 In some embodiments, R x is H, halo, or C 1~6 alkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and R y is (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10Cycloalkyl may be one or more halo or C 1~6 In some embodiments, R x is H, halo, or C 1~6 alkyl, and R y is (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 Optionally substituted with alkyl.

[0188] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is H, fluoro, chloro, or methyl, where methyl is optionally substituted with one or more fluoro; R y is (i) isopropyl, (ii) isopropenyl, (iii) sec-butyl, (iv) tert-butyl, or (v) C 3~4 is cycloalkyl, C 3~4 The cycloalkyl is optionally substituted with one or more fluoro or methyl.

[0189] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is fluoro or methyl optionally substituted with one or more fluoro, and R y is (i) isopropyl, (ii) one or more halo or C 1~6 C optionally substituted with alkyl 3~4 cycloalkyl, or (iii) butyl.

[0190] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R kis H or halo. In some embodiments of the compound of formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or fluoro. In some embodiments of the compound of formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0191] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0192] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 Ha-(C 1~4 alkyl)(5-20 membered heteroaryl), C 1~4 The alkyl is optionally substituted with one or more —OH, and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R s Ha, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 In some embodiments, R s C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy; R s The 3- to 15-membered heterocyclyl may have one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0193] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0194] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c and optionally substituted with R c is oxo, C 1~6 Alkyl, or -C(O)-C 1~6 is alkoxy, and R c C 1~6 The alkyl is optionally substituted with one or more halo, and R c -C(O)-C 1~6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0195] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)-(3- to 15-membered heterocyclyl), and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0196] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0197] In some embodiments of the compound of Formula (I-A2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is ethyl, and R 2 The ethyl group has one or more R a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-C 1~6 In some embodiments, R 2 teeth [ka] is.

[0198] As used herein, in some embodiments, the compound has the formula (I-A3): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R x But, H, Halo, C 1~6 alkyl, or -NH2, C 1~6 alkyl is optionally substituted with one or more halo, and R y However, (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 In some embodiments, R x H, halo, C1~6 alkyl, or -NH2, and R y is (i)C 1~6 alkyl or (ii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 Optionally substituted with alkyl.

[0199] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R x is H, fluoro, or methyl, and R y is (i) H, (ii) isopropyl, (iii) tert-butyl, or (iv) C 3~4 is cycloalkyl, C 3~4 The cycloalkyl is optionally substituted with one or more fluoro or methyl. In some embodiments, R x is H, fluoro, or methyl, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, C 3~4 The cycloalkyl is optionally substituted with one or more fluoro or methyl.

[0200] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or halo. In some embodiments of the compound of formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or fluoro. In some embodiments of the compound of formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0201] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R awherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0202] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 Ha-(C 1~4 alkyl)(5-20 membered heteroaryl), wherein the 5-20 membered heteroaryl is selected from one or more R s In some embodiments, R s Ha, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 In some embodiments, R s C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy; R s The 3- to 15-membered heterocyclyl may have one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0203] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] is.

[0204] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, in some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c and optionally substituted with R c is oxo, C 1~6 Alkyl, or -C(O)-C 1~6 is alkoxy, and R c C 1~6 The alkyl is optionally substituted with one or more halo, and R c -C(O)-C 1~6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 2 teeth, [ka] is.

[0205] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6Alkyl is one or more R a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)—(3- to 15-membered heterocyclyl). In some embodiments, R 2 teeth [ka] is.

[0206] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 alkyl)2, or —C(O)—(3- to 15-membered heterocyclyl), and R c or R d -C(O)-(3 to 15-membered heterocyclyl) is one or more halo, -C(O)-C 1~6 Alkoxy or C 1~6 optionally substituted with alkyl, R c or R d -C(O)-N(C1~6 C of alkyl)2 1~6 The alkyl may, independently of each other, be one or more halo or C 6~20 In some embodiments, R 2 teeth, [ka] is.

[0207] In some embodiments of the compound of Formula (I-A3), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d the other is a 5- to 20-membered heteroaryl, and R c or R d The 5- to 20-membered heteroaryl may independently comprise one or more C 1~6 In some embodiments, R 2 teeth [ka] is.

[0208] As used herein, in some embodiments, the compound is represented by formula (I-A4): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R z But, H, Halo, C 1~6alkyl, or -NH2, and R y However, (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 In some embodiments, R z is H, halo, or C 1~6 alkyl, and R y is (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments, R z is H or C 1~6 alkyl, and R y is (i)C 1~6 alkyl or (ii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 In some embodiments of the compounds of formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R z is H or methyl, and R y is (i) isopropyl, or (ii) C 3~4 It is cycloalkyl.

[0209] In some embodiments of the compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or halo. In some embodiments of the compound of formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R kis H or fluoro. In some embodiments of the compound of formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0210] In some embodiments of the compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0211] In some embodiments of the compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0212] In some embodiments of the compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 15-membered heterocyclyl, and R aThe 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more oxo or C 1~6 In some embodiments, R 2 teeth [ka] is.

[0213] In some embodiments of the compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R eis —C(O)—(3- to 15-membered heterocyclyl). In some embodiments, R 2 teeth [ka] is.

[0214] In some embodiments of the compound of Formula (I-A4), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-N(C 1~6 In some embodiments, R 2 teeth [ka] is.

[0215] As used herein, in some embodiments, the compound has the formula (IB): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein Y 1 But, CR x or N and R x , and R y If the ring carrying R x , and R y are each independently H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 cycloalkyl, or 5- to 20-membered heteroaryl, C 1~6 The alkyl may be one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 and 5-20 membered heteroaryl optionally substituted with alkyl, and 1~6 optionally substituted with alkyl, R x , and R y If the ring carrying R x , and R y are each independently H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 is cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 Optionally substituted with alkyl.

[0216] In some embodiments of the compound of formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, Y 1 is CH or N, and R x H, halo, C 1~6 alkyl, or NH2, and Y 1 If is CH, R x C 1~6 The alkyl may be optionally substituted with one or more halo, R y However, (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 In some embodiments, Y is optionally substituted with alkyl. 1 is CH or N, and R x is H or halo, and R y is C 1~6 Alkyl or C 3~10 is cycloalkyl, and R k is R m or R n and together with the atom to which they are attached form cyclopropyl. 1 is CH or N, and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, and R k is R m or R n and together with the atom to which they are attached form cyclopropyl. 1 is CH or N, and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, and R k is R mand together with the atom to which they are attached form cyclopropyl. 1 is CH or N, and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, and R k is R n and together with the atom to which they are attached form cyclopropyl. 1 is CH and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, and R k is R n or R n and together with the atom to which they are attached form cyclopropyl. 1 is N and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 is cycloalkyl, and R k is R n or R n together with the atom to which they are attached form a cyclopropyl.

[0217] In some embodiments of the compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R aThe 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0218] In some embodiments of the compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R2 teeth [ka] is.

[0219] In some embodiments of the compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more oxo or C 1~6 In some embodiments, R 2 teeth [ka] is.

[0220] In some embodiments of the compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)—(3- to 15-membered heterocyclyl). In some embodiments, R 2 teeth [ka] is.

[0221] In some embodiments of the compound of Formula (IB), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c)(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-N(C 1~6 In some embodiments, R 2 teeth [ka] is.

[0222] As used herein, in some embodiments, the compound is represented by formula (I-B1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein Y 1 But, CR x or N and R x , and R y If the ring carrying R x , and R y are each independently H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 cycloalkyl, or 5- to 20-membered heteroaryl, C 1~6 The alkyl may be one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 and 5-20 membered heteroaryl optionally substituted with alkyl, and 1~6 optionally substituted with alkyl, R x , and R y If the ring carrying R x , and R y are each independently H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 is cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 In some embodiments, Y is optionally substituted with alkyl. 1 is CH or N, and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 In some embodiments, Y is cycloalkyl. 1 is CH and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 In some embodiments, Y is cycloalkyl. 1 is N and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 It is cycloalkyl.

[0223] In some embodiments of the compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R aIn some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0224] In some embodiments of the compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0225] In some embodiments of the compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with Ra is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more oxo or C 1~6 In some embodiments, R 2 teeth [ka] is.

[0226] In some embodiments of the compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)—(3- to 15-membered heterocyclyl). In some embodiments, R 2 teeth [ka] is.

[0227] In some embodiments of the compound of Formula (I-B1), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more Ra is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the is H and R c and R d The other is -C(O)-N(C 1~6 In some embodiments, R 2 teeth [ka] is.

[0228] As used herein, in some embodiments, the compound is represented by formula (I-B2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein Y 1 But, CR x or N and R x , and R y If the ring carrying R x , and R y are each independently H, halo, C 1~6 Alkyl, C 2~6Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 cycloalkyl, or 5- to 20-membered heteroaryl, C 1~6 The alkyl may be one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 and 5-20 membered heteroaryl optionally substituted with alkyl, and 1~6 optionally substituted with alkyl, R x , and R y If the ring carrying R x , and R y are each independently H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 is cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 In some embodiments, Y is optionally substituted with alkyl. 1 is CH or N, and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 In some embodiments, Y is cycloalkyl. 1 is CH and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 In some embodiments, Y is cycloalkyl. 1 is N and R x is H or fluoro, and R y is (i) isopropyl or (ii) C 3~4 It is cycloalkyl.

[0229] In some embodiments of the compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0230] In some embodiments of the compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0231] In some embodiments of the compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 15-membered heterocyclyl, and R a The 3- to 15-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in ais substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more oxo or C 1~6 In some embodiments, R 2 teeth [ka] is.

[0232] In some embodiments of the compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)—(3- to 15-membered heterocyclyl). In some embodiments, R 2 teeth [ka] is.

[0233] In some embodiments of the compound of Formula (I-B2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-N(C 1~6 In some embodiments, R 2 teeth [ka] is.

[0234] As used herein, in some embodiments, the compound has the formula (IC): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein X 5 But H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 is cycloalkyl, and X 4 But, H, Halo, C 1~6 Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; R v -NH2, -NH-C(O)-(C 1~6 alkyl), or —NH—C(O)—(3- to 15-membered heterocyclyl), and R w H, -NH2, -NH-C(O)-(C 1~6 In some embodiments, X is —NH—C(O)—(3- to 15-membered heterocyclyl). 5 is H or C 1~6 is alkyl, and X 4 is H and R v -NH2, -NH-C(O)-(C 1~6 alkyl), or —NH—C(O)—(3- to 15-membered heterocyclyl), and R w are H, -NH2, -NH-C(O)-(C 1~6 In some embodiments, R w is H and R v is -NH-C(O)C 1~6 In some embodiments, R w is H and R v is -NH-C(O)CH3.

[0235] In some embodiments, the compound has the formula (ID): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein X 5 But H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 is cycloalkyl, and X 4 But, H, Halo, C 1~6 Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; R t and R u However, independently, H, C 1~6 In some embodiments, X is alkoxy, or -NH. 5 is C 1~6 is alkyl, and X 4 is H, halo, or C 1~6 alkyl, and R t and R u is independently H or —NH. In some embodiments, R t and R u In some embodiments, at least one of R t is H and R u is -NH. In some embodiments, R t is -NH2 and R u is H.

[0236] In some embodiments of a compound of Formula (IC) or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or halo. In some embodiments of a compound of Formula (IC) or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or fluoro. In some embodiments of a compound of Formula (IC) or (ID), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R kis fluoro.

[0237] In some embodiments, the compound has the formula (I-D1): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein X 5 But H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 is cycloalkyl, and X 4 But, H, Halo, C 1~6 Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; R t and R u However, independently, H, C 1~6 In some embodiments, X is alkoxy, or -NH. 5 is C 1~6 is alkyl, and X 4 is H, halo, or C 1~6 alkyl, and R u and R z is independently H, halo, or -NH. In some embodiments, R u and R z In some embodiments, at least one of R u is H and R z is -NH. In some embodiments, R u is -NH2 and R z is H. In some embodiments, R u and R z In some embodiments, at least one of R u is H and R z is fluoro. In some embodiments, R u is fluoro and R z is H.

[0238] In some embodiments, the compound has formula (I-D2): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein X 5 But H, C 1~6 Alkyl, C 1~6 Alkoxy or C 3~10 is cycloalkyl, and X 4 But, H, Halo, C 1~6 Alkyl, C 1~6 alkoxy, or 5- to 20-membered heteroaryl; X 4 C 1~6 alkyl is optionally substituted with one or more halo, and R t and R u However, independently, H, C 1~6 In some embodiments, X is alkoxy, or -NH. 5 is C 1~6 is alkyl, and X 4 is H, halo, or C 1~6 alkyl, and R u and R z is independently H, halo, or -NH. In some embodiments, R u and R z In some embodiments, at least one of R u is H and R z is -NH. In some embodiments, R u is -NH2 and R z is H. In some embodiments, R u and R z In some embodiments, at least one of R u is H and R z is fluoro. In some embodiments, R u is fluoro and R z is H.

[0239] In some embodiments, the compound has the formula (IE): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein R k and R m are independently H, OH, —NH, or —NH—C(O)C 1~6 In some embodiments, R k is H and R m is H, OH, -NH2, or -NH-C(O)C 1~6 In some embodiments, R k is H and R m is OH. In some embodiments, R k is H, OH, -NH2, or -NH-C(O)C 1~6 alkyl, and R m is H. In some embodiments, R k is OH, -NH2, or -NH-C(O)C 1~6 alkyl, and R m is H. In some embodiments, R k is OH, -NH2, or -NH-C(O)CH3, and R m is H.

[0240] In some embodiments, the compound has the formula (IF): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation or embodiment thereof, wherein Y 1 is CH or N, and R x But, H, Halo, C 1~6 alkyl, or -NH2, and Y1 If is CH, R x C 1~6 The alkyl may be optionally substituted with one or more halo, and R y However, (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 optionally substituted with alkyl, R k is H, halo, -OH, -NH2, or -NH-C(O)C 1~6 alkyl, and R n But H, C 1~6 Alkyl, or C 3~10 In some embodiments, Y is cycloalkyl. 1 is CH or N, and R x is H, halo, or C 1~6 alkyl, and R y is (i)C 1~6 alkyl, or (ii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 optionally substituted with alkyl, R k is H, halo, -OH, -NH2, or -NH-C(O)C 1~6 alkyl, and R n is H, C 1~6 Alkyl, or C 3~10 It is cycloalkyl.

[0241] In some embodiments of the compound of Formula (IF), Y 1 is CH or N, and R x is H, halo, or C 1~6 alkyl, and R y is (i)C 1~6 alkyl, (ii) C 2~6 alkenyl, or (iii) C 3~10 is cycloalkyl, C 3~10 Cycloalkyl may be one or more halo or C 1~6 optionally substituted with alkyl, Rk is H or halo, and R n is H, C 1~6 Alkyl, or C 3~6 In some embodiments, Y is cycloalkyl. 1 is N or CH, and R x is H or halo, and R y is C 1~6 Alkyl or C 3~6 is cycloalkyl, and R k is H or halo, and R n is C 1~6 Alkyl or C 3~6 In some embodiments, Y is cycloalkyl. 1 is N or CH, and R x is H or fluoro, and R y is C 1~6 Alkyl or C 3~6 is cycloalkyl, and R k is H or fluoro, and R n is C 1~6 Alkyl or C 3~6 In some embodiments, Y is cycloalkyl. 1 is N or CH, and R x is H or fluoro, and R y is C 1~6 Alkyl or C 3~6 is cycloalkyl, and R k is H or fluoro, and R n is C 1~6 Alkyl or C 3~6 In some embodiments, Y is cycloalkyl. 1 is N or CH, and R x is H or fluoro, and R y is C 1~6 Alkyl or C 3~6 is cycloalkyl, and R k is H and R n is C 1~6 Alkyl or C 3~6 In some embodiments, Y is cycloalkyl. 1 is N or CH, and R x is H or fluoro, and Ry is C 1~3 Alkyl or C 3~6 is cycloalkyl, and R k is H and R n is C 1~3 Alkyl or C 3~6 It is cycloalkyl.

[0242] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a is substituted with R a is —OH or 5- to 20-membered heteroaryl, and R a The 5- to 20-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more R b In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a The 5- to 10-membered heteroaryl may have one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, -NH 2、 -NH(C1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 In some embodiments, R 2 is methyl and R 2 The methyl in a is substituted with R a is —OH or 5-10 membered heteroaryl, and R a wherein the 5-10 membered heteroaryl is optionally substituted with one or more methyl, which is optionally substituted with one or more fluoro.

[0243] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0244] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] is selected from the group consisting of:

[0245] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] In some embodiments, R 2 teeth [ka] is.

[0246] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] is.

[0247] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a is a 3- to 8-membered heterocyclyl, and R a The 3- to 8-membered heterocyclyl may have one or more R c and optionally substituted with R c is oxo, C 1~6 Alkyl, or -C(O)-C 1~6 is alkoxy, and R c C 1~6 The alkyl is optionally substituted with one or more halo, and R c -C(O)-C 1~6 The alkoxy is optionally substituted with one or more halo. In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0248] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a HA-OR e and R e is —C(O)-(3- to 15-membered heterocyclyl), and R e -C(O)-(3- to 15-membered heterocyclyl) is one or more C 1~6 optionally substituted with alkyl, C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy or C 3~10 In some embodiments, R 2 teeth, [ka] is selected from the group consisting of:

[0249] In some embodiments of a compound of Formula (IC), (ID), (IE), or (IF), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 In some embodiments, R 2 teeth, [ka] is.

[0250] As used herein, in some embodiments, the compound has the formula (IG): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein ring A is (i) a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of ring A is optionally substituted with one or more oxo, (ii) a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of ring A is optionally substituted with one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 (iii) a 5- to 20-membered heteroaryl optionally substituted with alkyl; or (iv) C 3~10 It is cycloalkyl.

[0251] In some embodiments of the compound of formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, X 3 is H, fluoro, or methyl optionally substituted with one or more fluoro; and X 4 is (i) isopropyl, (ii) one or more halo or C 1~6 C optionally substituted with alkyl 3~4 cycloalkyl, or (iii) butyl, and R z is fluoro or methyl, provided that X 3 and X 4 At least one of is halo, CF2, or CF3.

[0252] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or halo. In some embodiments of the compound of formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is H or fluoro. In some embodiments of the compound of formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R k is fluoro.

[0253] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is a 5- to 20-membered heteroaryl or -(C 1~4 alkyl)(5-20 membered heteroaryl), C 1~4 Alkyl is one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R s Ha, Halo, C 1~6 Alkyl, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6 alkyl)2, -NH-C(O)-C 1~6 Alkyl, C 6~20 Aryl, C 3~10 Cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C 1~6 In some embodiments, R s C 1~6 Alkyl may contain one or more halo, C 1~6 Alkoxy, -NH2, -NH(C 1~6 alkyl), -N(C 1~6alkyl)2, -NH-C(O)C 1~6 Alkyl, or -NH-C(O)-C 1~6 optionally substituted with alkoxy; R s The 3- to 15-membered heterocyclyl may have one or more halo or —C(O)—C 1~6 Optionally substituted with alkoxy.

[0254] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 teeth, [ka] is selected from the group consisting of:

[0255] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, R 2 is methyl and R 2 The methyl in a is substituted with R a -N(R c )(R d ) and R c and R d One of the groups is H and R c and R d The other is -C(O)-C 1~6 Alkyl, -C(O)-N(C 1~6 In some embodiments, R 2 teeth [ka] is.

[0256] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is (i) a 3- to 15-membered heterocyclyl, wherein the 3- to 15-membered heterocyclyl of ring A is selected from the group consisting of one or more oxo, or C1~6 (ii) a 5- to 20-membered heteroaryl, wherein the 5- to 20-membered heteroaryl of ring A is optionally substituted with one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 optionally substituted with alkyl; or (iii) C 3~10 It is cycloalkyl.

[0257] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 3- to 15-membered heterocyclyl, and the 3- to 15-membered heterocyclyl of ring A is selected from the group consisting of one or more oxo, or C 1~6 In some embodiments, ring A is optionally substituted with alkyl. [ka] is selected from the group consisting of:

[0258] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of ring A is selected from the group consisting of one or more halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 optionally substituted with cycloalkyl, C 1~6 The alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may be one or more halo or C 1~6In some embodiments, Ring A is a 5-20 membered heteroaryl, and the 5-20 membered heteroaryl of Ring A is optionally substituted with one or more C 1~6 In some embodiments, ring A is optionally substituted with alkyl. [ka] is selected from the group consisting of:

[0259] In some embodiments of the compound of Formula (IG), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, ring A is C 3~10 In some embodiments, ring A is C 3~6 In some embodiments, Ring A is cyclopropyl.

[0260] As used herein, in some embodiments, the compound has the formula (IH): [ka] or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y 1 But, CR x or N and R x , R y and R z If the ring carrying R x , R y and R z But, H, Halo, C 1~6 Alkyl, C 2~6 Alkenyl, -NH2, -NH-C(O)-(C 1~6 alkyl), -NH-C(O)-(3- to 15-membered heterocyclyl), C 3~10 cycloalkyl, or 5- to 20-membered heteroaryl, C 1~6 The alkyl may be one or more halo, -NH-C(O)-NH(C 1~6 alkyl), -NH-C(O)-C 1~6 Alkyl, or -NH-C(O)-C1~6 optionally substituted with alkoxy, C 3~10 Cycloalkyl may contain one or more halo or C 1~6 and 5-20 membered heteroaryl optionally substituted with alkyl, and 1~6 optionally substituted with alkyl, R x , R y and R z If the ring carrying R x , R y and R z are each independently H, halo, C 1~6 Alkyl, C 2~6 Alkenyl, C 1~6 Alkoxy, -NH2, or C 3~10 is cycloalkyl, C 1~6 alkyl is optionally substituted with one or more halo, and C 3~10 Cycloalkyl may contain one or more halo or C 1~6 Optionally substituted with alkyl.

[0261] Provided herein in some embodiments are compounds of formula (I-1), e.g., compounds of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (IB), (I-B1), (I-B2), (IC), (ID), (I-D1), (I-D2), (IE), (IF), (IG), or (IH), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 2 is C 1~6 alkyl, and R 2 C 1~6 Alkyl is one or more R a In some embodiments, R 2 is C 3~10 is cycloalkyl, and R 2 C 3~10 Cycloalkyl can be one or more R q In other embodiments, R 2 is a 3- to 15-membered heterocyclyl, and R 2The 3- to 15-membered heterocyclyl may be one or more halo, oxo, C 1~6 Alkyl, -C(O)-C 1~6 In some embodiments, R 2 is a 5- to 20-membered heteroaryl, or -(C 1~4 alkyl)(5-20 membered heteroaryl), C 1~4 Alkyl is one or more of -OH, halo, -NH, -NH(C 1~6 alkyl), -N(C 1~6 and the 5- to 20-membered heteroaryl is optionally substituted with one or more R s In some embodiments, R 2 -N(R g )(R h ) and R g and R h are independently H or C 1~6 In some embodiments, R 2 -C(O)-R j and R j is C 3~10 Cycloalkyl, -NH(C 1~6 alkyl), -N(C 1~6 In some embodiments, R 2 is C 6~20 aryl, and R 2 C 6~20 Aryl is one or more 5- to 20-membered heteroaryl or —O(R p ), optionally substituted with R p is a 3- to 15-membered heterocyclyl, and R p The 3- to 15-membered heterocyclyl may have one or more -C(O)-C 1~6 Optionally substituted with alkyl.

[0262] In some embodiments of a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, (G1-Z1) and (G2-Z2) are each independently a moiety selected from Table 1A. In some embodiments, the (G1-Z1) and (G2-Z2) moieties selected from Table 1A are each independently substituted with a group attached to L. In some embodiments, the (G1-Z1) and (G2-Z2) moieties selected from Table 1A are each independently attached to L. In some embodiments, L is attached at any available position. In some embodiments, L is selected from R 2 In some embodiments, L is linked through a group corresponding to R n is bonded through a group corresponding to

[0263] Compound names contained in Table 1A and for all intermediates and compounds were generated using ChemDraw® Professional software version 17.1.1.0 or Collaborative Drug Discovery Inc. (CDD) CDD Vault update#3.

[0264] A KNIME workflow was created to retrieve structures from the internal ChemAxon Compound Registry, generate canonical smiles using the RDKit Canon SMILES node, remove stereochemistry using the ChemAxon / Infocom MolConverter node, and name the structures using the ChemAxon / Infocom Naming node. The following shows the versions of the KNIME Analytics Platform and extensions used in the workflow: ·Knime Analytics Platform 4.2.2 RDKit KNIME Integration 4.0.1.v202006261025 (This extension includes the RDKit Canon SMILES node) ChemAxon / Infocom Marvin Extensions Feature 4.3.0v202100 (This extension includes the MolConverter node) ChemAxon / Infocom JChem Extensions Feature 4.3.0v202100 (This extension includes the Naming node) [Table 1] [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] [Table 9] [Table 10] [Table 11] [Table 12] [Table 13] [Table 14] [Table 15] Table 16

Table 17

Table 18

Table 19

Table 33

Table 91

Table 93

Table 99

Table 100

[0265] Provided herein, in some embodiments, is a compound of Formula (I), or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (G2-Z2) are each independently a moiety selected from the group consisting of: 1-Cyclopropanecarbonyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-hydroxy-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-3-hydroxy-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-(3-carbamoyl-2-acetamidopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; tert-Butyl N-{2-oxo-2-[2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]ethyl}carbamate; 1-(2-hydroxyacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetamidoacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-(3-carbamoylpropanoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(5-cyclopropylpyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 2-acetyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-2-azabicyclo[3.1.0]hexane-3-carboxamide; 1-{2-[N-(carbamoylmethyl)acetamido]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-5-methyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1,3-oxazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(4H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(3-methyloxetan-3-yl)amino]acetyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-acetamido-5-[4-fluoro-2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-5-oxopentanoic acid; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-(3-acetamidopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxopyrrolidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,3-oxazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetamidobutanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 2-acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide; 3-acetyl-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-3-azabicyclo[3.1.0]hexane-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(oxetan-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-oxomorpholin-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-5-methylpyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-oxomorpholin-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-4H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[3-(1,3-oxazol-2-yl)propanoyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,2-oxazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(1,3-oxazol-2-yl)amino]acetyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2-oxoimidazolidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,4-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridazin-3-yloxy)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(1-methyl-5-oxopyrrolidine-2-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2-chloro-5-fluorophenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[4-(pyridin-3-yl)butanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-oxo-octahydroindolizine-6-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-oxopiperidine-4-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2-cyano-4-methoxyphenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-(1H-imidazol-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrimidin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(4-methylpyrimidine-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyridin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[3-(3,5-dimethyl-1,2-oxazol-4-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-fluoro-4-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(1,3-oxazole-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[4-(pyridin-4-yl)butanoyl]pyrrolidine-2-carboxamide; 1-[(dimethylcarbamoyl)carbonyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-imidazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-1-[2-methyl-3-(1H-1,2,4-triazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-fluoropyridin-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1H-indol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-acetamidophenyl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-imidazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyridin-3-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1,5-dimethyl-1H-pyrazol-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(2-methylpyridin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrimidin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyrazin-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2H-1,2,3-triazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-[3-(2,6-dimethylpyridin-3-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yloxy)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-5-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(5-methyl-1,3,4-thiadiazol-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[3-(3,5-dimethyl-1H-pyrazol-1-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(3-cyanopropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-indol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(5-methylpyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-ethyl-1,3-oxazole-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methyl-1,3-thiazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-3-(1H-pyrazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-indol-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-3-(pyridin-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-fluoro-1H-indol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{4-oxo-4H,5H,6H,7H,8H-pyrazolo[1,5-a][1,4]diazepine-2-carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-{2-[5-(propan-2-yl)-1,2,4-oxadiazol-3-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(6-oxopiperidine-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyrrolidine-1-sulfonyl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1,2-benzoxazol-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(2-{[1,2,4]triazolo[1,5-a]pyridin-6-yl}acetyl)pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(3-methoxypyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-imidazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-1,2-oxazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-pyrazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,3-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methylphenoxy)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1,2-oxazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-methyloxetane-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-chloro-1H-pyrazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-ethyl-1H-pyrazole-5-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyrimidin-5-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-methoxy-1-methyl-1H-pyrazole-4-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-pyrazol-4-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1,3-thiazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-(2-methyl-1H-imidazol-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(pyridin-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1,2,4-oxadiazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(6-methylpyridin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(3-{1H-pyrrolo[2,3-b]pyridin-3-yl}propanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-oxo-1,3-oxazolidine-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-1H-pyrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1-methyl-1H-pyrazol-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,4-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[5-(pyridin-4-yl)-1H-pyrazole-3-carbonyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(2-methylpyridin-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-hydroxy-3-methylbutanoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-(3-{1H-pyrrolo[2,3-b]pyridin-5-yl}propanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-oxo-4-(pyrrolidin-1-yl)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(quinolin-6-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(2,2,2-trifluoroacetamido)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yloxy)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1H-indol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-cyclopropyl-2-oxoacetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-fluoro-2-methoxyphenyl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(6-methoxypyridin-2-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyridin-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2,5-dioxoimidazolidin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(2,5-dimethyl-1,3-thiazol-4-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-3-(pyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxo-1,2-dihydropyrazin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(N-methylacetamido)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-2-(pyridin-2-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-oxopiperidin-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[3-(1H-1,2,4-triazol-1-yl)benzoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-{[(2-methylpropyl)carbamoyl]carbonyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-oxo-1,2,3,4-tetrahydroquinoline-7-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methyl-1,3-thiazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(6-oxo-1,6-dihydropyridazin-3-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-1H-pyrazol-1-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(pyridin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1H-pyrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetamidopyridine-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-pyrazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-2-[2-(1H-1,2,3-triazol-5-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-hydroxy-2-methylpropanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1H-1,2,3,4-tetrazol-1-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3,4-tetrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2H-1,2,3,4-tetrazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-4H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-1,2,3-triazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-1H-1,2,3-triazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,2-oxazol-4-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,2-oxazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1H-1,2,4-triazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(5-methyl-1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrimidin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrimidin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4-methyl-2,5-dioxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-(2-cyanoacetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-methanesulfonylacetyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 1-(4-acetylmorpholine-2-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-acetyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(4-acetyl-2-oxopiperazin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylpiperidine-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2,3-dihydroxypropanoyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{8-acetyl-8-azaspiro[4.5]decane-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-1-yl)-2-methylpropanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{6-acetyl-6-azaspiro[2.5]octane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-3-methylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(N-methylacetamido)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-5-oxa-2,6-diazaspiro[3.4]oct-6-ene-7-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[1-acetyl-2-(pyridin-3-yl)pyrrolidine-3-carbonyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[5-(methoxymethyl)-1,2-oxazole-4-carbonyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{6-acetyl-5H,6H,7H,8H-pyrido[3,4-b]pyrazine-7-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(1H-1,2,4-triazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 1-{5-acetyl-5-azaspiro[2.4]heptane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[3-(1-acetylpyrrolidin-2-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{4-[(1-acetylazetidin-3-yl)oxy]benzoyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-methoxy-2-(N-methylacetamido)butanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetylpyrrolidin-2-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{7-acetyl-1-oxa-2,7-diazaspiro[4.4]non-2-ene-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-hexahydro-1H-furo[3,4-c]pyrrole-3a-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(3-methyl-1H-pyrazol-5-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-2-oxa-5-azabicyclo[2.2.1]heptane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetylpiperidin-4-yl)propanoyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-methyl-2-(1H-1,2,4-triazol-5-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-methyl-2-(1,3,4-oxadiazol-2-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-imidazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,2-oxazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-[2-(1H-1,2,3-triazol-5-yl)acetyl]-4-azaspiro[2.4]heptane-5-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-{[1,2,4]triazolo[1,5-a]pyridin-6-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(quinolin-6-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-[2-(piperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-(1-acetyl-3-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-4-methylazepane-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylazepane-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetylmorpholine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-{2-acetyl-2-azaspiro[3.4]octan-5-yl}acetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-2-azaspiro[4.4]nonane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-2-azabicyclo[2.2.2]octane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetylpiperidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetyl-1,4-oxazepane-2-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-4-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(4-acetyl-2-methylmorpholine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-hexahydro-2H-furo[2,3-c]pyrrole-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{3-acetyl-3-azabicyclo[3.1.0]hexane-1-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-octahydrocyclopenta[c]pyrrole-4-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{8-acetyl-8-azabicyclo[3.2.1]octane-3-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-3-methylazetidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{5-acetyl-hexahydro-2H-furo[2,3-c]pyrrole-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{3-acetyl-3-azabicyclo[3.2.1]octane-8-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetyl-octahydro-1H-isoindole-4-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{7-acetyl-7-azabicyclo[2.2.1]heptane-2-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-5-oxa-2-azaspiro[3.4]octane-7-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetyl-3-methylazetidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-acetyl-5-oxa-2-azaspiro[3.4]octane-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-2-methylpiperidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{3-[N-(1-methyl-1H-pyrazol-3-yl)acetamido]propanoyl}-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-3-fluoroazetidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1-acetyl-3-methoxyazetidin-3-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{4-acetyl-hexahydro-2H-furo[3,2-b]pyrrole-6-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(1-acetyl-4-ethylpyrrolidine-3-carbonyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{7-acetyl-1-oxo-2,7-diazaspiro[4.4]nonane-4-carbonyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[1-(1,3,4-oxadiazol-2-yl)cyclopropanecarbonyl]pyrrolidine-2-carboxamide; 2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl N,N-dimethylcarbamate; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl N,N-dimethylcarbamate; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-1,2,3-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; tert-butyl 4-({2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}carbamoyl)piperazine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(quinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(4-acetylpiperazin-1-yl)acetyl]-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)(methyl)amino]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-oxo-1,3-oxazolidine-5-carbonyl)pyrrolidine-2-carboxamide; 2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethylpiperazine-1-carboxylate; 1-[2-(3,5-dimethyl-1H-pyrazol-4-yl)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-tert-butyl 4-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1,4-dicarboxylate; 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; tert-butyl N-({5-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-1,3,4-oxadiazol-2-yl}methyl)carbamate; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridazin-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-{2-[5-(trifluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]acetyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(pyridazin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-methylpiperazine-1-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(2,2,2-trifluoroethyl)piperazine-1-carboxamide; N-{2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-4-(2,2,2-trifluoroethyl)piperazine-1-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(2-methoxyethyl)piperazine-1-carboxamide; 1-{2-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(5-methyl-1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4-methyl-1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(piperazin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}pyrrolidine-2-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-4-(cyclopropylmethyl)piperazine-1-carboxamide; 4-(cyclopropylmethyl)-N-{2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}piperazine-1-carboxamide; N-{2-[4-fluoro-2-({phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-4-methylpiperazine-1-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4-methyl-1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methylquinolin-5-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; tert-butyl N-[(5-{2-[4-fluoro-2-({phenyl[4-(propan-2-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-1,3,4-oxadiazol-2-yl)methyl]carbamate; 1-{2-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; tert-butyl 4-(5-{2-[4-fluoro-2-({[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-1H-1,2,3-triazol-4-yl)piperazine-1-carboxylate; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[5-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-2H-1,2,3,4-tetrazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(acetamidomethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(aminomethyl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-{5-[(dimethylamino)methyl]-1H-1,2,3-triazol-1-yl}acetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(piperazin-1-yl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(morpholin-4-yl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 1-(2-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}acetyl)-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[5-(trifluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]morpholine-4-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethylazetidine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-indol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[5-(acetamidomethyl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-1H-imidazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(cyclopropylmethyl)piperazine-1-carboxylate; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-methylpiperazine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{imidazo[1,2-a]pyridin-3-yl}acetyl)pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{[1,2,4]triazolo[1,5-a]pyridin-6-yl}acetyl)pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[(pyrazin-2-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-{2-[4-(piperazin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(2-ethyl-2H-1,2,3-triazol-4-yl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(1-ethyl-1H-1,2,3-triazol-4-yl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methylquinolin-6-yl)acetyl]pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(2-methoxyethyl)piperazine-1-carboxylate; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[2-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[methyl(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(2-methylquinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-{2-[methyl(pyrazin-2-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl 4-(2,2,2-trifluoroethyl)piperazine-1-carboxylate; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-methylquinolin-5-yl)acetyl]pyrrolidine-2-carboxamide; tert-butyl 2-[2-(2-{[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]carbamoyl}-4-fluoropyrrolidin-1-yl)-2-oxoethyl]-1H-indole-1-carboxylate, 1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(carbamoylamino)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(2-ethyl-2H-1,2,3-triazol-4-yl)(methyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(1-ethyl-1H-1,2,3-triazol-4-yl)(methyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(dimethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propanoyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(methylcarbamoyl)amino]acetyl}-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[(methylcarbamoyl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-[2-(carbamoylamino)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-1-[3-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)propanoyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-[2-(carbamoylamino)acetyl]-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(methylcarbamoyl)amino]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(2-methylpyrimidin-4-yl)amino]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-(2-{[3-(trifluoromethyl)azetidine-1-carbonyl]amino}acetyl)pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(dimethylcarbamoyl)amino]propanoyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-4-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(3-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-2-yl}propanoyl)-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-(2-{[3-(trifluoromethyl)azetidine-1-carbonyl]amino}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; 5-methyl-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(3,3-difluoroazetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(diethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(3,3-difluoroazetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[(1,3-oxazol-2-yl)amino]acetyl}pyrrolidine-2-carboxamide; N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(3,3-difluoroazetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(diethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(diethylamino)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-5-methyl-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-2H-1,2,3-triazol-2-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-3-[2-(1H-1,2,3-triazol-5-yl)acetyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(2-oxo-1,2-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(3-ethyl-5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(6-ethoxy-5-methylpyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-5-methyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(4-ethyl-5-oxo-4,5-dihydropyrazin-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(3-oxo-3,4-dihydropyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-oxo-4,5-dihydropyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)-6-fluoropyridin-2-yl](phenyl)methyl}-1-[2-(4-ethyl-3-oxo-3,4-dihydropyrazin-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[(3,3-difluoroazetidine-1-carbonyl)amino]acetyl}-N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2-oxo-2,3-dihydro-1,3,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-{[5-(3,3-difluorocyclobutyl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide; 1-{2-[(azetidine-1-carbonyl)amino]acetyl}-N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoropyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}pyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(4-methyl-1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-{[4-(3,3-difluorocyclobutyl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](pyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethylazetidine-1-carboxylate; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxopiperazin-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}morpholine-4-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)propanoyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(2,5-dioxopiperazin-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-indol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; 2,2,2-trifluoroethyl 4-{2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-3-oxopiperazine-1-carboxylate; 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(2-methoxyethyl)piperazine-1-carboxylate; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-{2-[2-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}-1-[2-(4H-1,2,4-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-methylpiperazine-1-carboxylate; 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(cyclopropylmethyl)piperazine-1-carboxylate; 2-[4-fluoro-2-({[3-fluoro-4-(1-methylcyclopropyl)phenyl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl 4-(2,2,2-trifluoroethyl)piperazine-1-carboxylate; 1-[2-(1H-1,3-benzodiazol-1-yl)propanoyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-{2-[4-fluoro-2-({[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}morpholine-4-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-methyl-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1H-1,2,3-benzotriazol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(1H-1,3-benzodiazol-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-1H-indazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-indol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}-1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-1-yl)acetyl]pyrrolidine-2-carboxamide; tert-Butyl 2-{2-[4-fluoro-2-({[6-fluoro-5-(1-methylcyclopropyl)pyridin-2-yl](phenyl)methyl}carbamoyl)pyrrolidin-1-yl]-2-oxoethyl}-1H-indole-1-carboxylate; 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{[4-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(5-cyclobutylpyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-N-{[4-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[4-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[4-(difluoromethyl)-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[5-(propan-2-yl)-4-(trifluoromethyl)pyridin-2-yl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]acetyl}-4-fluoro-N-{[6-methyl-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; N-[(5-cyclobutylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-tert-butylpyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-methoxy-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(2-aminopyridin-3-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(1H-pyrazol-5-yl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](5-fluoropyridin-2-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](5-fluoropyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(2-aminopyridin-4-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](3-fluoropyridin-4-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(6-aminopyridin-3-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(6-aminopyridin-2-yl)[3-fluoro-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(2-aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-1-{2-[(dimethylcarbamoyl)amino]acetyl}-4-fluoropyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](1H-pyrazol-5-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(2-aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(2-aminopyridin-3-yl)[3-methyl-4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](2-methoxypyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(1-methylcyclopropyl)phenyl](2-methylpyridin-3-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl]({imidazo[1,5-a]pyridin-3-yl})methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl]({imidazo[1,5-a]pyridin-1-yl})methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-pyrazol-5-yl)methyl}-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl]({imidazo[1,5-a]pyridin-7-yl})methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-indazol-6-yl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](1-methyl-1H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](2-methyl-2H-indazol-6-yl)methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(1H-indazol-6-yl)methyl]-4-fluoropyrrolidine-2-carboxamide; Methyl N-({3-[({4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidin-2-yl}formamido)[6-fluoro-5-(propan-2-yl)pyridin-2-yl]methyl]phenyl}methyl)carbamate; 1-acetyl-N-[(2-methoxyphenyl)[4-(propan-2-yl)phenyl]methyl]pyrrolidine-2-carboxamide; 1-acetyl-N-[(2-methylphenyl)[4-(propan-2-yl)phenyl]methyl]pyrrolidine-2-carboxamide; 1-acetyl-N-[(2-methylphenyl)[5-(propan-2-yl)pyridin-2-yl]methyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(2-oxo-2,3-dihydro-1,3-benzoxazol-7-yl)methyl]-1-(2-acetamidoacetyl)pyrrolidine-2-carboxamide; N-[(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-4-yl)[4-(propan-2-yl)phenyl]methyl]-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](3-fluorophenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](4-fluorophenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(2-oxo-2,3-dihydro-1H-1,3-benzodiazol-4-yl)methyl]-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(3-acetamidophenyl)[4-(propan-2-yl)phenyl]methyl]-4-fluoro-1-[2-(1-methyl-1H-1,2,3-triazol-4-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluorophenyl)(1-methyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazol-4-yl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](3-methoxyphenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{cyclopropyl[3-fluoro-4-(propan-2-yl)phenyl]methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{2-cyclopropyl-1-[3-fluoro-4-(propan-2-yl)phenyl]ethyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](3-methoxyphenyl)methyl}pyrrolidine-2-carboxamide; N-{[3-(acetamidomethyl)phenyl][6-fluoro-5-(propan-2-yl)pyridin-2-yl]methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](3-{[(methylcarbamoyl)amino]methyl}phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(2-fluorophenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(4-fluorophenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-{[3,5-difluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[(1H-1,2,3-triazol-5-yl)methanesulfonyl]pyrrolidine-2-carboxamide; 1-acetyl-N-[(4-cyclobutyl-3-fluorophenyl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-{[3,5-difluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3,5-difluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[2-methyl-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1,3-oxazol-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(3-chloro-4-cyclopropylphenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-methylphenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3,5-difluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3,5-difluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3,5-difluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-methyl-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3-chloro-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclobutyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclobutyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3,4-tetrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-{[4-(butan-2-yl)-3-fluorophenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-5-methyl-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-{[3-(difluoromethyl)-4-(propan-2-yl)phenyl](phenyl)methyl}-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(1-methylcyclobutyl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-cyclopropyl-3-fluoro-5-methylphenyl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-2H-1,2,3,4-tetrazol-2-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)-3-(trifluoromethyl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(4-tert-butyl-3-fluorophenyl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1H-pyrazol-5-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(4H-1,2,4-triazol-3-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1H-pyrazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(2-acetamidoacetyl)-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1H-pyrazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1,3-oxazol-5-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1,2-oxazol-5-yl)phenyl]methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1-methyl-1H-pyrazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(3-methyl-1H-pyrazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-N-{[3-(1,3-dimethyl-1H-pyrazol-5-yl)phenyl][6-fluoro-5-(propan-2-yl)pyridin-2-yl]methyl}-4-fluoropyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1,2-oxazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1H-pyrazol-1-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-acetyl-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl][3-(1,3,4-oxadiazol-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-(oct-7-ynoyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(1-methyl-1H-indazole-5-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(4-methoxyphenyl)cyclopropanecarbonyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridine-2-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(2-methylpropoxy)pyridine-4-carbonyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[3-(1H-imidazol-4-yl)propanoyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[4-(1H-imidazol-1-yl)pyridine-2-carbonyl]-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{phenyl[4-(propan-2-yl)phenyl]methyl}-1-{[(pyridin-3-yl)carbamoyl]carbonyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-(5-methoxy-1-methyl-1H-pyrazole-3-carbonyl)-N-{phenyl[4-(propan-2-yl)phenyl]methyl}pyrrolidine-2-carboxamide; 1-[2-(1,4-dimethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 4-Fluoro-1-[2-(5-methoxy-1-methyl-1H-1,2,4-triazol-3-yl)acetyl]-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(diethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(3,3-difluoroazetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; 1-{2-[5-(azetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{phenyl[5-(propan-2-yl)pyridin-2-yl]methyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-(2-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-8-yl}acetyl)pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(4-methyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(1,4-dimethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-pyrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[4-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[3-(difluoromethyl)-1H-pyrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(2-oxo-1,2-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(3-ethyl-5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(6-ethoxy-5-methylpyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[4-(trifluoromethyl)-1,3-oxazol-2-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(1-ethyl-5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(1-ethyl-5-methyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(4-ethyl-5-oxo-4,5-dihydropyrazin-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-methoxy-1-methyl-1H-1,2,4-triazol-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-(2-{[benzyl(trifluoromethyl)carbamoyl]amino}acetyl)-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[5-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-[2-(5-oxo-4,5-dihydropyrazin-2-yl)acetyl]pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(diethylamino)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-3-methyl-1H-pyrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(4-ethyl-3-oxo-3,4-dihydropyrazin-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(difluoromethyl)-1-methyl-1H-pyrazol-5-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[5-(trifluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(difluoromethyl)-1H-1,2,3-triazol-5-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[4-(difluoromethyl)-1-methyl-1H-pyrazol-3-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(3,3-difluoroazetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[3-(difluoromethyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoro-1-{2-[5-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-[2-(4,5-dimethyl-1,3-oxazol-2-yl)acetyl]-4-fluoropyrrolidine-2-carboxamide; 1-{2-[5-(azetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-4-fluoropyrrolidine-2-carboxamide; N-[(5-cyclopropyl-6-fluoropyridin-2-yl)(phenyl)methyl]-1-{2-[5-(difluoromethyl)-1H-1,2,3,4-tetrazol-1-yl]acetyl}-4-fluoro-3-hydroxypyrrolidine-2-carboxamide; 1-(3-carbamoyl-2-acetamidopropanoyl)-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3,4-tetrazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-imidazol-1-yl)propanoyl]pyrrolidine-2-carboxamide; 4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)propanoyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[(1H-1,2,3-triazol-5-yl)methanesulfonyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}-1-[2-hydroxy-2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[4-(dimethylamino)-1H-1,2,3-triazol-5-yl]acetyl}-4-fluoro-N-{[3-fluoro-4-(propan-2-yl)phenyl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-1,2,3-triazol-5-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(3,5-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1,4-dimethyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-(3-{3-oxo-2H,3H-[1,2,4]triazolo[4,3-a]pyridin-2-yl}propanoyl)pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-1H-pyrazol-1-yl)acetyl]pyrrolidine-2-carboxamide; 1-{2-[5-(difluoromethyl)-1H-pyrazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-{2-[4-(azetidin-1-yl)-1H-1,2,3-triazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[4-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 1-{2-[3-(difluoromethyl)-1H-pyrazol-1-yl]acetyl}-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-{2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}pyrrolidine-2-carboxamide; 4-Fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(6-oxo-1,6-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}-1-[2-(2-oxo-1,2-dihydropyridin-3-yl)acetyl]pyrrolidine-2-carboxamide; 1-[2-(3-ethyl-5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(1-ethyl-2-oxo-1,2-dihydropyridin-3-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(1-ethyl-5-methyl-6-oxo-1,6-dihydropyridin-3-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamide; 1-[2-(4-ethyl-5-oxo-4,5-dihydropyrazin-2-yl)acetyl]-4-fluoro-N-{[6-fluoro-5-(propan-2-yl)pyridin-2-yl](phenyl)methyl}pyrrolidine-2-carboxamid...

Claims

1. Formula (I): (G1-Z1)-L-(G2-Z2)(I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: (i) G1 and / or G1-Z1, and (ii) G2 and / or G2-Z2 are each independently a GYS1 inhibitory moiety; and A compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is a linker.

2. L is a bond or (C １ ~C ５０ ) alkyl; Said (C １ ~C ５０ ) alkyl is one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘ ) (R ｙ ) -, C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ optionally substituted with aryl, or 5- to 20-membered heteroaryl; and Said (C １ ~C ５０ One or more of the C atoms in the alkyl is / are bonded to one or more —C(R ｘ ) = C(R ｘ )-, -C≡C-, -O-, -C(O)-, -C(O)O-, -OC(O)-, -OC(O)O-, -OC(O)N(R ｘ ) -, -N(R ｘ )C(O)O-,-N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ ) -, -S(O) ｎ -, -S(O) ｎ O-, -OS(O) ｎ -, -OS(O) ｎ O-, -OS(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ O-, -N(R ｘ ) S (O) ｎ N (R ｙ ) -, -S(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ -, C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ optionally substituted with aryl, or 5-20 membered heteroaryl; Each C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ The aryl or 5- to 20-membered heteroaryl may be substituted with one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘｘ ) (R ｙｙ ), -C(O)R ｚ , -C(O)OR ｚ , -OC(O)R ｚ , -OC(O)OR ｚ , -OC(O)N(R ｘｘ ) (R ｙｙ ), -N(R ｘｘ )C(O)OR ｚ , -N(R ｘｘ )C(O)N((R ｘｘ ) (R ｙｙ ), -C(O)N(R ｘｘ ) (R ｙｙ ), -N(R ｘｘ ) C(O)R ｚ , -N(R ｘｘ ) (R ｙｙ ), -S(O) ｎ R ｚ , -S(O) ｎ OR ｚ , -OS(O) ｎ R ｚ , -OS(O) ｎ OR ｚ , -OS(O) ｎ N (R ｘｘ ) (R ｙｙ ), -N(R ｘｘ ) S (O) ｎ OR ｚ , -N(R ｘｘ ) S (O) ｎ N (R ｘｘ ) (R ｙｙ ), -S(O) ｎ N (R ｘｘ ) (R ｙｙ ), or -N(R ｘｘ ) S (O) ｎ R ｚ and optionally substituted with Each R ｘ , R ｘｘ , R ｙ , R ｙｙ , and R ｚ are independently H, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, or (C １ ~C ６ ) cycloalkyl, and 2. The compound of claim 1, wherein each n is independently 0 to 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

3. L is one or more of deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘ ) (R ｙ ) -, C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ Optionally substituted aryl, or 5- to 20-membered heteroaryl (C １ ~C ５０ ) alkyl, Said (C １ ~C ５０ ) alkyl, one or more C atoms of which are bonded to one or more —C(R ｘ ) = C(R ｘ )-, -C≡C-, -O-, -C(O)-, -N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ ) -, -S(O) ｎ -, -N(R ｘ ) S (O) ｎ N (R ｙ ) -, -S(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ -, C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ optionally substituted with aryl, or 5- to 20-membered heteroaryl; Each C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ Aryl and 5- to 20-membered heteroaryl may be substituted with one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘｘ ) (R ｙｙ ), -C(O)R ｚ , -C(O)OR ｚ , -OC(O)R ｚ , -N(R ｘｘ )C(O)N((R ｘｘ ) (R ｙｙ ), -C(O)N(R ｘｘ ) (R ｙｙ ), -N(R ｘｘ ) (R ｙｙ ), -S(O) ｎ R ｚ , -N(R ｘｘ ) S (O) ｎ N (R ｘｘ ) (R ｙｙ ), -S(O) ｎ N (R ｘｘ ) (R ｙｙ ), or -N(R ｘｘ ) S (O) ｎ R ｚ and optionally substituted with Each R ｘ , R ｘｘ , R ｙ , R ｙｙ , and R ｚ are independently H, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, or (C １ ~C ６ ) cycloalkyl, and 3. The compound of claim 2, wherein each n is independently 0 to 2.

4. L is (C １ ~C ２０ ) alkyl, Said (C １ ~C ２０ ) alkyl is one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘ ) (R ｙ ) -, C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ optionally substituted with aryl, or 5- to 20-membered heteroaryl; and Said (C １ ~C ２０ ) alkyl, one or more C atoms of which are bonded to one or more —C(R ｘ ) = C(R ｘ )-, -C≡C-, -O-, -C(O)-, -N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ ) -, -S(O) ｎ -, -N(R ｘ ) S (O) ｎ N (R ｙ ) -, -S(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ -, C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ optionally substituted with aryl, or 5- to 20-membered heteroaryl; Each C ３ ~C １５ Carbocyclyl, 3- to 15-membered heterocyclyl, C ６ ~C １４ Aryl and 5- to 20-membered heteroaryl may be substituted with one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘｘ ) (R ｙｙ ), -C(O)R ｚ , -C(O)OR ｚ , -OC(O)R ｚ , -N(R ｘｘ )C(O)N((R ｘｘ ) (R ｙｙ ), -C(O)N(R ｘｘ ) (R ｙｙ ), -N(R ｘｘ ) (R ｙｙ ), -S(O) ｎ R ｚ , -N(R ｘｘ ) S (O) ｎ N (R ｘｘ ) (R ｙｙ ), -S(O) ｎ N (R ｘｘ ) (R ｙｙ ), or -N(R ｘｘ ) S (O) ｎ R ｚ and optionally substituted with Each R ｘ , R ｘｘ , R ｙ , R ｙｙ , and R ｚ are independently H, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, or (C １ ~C ６ ) cycloalkyl, and 4. The compound of claim 3, wherein each n is independently 0 to 2.

5. Said (C １ ~C ２０ ) alkyl is one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘ ) (R ｙ ) -, C ３ ~C ８ cycloalkyl, 3- to 8-membered heterocyclyl, C ６ ~C １０ optionally substituted with aryl, or 5- to 10-membered heteroaryl; and Said (C １ ~C ２０ ) alkyl, one or more C atoms of which are bonded to one or more —C(R ｘ ) = C(R ｘ )-, -C≡C-, -O-, -C(O)-, -N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ ) -, -S(O) ｎ -, -N(R ｘ ) S (O) ｎ N (R ｙ ) -, -S(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ -, C ３ ~C ８ cycloalkyl, 3- to 8-membered heterocyclyl, C ６ ~C １０ optionally substituted with aryl, or 5-10 membered heteroaryl; Each C ３ ~C ８ cycloalkyl, 3- to 8-membered heterocyclyl, C ６ ~C １０ Aryl and 5- to 10-membered heteroaryl may be substituted with one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘｘ ) (R ｙｙ ), -C(O)R ｚ , -C(O)OR ｚ , -OC(O)R ｚ , -N(R ｘｘ )C(O)N((R ｘｘ ) (R ｙｙ ), -C(O)N(R ｘｘ ) (R ｙｙ ), -N(R ｘｘ ) (R ｙｙ ), -S(O) ｎ R ｚ , -N(R ｘｘ ) S (O) ｎ N (R ｘｘ ) (R ｙｙ ), -S(O) ｎ N (R ｘｘ ) (R ｙｙ ), or -N(R ｘｘ ) S (O) ｎ R ｚ and optionally substituted with Each R ｘ , R ｘｘ , R ｙ , R ｙｙ , and R ｚ are independently H, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, or (C １ ~C ６ ) cycloalkyl, and 5. The compound of claim 4, wherein each n is independently 0 to 2.

6. Said (C １ ~C ２０ ) alkyl is one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, —N(R ｘ ) (R ｙ ) -, C ３ ~C ８ cycloalkyl, 3- to 8-membered heterocyclyl, C ６ ~C １０ optionally substituted with aryl, or 5- to 10-membered heteroaryl; and Said (C １ ~C ２０ ) alkyl, one or more C atoms of which are bonded to one or more —C(R ｘ ) = C(R ｘ )-, -C≡C-, -O-, -C(O)-, -N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ ) -, -S(O) ｎ -, -N(R ｘ ) S (O) ｎ N (R ｙ ) -, -S(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ -, C ３ ~C ８ cycloalkyl, 3- to 8-membered heterocyclyl, C ６ ~C １０ optionally substituted with aryl, or 5-10 membered heteroaryl; Each R ｘ and R ｙ are independently H, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, or (C １ ~C ６ ) cycloalkyl, and 6. The compound of claim 5, wherein each n is independently 0 to 2.

7. Said (C １ ~C ２０ ) alkyl is one or more deuterium, halo, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, oxo (C═O), —O(C １ ~C ６ ) alkyl, —O(C １ ~C ６ ) haloalkyl, —O(C １ ~C ６ ) cycloalkyl, or —N(R ｘ ) (R ｙ )-, and Said (C １ ~C ２０ ) alkyl, one or more of the C atoms of which is one or more of -O-, -C(O)-, -N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ ) -, -S(O) ｎ -, -N(R ｘ ) S (O) ｎ N (R ｙ ) -, -S(O) ｎ N (R ｘ ) -, -N(R ｘ ) S (O) ｎ -, C ３ ~C ８ cycloalkyl, 3- to 8-membered heterocyclyl, C ６ ~C １０ optionally substituted with aryl, or 5-10 membered heteroaryl; Each R ｘ and R ｙ are independently H, (C １ ~C ６ ) alkyl, (C １ ~C ６ ) haloalkyl, or (C １ ~C ６ ) cycloalkyl, and 7. The compound of claim 6, wherein each n is independently 0 to 2.

8. Said (C １ ~C ２０ ) alkyl is one or more deuterium, halo, (C １ ~C ４ ) alkyl, (C １ ~C ４ ) haloalkyl, oxo (C═O), —O(C １ ~C ４ ) alkyl, —O(C １ ~C ４ ) haloalkyl, or —O(C １ ~C ４ ) optionally substituted with cycloalkyl; and Said (C １ ~C ２０ ) alkyl, one or more of the C atoms of which is one or more of -O-, -C(O)-, -N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-,-N(R ｘ )-, 3- to 8-membered heterocyclyl, C ６ ~C １０ optionally substituted with aryl, or 5-10 membered heteroaryl; Each R ｘ and R ｙ are independently H, (C １ ~C ３ ) alkyl, (C １ ~C ３ ) haloalkyl, or (C １ ~C ３ ) cycloalkyl, and 8. The compound of claim 7, wherein each n is independently 0 to 2.

9. Said (C １ ~C ２０ ) alkyl, one or more C atoms of which are substituted with one or more —O—, —C(O)—, —N(R ｘ )C(O)N(R ｙ )-, -C(O)N(R ｘ ) -, -N(R ｘ )C(O)-, or -N(R ｘ ) - is optionally replaced by Each R ｘ and R ｙ are independently H, (C １ ~C ３ ) alkyl, (C １ ~C ３ ) haloalkyl, or (C １ ~C ３ ) cycloalkyl, and 9. The compound of claim 8, wherein each n is independently 0 to 2.

10. Said (C １ ~C ２０ 10. The compound according to claim 9, wherein one or more of the C atoms of the alkyl are replaced by one or more -O-.

11. L is -(-O-CH ２ CH ２ ) ｍ 11. The compound of claim 10, wherein m is selected from the group consisting of —O— and m is 1 to 12.

12. 3. The compound of claim 1 or 2, wherein L comprises an optionally substituted alkylene, an optionally substituted heteroalkylene, an optionally substituted alkenylene, an optionally substituted heteroalkenylene, an optionally substituted alkynylene, an optionally substituted heteroalkynylene, an optionally substituted carbocyclylene, an optionally substituted heterocyclylene, an optionally substituted arylene, an optionally substituted heteroarylene, or any combination thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

13. 13. The compound of any one of claims 1-2, or 12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is selected from the group consisting of ethylene glycol, polyethylene glycol (PEG), and PEG derivatives.

14. 14. The compound of any one of claims 1-2, 12, or 13, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L comprises a polymer.

15. 15. The compound of any one of claims 1-2, or 12-14, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein L is polyethylene glycol.

16. 16. The compound of claim 15, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the polyethylene glycol comprises from about 2 to about 20 ethylene glycol units.

17. 17. The compound of any one of claims 1 to 16, wherein G1 and G2 are the same and / or G1-Z1 and G2-Z2 are the same, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

18. 17. The compound of any one of claims 1 to 16, wherein G1 and G2 are different and / or G1-Z1 and G2-Z2 are different, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

19. 19. The compound of any one of claims 1 to 16 or 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein one of (i) G1 or G1-Z1, and (ii) G2 or G2-Z2 has enhanced GYS1 inhibition compared to the other of (i) G1 or G1-Z1, and (ii) G2 or G2-Z2.

20. 20. The compound of any one of claims 1 to 19, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein said compound of formula (I) has enhanced GYS1 inhibition compared to G1, G1-Z1, G2, and / or G2-Z2.

21. (G1-Z1) and (G2-Z2) are each independently represented by formula (I-1) or (I-2): 【Chemical 1】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Y ２ and Y ３ are each C, or Y ２ and Y ３ One of the two is N, and Y ２ and Y ３ the other of which is C, X １ and X ２ are each independently H, C １～６ Alkyl, or C １～６ is an alkoxy, X ３ and X ４ each independently represents H, halo, C １～６ Alkyl, C １～６ alkoxy, or 5- to 20-membered heteroaryl; X ３ and X ４ The above C １～６ the alkyl is optionally substituted with one or more halo; X ５ But H, C １～６ Alkyl, C １～６ Alkoxy, or C ３～１０ is cycloalkyl, (1) L １ does not exist, and Q １ However, (i) to (iv): (i) phenyl, wherein Q １ wherein said phenyl is selected from the group consisting of one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, —NH ２ , -NH-C(O)-(C １～６ alkyl), —NH—C(O)—(3- to 15-membered heterocyclyl), C ３～１０ substituted with cycloalkyl or 5- to 20-membered heteroaryl; Said C １～６ The alkyl may be one or more halo, —NH—C(O)—NH(C １～６ alkyl), —NH—C(O)—C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy; Said C ３～１０ Cycloalkyl is one or more halo or C １～６ optionally substituted with alkyl, and The 5- to 20-membered heteroaryl is one or more C １～６ phenyl optionally substituted with alkyl; (ii) 3- to 15-membered heterocyclyl, wherein Q １ wherein the 3- to 15-membered heterocyclyl is one or more oxo, or C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl; (iii) 5- to 20-membered heteroaryl, wherein Q １ wherein said 5- to 20-membered heteroaryl is one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Alkoxy, —NH ２ , or C ３～１０ optionally substituted with cycloalkyl; Said C １～６ alkyl is optionally substituted with one or more halo; and Said C ３～１０ Cycloalkyl is one or more halo or C １～６ 5- to 20-membered heteroaryl optionally substituted with alkyl, and (iv) C ３～１０ cycloalkyl; or or (2) L １ Ga-CH ２ - and Q １ is C ３～１０ or cycloalkyl; L ２ is -C(O)- or -S(O) ２ - and R １ is H or C １～６ is alkyl, R ｋ H, halo, -OH, -NH ２ , or —NH—C(O)C １～６ is alkyl, R ｍ is H, —OH, or C １～６ is alkyl, R ｎ But H, C １～６ Alkyl or C ３～１０ cycloalkyl or R ｎ together with the carbon atom to which it is attached, ３～５ forming a cycloalkyl, or R ｋ But, R ｍ or R ｎ together with the atom to which they are attached form a cyclopropyl; R ２ However, (i) to (vii): (i) C １～６ alkyl, and R ２ The above C １～６ The alkyl is one or more R ａ and R ａ but, (a) —OH, (b) cyano, (c) C ２～６ Alkynyl, (d) C ６～２０ Aryl, R ａ The above C ６～２０ The aryl is selected from the group consisting of one or more of halo, cyano, C １～６ Alkoxy, or —NH—C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, (e) 3- to 15-membered heterocyclyl, wherein R ａ wherein the 3- to 15-membered heterocyclyl is one or more R ｃ and optionally substituted with R ｃ But, halo, oxo, C １～６ Alkyl, C １～６ Alkoxy, —C(O)—C １～６ Alkyl, or —C(O)—C １～６ is an alkoxy, R ｃ The above C １～６ The alkyl may be one or more halo or C ２～６ optionally substituted with alkynyl, and R ｃ The —C(O)—C １～６ alkoxy is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo; (f) -N(R ｃ ) (R ｄ ) where -N(R ｃ ) (R ｄ ) R ｃ and R ｄ are, independently of each other, H, C １～６ Alkyl, —C(O)—C １～６ Alkyl, —C(O)—C １～６ Alkoxy, —C(O)—NH ２ , -C(O)-NH(C １～６ alkyl), —C(O)—N(C １～６ alkyl) ２ , —C(O)—(3- to 15-membered heterocyclyl), —CH ２ —C(O)—NH ２ , 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R ｃ Or R ｄ The above C １～６ The alkyl group is one or more —C(O)—NH ２ and optionally substituted with R ｃ Or R ｄ The —C(O)—C １～６ the alkyl is optionally substituted with one or more halo; R ｃ Or R ｄ wherein said 3- to 15-membered heterocyclyl and said 5- to 20-membered heteroaryl independently comprise one or more C １～６ optionally substituted with alkyl; R ｃ Or R ｄ wherein the —C(O)—(3- to 15-membered heterocyclyl) is one or more halo, —C(O)—C １～６ Alkoxy or C １～６ Optionally substituted with alkyl, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ optionally substituted with cycloalkyl, and R ｃ Or R ｄ The —C(O)—N(C １～６ alkyl) ２ The above C １～６ The alkyl may, independently of each other, be one or more halo or C ６～２０ -N(R ｃ ) (R ｄ ), (g) -O-R ｅ and R ｅ But C １～６ Alkyl, C ６～２０ Aryl, —C(O)—(3- to 15-membered heterocyclyl), —C(O)—N—(C １～６ alkyl) ２ or 5- to 20-membered heteroaryl; R ｅ The above C １～６ The alkyl is one or more C １～６ Optionally substituted with alkoxy, １～６ Alkoxy is one or more C ２～６ optionally substituted with alkynyl; R ｅ The above C ６～２０ The aryl is one or more C １～６ optionally substituted with alkyl, and R ｅ The —C(O)—(3- to 15-membered heterocyclyl) is one or more C １～６ Alkyl, C １～６ Alkoxy or —C(O)—C １～６ Optionally substituted with alkoxy, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ -O-R optionally substituted with cycloalkyl ｅ , (h)-C(O)-R ｅ and R ｅ But -NH ２ , —OH, or 3- to 15-membered heterocyclyl, —C(O)—R ｅ , or (i) -S(O) ２ -R ｆ and R ｆ But C １～６ alkyl or 3- to 15-membered heterocyclyl, ２ -R ｆ , is, C １～６ Alkyl, (ii) C ３～１０ Cycloalkyl, R ２ The above C ３～１０ Cycloalkyl is one or more R ｑ and R ｑ is 5- to 20-membered heteroaryl or C ６～２０ aryl, and R ｑ The above C ６～２０ The aryl is one or more C １～６ C optionally substituted with alkoxy ３～１０ cycloalkyl, (iii) 3- to 15-membered heterocyclyl, wherein R ２ wherein the 3- to 15-membered heterocyclyl is one or more of halo, oxo, C １～６ Alkyl, —C(O)—C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iv) 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), １～４ The alkyl group may be one or more of -OH, halo, -NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ and optionally substituted with said 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), wherein the 5- to 20-membered heteroaryl is one or more R ｓ and optionally substituted with R ｓ But, Halo, C １～６ Alkyl, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)-C １～６ Alkyl, C ６～２０ Aryl, C ３～１０ cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C １～６ is an alkoxy, R ｓ The above C １～６ The alkyl may be one or more halo, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy, and R ｓ wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C １～６ 5-20 membered heteroaryl optionally substituted with alkoxy or -(C １～４ alkyl) (5- to 20-membered heteroaryl), (v) -N(R ｇ ) (R ｈ ) where R ｇ and R ｈ are independently H or C １～６ alkyl, —N(R ｇ ) (R ｈ ), (vi)-C(O)-R ｊ and R ｊ But C ３～１０ Cycloalkyl, —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ or —NH(5-20 membered heteroaryl), —C(O)—R ｊ ,and (vii) C ６～２０ Aryl, R ２ The above C ６～２０ The aryl is one or more 5- to 20-membered heteroaryl or —O—R ｐ and R ｐ is 3- to 15-membered heterocyclyl, and R ｐ The 3- to 15-membered heterocyclyl is one or more —C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, 21. The compound of any one of claims 1 to 20, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein (G1-Z1) and (Z2-G2) are each independently substituted with a group attached to L.

22. R ２ is unsubstituted methyl, (1) Q １ is a 5- to 20-membered heteroaryl; and Q １ wherein said 5- to 20-membered heteroaryl is one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Alkoxy, —NH ２ , C ３～１０ optionally substituted with cycloalkyl or —OH; １ is not unsubstituted pyridyl, or (2) Q １ is phenyl, and Q １ wherein the phenyl is (i) at least one C ３～６ alkyl, wherein said at least one C ３～６ the alkyl is optionally substituted with one or more halo; or (ii) at least one C ３～１０ cycloalkyl, wherein said at least one C ３～１０ Cycloalkyl is one or more halo or C １～６ optionally substituted with alkyl, or (iii) is substituted with at least one 5- to 20-membered heteroaryl, wherein the at least one 5- to 20-membered heteroaryl is substituted with one or more C １～６ 22. The compound of claim 21, wherein:

23. 22. The compound of claim 21, wherein the group attached to L comprises a carbon, oxygen, or nitrogen atom.

24. G1 and G2 are each independently 【Chemistry 2】 or a moiety of formula (I-1) represented by 【Chemistry 3】 and R is a moiety of formula (I-1) or (I-2) represented by ｋ , R ｍ , R ｎ , R １ , X １ , X ２ , X ３ , X ４ , X ５ , Y ２ , Y ３ , L １ , and Q １ is as defined for compounds of formula (I-1) or (I-2) as defined in claim 21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

25. (Z1) and (Z2) are each independently 【Chemistry 4】 and L ２ and R ２ is as defined for compounds of formula (I-1), or (I-2) as defined in claim 21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

26. formula: 【Chemistry 5】 The part represented by is a part with carbon atoms. 【Chemistry 6】 R ｋ , R ｍ , R ｎ , and R １ With the formula: 【Chemistry 7】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

27. L, (i) the Z1 portion of (G1-Z1), and (ii) the Z2 moiety of (G2-Z2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

28. L, (i) the G1 portion of (G1-Z1), and (ii) the G2 moiety of (G2-Z2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

29. The compound has the formula (II): 【Chemistry 8】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

30. The compound has the formula (III): 【Chemistry 9】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

31. The compound has the formula (IV): 【Chemistry 10】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

32. The compound has the formula (V): 【Chemistry 11】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

33. Each L, L １ , L ２ , Y ２ , Y ３ , R １ , R ２ , R ｋ , R ｍ , R ｎ , X １ , X ２ , X ３ , X ４ , X ５ , and Q １ Independently about Y ２ and Y ３ One of the two is N, and Y ２ and Y ３ the other of which is C, X １ and X ２ are each independently H; X ３ and X ４ are each independently H or halo; X ５ is C ３～６ is cycloalkyl, L １ does not exist, Q １ is phenyl, L ２ is —C(O)—, R １ is H, R ｋ is the halo, R ｍ is H, R ｎ is H, R ２ However, (i) to (ii): (i) C １～３ alkyl, and R ２ The above C １～３ The alkyl is one or more R ａ and R ａ is a 3- to 10-membered heterocyclyl, and R ａ wherein the 3- to 10-membered heterocyclyl is one or more R ｃ and R ｃ is oxo or C １～３ alkyl, C １～３ alkyl, or (ii) 5- to 10-membered heteroaryl or -(C １～３ alkyl) (5-10 membered heteroaryl); L is (C １ ~C ２０ ) alkyl, Said (C １ ~C ２０ At least one of the C atoms in the alkyl is at least one of -O-, -N(R ｘ )- or 3- to 10-membered heterocyclyl; Each 3- to 10-membered heterocyclyl is selected from one or more (C １ ~C ３ ) optionally substituted with alkyl, or oxo (C=O), and Each R ｘ is independently H, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

34. Each L, L １ , L ２ , Y ２ , Y ３ , R ２ , X １ , X ２ , X ３ , X ４ , X ５ , and Q １ Independently about Y ２ and Y ３ One of the two is N, and Y ２ and Y ３ the other of which is C, X １ and X ２ are each independently H; X ３ and X ４ are each independently H or halo; X ５ is C ３～６ is cycloalkyl, L １ does not exist, Q １ is phenyl, L ２ is —C(O)—, R ２ However, (i) to (ii): (i) C １～３ alkyl, and R ２ The above C １～３ The alkyl is one or more R ａ and R ａ is a 3- to 10-membered heterocyclyl, and R ａ wherein the 3- to 10-membered heterocyclyl is one or more R ｃ and R ｃ is oxo or C １～３ alkyl, C １～３ alkyl, or (ii) 5- to 10-membered heteroaryl or -(C １～３ alkyl) (5-10 membered heteroaryl); L is (C １ ~C ２０ ) alkyl, Said (C １ ~C ２０ At least one of the C atoms in the alkyl is at least one of -O-, -N(R ｘ )- or 3- to 10-membered heterocyclyl; Each 3- to 10-membered heterocyclyl is selected from one or more (C １ ~C ３ ) optionally substituted with alkyl, or oxo (C=O), and Each R ｘ is independently H, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

35. The compound is 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

36. 30. A process for preparing a compound of any one of claims 1 to 17, 19 to 27, or 29, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, comprising: Formula (I-1B): 【Chemistry 16】 Compounds of (In the formula, Y ２ and Y ３ are each C, or Y ２ and Y ３ One of the two is N, and Y ２ and Y ３ the other of which is C, X １ and X ２ are each independently H, C １～６ Alkyl, or C １～６ is an alkoxy, X ３ and X ４ are each independently H, halo, C １～６ Alkyl, C １～６ alkoxy, or 5- to 20-membered heteroaryl; X ３ and X ４ The above C １～６ the alkyl is optionally substituted with one or more halo; X ５ is H, C １～６ Alkyl, C １～６ Alkoxy, or C ３～１０ is cycloalkyl, (1) L １ does not exist, and Q １ are (i) to (iv): (i) phenyl, wherein Q １ wherein said phenyl is selected from the group consisting of one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, —NH ２ , -NH-C(O)-(C １～６ alkyl), —NH—C(O)—(3- to 15-membered heterocyclyl), C ３～１０ substituted with cycloalkyl or 5- to 20-membered heteroaryl; Said C １～６ The alkyl may be one or more halo, —NH—C(O)—NH(C １～６ alkyl), —NH—C(O)—C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy; Said C ３～１０ Cycloalkyl is one or more halo or C １～６ optionally substituted with alkyl, and The 5- to 20-membered heteroaryl is one or more C １～６ phenyl optionally substituted with alkyl; (ii) 3- to 15-membered heterocyclyl, wherein Q １ wherein the 3- to 15-membered heterocyclyl is one or more oxo, or C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl; (iii) 5- to 20-membered heteroaryl, wherein Q １ wherein said 5- to 20-membered heteroaryl is one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Alkoxy, —NH ２ , or C ３～１０ optionally substituted with cycloalkyl; Said C １～６ alkyl is optionally substituted with one or more halo; and Said C ３～１０ Cycloalkyl is one or more halo or C １～６ 5- to 20-membered heteroaryl optionally substituted with alkyl, and (iv) C ３～１０ cycloalkyl; or or (2) L １ Ha-CH ２ - and Q １ is C ３～１０ or cycloalkyl; R １ is H or C １～６ is alkyl, R ｋ is H, halo, -OH, -NH ２ , or —NH—C(O)C １～６ is alkyl, R ｍ is H, —OH, or C １～６ is alkyl, R ｎ is H, C １～６ Alkyl or C ３～１０ cycloalkyl or R ｎ together with the carbon atom to which it is attached, ３～５ forming a cycloalkyl, or R ｋ is R ｍ Or R ｎ and together with the atom to which they are attached form cyclopropyl) to the formula (L-1): RG-L ２ -R ２ -L-R ２ -L ２ -RG(L-1) (In the formula, L ２ is -C(O)- or -S(O) ２ - and R ２ are (i) to (vii): (i) C １～６ alkyl, and R ２ The above C １～６ The alkyl is one or more R ａ and R ａ but, (a) —OH, (b) cyano, (c) C ２～６ Alkynyl, (d) C ６～２０ Aryl, R ａ The above C ６～２０ The aryl is selected from the group consisting of one or more of halo, cyano, C １～６ Alkoxy, or —NH—C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, (e) 3- to 15-membered heterocyclyl, wherein R ａ wherein the 3- to 15-membered heterocyclyl is one or more R ｃ and optionally substituted with R ｃ But, halo, oxo, C １～６ Alkyl, C １～６ Alkoxy, —C(O)—C １～６ Alkyl, or —C(O)—C １～６ is an alkoxy, R ｃ The above C １～６ The alkyl may be one or more halo or C ２～６ optionally substituted with alkynyl, and R ｃ The —C(O)—C １～６ alkoxy is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo; (f) -N(R ｃ ) (R ｄ ) where -N(R ｃ ) (R ｄ ) R ｃ and R ｄ are, independently of each other, H, C １～６ Alkyl, —C(O)—C １～６ Alkyl, —C(O)—C １～６ Alkoxy, —C(O)—NH ２ , -C(O)-NH(C １～６ alkyl), -C(O)-N(C １～６ alkyl) ２ , —C(O)—(3- to 15-membered heterocyclyl), —CH ２ —C(O)—NH ２ , 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R ｃ or R ｄ The above C １～６ The alkyl group is one or more —C(O)—NH ２ and optionally substituted with R ｃ or R ｄ The —C(O)—C １～６ the alkyl is optionally substituted with one or more halo; R ｃ or R ｄ wherein said 3- to 15-membered heterocyclyl and said 5- to 20-membered heteroaryl independently comprise one or more C １～６ optionally substituted with alkyl; R ｃ or R ｄ wherein the —C(O)—(3- to 15-membered heterocyclyl) is one or more halo, —C(O)—C １～６ Alkoxy or C １～６ Optionally substituted with alkyl, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ optionally substituted with cycloalkyl, and R ｃ or R ｄ The —C(O)—N(C １～６ alkyl) ２ The above C １～６ The alkyl may, independently of each other, be one or more halo or C ６～２０ -N(R ｃ ) (R ｄ ), (g) -O-R ｅ and R ｅ But C １～６ Alkyl, C ６～２０ Aryl, —C(O)—(3- to 15-membered heterocyclyl), —C(O)—N—(C １～６ alkyl) ２ or 5- to 20-membered heteroaryl; R ｅ The above C １～６ The alkyl is one or more C １～６ Optionally substituted with alkoxy, １～６ Alkoxy is one or more C ２～６ optionally substituted with alkynyl; R ｅ The above C ６～２０ The aryl is one or more C １～６ optionally substituted with alkyl, and R ｅ The —C(O)—(3- to 15-membered heterocyclyl) is one or more C １～６ Alkyl, C １～６ Alkoxy or —C(O)—C １～６ Optionally substituted with alkoxy, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ -O-R optionally substituted with cycloalkyl ｅ , (h)-C(O)-R ｅ and R ｅ But -NH ２ , —OH, or 3- to 15-membered heterocyclyl, —C(O)—R ｅ , or (i) -S(O) ２ -R ｆ and R ｆ But C １～６ alkyl or 3- to 15-membered heterocyclyl, ２ -R ｆ C １～６ Alkyl, (ii) C ３～１０ Cycloalkyl, R ２ The above C ３～１０ Cycloalkyl is one or more R ｑ and R ｑ is 5- to 20-membered heteroaryl or C ６～２０ aryl, and R ｑ The above C ６～２０ The aryl is one or more C １～６ C optionally substituted with alkoxy ３～１０ cycloalkyl, (iii) 3- to 15-membered heterocyclyl, wherein R ２ wherein the 3- to 15-membered heterocyclyl is one or more of halo, oxo, C １～６ Alkyl, —C(O)—C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iv) 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), １～４ The alkyl group may be one or more of -OH, halo, -NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ and optionally substituted with said 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), wherein the 5- to 20-membered heteroaryl is one or more R ｓ and optionally substituted with R ｓ But, Halo, C １～６ Alkyl, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)-C １～６ Alkyl, C ６～２０ Aryl, C ３～１０ cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C １～６ is an alkoxy, R ｓ The above C １～６ The alkyl may be one or more halo, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy, and R ｓ wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C １～６ 5-20 membered heteroaryl optionally substituted with alkoxy or -(C １～４ alkyl) (5- to 20-membered heteroaryl), (v) -N(R ｇ ) (R ｈ ) where R ｇ and R ｈ are independently H or C １～６ alkyl, —N(R ｇ ) (R ｈ ), (vi)-C(O)-R ｊ and R ｊ But C ３～１０ Cycloalkyl, —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ or —NH(5-20 membered heteroaryl), —C(O)—R ｊ ,and (vii) C ６～２０ Aryl, R ２ The above C ６～２０ The aryl is one or more 5- to 20-membered heteroaryl or —O—R ｐ and R ｐ is 3- to 15-membered heterocyclyl, and R ｐ The 3- to 15-membered heterocyclyl is one or more —C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, Each RG is independently a reactive group suitable for attaching L-1 to a compound of formula (I-1B). to form a compound of any one of claims 1-17, 19-27, or 29.

37. 10. A process for preparing a compound according to any one of claims 1 to 17, or 19 to 25, 27, or 30, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, comprising: Formula (I-2B): 【Chemistry 17】 Compounds of (In the formula, Y ２ and Y ３ are each C, or Y ２ and Y ３ One of the two is N, and Y ２ and Y ３ the other of which is C, X １ and X ２ are each independently H, C １～６ Alkyl, or C １～６ is an alkoxy, X ３ and X ４ are each independently H, halo, C １～６ Alkyl, C １～６ alkoxy, or 5- to 20-membered heteroaryl; X ３ and X ４ The above C １～６ the alkyl is optionally substituted with one or more halo; X ５ is H, C １～６ Alkyl, C １～６ Alkoxy, or C ３～１０ is cycloalkyl, (1) L １ does not exist, and Q １ are (i) to (iv): (i) phenyl, wherein Q １ wherein said phenyl is selected from the group consisting of one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, —NH ２ , -NH-C(O)-(C １～６ alkyl), —NH—C(O)—(3- to 15-membered heterocyclyl), C ３～１０ substituted with cycloalkyl or 5- to 20-membered heteroaryl; Said C １～６ The alkyl may be one or more halo, —NH—C(O)—NH(C １～６ alkyl), —NH—C(O)—C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy; Said C ３～１０ Cycloalkyl is one or more halo or C １～６ optionally substituted with alkyl, and The 5- to 20-membered heteroaryl is one or more C １～６ phenyl optionally substituted with alkyl; (ii) 3- to 15-membered heterocyclyl, wherein Q １ wherein the 3- to 15-membered heterocyclyl is one or more oxo, or C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl; (iii) 5- to 20-membered heteroaryl, wherein Q １ wherein said 5- to 20-membered heteroaryl is one or more halo, C １～６ Alkyl, C ２～６ Alkenyl, C １～６ Alkoxy, —NH ２ , or C ３～１０ optionally substituted with cycloalkyl; Said C １～６ alkyl is optionally substituted with one or more halo; and Said C ３～１０ Cycloalkyl is one or more halo or C １～６ 5- to 20-membered heteroaryl optionally substituted with alkyl, and (iv) C ３～１０ cycloalkyl; or or (2) L １ Ha-CH ２ - and Q １ is C ３～１０ or cycloalkyl) to the formula (L-1): RG-L ２ -R ２ -L-R ２ -L ２ -RG(L-1) (In the formula, L ２ is -C(O)- or -S(O) ２ - and R ２ are (i) to (vii): (i) C １～６ alkyl, and R ２ The above C １～６ The alkyl is one or more R ａ and R ａ but, (a) —OH, (b) cyano, (c) C ２～６ Alkynyl, (d) C ６～２０ Aryl, R ａ The above C ６～２０ The aryl is selected from the group consisting of one or more of halo, cyano, C １～６ Alkoxy, or —NH—C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, (e) 3- to 15-membered heterocyclyl, wherein R ａ wherein the 3- to 15-membered heterocyclyl is one or more R ｃ and optionally substituted with R ｃ But halo, oxo, C １～６ Alkyl, C １～６ Alkoxy, —C(O)—C １～６ Alkyl, or —C(O)—C １～６ is an alkoxy, R ｃ The above C １～６ The alkyl may be one or more halo or C ２～６ optionally substituted with alkynyl, and R ｃ The —C(O)—C １～６ alkoxy is a 3- to 15-membered heterocyclyl optionally substituted with one or more halo; (f) -N(R ｃ ) (R ｄ ) where -N(R ｃ ) (R ｄ ) R ｃ and R ｄ are, independently of each other, H, C １～６ Alkyl, —C(O)—C １～６ Alkyl, —C(O)—C １～６ Alkoxy, —C(O)—NH ２ , -C(O)-NH(C １～６ alkyl), -C(O)-N(C １～６ alkyl) ２ , —C(O)—(3- to 15-membered heterocyclyl), —CH ２ —C(O)—NH ２ , 3- to 15-membered heterocyclyl, or 5- to 20-membered heteroaryl; R ｃ or R ｄ The above C １～６ The alkyl group is one or more —C(O)—NH ２ and optionally substituted with R ｃ or R ｄ The —C(O)—C １～６ the alkyl is optionally substituted with one or more halo; R ｃ or R ｄ wherein said 3- to 15-membered heterocyclyl and said 5- to 20-membered heteroaryl independently comprise one or more C １～６ optionally substituted with alkyl; R ｃ or R ｄ wherein the —C(O)—(3- to 15-membered heterocyclyl) is one or more halo, —C(O)—C １～６ Alkoxy or C １～６ Optionally substituted with alkyl, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ optionally substituted with cycloalkyl, and R ｃ or R ｄ The —C(O)—N(C １～６ alkyl) ２ The above C １～６ The alkyl may, independently of each other, be one or more halo or C ６～２０ -N(R ｃ ) (R ｄ ), (g) -O-R ｅ and R ｅ But C １～６ Alkyl, C ６～２０ Aryl, —C(O)—(3- to 15-membered heterocyclyl), —C(O)—N—(C １～６ alkyl) ２ or 5- to 20-membered heteroaryl; R ｅ The above C １～６ The alkyl is one or more C １～６ Optionally substituted with alkoxy, １～６ Alkoxy is one or more C ２～６ optionally substituted with alkynyl; R ｅ The above C ６～２０ The aryl is one or more C １～６ optionally substituted with alkyl, and R ｅ The —C(O)—(3- to 15-membered heterocyclyl) is one or more C １～６ Alkyl, C １～６ Alkoxy or —C(O)—C １～６ Optionally substituted with alkoxy, １～６ The alkyl may be one or more halo, C １～６ Alkoxy or C ３～１０ -O-R optionally substituted with cycloalkyl ｅ , (h)-C(O)-R ｅ and R ｅ But -NH ２ , —OH, or 3- to 15-membered heterocyclyl, —C(O)—R ｅ , or (i) -S(O) ２ -R ｆ and R ｆ But C １～６ alkyl or 3- to 15-membered heterocyclyl, ２ -R ｆ C １～６ Alkyl, (ii) C ３～１０ Cycloalkyl, R ２ The above C ３～１０ Cycloalkyl is one or more R ｑ and R ｑ is 5- to 20-membered heteroaryl or C ６～２０ aryl, and R ｑ The above C ６～２０ The aryl is one or more C １～６ C optionally substituted with alkoxy ３～１０ cycloalkyl, (iii) 3- to 15-membered heterocyclyl, wherein R ２ wherein the 3- to 15-membered heterocyclyl is one or more of halo, oxo, C １～６ Alkyl, —C(O)—C １～６ 3- to 15-membered heterocyclyl optionally substituted with alkyl, or 5- to 20-membered heteroaryl; (iv) 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), １～４ The alkyl group may be one or more of -OH, halo, -NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ and optionally substituted with said 5- to 20-membered heteroaryl or -(C １～４ alkyl)(5- to 20-membered heteroaryl), wherein the 5- to 20-membered heteroaryl is one or more R ｓ and optionally substituted with R ｓ But, Halo, C １～６ Alkyl, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)-C １～６ Alkyl, C ６～２０ Aryl, C ３～１０ cycloalkyl, 3- to 15-membered heterocyclyl, 5- to 20-membered heteroaryl, or —C(O)—C １～６ is an alkoxy, R ｓ The above C １～６ The alkyl may be one or more halo, C １～６ Alkoxy, —NH ２ , —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ , -NH-C(O)C １～６ Alkyl, or —NH—C(O)—C １～６ optionally substituted with alkoxy, and R ｓ wherein the 3- to 15-membered heterocyclyl is one or more halo or —C(O)—C １～６ 5-20 membered heteroaryl optionally substituted with alkoxy or -(C １～４ alkyl) (5- to 20-membered heteroaryl), (v) -N(R ｇ ) (R ｈ ) where R ｇ and R ｈ are independently H or C １～６ alkyl, —N(R ｇ ) (R ｈ ), (vi)-C(O)-R ｊ and R ｊ But C ３～１０ Cycloalkyl, —NH(C １～６ alkyl), -N(C １～６ alkyl) ２ or —NH(5-20 membered heteroaryl), —C(O)—R ｊ ,and (vii) C ６～２０ Aryl, R ２ The above C ６～２０ The aryl is one or more 5- to 20-membered heteroaryl or —O—R ｐ and R ｐ is 3- to 15-membered heterocyclyl, and R ｐ The 3- to 15-membered heterocyclyl is one or more —C(O)—C １～６ C optionally substituted with alkyl ６～２０ aryl, Each RG is independently a reactive group suitable for attaching L-1 to a compound of formula (I-1B). to form a compound of any one of claims 1 to 17, or 19 to 25, 27, or 30.

38. 38. The process of claim 36 or 37, wherein RG is an —OH group.

39. 36. A pharmaceutical composition comprising: (i) a compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; and (ii) one or more pharmaceutically acceptable excipients.

40. 40. A method of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to said individual an effective amount of a compound of any one of claims 1 to 33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 39.

41. 41. The method of claim 40, wherein the disease, disorder, or condition is a glycogen storage disorder (GSD).

42. 42. The method of claim 40 or 41, wherein the disease, disorder, or condition is selected from the group consisting of Pompe disease, Cori disease (GSD III), adult polyglucosan body disease (APBD), and Lafora disease.

43. 43. The method of any one of claims 40 to 42, wherein the disease, disorder, or condition is Pompe disease.

44. 41. The method of claim 40, wherein the disease, disorder, or condition is cancer.

45. 45. The method of claim 44, wherein the disease, disorder, or condition is selected from the group consisting of Ewing's sarcoma (ES), clear cell renal cell carcinoma (ccRCC), glycogen-rich clear cell carcinoma (GRCC), breast cancer, non-small cell lung cancer (NSCLC), and acute myeloid leukemia (AML).

46. 41. The method of claim 40, wherein the individual has a GAA mutation.

47. 47. The method of claim 46, wherein the GAA mutation comprises a loss-of-function mutation.

48. A kit comprising (i) a compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, and (ii) instructions for use thereof in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

49. 49. The kit of claim 48, wherein the disease, disorder, or condition comprises a glycogen storage disorder (GSD).

50. 50. The kit of claim 48 or 49, wherein the disease, disorder, or condition is selected from the group consisting of Pompe disease, Cori disease (GSD III), adult polyglucosan body disease (APBD), and Lafora disease.

51. 51. The kit of any one of claims 48 to 50, wherein the disease, disorder, or condition is Pompe disease.

52. 52. The kit of claim 51, wherein the disease, disorder, or condition is cancer.

53. 53. The kit of claim 48 or 52, wherein the disease, disorder, or condition is selected from the group consisting of Ewing's sarcoma (ES), clear cell renal cell carcinoma (ccRCC), glycogen-rich clear cell carcinoma (GRCC), breast cancer, non-small cell lung cancer (NSCLC), and acute myeloid leukemia (AML).

54. 49. The kit of claim 48, wherein the individual has a GAA mutation.

55. 55. The kit of claim 54, wherein the GAA mutation comprises a loss-of-function mutation.

56. 40. A method of modulating GYS1 in a cell, comprising exposing the cell to an effective amount of a composition comprising a compound of any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 39.

57. 40. A method of inhibiting GYS1 in a cell, comprising exposing the cell to a composition comprising an effective amount of a compound of any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or to a pharmaceutical composition of claim 39.

58. 40. A method of reducing tissue glycogen stores in an individual in need thereof, comprising administering to said individual an effective amount of a compound of any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 39.

59. 40. A method of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof, comprising subjecting said individual to glycogen substrate-reducing therapy, said glycogen substrate-reducing therapy comprising administering to said individual an effective amount of a compound of any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 39.

60. 60. The method of claim 59, comprising subjecting the individual to glycogen substrate reduction therapy in combination with enzyme replacement therapy.

61. 61. The method of claim 60, wherein the enzyme replacement therapy is selected from the group consisting of alglucosidase alfa (human recombinant alpha-glucosidase (human GAA)), Myozyme, and Lumizyme.

62. 62. The method of any one of claims 59 to 61, wherein the disease, disorder, or condition is a glycogen storage disorder (GSD).

63. 63. The method of any one of claims 59-62, wherein the disease, disorder, or condition is selected from the group consisting of Pompe disease, Cori disease (GSD III), adult polyglucosan body disease (APBD), and Lafora disease.

64. 64. The method of any one of claims 59 to 63, wherein the disease, disorder, or condition is Pompe disease.

65. 62. The method of any one of claims 59 to 61, wherein the disease, disorder, or condition is cancer.

66. 66. The method of any one of claims 59-61, or 65, wherein the disease, disorder, or condition is selected from the group consisting of Ewing's sarcoma (ES), clear cell renal cell carcinoma (ccRCC), glycogen-rich clear cell carcinoma (GRCC), breast cancer, non-small cell lung cancer (NSCLC), and acute myeloid leukemia (AML).

67. 62. The method of any one of claims 59 to 61, wherein the individual has a GAA mutation.

68. 68. The method of claim 67, wherein the GAA mutation comprises a loss-of-function mutation.

69. 59. The method of any one of claims 56 to 58, wherein the compound is selective for GYS1 over GYS2.

70. 70. The method of claim 69, wherein the compound is 500-fold or 1,000-fold or 1,500-fold or 1,700-fold selective for GYS1 over GYS2.

71. 71. The method of any one of claims 40-47 or 57-70, comprising reducing glycogen levels in skeletal muscle.

72. 40. A compound according to any one of claims 1 to 33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, for use in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

73. 40. A compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, for use in modulating GYS1 in a cell.

74. 40. A compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, for use in inhibiting GYS1 in a cell.

75. 40. A compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, for use in reducing tissue glycogen stores in an individual in need thereof.

76. 40. A compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, for use in glycogen substrate reduction therapy for the treatment of a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

77. 40. Use of a compound according to any one of claims 1 to 33, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, in the manufacture of a medicament for use in treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

78. 40. Use of a compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, in the manufacture of a medicament for use in modulating GYS1 in a cell.

79. 40. Use of a compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, in the manufacture of a medicament for use in inhibiting GYS1 in a cell.

80. 40. Use of a compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, in the manufacture of a medicament for use in reducing tissue glycogen stores in an individual in need thereof.

81. 40. Use of a compound according to any one of claims 1 to 35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition according to claim 39, in the manufacture of a medicament for use in glycogen substrate reduction therapy for the treatment of a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

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